v>EPA
CH/?
United States
Environmental Protection
Agency
A U.S. EPA Program
Presidential
Green Chemistry Challenge
Award Recipients
1996-2012
-------
The Presidential
Green Chemistry Challenge
Award Recipients
1996-2012
-------
-------
Academic Awards.-
Professor Geoffrey W. Coates,
Cornell University 2
Professor Robert M. Waymouth,
Stanford University
Dr. James L. Hedrick,
IBM Almaden Research Center 3
Small Business Award:
Elevance Renewable Sciences, Inc. 4
Greener Synthetic Pathways Award:
Codexis, Inc.
Professor Yi Tang,
University of California, Los Angeles 5
Greener Reaction Conditions Award:
Cytec Industries Inc 6
Designing Greener Chemicals Award:
Buckman International, Inc. 7
Academic Award:
Professor Bruce H. Lipshutz,
University of California,
Santa Barbara 8
Small Business Award:
BioAmber, Inc 9
Greener Synthetic Pathways Award:
Genomatica 10
Greener Reaction Conditions Award:
Kraton Performance Polymers, Inc //
Designing Greener Chemicals Award:
The Sherwin-Williams Company 12
Academic Award:
James C. Liao, Ph.D.,
Easel Biotechnologies, LLCand
University of California, Los Angeles 13
Small Business Award:
LS9,lnc 14
Contents ill
-------
Greener Synthetic Pathways Award:
The Dow Chemical Company
BASF [[[ 15
Greener Reaction Conditions Award:
Merck & Co., Inc.
Codexis, Inc. [[[ 76
Designing Greener Chemicals Award:
Clarke [[[ 77
Academic Award:
Professor Krzysztof Mat yjaszewski,
Carnegie Mellon University [[[ 78
Small Business Award:
Virent Energy Systems, Inc. [[[ 79
Greener Synthetic Pathways Award:
Eastman Chemical Company [[[ 20
Greener Reaction Conditions Award:
CEM Corporation [[[ 27
Designing Greener Chemicals Award:
The Procter & Gamble Company,
Cook Composites and Polymers Company. [[[ 22
Academic Award:
Professors Robert E. Maleczka and
Milton R. Smith, III,
Michigan State University [[[ 23
Small Business Award:
SiGNa Chemisty, Inc. [[[ 24
-------
Greener Reaction Conditions Award:
Headwaters Technology Innovation [[[ 31
Designing Greener Chemicals Award:
Cargill, Incorporated [[[ 32
Academic Award:
Professor Galen J. Suppes,
University of Missouri-Columbia [[[ 33
Small Business Award:
Arkon Consultants, NuPro Technologies, Inc.
(now Eastman Kodak Company) [[[ 34
Greener Synthetic Pathways Award:
Merck & Co., Inc. [[[ 35
Greener Reaction Conditions Award:
Codexis, Inc. [[[ 36
Designing Greener Chemicals Award:
S.C.Johnson &Son, Inc. [[[ 37
Academic Award:
Professor Robin D. Rogers,
The University of Alabama [[[ 38
Small Business Award:
Metabolix, Inc [[[ 39
Greener Synthetic Pathways Award:
Archer Daniels Midland Company, Novozymes ................................................ 40
Merck & Co., Inc [[[ 41
Greener Reaction Conditions Award:
BASF Corporation [[[ 42
-------
Academic Award:
Professor Richard A. Gross,
Polytechnic University 49
Small Business Award:
AgraQuest, Inc 50
Greener Synthetic Pathways Award:
Sud-Chemie Inc 51
Greener Reaction Conditions Award:
DuPont 52
Designing Greener Chemicals Award:
Shaw Industries, Inc 53
Academic Award:
Professor EricJ. Beckman,
University of Pittsburgh 54
Small Business Award:
SC Fluids, Inc 55
Greener Synthetic Pathways Award:
Pfizer, Inc. 56
Greener Reaction Conditions Award:
Cargill Dow LLC (now NatureWorks LLC) 57
Designing Greener Chemicals Award:
Chemical Specialties, Inc. (CSI) (nowViance) 58
Academic Award:
Professor Chao-Jun Li,
Tulane University 59
Small Business Award:
EDEN Bioscience Corporation 60
Greener Synthetic Pathways Award:
Bayer Corporation, Bayer AC (technology acquired by LANXESS) 61
Greener Reaction Conditions Award:
Novozymes North America, Inc. 62
Designing Greener Chemicals Award:
PPG Industries 63
Academic Award:
Professor Chi-Huey Wong,
The Scripps Research Institute 64
Small Business Award:
RevTech, Inc 65
Greener Synthetic Pathways Award:
Roche Colorado Corporation 66
vi Contents
-------
Greener Reaction Conditions Award:
Bayer Corporation, Bayer AC 67
Designing Greener Chemicals Award:
Dow AgroSciences LLC 68
Academic Award:
Professor Terry Collins,
Carnegie Mellon University 69
Small Business Award:
Biofine, Inc. (now BioMetics, Inc.) 70
Greener Synthetic Pathways Award:
Lilly Research Laboratories 71
Greener Reaction Conditions Award:
Nalco Chemical Company 72
Designing Greener Chemicals Award:
DowAgroSciences LLC 73
Academic Award:
Professor Barry M. Trost,
Stanford University 74
Dr. Karen M. Draths and Professor John W. Frost,
Michigan State University 75
Small Business Award:
Pyrocool Technologies, Inc 76
Greener Synthetic Pathways Award:
Flexsys America L.P. 77
Greener Reaction Conditions Award:
Argonne National Laboratory 78
Designing Greener Chemicals Award:
Rohm and Haas Company (now The Dow Chemical Company) 79
Academic Award:
Professor Joseph M. DeSimone,
University of North Carolina at Chapel Hill and
North Carolina State University 80
Small Business Award:
Legacy Systems, Inc. 81
Greener Synthetic Pathways Award:
BHC Company (now BASF Corporation) 82
Greener Reaction Conditions Award:
Imation (technology acquired by Eastman Kodak Company) 83
Designing Greener Chemicals Award:
Albright & Wilson Americas (now Rhodia) 84
Contents vii
-------
Academic Award:
Professor Mark Holtzapple,
Texas A&M University 85
Small Business Award:
Donlar Corporation (nowNanoChem Solutions, Inc.) 86
Greener Synthetic Pathways Award:
Monsanto Company 87
Greener Reaction Conditions Award:
The Dow Chemical Company 88
Designing Greener Chemicals Award:
Rohm and Haas Company (now The Dow Chemical Company) 89
fr"0|,-mi lnKHin;:jirHi go
j'h.->- b'lMK:! 90
,id-;\ 91
viii Contents
-------
The Presidential Green Chemistry Challenge Awards Program enables individuals, groups, and organizations to
compete for annual presidential-rank awards that recognize innovations in cleaner, cheaper, smarter chemistry.
By honoring and highlighting outstanding chemical technologies that incorporate principles of green chemistry
into chemical design, manufacture, and use, this awards program better enables industry to meet its pollution
prevention goals.
This booklet presents the 1996 through 2012 Presidential Green Chemistry Challenge Award recipients and
describes their award-winning technologies. Each winner demonstrates a commitment to designing, developing,
and implementing a green chemical technology that is scientifically innovative, economically feasible, and less
hazardous to human health and the environment.
EPA typically honors five winners each year, one in each of the following categories:
• Academia
• Small Business
• Greener Synthetic Pathways, such as the use of innocuous and renewable feedstocks (e.g., biomass, natural
oils); novel reagents or catalysts including biocatalysts and microorganisms; natural processes including
fermentation and biomimetic syntheses; atom-economical syntheses; and convergent syntheses
• Greener Reaction Conditions, such as the replacement of hazardous solvents with greener solvents; solventless
or solid-state reactions; improved energy efficiency; novel processing methods; and the elimination of energy-
and material-intensive separations and purifications
• Designing Greener Chemicals, such as chemicals that are less toxic than current alternatives; inherently safer
chemicals with regard to accident potential; chemicals recyclable or biodegradable after use; and chemicals
safer for the atmosphere (e.g., do not deplete ozone or form smog)
The Presidential Green Chemistry Challenge has had 88 winners over its 17 years. Collectively each year these
winning technologies:
• Eliminate 825 million pounds of hazardous chemicals and solvents
• Save over 21 billion gallons of water
• Eliminate 7.9 billion pounds of carbon dioxide releases to the air
Added together, the environmental, health, and cost benefits of all 1,492 technologies nominated for these
awards over the past 17 years are huge. Congratulations to all of our winners and nominees! In the future, EPA
looks forward to honoring many more nominees and winners on the cutting edge of pollution prevention.
-------
2012 Winners
Synthesizing Biodegradable Polymers from Carbon Dioxide and Carbon Monoxide
Carbon monoxide and carbon dioxide derived from biomass or other carbon sources are ideal feedstocks for chemicals,
but there had been no efficient way to make them into valuable polymers. Professor Coates developed a family of
catalysts that convert carbon dioxide and carbon monoxide into polymers. Novomer, Inc. is using his discoveries to
develop a range of innovative, high-performance products, including can and coil coatings, adhesives, foams, and
plastics.
i lastics improve our lives in countless ways, but they also pose a serious threat to our environment. Virtually all
plastics are derived from scarce fossil fuels that pose their own danger, including oil well leaks and global warming
induced by carbon dioxide (CO2). Of the 150 million tons of plastics made each year worldwide, only a small fraction
is recycled. The rest end up in landfills or worse as litter.
CO2 and carbon monoxide (CO) are ideal feedstocks for polymer synthesis. They can be derived from many
low-cost sources including biorenewable agricultural waste, abundant coal, or even from industrial waste gas. The
challenge with using them, however, lies in converting them into useful products efficiently. Professor Geoffrey
Coates has developed innovative processes to synthesize plastics from inexpensive, biorenewable substances
including carbon dioxide, carbon monoxide, plant oils, and lactic acid.
Professor Coates has developed a new family of catalysts over the last decade that can effectively and economically
turn CO2 and CO into valuable polymers. These catalysts have high turnover frequencies, turnover numbers, and
selectivities. As a result, only a small amount of catalyst is required leading to cost-effective commercial production
for the first time. These catalysts can also be used in highly efficient continuous flow processes.
Professor Coates has invented active and selective catalysts to copolymerize CO2 and epoxides into
high-performance polycarbonates. Professor Coates also invented a class of catalysts that can insert one or two
molecules of CO into an epoxide ring to produce (3-lactones and succinic anhydrides. Both of these products
have many uses in synthesizing Pharmaceuticals, fine chemicals, and plastics. Polymers made from CO2 and CO
contain ester and carbonate linkages. These polymers exhibit unique performance in current commodity plastic
applications and in some cases are ultimately biodegradable.
Professor Coates's work forms the scientific foundation of Novomer Inc., a start-up company backed by venture
capital. In 2010, Novomer and DSM announced an agreement to develop coatings using the new polycarbonates
made with Coates's catalysts. Prototype high-performance industrial coil coatings are moving from development
toward commercialization. There is potential to develop a coating system to replace the bisphenol A (BPA) epoxy
coatings that line most food and drink cans worldwide. This discovery is important, as BPA is a suspected endocrine
disrupter that can migrate out of coatings over time. The novel polymer is currently sold to companies that
manufacture electronics because the thermally degradable nature of the polymer allows more efficient production
of electronic components. The new polycarbonate coating is expected to require 50 percent less petroleum to
produce and will sequester up to 50 weight percent CO2. Lifecycle analysis shows that at full market penetration,
Novomer's materials have the potential to sequester and avoid approximately 180 million metric tons of annual CO2
emissions.
2 2012 Academic Award
-------
Organic Catalysis: A Broadly Useful Strategy for Green Polymer Chemistry
Traditional metal catalysts required to synthesize polyesters and other common plastics end up trapped in the plastic,
raising human health and environmental concerns. Professor Waymouth and Dr. Hedrick discovered an array of
alternatives—metal-free catalysts—that are highly active and able to make a wide variety of plastics. Their discoveries
include catalysts that can depolymerize plastic and enable cradle-to-cradle recycling.
Latalysis is a foundation for sustainable chemical processes, and the discovery of highly active, environmentally
benign, catalytic processes is a central goal of green chemistry. Conventional routes to polyesters rely on
metal catalysts such as those derived from tin complexes, even though the residual metal catalysts used for
high-volumes plastics can have negative environmental impacts in solid waste, for this reason, the European
Union recently phased out many organotin compounds. As a result, research on organic catalysts to replace
the tin-based workhorse catalysts has gained significant prominence in industrial settings related to important
commodity polymers such as siloxanes, urethanes, nylons, and polyesters.
Dr. James L Hedrick and Professor Robert M. Waymouth have developed a broad class of highly active,
environmentally benign organic catalysts for synthesizing biodegradable and biocompatible plastics. Their
technology applies metal-free organic catalysts to the synthesis and recycling of polyesters. They discovered
new organic catalysts for polyester synthesis whose activity and selectivity rival or exceed those of metal-based
alternatives. Their approach provides an environmentally attractive, atom-economical, low-energy alternative to
traditional metal-catalyzed processes. Their technology includes organocatalytic approaches to ring-opening,
anionic, zwitterionic, group transfer, and condensation polymerization techniques. Monomer feedstocks include
those from renewable resources, such as lactides, as well as petrochemical feedstocks. In addition to polyesters,
Dr. Hedrick and Professor Waymouth have discovered organocatalytic strategies (1) to synthesize polycarbonates,
polysiloxanes, and polyacrylates, (2) to chemically recycle polyesters, (3) to use metal-free polymers as templates
for inorganic nanostructures for microelectronic applications, and (4) to develop new syntheses for
high-molecular-weight cyclic polyesters. This team has shown that the novel mechanisms of enchainment
brought about by organic catalysts can create polymer architectures that are difficult to synthesize by conventional
approaches.
The team also developed organic catalysts to depolymerize poly(ethylene terephthalate) (PET) quantitatively,
allowing recycling for PET from bottles into new bottles as a way to mitigate the millions of pounds of PET that
plague our landfills. Dr. Hedrick and Professor Waymouth also demonstrated that their organic catalysts tolerate a
wide variety of functional groups, enabling the synthesis of well-defined biocompatible polymers for biomedical
applications. Because these catalysts do not remain bound to the polymer chains, they are effective at low
concentrations. These results, coupled with cytotoxicity measurements in biomedical applications, highlight the
environmental and human health benefits of this approach. Professor Waymouth and Dr. Hedrick have produced
over 80 manuscripts and eight patents on the design of organic catalysts for polymer chemistry with applications
in sustainable plastics, biomedical materials, and plastics for recycling.
2012 Academic Award 3
-------
Using Metathesis Catalysis to Produce High-Performing, Green Specialty Chemicals at Advantageous Costs
Elevance employs Nobel-prize-winning catalyst technology to break down natural oils and recombine the fragments into
novel, high-performance green chemicals. These chemicals combine the benefits of both petrochemicals and biobased
chemicals. The technology consumes significantly less energy and reduces greenhouse gas emissions by 50 percent
compared to petrochemical technologies. Elevance is producing specialty chemicals for many uses, such as highly
concentrated cold-water detergents that provide better cleaning with reduced energy costs.
I levance produces high-performance, cost-advantaged green chemicals from renewable oils. Its processes use
Nobel Prize-winning innovations in metathesis catalysis, consume significantly less energy, and reduce greenhouse
gas (GHG) emissions by 50 percent compared to petrochemical technologies. The processes use a highly efficient,
selective catalyst to break down natural oils and recombine fragments. The core technology is based on the work
of Nobel Laureate Dr. Robert H. Grubbs. In 2011, Elevance expanded its proprietary technology with a licensing
agreement with XiMo AG to use proprietary molybdenum and tungsten metathesis catalysts based on the work of
Nobel Laureate Dr. Richard Schrock.
The resulting products are high-value, difunctional chemicals with superior functional attributes previously unavailable
commercially. These molecules combine the functional attributes of an olefin, typical of petrochemicals, and a
monofunctional ester or acid, typical of biobased oleochemicals, into a single molecule. Conventional producers
have to blend petrochemicals and biobased oleochemicals in attempts to achieve these functional attributes
simultaneously, which when possible, increase their production costs. Elevance's difunctional building blocks change
this paradigm by creating specialty chemical molecules which simultaneously include desired attributes enabled by
both chemical families, such as lubricant oils with improved stability or surfactants with improved solvency.
Elevance's low-pressure, low-temperature processes use a diversity of renewable feedstocks that yield products
and byproducts with lowtoxicity. Elevance's processes result in lower source pollution, production costs, and
capital expenditures than petrochemical refineries. Currently, Elevance is the only company that can produce these
difunctional chemicals. The company's ability to manufacture biochemicals for multiple products reduces reliance on
petrochemicals and provides more effective, sustainable products to consumers.
The company makes difunctional molecules as part of its specialty chemical business. Elevance's products enable
novel surfactants, lubricants, additives, polymers, and engineered thermoplastics. For instance, Elevance is producing
specialty chemicals to enable cold water detergents that have more concentrated formulations and improved solvency
for better cleaning, to improve sustainability metrics, and to reduce energy costs for customers and consumers. Other
examples include biobased anti-frizz and shine additives for leave-in hair care products to replace petroleum-based
petrolatum, alternatives to paraffin for high performance waxes, novel plastic additives for poly(vinyl chloride) (PVC)
and unique monomers for biobased polymers and engineered plastics.
Elevance has completed validation in toll manufacturing. It is building world-scale facilities in Gresik, Indonesia,
and Natchez, Mississippi, with combined annual production capacity over 1 billion pounds and exploring sites in
South America. Elevance has also secured strategic partnerships with value chain global leaders to accelerate rapid
deployment and commercialization for these products.
4 2012 Small Business Award
-------
An Efficient Biocatalytic Process to Manufacture Simvastatin
Simvastatin, a leading drug for treating high cholesterol, is manufactured from a natural product. The traditional
multistep synthesis was wasteful and used large amounts of hazardous reagents. Professor Tang conceived a synthesis
using an engineered enzyme and a practical low-cost feedstock. Codexis optimized both the enzyme and the
chemical process. The resulting process greatly reduces hazard and waste, is cost-effective and meets the needs of
customers. Some manufacturers in Europe and India use this process to make Simvastatin.
bimvastatin, a leading cholesterol lowering drug, was originally developed by Merck under the brand name
Zocor®. In 2005, Zocor® was Merck's best selling drug and the second-largest selling statin in the world with about
$5 billion in sales. After when Zocor® went off patent in 2006, Simvastatin became the most-prescribed statin,
with 94 million prescriptions filled in 2010, according to IMS Health.
Simvastatin is a semisynthetic derivative of lovastatin, a fungal natural product. Simvastatin contains an additional
methyl group at the C2' position of the lovastatin side chain. Introduction of this methyl group in lovastatin using
traditional methods requires a multistep chemical synthesis. In one route, lovastatin is hydrolyzed to the triol,
monacolin J, which is protected by selective silylation, esterified with dimethylbutyryl chloride, and deprotected.
Another route involves protecting the carboxylic acid and alcohol, methylating the C2' with methyl iodide, and
deprotecting. Despite considerable optimization, these processes have overall yields of less than 70 percent, are
mass-intensive due to protection/deprotection, and require copious amounts of toxic and hazardous reagents.
Professor Yi Tang and his group at UCLA conceived a new Simvastatin manufacturing process and identified
both a biocatalyst for regioselective acylation and a practical, low-cost acyl donor. The biocatalyst is LovD, an
acyltransferase that selectively transfers the 2-methylbutyryl side chain to the C8 alcohol of monacolin J sodium or
ammonium salt. The acyl donor, dimethylbutyryl-5-methylmercaptopropionate (DMB-SMMP), is very efficient for
the LovD-catalyzed reaction, is safer than traditional alternatives, and is prepared in a single step from inexpensive
precursors. Codexis licensed this process from UCLA and subsequently optimized the enzyme and the chemical
process for commercial manufacture. Codexis carried out nine iterations of in vitro evolution, creating 216 libraries
and screening 61,779 variants to develop a LovD variant with improved activity, in-process stability, and tolerance
to product inhibition. The approximately 1,000-fold improved enzyme and the new process pushed the reaction to
completion at high substrate loading and minimized the amounts of acyl donor and of solvents for extraction and
product separation.
In the new route, lovastatin is hydrolyzed and converted to the water-soluble ammonium salt of monacolin J.
Then a genetically evolved variant of LovD acyltransferase from E. coll uses DMB-SMMP as the acyl donor to
make the water-insoluble ammonium salt of Simvastatin. The only coproduct of Simvastatin synthesis is methyl
3-mercaptopropionic acid, which is recycled. The final yield of Simvastatin ammonium salt is over 97 percent at a
loading of 75 grams per liter of monacolin J. The nominated technology is practical and cost-effective. It avoids
the use of several hazardous chemicals including fert-butyl dimethyl silane chloride, methyl iodide, and n-butyl
lithium. Customers have evaluated the Simvastatin produced biocatalyticallyand confirmed that it meets their
needs. Over 10 metric tons of Simvastatin have been manufactured using this new process.
2012 Greener Synthetic Pathways Award 5
-------
MAX HT® Bayer Sodalite Scale Inhibitor
The "Bayer process" converts bauxite to alumina, the raw material for making aluminum. Mineral scale deposited on
the heat exchangers and pipes in Bayer process plants increases energy use. Removing the scale requires stopping
production and cleaning with sulfuric acid. Cytec's product hinders scale growth. Eighteen plants worldwide are using
MAX HT® inhibitor, saving trillions of Btu (British thermal units) annually. Fewer cleaning cycles also reduce hazardous
acid waste by millions of pounds annually.
1 he Bayer process converts bauxite ore to alumina, the primary raw material for aluminum. The process involves
extracting alumina trihydrate from bauxite ore using hot caustic solution. After separating out the insoluble
solids, the alumina trihydrate is precipitated and the spent liquor is recycled. Heat exchangers re-concentrate
the liquor to the optimum concentration of caustic and then heat it to the proper temperature for digestion.
Silica present as silicates, primarily clay materials, dissolves quickly in typical Bayer liquor used to digest alumina,
resulting in the liquor being supersaturated in silica, particularly after precipitation of the alumina trihydrate. The
silica in the liquor reacts with the caustic and alumina on the hot surfaces of the heat exchangers; as a result,
sodalite scale (i.e., crystalline aluminosilicate) builds up on the heat exchangers and interstage piping in the
process. This reduces the efficiency of the heat exchangers. Periodically, Bayer process plant operators must take
the equipment off line for cleaning that involves removing the scale with sulfuric acid. The used acid is a waste
stream that requires disposal. In addition to the acid cleaning, much of the interstage piping requires cleaning
with mechanical means such as jackhammers to remove the scale.
Cytec developed its MAX HT® Bayer Sodalite Scale Inhibitor products for the Bayer process. There are no other
scale inhibitors on the market for this application. The active polymeric ingredient contains silane functional
groups that inhibit crystal growth by incorporation into the crystal or adsorption onto its surface. The polymers
have molecular weights in the range 10,000 and 30,000. Their synthesis involves polymerizing a monomer
containing a silane group or reacting polymer backbone with a reagent containing the silane group. Dosages
range from 20 to 40 ppm. Assessments of these polymers under EPA's Sustainable Futures Program indicate low
overall concern for human health and the aquatic environment.
Eliminating sodalite scale from heater surfaces has many benefits. Heat recovery from the steam produced in
various unit operations is more efficient. Increased evaporation makes the countercurrent washing circuit more
efficient and reduces caustic losses. Reducing the use of steam reduces emissions from burning carbon-based
fuels. Finally, reducing the sulfuric acid used to clean heaters reduces both worker exposure and waste. Typically,
MAX HT® inhibitor increases the on-stream time for a heater from 8-10 days to 45-60 days for digestion and from
20-30 days to over 150 days for evaporators.
There are about 73 operating Bayer process plants worldwide with annual capacities of 0.2-6 million tons of
alumina per plant; most plants are in the 1.5-3 million ton range. Eighteen Bayer process plants worldwide have
adopted this technology; seven more plants are testing it. Each plant using MAX HT® saves $2 million to
$20 million annually. The realized annual energy savings for all plants together are 9.5 trillion to 47.5 trillion Btu,
which is the equivalent of about 1.1 billion to 7.7 billion pounds of carbon dioxide (CO2) not released to the
atmosphere. Fewer cleaning cycles and less acid per cycle result in a realized annual hazardous waste reduction
of 76 million to 230 million pounds for all plants together.
6 2012 Greener Reaction Conditions Award
-------
Enzymes Reduce the Energy and Wood Fiber Required to Manufacture High-Quality Paper and Paperboard
Traditionally, making strong paper required costly wood pulp, energy-intensive treatment, or chemical additives. But
that may change. Buckman's Maximyze® enzymes modify the cellulose in wood to increase the number of "fibrils"
that bind the wood fibers to each other, thus making paper with improved strength and quality - without additional
chemicals or energy. Buckman's process also allows papermaking with less wood fiber and higher percentages of
recycled paper, enabling a single plant to save $1 million per year.
\ he paper and packaging industry is an important part of the U.S. economy, with product sales of $115 billion per
year and employment of about 400,000 people. Previously, papermakers who needed to improve paper strength
were limited to adding costly pulps, increasing mechanical treatment that expends significant energy, or using
various chemical additives such as glyoxalated polyacrylamides and polyacrylamide copolymers.
Enzymes are extremely efficient tools for replacing conventional chemicals in papermaking applications.
Buckman's Maximyze® technology consists of new cellulase enzymes and combinations of enzymes derived
from natural sources and produced by fermentation. These enzymes were not previously available commercially.
Wood fibers treated with Maximyze® enzymes prior to refining (a mechanical treatment unique to papermaking)
have substantially more fibrils that bind the wood fibers to each other. Maximyze® enzymes modify the cellulose
polymers in the wood fiber so that the same level of refining produces much more surface area for hydrogen
bonding, which is the basic source of strength in paper. As a result, Maximyze® treatment produces paper and
paperboard with improved strength and quality.
Maximyze® improves strength so the weight of the paper product can be reduced or some of the wood fiber can
be replaced with a mineral filler such as calcium carbonate. Maximyze® treatment makes it possible to use higher
percentages of recycled paper. Maximyze® treatment uses less steam because the paper drains faster (increasing
the production rate) and uses less electricity for refining. Maximyze® treatment is less toxic than current
alternatives and is safer to handle, manufacture, transport, and use than current chemical treatments. These and
other benefits are produced by Maximyze® treatment, a biotechnology that comes from renewable resources, is
safe to use, and is itself completely recyclable.
The first commercial application began with the production of fine paper within the past two years. In 2011, a
pulp and paper manufacturer in the Northwest began to add Maximyze® enzymes to the bleached pulp used
to produce paperboard for food containers. This change increased machine speed by 20 feet per minute for a
2 percent increase in production. It also reduced the level of mechanical refining by 40 percent for a substantial
savings in energy. Finally, it reduced the basis weight (density) of the paper by 3 pounds per 1,000 square feet
without changing the specifications for quality. Overall, Maximyze® treatment reduced the amount of wood
pulp required by at least 1 percent, which reduced the annual amount of wood needed to produce the food
containers by at least 2,500 tons. Buckman estimates that using Maximyze® technology for this one machine can
save wood pulp equivalent to 25,000 trees per year. Another large mill producing fine paper has used Buckman's
technology since January 2010 and saved over $1 million per year. Since introducing this new technology,
Buckman has expanded it and is now applying it successfully in over 50 paper mills in the United States
and beyond.
2012 Designing Greener Chemicals Award 7
-------
SO 11 Winners
Towards Ending Our Dependence on Organic Solvents
Most chemical manufacturing processes rely on organic solvents, which tend to be volatile, toxic, and flammable.
Chemical manufacturers use billions of pounds of organic solvents each year, much of which becomes waste. Water
itself cannot replace organic solvents as the medium for chemical reactions because many chemicals do not dissolve
and do not react in water. Professor Lipshutz has designed a safe surfactant that forms tiny droplets in water. Organic
chemicals dissolve in these droplets and react efficiently, allowing water to replace organic solvents.
! , rganic solvents are routinely used as the medium for organic reactions and constitute a large percentage
of the world's chemical production waste. Most organic solvents are derived from petroleum and are volatile,
flammable, and toxic. Typically, organic reactions cannot be done in water because the reactants themselves are
insoluble. Surfactants can be used to increase the solubility of organic reactants in water, but they often disperse
the reactants, slowing the reactions.
Professor Lipshutz has designed a novel, second-generation surfactant called TPGS-750-M. It is a "designer"
surfactant composed of safe, inexpensive ingredients: tocopherol (vitamin E), succinicacid (an intermediate in
cellular respiration), and methoxy poly(ethylene glycol) (a common, degradable hydrophilic group also called
MPEG-750). TPGS-750-M forms "nanomicelles" in water that are lipophilic on the inside and hydrophilic on the
outside. A small amount of TPGS-750-M is all that is required to spontaneously form 50-100 nm diameter micelles
in water to serve as nanoreactors. TPGS-750-M is engineered to be the right size to facilitate broadly used organic
reactions, such as cross-couplings. Reactants and catalysts dissolve in the micelles, resulting in high concentrations
that lead to dramatically increased reaction rates at ambient temperature. No additional energy is required.
Several very common organic reactions that are catalyzed by transition metals can take place within TPGS-750-M
micelles in water at room temperature and in high isolated yields. These reactions include ruthenium-catalyzed
olefin metatheses (Grubbs), palladium-catalyzed cross-couplings (Suzuki, Heck, and Sonogashira), unsymmetrical
aminations, allylic aminations and silylations, and aryl borylations. Even palladium-catalyzed aromatic carbon-
hydrogen bond activation to make new carbon-carbon bonds can be done at room temperature, an extraordinary
achievement. Product isolation is straightforward; complications such as frothing and foaming associated with
other surfactants are not observed. Recycling the surfactant after use is also very efficient: the insoluble product
can be recovered by extraction, and the aqueous surfactant is simply reused with negligible loss of activity. Future
generations of surfactants may include a catalyst tethered to a surfactant to provide both the "reaction vessel" (the
inside of the micelle) and the catalyst to enable the reaction. Tethering catalysts in this way may reduce one-time
use of rare-earth minerals as catalysts.
In all, this technology offers opportunities for industrial processes to replace large amounts of organic solvents with
very small amounts of a benign surfactant nanodispersed in water only. High-quality water is not needed: these
reactions can even be run in seawater. Sigma-Aldrich is currently selling TPGS-750-M, making it broadly available to
research laboratories.
8 2011 Academic Award
-------
Integrated Production and Downstream Applications of Biobased Succinic Acid
Succinic acid is a true "platform molecule," that is, a starting material for other important chemicals, but the high cost
of producing succinic acid from fossil fuels has restricted its use. Now, however, BioAmber is producing succinic acid
that is both renewable and lower cost by combining an £ coli biocatalyst licensed from the Department of Energy with
a novel purification process. BioAmber's process uses 60 percent less energy than succinic acid made from fossil fuels,
offers a smaller carbon footprint, and costs 40 percent less.
buccinic acid has traditionally been produced from petroleum-based feedstocks. In addition to its current use
in food, drug, and cosmetic applications, succinic acid is a platform molecule that can be used to make a wide
range of chemicals and polymers.
BioAmber has developed an integrated technology that produces large, commercial quantities of succinic acid
by fermentation rather than from petroleum feedstocks. Since early 2010, BioAmber has been producing succinic
acid by bacterial fermentation of glucose in the world's only large-scale, dedicated, biobased succinic acid plant.
This $30 million plant includes an integrated, continuous downstream process. BioAmber believes its renewable
succinic acid is the first direct substitution of a fermentation-derived chemical for a petroleum-derived chemical.
BioAmber has successfully scaled up an £ coli biocatalyst licensed from the Department of Energy and integrated
a novel, water-based downstream purification process. The fermentation process, although pH neutral, produces
no significant byproducts. BioAmber's technology produces succinic acid at a cost that is 40 percent below
that of petroleum-based succinic acid. Even at oil prices below $40 per barrel, BioAmber's product boasts cost
advantages over succinic acid derived from fossil fuels.
BioAmber's economic advantage has given a number of chemical markets the confidence both to use succinic
acid as a substitute for existing petrochemicals and to develop new applications for succinic acid. Succinic acid
can replace some chemicals directly, including adipic acid for polyurethane applications and highly corrosive
acetate salts for deicing applications. BioAmber has also made it economically feasible to (1) transform biobased
succinic acid into renewable 1,4-butanediol and other four-carbon chemicals; (2) produce succinate esters
for use as nontoxic solvents and substitutes for phthalate-based plasticizers in PVC (poly(vinyl chloride)) and
other polymers; and (3) produce biodegradable, renewable performance plastics. BioAmber is leading the
development of modified polybutylene succinate (mPBS), a polyester that is over 50 percent biobased and offers
good heat-resistance (above 100 °C) and biodegradability (ASTM D6400 compliant). BioAmber's process reduces
energy consumption by 60 percent compared to its petrochemical equivalent and actually consumes carbon
dioxide (CO2), rather than generating it.
In 2011, BioAmber plans to begin constructing a 20,000 metric ton facility in North America that will sequester
over 8,000 tons of CO2 per year, an amount equal to the emissions of 8,000 cross-country airplane flights or
2,300 compact cars annually. BioAmber has also signed partnership agreements with several major companies,
including Cargill, DuPont, Mitsubishi Chemical, and Mitsui & Co. The scale up of biobased succinic acid to
commercial quantities will expand markets, reducing pollution at the source and increasing health benefits at
numerous points in the lifecycles of a variety of chemicals made from succinic acid.
2011 Small Business Award 9
-------
Production of Basic Chemicals from Renewable Feedstocks at Lower Cost
1,4-Butanediol (BDO) is a high-volume chemical building block used to make many common polymers, such as
spandex. Using sophisticated genetic engineering, Genomatica has developed a microbe that makes BDO by
fermenting sugars. When produced at commercial scale, Genomatica's Bio-BDO will be less expensive, require about
60 percent less energy, and produce 70 percent less carbon dioxide emissions than BDO made from natural gas.
Genomatica is partnering with major companies to bring Bio-BDO to the market.
\ lost high-volume commodity chemicals, including monomers, are made from natural gas or petroleum.
Genomatica is developing and commercializing sustainable basic and intermediate chemicals made from
renewable feedstocks including readily available sugars, biomass, and syngas. The company aims to transform
the chemical industry through the cost-advantaged, smaller-footprint production of biobased chemicals as direct
replacements for major industrial chemicals that are currently petroleum-based in a trillion-dollar global market.
By greening basic and intermediate chemicals at the source, Genomatica's technology enables others to make
thousands of downstream products more sustainably without changing their manufacturing processes. By
producing the building-block chemicals directly, Genomatica also reduces unwanted byproducts.
The first target molecule for Genomatica is 1,4-butanediol (BDO). BDO is used to make spandex, automotive
plastics, running shoes, and many other products. It has an approximately 2.8 billion pound, $3 billion worldwide
market. Genomatica has been producing Bio-BDO at pilot scale in 3,000 liter fermentations since the first half
of 2010 and is moving to production at demonstration scale in 2011. Multiple large chemical companies have
successfully tested Genomatica's Bio-BDO as a feedstock for polymers. The performance of Bio-BDO has met
the standards set for petroleum-based BDO. Initial lifecycle analyses show that Genomatica's Bio-BDO will
require about 60 percent less energy than acetylene-based BDO. Also, the biobased BDO pathway consumes
carbon dioxide (CO2), resulting in a reduction of 70 percent in CO2 emissions. Fermentation requires no organic
solvent, and the water used is recycled. Furthermore, the Bio-BDO fermentation process operates near ambient
pressure and temperature, thus providing a safer working environment. These advantages lead to reduced costs:
production facilities should cost significantly less, and production expenses for Bio-BDO should be 15-30 percent
less than petroleum-based BDO. Genomatica expects Bio-BDO to be competitive at oil prices of $45 per barrel or
at natural gas prices of $3.50 per million Btu.
Genomatica's unique, integrated bioprocess engineering and extensive intellectual property allow it to
develop organisms and processes rapidly for many other basic chemicals. Because the chemical industry uses
approximately 8 percent of the world's fossil fuels, Genomatica's technology has the potential to reduce carbon
emissions by hundreds of millions of tons annually.
Genomatica has entered into partnerships with several major companies including Tate & Lyle, M&G (a major
European chemicals producer), Waste Management, and Mitsubishi Chemical to implement their technology at a
commercial scale. Genomatica expects to begin commercial production of Bio-BDO in 2012. They plan to roll out
plants in the United States, Europe, and Asia over time.
10 2011 Greener Synthetic Pathways Award
-------
NEXAR™ Polymer Membrane Technology
Purification of salt water by reverse osmosis is one of the highest-volume uses of membrane filtration. Kraton has
developed a family of halogen-free, high-flow, polymer membranes made using less solvent. The biggest benefits are
during use: A reverse osmosis plant using NEXAR™ membranes can purify hundreds of times more water than one
using traditional membranes, save 70 percent in membrane costs, and save 50 percent in energy costs.
i olymer membranes are used in a variety of purification processes. Membranes selectively allow some
molecules to pass while preventing others from crossing the barrier. Membrane purifications include water
desalination by reverse osmosis, water ultra-purification, salt recovery, and waste acid recovery. Membrane
efficiency is limited by the rate at which water (or another molecule) crosses the membrane, a property called
the flux. Increasing the pressure of the "dirty" side of the membrane can increase the flux, but a higher pressure
requires a stronger membrane.
Kraton Performance Polymers has developed NEXAR™ polymer membrane technology for applications requiring
high water or ion flux. Kraton's NEXAR™ polymers are block copolymers with separate regions that provide
strength (poly(/-butyl styrene)), toughness and flexibility (poly(ethylene-propylene)), and water or ion transport
(styrene-sulfonated styrene). These A-B-C-B-A pentablock copolymers exhibit strength and toughness in dry and
wet conditions. Kraton's production process for NEXAR™ polymers uses up to 50 percent less hydrocarbon solvent
and completely eliminates halogenated cosolvents.
The biggest benefits are during use. NEXAR™ polymers have an exceptionally high water flux of up to 400 times
higher than current reverse osmosis membranes. This could translate into significant reductions in energy and
materials use. Modeling shows that a medium-sized reverse osmosis (RO) plant could save, conservatively,
over 70 percent of its membrane costs and approximately 50 percent of its energy costs. For applications
in electrodialysis reversal (EDR), the higher mechanical strength of NEXAR™ polymers makes it possible to
use thinner membranes, which reduces material use by up to 50 percent and reduces energy loss due to
membrane resistance. More important, NEXAR™ polymers eliminate the current use of PVC (poly(vinyl chloride))
in electrodialysis membranes. The outstanding water transport rate of NEXAR™ membranes also significantly
improves energy recovery ventilation (ERV), by which exhausted indoor air conditions incoming fresh air. For
other humidity regulation applications, including high-performance textiles and clothing, NEXAR™ polymers offer
environmental benefits by completely eliminating halogenated products such as Nafion® polymers and PTFE
(poly(tetrafluoroethylene)) that may require hazardous halogenated processing aids.
Kraton introduced NEXAR™ polymers in the United States, China, and Germany during 2010. In the third quarter of
2010, Kraton completed its first successful large-scale production of NEXAR™ of about 10 metric tons.
2011 Greener Reaction Conditions Award 11
-------
Water-based Acrylic Alkyd Technology
Oil-based "alkyd" paints have high levels of volatile organic compounds (VOCs) that become air pollutants as the paint
dries. Previous acrylic paints contained lower VOCs, but could not match the performance of alkyds. Sherwin-Williams
developed water-based acrylic alkyd paints with low VOCs that can be made from recycled soda bottle plastic (PET),
acrylics, and soybean oil. These paints combine the performance benefits of alkyds and lowVOC content of acrylics. In
2010, Sherwin-Williams manufactured enough of these new paints to eliminate over 800,000 pounds of VOCs.
\ he high cost and uncertain availability of petroleum-based raw materials makes dependence on these materials
unsustainable. Furthermore, the tightening of volatile organic compound (VOC) regulations by the Ozone
Transport Commission (OTC) and the South Coast Air Quality Management District (SCAQMD) necessitates VOC-
compliant waterborne coatings in place of solventborne coatings. Today, acrylic latex emulsions dominate the
low-VOC waterborne coatings and alkyds dominate the solventborne coatings, but latex-based coatings have
difficulty meeting all the performance and application properties of solventborne coatings.
To address this challenge, The Sherwin-Williams Company developed a novel, low-VOC, water-based acrylic alkyd
technology based on sustainability principles. At the heart of this water-based acrylic alkyd technology is a low-
VOC, alkyd-acrylic dispersion (LAAD). This polymer dispersion has PET (poly(ethylene terephthalate)) segments for
rigidity, hardness, and hydrolytic resistance; it has acrylic functionality for improved dry times and durability; and it
has soya functionality (from soybean oil) to promote film formation, gloss, flexibility, and cure. Sherwin-Williams
designed this water-based acrylic alkyd technology to meet key performance attributes of solvent-based alkyds
for architectural and industrial maintenance coatings applications, but with lower VOCs, without surfactants, and
with excellent hydrolytic stability similar to that of latex paints. Sherwin-Williams water-based acrylic alkyd coatings
bring together the best performance benefits of alkyd and acrylic paints, offering the application and finish of
alkyds, including high gloss and excellent adhesion and moisture resistance, with the low VOC content, low odor,
and non-yellowing properties of acrylics.
Since the launch of their LAAD products, ProClassic Waterbased Acrylic Alkyd, ProMar 200 Waterbased Acrylic
Alkyd, and Prolndustrial Waterborne Enamel, in 2010, Sherwin-Williams has eliminated the use of over 800,000
pounds of VOC solvents and other petroleum-based feedstocks.
12 2011 Designing Greener Chemicals Award
-------
SO 10 Winners
Recycling Carbon Dioxide to Biosynthesize Higher Alcohols
|iHif;\;.VI!(;.n -iHSJ BrjK'.iMt.
Ethanol made by fermentation can be used as a fuel additive, but its use is limited by its low energy content. "Higher"
alcohols (those with more than two carbons in the molecule) have higher energy content, but naturally occurring
microorganisms do not produce them. Dr. James Liao has genetically engineered microorganisms to make higher
alcohols from glucose or directly from carbon dioxide. His work makes renewable higher alcohols available for use as
chemical building blocks or as fuel.
I ligher alcohols, especially those with 3-8 carbon atoms, are useful as chemical feedstocks and transportation
fuels. The efficient biosynthesis of these alcohols directly from carbon dioxide (CO2) or indirectly from
carbohydrates would reduce net carbon emissions. Unfortunately, native organisms do not synthesize these
alcohols. Until now, none of these alcohols have been synthesized directly from CO2, and alcohols above five
carbons have never been synthesized in the biosphere.
Dr. Liao, an Easel Biotechnologies board member and professor at the University of California, Los Angeles
(UCLA), has developed a microbial technology to produce alcohols with 3-8 carbon atoms from CO2. His
technology leverages the highly active amino acid biosynthetic pathway, diverting its 2-keto acid intermediates
toward alcohols. With this technology, Professor Liao and his group have produced isobutanol from glucose in
near-theoretical yields with high efficiency and specificity. They also transferred the pathway into a photosynthetic
microorganism, Synechococcus e/ongafus PCC7942, which produces isobutyraldehyde and isobutanol directly
from CO2. The engineered strain produces isobutanol at a higher rate than those reported for ethanol, hydrogen,
or lipid production by cyanobacteria or algae. This productivity is also higher than the current rate of ethanol
production from corn. The technology shows promise for direct bioconversion of solar energy and CO2 into
chemical feedstocks.
Higher alcohols are also good fuels. As fuel substitutes, they have several advantages over ethanol, including
higher energy density, lower hygroscopicity, and lower vapor pressure leading to better air quality. After excretion
by the cells as aldehydes, the products are readily stripped from the bioreactor, avoiding toxicity to the microbes.
Chemical catalysis then converts the harvested aldehydes to alcohols or other chemicals.
If 60 billion gallons of higher alcohols were used each year as chemical feedstocks and fuel (replacing 25 percent
of gasoline), Dr. Liao's technology could eliminate about 500 million tons of CO2 emissions or about 8.3 percent
of the total U.S. CO2 emissions. Easel Biotechnologies is commercializing the CO2-to-fuels technology under
exclusive license from UCLA.
2010 Academic Award 13
-------
Microbial Production of Renewable Petroleum™ Fuels and Chemicals
Industrial microbes usually make single substances, such as triglycerides like those in vegetable oil. Each single
substance is then purified and converted into other chemicals, such as biodiesel fuel. LS9, Inc. has genetically
engineered a variety of microorganisms to act like refineries. Each microbe makes a specific, final chemical product.
Among these products is UltraClean™ diesel. This fuel, produced from biomass, eliminates the benzene, sulfur, and
heavy metals found in petroleum-based diesel.
I he renewable, scalable fuels and chemicals with the greatest potential for rapid and widespread adoption by
consumers are those that are both cost-competitive with petroleum and compatible with the existing distribution
and consumer infrastructure. LS9 has developed a platform technology to produce a wide variety of advanced
biofuelsand renewable chemicals cost-effectively by a simple, efficient, one-step fermentation process. LS9 has
engineered established industrial microorganisms to convert fermentable sugars selectively to alkanes, olefins,
fatty alcohols, or fatty esters, each in a single-unit operation. The process enables precise genetic control of
the molecular composition and performance characteristics of each resulting fuel or chemical product. LS9's
technology leverages the natural efficiency of microbial fatty acid metabolism to biosynthesize long hydrocarbon
chains. It combines this with new biochemical pathways engineered into microorganisms to convert the long-
chain intermediates into specific finished fuel and chemical products that are secreted by the cells. The products
are immiscible with the aqueous fermentation medium and form a light organic phase that is both nontoxic to
the whole-cell catalyst and easily recoverable by centrifugation. LS9 is actively developing the
technology for the production of alkanes (diesel, jet fuel, gasoline), alcohols (surfactants), esters (biodiesel,
chemical intermediates), olefins (lubricants, polymers), aldehydes (insulation, resins), and fatty acids (soaps,
chemical intermediates). Specific product performance is enabled through the genetic control of each product's
chain length, extent of saturation, and degree of branching. Unlike the competing biofuel processes, LS9's
process does not require any metal catalysts.
LS9 has successfully scaled up its technology to produce UltraClean™ diesel at the pilot-plant level. UltraClean™
diesel meets or exceeds all of the ASTM 6751 specifications for on-road vehicle use. It eliminates the
environmental pollutants benzene, sulfur, and the heavy metals found in petroleum-based diesel and will result in
an 85 percent decrease in greenhouse gas (GHG) emissions according to the GREET model for life cycle analysis
(EGA). Without subsidy, UltraClean Diesel™ will be competitive in the market with diesel from oil priced at
$45-50 per barrel. LS9 is advancing toward commercial scale with its Renewable Petroleum™ facility, which will
come on line in 2010. Initially, this facility will produce UltraClean™ diesel; other products will follow. LS9 has
achieved some success in direct biomass-to-fuel conversion.
LS9 is applying this technology platform through a strategic partnership with Procter & Gamble to produce
surfactants for consumer chemical products. These and other LS9 drop-in, renewable products are on target to
facilitate broad environmental benefits through rapid product adoption. The efficiency, affordability, and product
performance bodes well for the LS9 technology to become one of the keys to sustainable fuels.
14 2010 Small Business Award
-------
Innovative, Environmentally Benign Production of Propylene Oxide via Hydrogen Peroxide
Propylene oxide is one of the biggest volume industrial chemicals in the world. It is a chemical building block for
a vast array of products including detergents, polyurethanes, de-icers, food additives, and personal care items. Its
manufacture creates byproducts, including a significant amount of waste. Dow and BASF have jointly developed a new
route to make propylene oxide with hydrogen peroxide that eliminates most of the waste and greatly reduces water
and energy use.
i 'ropylene oxide (PO) is among the top 30 largest-volume chemical intermediates produced in the world; its
annual worldwide demand is estimated to be over 14 billion pounds. It is a key raw material for manufacturing a
wide range of industrial and commercial products, including polyurethanes, propylene glycols, and glycol ethers,
which are used in a diverse array of applications including automobiles, furniture, and personal care. Historically,
manufacturing propylene oxide either produced significant volumes of coproducts or required recycling of
organic intermediates. Traditional PO production uses chlorohydrin or one of a variety of organic peroxides, which
lead to coproducts such as /-butyl alcohol, styrene monomer, or cumene. In each case, there is a substantial
amount of coproduct and waste. Although most of the coproducts are recovered and sold, demand for these
coproducts does not necessarily parallel the demand for PO, leading to imbalances in supply and demand.
Dow and BASf have developed the Hydrogen Peroxide to Propylene Oxide (HPPO) process, a new, innovative
route to PO based on the reaction of hydrogen peroxide and propylene. It has high yields and produces only
water as a coproduct. The Dow-BASf catalyst is a ZSM-5-type zeolite with channels of about 0.5 nm in diameter.
In this catalyst, titanium replaces several percent of the silicon of the zeolite in a tetrahedral coordination
environment. With this novel catalyst, the HPPO process is relatively straightforward. Propylene is epoxidized
by hydrogen peroxide in a fixed-bed reactor at moderate temperature and pressure. The reaction occurs in the
liquid phase in the presence of methanol as a solvent. The process is characterized by both high conversions of
propylene and high selectivity for propylene oxide. Hydrogen peroxide is completely converted to product. In
contrast with processes using organic peroxides, the HPPO process uses substantially less peroxide and eliminates
the need to recycle peroxide. Production facilities are up to 25 percent cheaper to build because there is no need
for equipment to collect and purify the coproduct.
The HPPO process also provides substantial environmental benefits. It reduces the production ofwastewater by
as much as 70-80 percent and the use of energy by 35 percent over traditional technologies. BASf performed an
Eco-Efficiency Analysis of the various PO processes and found the HPPO process is cheaper and has substantially
lower negative impacts than alternative processes. The first commercial process based on this technology was
successfully commissioned in 2008 at the BASf production facility in Antwerp, Belgium. A second PO plant based
on this technology is scheduled to begin production in Map Ta Phut, Thailand in 2011.
2010 Greener Synthetic Pathways Award 15
-------
Greener Manufacturing of Sitagliptin Enabled by an Evolved Transaminase
Merck and Codexis have developed a second-generation green synthesis of sitagliptin, the active ingredient in
Januvia™, a treatment for type 2 diabetes. This collaboration has lead to an enzymatic process that reduces waste,
improves yield and safety, and eliminates the need for a metal catalyst. Early research suggests that the new
biocatalysts will be useful in manufacturing other drugs as well.
Sitagliptin is the active ingredient in Januvia®, an important treatment for type 2 diabetes that is in high demand
worldwide. The current manufacturing process includes a novel and efficient asymmetric catalytic hydrogenation
of an unprotected enamine. The process has some inherent liabilities however: inadequate stereoselectivity
requires a crystallization step, and high-pressure hydrogenation (at 250 psi) requires expensive, specialized
manufacturing equipment, and a rhodium catalyst.
Merck and Codexis were independently aware that transaminase enzymes could, in principle, improve the
manufacturing process for sitagliptin by converting a precursor ketone directly to the desired chiral amine. Merck's
tests of available transaminases failed to identify an enzyme with any detectable activity on the sitagliptin ketone.
Collaboration between Merck and Codexis has lead to an improved, greener route for the manufacture of
sitagliptin. Starting from an ^-selective transaminase with some slight activity on a smaller, truncated methyl
ketone analog of the sitagliptin ketone, Codexis evolved a biocatalyst to enable a new manufacturing process to
supplant the hydrogenation route. The evolved transaminase had a compounded improvement in biocatalytic
activity of over 25,000-fold, with no detectable amounts of the undesired, 5-enantiomer of sitagliptin being
formed. The streamlined, enzymatic process eliminates the high-pressure hydrogenation, all metals (rhodium and
iron), and the wasteful chiral purification step. The benefits of the new process include a 56 percent improvement
in productivity with the existing equipment, a 10-13 percent overall increase in yield, and a 19 percent reduction
in overall waste generation.
Evolved transaminases are proving to be a general tool for the synthesis of R-amines directly from ketones,
constituting an important new green methodology, one of the key transformations identified by the American
Chemical Society Green Chemistry Institute's Pharmaceutical Roundtable. Merck and Codexis have used scientific
innovation to benefit the environment, meet the manufacturing demands of an important drug in growing
demand, and potentially enable a broad class of chemistry. During 2009, Merck scaled up the new process to pilot
scale. Plans to commercialize this technology are moving forward.
16 2010 Greener Reaction Conditions Award
-------
Natular™ Larvicide: Adapting Spinosad for Next-Generation Mosquito Control
Spinosad is an environmentally safe pesticide but is not stable in water and so therefore cannot be used to control
mosquito larvae. Clarke has developed away to encapsulate spinosad in a plaster matrix, allowing it to be released
slowly in water and provide effective control of mosquito larvae. This pesticide, Natular™, replaces organophosphates
and other traditional, toxic pesticides and is approved for use in certified organic farming.
bpinosad, a 1999 Presidential Green Chemistry Challenge Award winner, is an effective insecticide with excellent
control in many terrestrial applications. Its instability in water, however, renders it ineffective for extended
application in aquatic environments.
Clarke has created a "sequential" plaster matrix that protects the spinosad molecule from water and releases
it slowly, allowing extended performance of spinosad formulations for up to 180 days. This matrix is insoluble
calcium sulfate hemihydrate plaster and water-soluble polyethylene glycol (PEG) binders fine-tuned for varying
durations of insecticide release. The PEG dissolves slowly, exposing the spinosad and calcium sulfate to water.
The calcium sulfate takes up the water to form the mineral gypsum and releases spinosad. Clarke formulated the
plaster matrix for Natular™ larvicide entirely with approved pesticide inerts that also meet the U.S. Department of
Agriculture's (USDA's) National Organics Standard (NOS). The resulting formulations of Natular™ larvicide provide
excellent control of mosquito larvae in a range of aquatic environments from catch basins to salt marshes. Clarke
manufactures the dustless, extended-release tablets with a solventless process that increases the environmental
benefits.
Natular™ larvicide is effective at application rates 2-10-fold lower than traditional synthetic larvicides. It is 15-fold
less toxic than the organophosphate alternative, does not persist in the environment, and is not toxic to wildlife.
Its manufacture eliminates hazardous materials and processes. Natular™ is the first new, chemical larvicide for
mosquito control in decades; it meets the highest standards for environmental stewardship and offers a new
choice for Integrated Pest Management (IPM). It is especially useful in environments with intermittent water, such
as tidal pools and flood plains. These intermittently wet areas provide excellent, short-term pools for mosquito
breeding; the transient nature of the pooling makes traditional mosquito control difficult. The Natular™ larvicide
can be applied in dry or wet conditions, however, and only releases the active ingredient when water is present.
The benefits of using Clarke's new formulations extend beyond the reduced environmental impact. Traditional
larvicides require up to three applications per season. In contrast, Natular™ tablets require just one or two
applications.
Altogether, Natular™ larvicide demonstrates green chemistry innovation through the development and
design of its controlled-release matrix. With the projected adoption of Natular™ larvicide by local and federal
agencies, Clarke anticipates a shift in the mosquito-borne disease management industry toward reduced overall
synthetic load in the environment and improved health and quality of life in treated areas. In 2009, Clarke began
commercial-scale production of Natular™ larvicide in the United States. This patent-pending formulation has
been accepted for use domestically and abroad. Clarke also expects its slow-release matrix will enable controlled
release of other active ingredients, including herbicides and veterinary drugs.
2010 Designing Greener Chemicals Award 17
-------
2009 Winners
Atom Transfer Radical Polymerization: Low-impact Polymerization Using a Copper Catalyst and Environmentally
Friendly Reducing Agents
|iHif;\;.VI!(;.n -iHSJ BrjK'.iMt.
Hazardous chemicals are often required in the manufacture of important polymers such as lubricants, adhesives,
and coatings. Professor Matyjaszewski developed an alternative process called "Atom Transfer Radical Polymerization
(ATRP)" for manufacturing polymers. The process uses chemicals that are environmentally friendly, such as ascorbic
acid (vitamin C) as a reducing agent, and requires less catalyst. ATRP has been licensed to manufacturers throughout
the world, reducing risks from hazardous chemicals.
\ \ orldwide production of synthetic polymers is approximately 400 billion pounds per year; approximately half of
this involves free radical polymerization. With the recent development of controlled radical polymerization (CRP),
it is now possible to make well-defined polymers with precisely controlled molecular structures. Atom transfer
radical polymerization (ATRP) is one such technology; it is a transition-metal-mediated, controlled polymerization
process that was discovered at Carnegie Mellon University (CMU) in 1995. Since then, Professor Matyjaszewski
and his group have published over 500 scientific papers on CRP; these papers have been cited over 30,000
times, making Professor Matyjaszewski the second-most cited researcher in all fields of chemistry in 2008. This
explosive interest in ATRP is due to its simplicity and ability to tailor-make functional macromolecules for specialty
applications. ATRP has become the most versatile and robust of the CRP methods.
Professor Matyjaszewski has been working continually to increase the environmental friendliness of his process.
During the last four years, he and his team at CMU have developed new catalytic systems that dramatically
decrease the concentration of transition metal, while preserving good control over polymerization and polymer
architecture. The latest improvements are activators generated by electron transfer (AGET, 2004), activators
regenerated by electron transfer (ARGET, 2005), and initiators for continuous activator regeneration (ICAR, 2006).
These methods allow the preparation, storage, and use of the most active ATRP catalysts in their oxidatively stable
state as well as their direct use under standard industrial conditions. The recent discovery of ARGET ATRP reduces
the amount of copper catalyst from over 1,000 ppm to around 1 ppm in the presence of environmentally friendly
reducing agents such as amines, sugars, or ascorbic acid. AGET and ARGET ATRP provide routes to pure block
copolymers. The new processes allow oxidatively stable catalyst precursors to be used in aqueous homogeneous,
dispersed (miniemulsion, inverse miniemulsion, microemulsion, emulsion, and suspension), and solventless bulk
polymerizations. Professor Matyjaszewski's work is opening new "green" routes for producing many advanced
polymeric materials.
ATRP has become an industrially important means to produce polymers. Since 2003, ATRP has been licensed to
8 of the over 40 corporations funding the research at CMU (PPG, Dionex, Ciba, Kaneka, Mitsubishi, WEP, ATRP
Solutions, and Encapson). Licensees around the world have begun commercial production of high-performance,
less-hazardous, safer materials including sealants, coatings, adhesives, lubricants, additives, pigment dispersants,
and materials for electronic, biomedical, health, and beauty applications.
18 2009 Academic Award
-------
BioForming® Process: Catalytic Conversion of Plant Sugars into Liquid Hydrocarbon Fuels
Virent's BioForming® process is a water-based, catalytic method to make gasoline, diesel, or jet fuel from the sugar,
starch, or cellulose of plants that requires little external energy other than the plant biomass. The process is
flexible and can be modified to generate different fuels based on current market conditions. It can compete
economically with current prices for conventionally produced petroleum-based fuels. Using plants as a renewable
resource helps reduce dependence on fossil fuels.
. irent has discovered and is developing an innovative green synthetic pathway to convert plant sugars into
conventional hydrocarbon fuels and chemicals. Virent's catalytic BioForming® process combines proprietary
aqueous-phase reforming (APR) technology with established petroleum refining techniques to generate the
same range of hydrocarbon molecules now refined from petroleum. First, water-soluble carbohydrates are
catalytically hydrotreated. Next, in the APR process, resultant sugar alcohols react with water over a proprietary
heterogeneous metal catalyst to form hydrogen and chemical intermediates. Finally, processing with one of
multiple catalytic routes turns these chemicals into gasoline, diesel, or jet fuel components. The technology also
produces alkane fuel gases and other chemicals. Virent's BioForming® platform can generate multiple end-
products from a single feedstock and enable product optimization based on current market conditions.
Compared to other biomass conversion systems, Virent's technology broadens the range of viable feedstocks,
provides more net energy, and produces fuels compatible with today's infrastructure. The process uses either
food or non-food biomass; it is scalable to match feedstock supply. Unlike fermentation, Virent's robust process
can use mixed sugar streams, polysaccharides, and C5 and C6 sugars derived from cellulosic biomass. By using
more plant mass per acre, the process provides better land use and higher value for farmers. The technology
needs little energy input and can be completely renewable. Virent's energy-dense biofuels separate naturally
from water,- as a result, the process eliminates the energy-intensive distillation to separate and collect biofuels
required by other technologies. The hydrocarbon biofuels from Virent's process are interchangeable with
petroleum products, matching them in composition, functionality, and performance; they work in today's
engines, fuel pumps, and pipelines. Preliminary analysis suggests that Virent's BioForming® process can compete
economically with petroleum-based fuels and chemicals at crude oil prices of $60 a barrel.
The BioForming® process can speed the use of non-food plant sugars to replace petroleum as an energy source,
thus both decreasing dependence on fossil hydrocarbons and minimizing the impact on global water and food
supplies. Fuels derived from the process can have a 20-30 percent per Btu cost advantage over ethanol. The
BioForming® platform is near commercialization. During 2008, Virent produced over 40 liters of biogasoline for
engine testing and began fabrication of its first 10,000-gallon-per-year pilot plant to produce biogasoline.
2009 Small Business Award 19
-------
A Solvent-Free Biocatalytic Process for Cosmetic and Personal Care Ingredients
Esters are an important class of ingredients in cosmetics and personal care products. Usually, they are manufactured
by harsh chemical methods that use strong acids and potentially hazardous solvents; these methods also require a
great deal of energy. Eastman's new method uses immobilized enzymes to make esters, saving energy and avoiding
both strong acids and organic solvents. This method is so gentle that Eastman can use delicate, natural raw materials to
make esters never before available.
1 he cosmetics and personal care market is a vast enterprise of formulated specialty chemicals. Esters are
an important class of cosmetic ingredients, comprising emollients, emulsifiers, and specialty performance
ingredients. In 2006, the estimated North American consumption of esters as emollients and emulsifiers was
50,000 metric tons. Usually, such esters are manufactured using strong acid catalysts at high temperatures;
unfortunately, this produces undesirable byproducts that must be removed by energy-intensive purifications.
Other methods of producing cosmetic esters require organic solvents that are potentially hazardous to workers
and the environment. The growing trend for natural ingredients and environmentally responsible processes in the
cosmetics market requires new manufacturing methods.
In 2005, scientists at Eastman began investigating enzymes as catalysts to produce cosmetic esters. Eastman
has now synthesized a variety of esters via enzymatic esterifications at mild temperatures. The esterifications
are driven to high conversion by removing the coproduct, usually water from esterification of an acid or a lower
alcohol from transesterification of an ester. The mild processing conditions do not lead to formation of
undesirable byproducts that may contribute color or odor. The immobilized enzyme, such as lipase, is easily
removed by filtration. The specificity of the enzymatic conversions and the relatively low reaction temperatures
minimize the formation of byproducts, increase yield, and save energy.
Eastman's process can use delicate raw materials such as unsaturated fatty acids that would oxidize during
conventional esterifications. Thus, Eastman can make ingredients never before available. It has manufactured
hundreds of such new esters by combining different alcohols and acids. Biocatalysis can even yield new products
that offer superior performance.For example, two esters can be formed from 4-hydroxybenzyl alcohol and acetic
acid. One—esterification at the benzyl moiety—is only accessible via the enzymatic route. This particular ester
inhibits tyrosinase, a key enzyme in melanin synthesis, and, therefore, is effective in reducing undesirable skin
pigmentation and providing a more uniform skin tone.
Eastman's biocatalytic process can save over ten liters of organic solvent per kilogram of product. The ester
product is often pure enough to obviate post-reaction processing. An early lifecycle assessment identifies
Eastman's process as vastly improved over conventional processes, especially in energy use. Overall, this process
improves quality, yield, cost, and environmental footprint compared to conventional chemical syntheses.
Leading cosmetic companies are currently evaluating many of Eastman's new esters, including emollient esters
made from rice bran oil, glyceride emulsifiers, and new ingredients that combat the visible signs of aging.
20 2009 Greener Synthetic Pathways Award
-------
Innovative Analyzer Tags Proteins for Fast, Accurate Results without Hazardous Chemicals or High Temperatures
Each year, laboratories test millions of samples of food for the presence of protein. Such tests generally use large
amounts of hazardous substances and energy. CEM has developed a fast, automated process that uses less toxic
reagents and less energy. The new system can eliminate 5.5 million pounds of hazardous waste generated by
traditional testing in the United States each year. What's more, it differentiates between protein and other chemicals
used to adulterate food, such as melamine.
I he recent use of melamine to masquerade as protein and adulterate both baby formula in China and pet food
in the United States makes accurate testing for protein imperative. The standard Kjeldahl and combustion tests
for protein measure total nitrogen, however, and cannot distinguish melamine from protein. Kjeldahl testing uses
sulfuric acid, sodium hydroxide, hydrochloric acid, and boric acid along with a catalyst of copper sulfate, selenium,
or mercury. U.S. companies generate 5.5 million pounds of hazardous waste annually from Kjeldahl testing.
Trained chemists are required to run these tests due to the hazardous materials and high temperatures required.
The Sprint™ Rapid Protein Analyzer automates a technique that tags protein directly and provides fast, accurate
results. CEM's proprietary 1TAG™ solution actually tags protein by attaching only to histidine, arginine, and lysine,
the three basic amino acids commonly found in proteins. The proprietary iTAG™ solution contains an acidic
group that readily attaches to the basic amino acids; iTAG™ also has an extensive aromatic group that readily
absorbs light and appears orange. The iTAG™ bound to the protein is removed from solution by a filter and the
remaining iTAG™ is then measured by colorimetry. The Sprint™ System ignores any other nitrogen that may be
present, including the nitrogen in melamine. As a result, it enables food and pet food processors to be absolutely
certain of the bulk protein content of their ingredients and final products for quality control, product safety,
and nutritional labeling. Sprint™ may be used in the laboratory, on the processing line, or as a rapid check for
incoming raw materials. The system does not require a trained chemist to obtain accurate results.
Sprint™ uses a green chemistry method: its 1TAG™ solution is nontoxic, nonreactive, and water-soluble. It
eliminates all of the hazardous waste created by Kjeldahl testing. In addition, Sprint™ does not require high
temperatures, making it a much safer method than Kjeldahl or combustion techniques. It is easy to operate and
can test most samples in 2-3 minutes, compared to 4 hours for a Kjeldahl analysis. It uses disposable filters and
recyclable sample cups and lids; all other parts of the system that touch the sample are self-cleaning. Remarkably
fast, accurate, cost-effective, and safe, Sprint™ is poised to become the method of choice for protein testing. The
methods it automates are approved by AOAC (Association of Analytical Communities) and AACC International
(previously: American Association of Cereal Chemists). It was commercialized in January 2008.
2009 Greener Reaction Conditions Award 21
-------
Chempol® MRS Resins and Sefose® Sucrose Esters Enable
High-Performance Low-VOC Alkyd Paints and Coatings
Conventional oil-based "alkyd" paints provide durable, high-gloss coatings but use hazardous solvents. Procter &
Gamble and Cook Composites and Polymers are developing innovative Chempol® MPS paint formulations using
biobased Sefose® oils to replace petroleum-based solvents. Sefose® oils, made from sugar and vegetable oil, enable
new high-performance alkyd paints with less than half the solvent. Paints with less hazardous solvent will help improve
worker safety, reduce fumes indoors as the paint dries, and improve air quality.
Solvent-borne alkyd coatings are in demand because they are cost-effective and high-performing in many
applications, including architectural finishes, industrial metal, and equipment for agriculture and construction.
Millions of gallons of these paints and coatings are sold in the United States and around the world. Conventional
alkyd resin paints and coatings require large amounts of volatile solvents to solubilize the organic components
and attain appropriate viscosities. These solvents contribute to the formation of ground-level ozone and smog.
Low-VOC alkyd coatings exist, but suffer from inferior performance. Some take too long to dry; others use
substitute, VOC-exempt solvents that tend to be expensive and often have an undesired odor or other inferior
performance. Low-VOC, waterborne acrylic latex paints are also available, but they have performance trade-offs
such as low gloss and reduced corrosion resistance compared to solvent-borne alkyd coatings.
The Procter & Gamble Company (P&G) and Cook Composites and Polymers Company (CCP) have collaborated
to develop a new alkyd resin technology that enables formulation of paints and coatings with less than half the
VOCs of solvent-borne alkyd coatings. These alkyd formulations are enabled by Sefose® sucrose esters, which
are prepared from renewable feedstocks by esterifying sucrose with fatty acids in a patented, solventless process.
The molecular architecture and functional density of Sefose® are controlled by selecting natural oil feedstocks
with optimal fatty acid chain length distribution, unsaturation level, and degree of esterification. In applied paint
films, Sefose® undergoes auto-oxidative cross-linking with other constituents and becomes an integral part of the
coating films. Chempol® MPS alkyd resins are specially formulated to deliver performance advantages such as
fast drying, high gloss, film toughness, and increased renewable content.
Replacement of conventional alkyd resins by Chempol® MPS could (1) reduce VOCs equivalent to the emissions
from 7,000,000 cars per year, (2) reduce ground-level ozone by 215,000 tons per year, and (3) save 900,000 barrels
per year of crude oil from the solvents and alkyd polymers it replaces. Chempol® MPS is cost-competitive with
conventional alkyds on an equal-dry-film basis. In October 2008, CCP launched Chempol® MPS and began
actively sampling the coatings industry. P&G is also evaluating and testing Sefose® oils as biobased alternatives to
replace petroleum-based lubricants.
2009 Designing Greener Chemicals Award
-------
2008 Winners
Green Chemistry for Preparing Boronic Esters
One way to build complex molecules, such as Pharmaceuticals and pesticides, is with a Suzuki "coupling" reaction.
This versatile coupling reaction requires precursors with a carbon-boron bond. Making these precursors, however,
typically requires harsh conditions and generates significant amounts of hazardous waste. Professors Maleczka and
Smith developed a new catalytic method to make these compounds under mild conditions and with minimal waste
and hazard. Their discovery allows the rapid, green manufacture of chemical building blocks, including some that had
been commercially unavailable or environmentally unattractive.
( oupling" reactions are one way to build valuable molecules, such as Pharmaceuticals, pesticides, and similar
complex substances. Coupling reactions connect two smaller molecules, usually through a new carbon-carbon
(C-C) bond. A particularly powerful coupling reaction is the Suzuki coupling, which uses a molecule containing
a carbon-boron bond to make a larger molecule through a new C-C bond. In fact, the Suzuki coupling is a
well-established, mild, versatile method for constructing C-C bonds and has been reported to be the third most
common C-C bond-forming reaction used to prepare drug candidates.
Chemical compounds with a carbon-boron bond are often prepared from the corresponding halides by Grignard
or lithiate formation followed by reaction with trialkyl borate esters and hydrolytic workup. Miyaura improved this
reaction with a palladium catalyst, but even this new reaction requires a halide precursor.
Several years ago, Professors Milton R. Smith, III and Robert E. Maleczka, Jr. began collaborating to find a
"halogen-free" way to prepare the aryl and heteroaryl boronic esters that are the key building blocks for Suzuki
couplings. Their collaboration builds upon Smith's invention of the first thermal, catalytic arene carbon-hydrogen
bond (C-H) activation/borylation reaction. This led to transformations using iridium catalysts that are efficient,
have high yields, and are tolerant of a variety of functional groups (alkyl, halo-, carboxy, alkoxy-, amino, etc.).
Sterics, not electronics dictate the regiochemistry of the reactions. As a consequence, 1,3-substituted arenes give
only 5-boryl (i.e., meta-substituted) products, even when both the 1-and 3-substituentsare ortho/para directing.
Just as significantly, the reactions are inherently clean as they can often be run without solvent, and they occur
with hydrogen being the only coproduct. The success of these reactions has led Miyaura, Ishiyama, Hartwig, and
others to use them as well.
In brief, catalytic C-H activation/borylation allows the direct construction of aryl boronic esters from hydrocarbon
feedstocks in a single step, without aryl halide intermediates, without the limitations of the normal rules of
aromatic substitution chemistry, and without many common functional group restrictions. Moreover, due to its
mildness, the borylation chemistry combines readily in situ with subsequent chemical reactions.
This technology allows rapid, low-impact preparations of chemical building blocks that currently are commercially
unavailable or only accessible by protracted, costly, and environmentally unattractive routes. Indeed, most
recently, Michigan State University licensed the nominated technology to BoroPharm, Inc., which is using these
catalytic borylations to produce much of the company's product line. Thus, the nominated technology is proving
to be practical green chemistry beyond the laboratory bench.
2008 Academic Award 23
-------
New Stabilized Alkali Metals for Safer, Sustainable Syntheses
Alkali metals, such as sodium and lithium, are powerful tools in synthetic chemistry because they are highly reactive.
However, unless they are handled very carefully, their reactivity also makes them both flammable and explosive. SiGNa
Chemistry developed a way to stabilize these metals by encapsulating them within porous, sand-like powders, while
maintaining their usefulness in synthetic reactions. The stabilized metals are much safer to store, transport, and handle.
They may also be useful for removing sulfur from fuels, storing hydrogen, and remediating a variety of hazardous
wastes.
'' Ikali metals have a strong propensity for donating electrons, which makes these metals especially reactive. That
reactivity has enormous potential for speeding chemical reactions throughout science and industry, possibly
including new pathways to clean energy and environmental remediation. Unfortunately, that same reactivity
also makes them highly unstable and dangerous to store and handle. In addition, increased risk of supply-chain
interruption and the expense of handling these metals have made them unattractive to the chemical industry.
Industries from pharmaceutical to petroleum have developed alternative synthetic routes to avoid using alkali
metals, but these alternates require additional reactants and reaction steps that lead to inefficient, wasteful
manufacturing processes.
SiGNa Chemistry addresses these problems with its technology for nanoscale absorption of reactive alkali metals
in porous metal oxides. These new materials are sand-like powders. SiGNa's materials eliminate the danger and
associated costs of using reactive metals directly but retain the utility of the alkali metals. Far from their hazardous
precursors, SiGNa's materials react controllably with predictable activation that can be adapted to a variety of
industry needs. By enabling practical chemical shortcuts and continuous flow processes, the encapsulated alkali
metals create efficiencies in storage, supply chain, manpower, and waste disposal.
For the pharmaceutical, petrochemical, and general synthesis industries, SiGNa's breakthrough eliminates the
additional steps that these industries usually take to avoid using the alkali metals and produces the desired
reaction in 80-90 percent less time. For the pharmaceutical industry in particular, the materials can accelerate
drug discovery and manufacturing while bolstering worker safety.
Beyond greening conventional chemical syntheses, SiGNa's materials enable the development of entirely
new areas of chemistry. In clean-energy applications, the company's stabilized alkali metals safely produce
record levels of pure hydrogen gas for the nascent fuel cell sector. With yield levels that already exceed the U.S.
Department of Energy's targets for 2015, SiGNa's materials constitute the most effective means for processing
water into hydrogen. SiGNa's materials also allow alkali metals to be safely applied to environmental remediation
of oil contamination and the destruction of PCBs and CFCs.
SiGNa's success in increasing process efficiencies, health, and environmental safety and in enabling new
chemical technologies has helped it attract more than 50 major global pharmaceutical, chemical, and energy
companies as customers.
24 2008 Small Business Award
-------
Development and Commercialization of Biobased Toners
Laser printers and copiers use over 400 million pounds of toner each year in the United States. Traditional toners fuse
so tightly to paper that they are difficult to remove from waste paper for recycling. They are also made from petroleum-
based starting materials. Battelle and its partners, Advanced Image Resources and the Ohio Soybean Council, have
developed a soy-based toner that performs as well as traditional ones, but is much easier to remove. The new toner
technology can save significant amounts of energy and allow more paper fiber to be recycled.
• >.ore than 400 million pounds of electrostatic dry toners based on petroleum-derived resins are used in the
United States annually to make more than 3 trillion copies in photocopiers and printers. Conventional toners
are based on synthetic resins such as styrene acrylates and styrene butadiene. These conventional resins make
it difficult to remove the toner during recycling, a process called de-inking. This makes paper recycling more
difficult. Although others have developed de-inkable toners, none of the competing technologies has become
commercial due to high costs and inadequate de-inking performance.
With early-stage funding from the Ohio Soybean Council, Battelle and Advanced Image Resources (AIR) formed
a team to develop and market biobased resins and toners for office copiers and printers. This novel technology
uses soy oil and protein along with carbohydrates from corn as chemical feedstocks. Battelle developed
bioderived polyester, polyamide, and polyurethane resins and toners from these feedstocks through innovative,
cost-effective chemical modifications and processing, with the de-inking process in mind. By incorporating
chemical groups that are susceptible to degradation during the standard de-inking process, Battelle created new
inks that are significantly easier to remove from the paper fiber. AIR then scaled up the process with proprietary
catalysts and conditions to make the new resins.
The new technology offers significant advantages in recycling waste office paper without sacrificing print quality.
Improved de-inking of the fused ink from waste copy paper results in higher-quality recovered materials and
streamlines the recycling process. Preliminary life-cycle analysis shows significant energy savings and reduced
carbon dioxide (CO2) emissions in the full value chain from resin manufacture using biobased feedstocks to toner
production and, finally, to the recovery of secondary fibers from the office waste stream. At 25 percent market
penetration in 2010, this technology could save 9.25 trillion British thermal units per year (Btu/yr) and eliminate
over 360,000 tons of CO2 emissions per year.
Overall, soy toner provides a cost-effective, systems-oriented, environmentally benign solution to the growing
problem of waste paper generated from copiers and printers. In 2006, AIR, the licensee of the technology,
successfully scaled up production of the resin and toners for use in HP LaserJet 4250 Laser Printer cartridges.
Battelle and AIR coordinated to move from early-stage laboratory development to full-scale manufacturing and
commercialization. Their efforts have resulted in a cost-competitive, highly marketable product that is compatible
with current hardware. The new toner will be sold under trade names BioRez® and Rezilution®. Once commercial,
it will provide users with seamless, environmentally friendly printing and copying.
2008 Greener Synthetic Pathways Award 25
-------
3 DTRASAR® Technology
Cooling water touches many facets of human life, including cooling for comfort in commercial buildings and cooling
industrial processes. Cooling systems require added chemicals to control microbial growth, mineral deposits, and
corrosion. Nalco developed 3 DTRASAR® technology to monitor the condition of cooling water continuously and add
appropriate chemicals only when needed, rather than on a fixed schedule. The technique saves water and energy,
minimizes the use of water-treatment chemicals, and decreases environmental damage from discharged water.
'• '.ost commercial buildings, including offices, universities, hospitals, and stores, as well as many industrial
processes, use cooling systems based on water. These cooling systems can consume vast quantities of water.
Also, unless mineral scale and microbes are well-controlled, several problems can arise leading to increased water
and energy consumption and negative environmental impacts.
Mineral scale, which consists mostly of carbonates of calcium and magnesium, forms on heat-exchange surfaces;
this makes heat transfer inefficient and increases energy use. Similarly, microbial growth can lead to the formation
of biofilms on heat-exchange surfaces, decreasing exchange efficiency. Conversely, high levels of biocide
intended to prevent biofilm cause several adverse effects including increased corrosion of system components.
Gradually, the integrity of the system becomes compromised, increasing the risk of system leaks. The material
from these leaks, along with metal-containing byproducts of corrosion and the additional biocide, are ultimately
discharged with the cooling water. Every time water is discharged, called "blowdown", pollutants are released in
the wastewater, and fresh water is used to replace the blowdown. Traditionally, antiscalants and antimicrobials are
added at regular intervals or, at best, after manual or indirect measurements show scale or microbial buildup.
In 2004, Nalco commercialized its 3D TRASAR® Cooling System Chemistry and Control technology. By detecting
scaling tendency early, cooling systems with Nalco's technology can operate efficiently; in addition, they can use
less water or use poor-quality water.
3D Scale Control, part of the 3D TRASAR® system, prevents the formation of mineral scale on surfaces,
maintaining efficient heat transfer. The system monitors antiscalant levels using a fluorescent-tagged, scale-
dispersant polymer and responds quickly when conditions favor scale formation. In addition, 3D Bio-control, also
part of the 3D TRASAR® system, is the only online, real-time test for measuring planktonic and sessile bacteria.
It uses resazurin, another fluorescent molecule, which changes its fluorescent signature when it interacts with
respiring microbes. By adding an oxidizing biocide in response to microbial activity, 3D Bio-control generally
reduces the use of biocide and also prevents biofilm from building up on surfaces, maintaining efficient heat
transfer.
A proprietary corrosion monitor and a novel corrosion inhibitor, phosphino succinic oligomer, provide improved
corrosion protection. In 2006, the 2,500 installations using the 3D TRASAR® system saved approximately
21 billion gallons of water. These installations have also significantly reduced the discharge of water-treatment
chemicals to water-treatment plants or natural waterways.
26 2008 Greener Reaction Conditions Award
-------
Spinetoram: Enhancing a Natural Product for Insect Control
Spinosad biopesticide from Dow AgroSciences controls many insect pests on vegetables, but is not particularly
effective against certain key pests of tree fruits. To solve this problem, Dow AgroSciences used an "artificial neural
network" to identify analogous molecules that might be more effective against fruit-tree pests. They then developed
a green chemical synthesis for the new insecticide, called spinetoram. Spinetoram retains the favorable environmental
benefits of spinosad while replacing organophosphate pesticides for tree fruits, tree nuts, small fruits, and vegetables.
bpinosad biopesticide won the Presidential Green Chemistry Challenge Award for Designing Greener Chemicals
in 1999. Spinosad, a combination of spinosyns A and D, is effective against insect pests on vegetables, but there
have been few green chemistry alternatives for insect-pest control in tree fruits and tree nuts. Dow AgroSciences
has now developed spinetoram, a significant advancement over spinosad that extends the success of spinosad to
new crops.
The discovery of spinetoram involved the novel application of an artificial neural network (ANN) to the molecular
design of insecticides. Dow AgroSciences researchers used an ANN to understand the quantitative structure-
activity relationships of spinosyns and to predict analogues that would be more active. The result is spinetoram, a
mixture of 3'-O-ethyl-5,6-dihydro spinosyn J and 3'-O-ethyl spinosyn L. Dow AgroSciences makes spinetoram from
naturally occurring fermentation products spinosyns J and L by modifying them with a low-impact synthesis in
which catalysts and most reagents and solvents are recycled. The biology and chemistry of spinetoram have been
extensively researched; the results have been published in peer-reviewed scientific journals and presented at
scientific meetings globally.
Spinetoram provides significant and immediate benefits to human health and the environment over existing
insecticides. Azinphos-methyl and phosmet, two organophosphate insecticides, are widely used in pome fruits
(such as apples and pears), stone fruits (such as cherries and peaches), and tree nuts (such as walnuts and
pecans). The mammalian acute oral toxicity of spinetoram is more than 1,000 times lower than that of azinphos-
methyl and 44 times lower than that of phosmet. The low toxicity of spinetoram reduces the risk of exposures
throughout the supply chain: in manufacturing, transportation, and application and to the public.
Spinetoram has a lower environmental impact than do many current insecticides because both its use rate and
its toxicity to non-target species are low. Spinetoram is effective at much lower rates than many competing
insecticides. It is effective at use rates that are 10-34 times lower than azinphos-methyl and phosmet. Spinetoram
is also less persistent in the environment compared with other traditional insecticides. In the United States alone,
Dow AgroSciences expects spinetoram to eliminate about 1.8 million pounds of organophosphate insecticides
applied to pome fruit, stone fruit, and tree nuts during its first five years of use. In 2007, EPA granted pesticide
registrations to the spinetoram products Radiant™ and Delegate™, and Dow AgroSciences began commercial
sales.
! Designing Green Chemicals Award 27
-------
2007 Winners
Hydrogen-Mediated Carbon—Carbon Bond Formation
innsA,;•;)(;•!'; ,;IV' i ;Y; n >": H hv
A fundamental aspect of chemistry involves creating chemical bonds between carbon atoms. Chemical processes
commonly used to make such bonds usually also generate significant amounts of waste. Professor Krische developed
a broad new class of chemical reactions that make bonds between carbon atoms using hydrogen and metal
catalysts. This new class of reactions can be used to convert simple chemicals into complex substances, such as
Pharmaceuticals, pesticides, and other important chemicals, with minimal waste.
'•'eductions mediated by hydrogen, termed "hydrogenations", rank among the most widely used catalytic
methods employed industrially. They are generally used to form carbon-hydrogen (C-H) bonds. Professor
Michael J. Krische and his coworkers at the University of Texas at Austin have developed a new class of
hydrogenation reactions that form carbon-carbon (C-C) bonds. In these metal-catalyzed reactions, two or more
organic molecules combine with hydrogen gas to create a single, more complex product. Because all atoms
present in the starting building-block molecules appear in the final product, Professor Krische's reactions do not
generate any byproducts or wastes. Hence, Professor Krische's C-C bond-forming hydrogenations eliminate
pollution at its source.
Prior to Professor Krische's work, hydrogen-mediated C-C bond formations were limited almost exclusively to the
use of carbon monoxide in reactions such as alkene hydroformylation (1938) and the fischer-Tropsch reaction
(1923). These prototypical hydrogen-mediated C-C bond formations are practiced industrially on an enormous
scale. Yet, despite the importance of these reactions, no one had engaged in systematic research to develop
related C-C bond-forming hydrogenations. Only a small fraction of hydrogenation's potential as a method of
C-C coupling had been realized, and the field lay fallow for nearly 70 years.
Professor Krische's hydrogen-mediated couplings circumvent the use of preformed organometallic reagents,
such as Grignard and Gilman reagents, in carbonyl and imine addition reactions. Such organometallic reagents
are highly reactive, typically moisture-sensitive, and sometimes pyrophoric, meaning that they combust when
exposed to air. Professor Krische's coupling reactions take advantage of catalysts that avoid the hazards of
traditional organometallic reagents, further, using chiral hydrogenation catalysts, Professor Krische's couplings
generate C-C bonds in a highly enantioselective fashion.
Catalytic hydrogenation has been known for over a century and has stood the test of time due its efficiency, atom
economy, and cost-effectiveness. By exploiting hydrogenation as a method of C-C bond formation, Professor
Krische has added a broad, new dimension to one of chemistry's most fundamental catalytic processes. The
C-C bond-forming hydrogenations developed by Professor Krische allow chemists to create complex organic
molecules in a highly selective fashion, eliminating both hazardous starting materials and hazardous waste.
Commercial application of this technology may eliminate vast quantities of hazardous chemicals. The resulting
increases in plant and worker safety may enable industry to perform chemical transformations that were too
dangerous using traditional reagents.
28 2007 Academic Award
-------
Environmentally Benign Medical Sterilization Using Supercritical Carbon Dioxide
Sterilizing biological tissue for transplant is critical to safety and success in medical treatment. Common existing
sterilization techniques use ethylene oxide or gamma radiation, which are toxic or have safety problems. NovaSterilis
invented a technology that uses carbon dioxide and a form of peroxide to sterilize a wide variety of delicate biological
materials such as graft tissue, vaccines, and biopolymers. Their Nova 2200™ sterilizer requires neither hazardous
ethylene oxide nor gamma radiation.
..one of the common methods for medical sterilization is well-suited to sterilizing delicate biological materials.
The sterility of these materials is critical. Distribution of contaminated donor tissues by tissue banks has resulted
in serious infections and illnesses in transplant patients. The two most widely used sterilants (ethylene oxide and
gamma radiation) also raise toxicity and safety concerns. Ethylene oxide is a mutagenic, carcinogenic, volatile,
flammable, reactive gas. Residues of ethylene oxide remain in the sterilized material, increasing the risk of toxic
side effects. Gamma radiation is highly penetrating and is lethal to all cells. Neither ethylene oxide nor gamma
radiation can sterilize packaged biological products without eroding their physical integrity.
NovaSterilis, a privately held biotechnology company in Ithaca, NY, has successfully developed and
commercialized a highly effective and environmentally benign technique for sterilizing delicate biological
materials using supercritical carbon dioxide (CO2). NovaSterilis licensed a patent for bacterial inactivation in
biodegradable polymers that was issued to Professor Robert S. Langer and his team at the Massachusetts Institute
of Technology. NovaSterilis then enhanced, expanded, and optimized the technology to kill bacterial endospores.
Their supercritical CO2 technology uses low temperature and cycles of moderate pressure along with a peroxide
(peracetic acid) and small amounts of water. Their Nova 2200™ sterilizer consistently achieves rapid (less than
one hour) and total inactivation of a wide range of microbes, including bacterial endospores. The mechanism
of bacterial inactivation is not well-understood, but does not appear to involve bacterial cell lysis or wholesale
degradation of bacterial proteins.
The new technology is compatible with sensitive biological materials and is effective for a wide range of
important biomedical materials including: (a) musculoskeletal allograft tissue (e.g., human bone, tendons,
dermis, and heart valves) for transplantation; (b) biodegradable polymers and related materials used in
medical devices, instruments, and drugs; (c) drug delivery systems; and (d) whole-cell vaccines that retain high
antigenicity. Besides being a green chemical technology, supercritical CO2 sterilization achieves "terminal"
sterilization, that is, sterilization of the final packaged product. Terminal sterilization provides greater assurance of
sterility than traditional methods of aseptic processing. Sterilization of double-bagged tissue allows tissue banks to
ship terminally sterilized musculoskeletal tissues in packages that can be opened in operating rooms by surgical
teams immediately prior to use. NovaSterilis's patented technology addresses the market need in tissue banks as
well as other needs in the biomedical, biologies, medical device, pharmaceutical, and vaccine industries. By the
end of 2006, NovaSterilis had sold several units to tissue banks.
2007 Small Business Award 29
-------
Development and Commercial Application of Environmentally Friendly Adhesives for Wood Composites
Adhesives used in manufacturing plywood and other wood composites often contain formaldehyde, which is toxic.
Professor Kaichang Li of Oregon State University, Columbia Forest Products, and Hercules Incorporated developed an
alternate adhesive made from soy flour. Their environmentally friendly adhesive is stronger than and cost-competitive
with conventional adhesives. During 2006, Columbia used the new, soy-based adhesive to replace more than
47 million pounds of conventional formaldehyde-based adhesives.
bince the 1940s, the wood composites industry has been using synthetic adhesive resins to bind wood pieces
into composites, such as plywood, particleboard, and Fiberboard. The industry has been the predominate user of
formaldehyde-based adhesives such as phenol-formaldehyde and urea-formaldehyde (UF) resins. Formaldehyde
is a probable human carcinogen. The manufacture and use of wood composite panels bonded with
formaldehyde-based resins release formaldehyde into the air, creating hazards for both workers and consumers.
Inspired by the superior properties of the protein that mussels use to adhere to rocks, Professor Li and his group
at Oregon State University invented environmentally friendly wood adhesives based on abundant, renewable
soy flour. Professor Li modified some of the amino acids in soy protein to resemble those of mussels' adhesive
protein. Hercules Incorporated provided a critical curing agent and the expertise to apply it to commercial
production of plywood.
Oregon State University, Columbia Forest Products (CFP), and Hercules have jointly commercialized soy-based
adhesives to produce cost-competitive plywood and particleboard for interior uses. The soy-based adhesives
do not contain formaldehyde or use formaldehyde as a raw material. They are environmentally friendly, cost-
competitive with the UF resin in plywood, and superior to the UF resin in strength and water resistance. All CFP
plywood plants now use soy-based adhesives, replacing more than 47 million pounds of the toxic UF resin in
2006 and reducing the emission of hazardous air pollutants (HAPs) from each CFP plant by 50 to 90 percent. This
new CFP plywood is sold under the PureBond™ name. During 2007, CFP will replace UF at its particleboard plant;
the company is also seeking arrangements with other manufacturers to further the adoption of this technology.
With this technology, those who make and use furniture, kitchen cabinetry, and other wood composite materials
have a high-performing formaldehyde-free alternative. As a result, indoor air quality in homes and offices could
improve significantly. This technology represents the first cost-competitive, environmentally friendly adhesive
that can replace the toxic UF resin. The technology can greatly enhance the global competitiveness of U.S. wood
composite companies. In addition, by creating a new market for soy flour, currently in over-supply, this technology
provides economic benefits for soybean farmers.
30 2007 Greener Synthetic Pathways Award
-------
Direct Synthesis of Hydrogen Peroxide by Selective Nanocatalyst Technology
Hydrogen peroxide is an environmentally friendly alternative to chlorine and chlorine-containing bleaches and
oxidants. It is expensive, however, and its current manufacturing process involves the use of hazardous chemicals.
Headwaters Technology Innovation (HTI) developed an advanced metal catalyst that makes hydrogen peroxide directly
from hydrogen and oxygen, eliminates the use of hazardous chemicals, and produces water as the only byproduct.
HTI has demonstrated their new technology and is partnering with Degussa AG to build plants to produce hydrogen
peroxide.
' 'ydrogen peroxide (H2O2) is a clean, versatile, environmentally friendly oxidant that can substitute for
environmentally harmful chlorinated oxidants in many manufacturing operations. However, the existing
manufacturing process for H2O2 is complex, expensive, and energy-intensive. This process requires an
anthraquinone working solution containing several toxic chemicals. The solution is reduced by hydrogen in the
presence of a catalyst, forming anthrahydroquinone, which then reacts with oxygen to release H2O2. The H2O2
is removed from the solution with an energy-intensive stripping column and then concentrated by vacuum
distillation. The bulk of the working solution is recycled, but the process generates a waste stream of undesirable
quinone-derived byproducts that requires environmentally acceptable disposal.
Headwaters Technology Innovation (HTI) has produced a robust catalyst technology that enables the synthesis of
H2O2 directly from hydrogen and oxygen. This breakthrough technology, called NxCat™, is a palladium-platinum
catalyst that eliminates all the hazardous reaction conditions and chemicals of the existing process, along with its
undesirable byproducts. It produces H2O2 more efficiently, cutting both energy use and costs. It uses innocuous,
renewable feedstocks and generates no toxic waste.
NxCat™ catalysts work because of their precisely controlled surface morphology. HTI has engineered a set
of molecular templates and substrates that maintain control of the catalyst's crystal structure, particle size,
composition, dispersion, and stability. This catalyst has a uniform 4-nanometer feature size that safely enables
a high rate of production with a hydrogen gas concentration below 4 percent in air (i.e., below the flammability
limit of hydrogen). It also maximizes the selectivity for H2O2 up to 100 percent.
The NxCat™ technology enables a simple, commercially viable H2O2 manufacturing process. In partnership with
Degussa AG (a major H2O2 manufacturer), HTI successfully demonstrated the NxCat™ technology and, in 2006,
completed construction of a demonstration plant. This demonstration plant will allow the partners to collect
the data necessary to design a full-scale plant and begin commercial production in 2009. The NxCat™ process
has the potential to cut the cost of H2O2 significantly, generating a more competitively priced supply of H2O2
and increasing its market acceptance as an industrial oxidant. Except for its historically higher price, H2O2 is an
excellent substitute for the more frequently used—and far more deleterious—chlorinated oxidants. The NxCat™
technology has the benefit of producing an effective, environmentally preferable oxidant (H2O2) without the
waste or high cost associated with the traditional process.
2007 Greener Reaction Conditions Award 31
-------
BiOH™ Polyols
Foam cushioning used in furniture or bedding is made from polyurethane, a man-made material. One of the two
chemical building blocks used to make polyurethane is a "polyol." Polyols are conventionally manufactured from
petroleum products. Cargill's BiOH™ polyols are manufactured from renewable, biological sources such as vegetable
oils. Foams made with BiOH™ polyols are comparable to foams made from conventional polyols. As a result, each
million pounds of BiOH™ polyols saves nearly 700,000 pounds of crude oil. In addition, Cargill's process reduces total
energy use by 23 percent and carbon dioxide emissions by 36 percent.
I 'olyolsare key ingredients in flexible polyurethane foams, which are used in furniture and bedding. Historically,
polyurethane has been made from petrochemical polyols. The idea of replacing these polyols with biobased
polyols is not new, but the poor performance, color, quality, consistency, and odor of previous biobased polyols
restricted them to limited markets. Previous biobased polyols also suffer from poor chemical reactivity, resulting in
foam with inferior properties.
Cargill has successfully developed biobased polyols for several polyurethane applications, including flexible
foams, which are the most technically challenging. Cargill makes BiOH™ polyols by converting the carbon-
carbon double bonds in unsaturated vegetable oils to epoxide derivatives and then further converting these
derivatives to polyols using mild temperature and ambient pressure. BiOH™ polyols provide excellent reactivity
and high levels of incorporation leading to high-performing polyurethane foams. These foams set a new
standard for consistent quality with low odor and color. Foams containing BiOH™ polyols retain their white color
longer without ultraviolet stabilizers. They also are superior to foams containing only petroleum-based polyols in
standard tests. In large slabstock foams, such as those used in furniture and bedding, BiOH 5000 polyol provides
a wide processing window, improved comfort factor, and reduced variations in density and load-bearing capacity.
In molded foams such as automotive seating and headrests, BiOH 2100 polyol can enhance load-bearing or
hardness properties relative to conventional polyols.
Use of BiOH™ polyols reduces the environmental footprint relative to today's conventional polyols for
polyurethane production. BiOH™ polyols "harvest" carbon that plants remove from the air during photosynthesis.
All of the carbon in BiOH™ polyols is recently fixed. In conventional polyols, the carbon is petroleum-based.
Replacing petroleum-based polyols with BiOH™ polyols cuts total energy use by 23 percent including a
61 percent reduction in nonrenewable energy use, leading to a 36 percent reduction in carbon dioxide emissions.
For each million pounds of BiOH™ polyol used in place of petroleum-based polyols, about 700,000 pounds
(2,200 barrels) of crude oil are saved, thereby reducing the dependence on petroleum. BiOH™ polyols diversify
the industry's supply options and help mitigate the effects of uncertainty and volatility of petroleum supply and
pricing. Cargill is the first company to commercialize biobased polyols on a large scale in the flexible foam market.
Formulators can now use biobased polyols in flexible foam without compromising product performance. That the
top North American polyol users choose BiOH™ polyols is validation of Cargill's accomplishment.
32 2007 Designing Greener Chemicals Award
-------
2006 Winners
Biobased Propylene Glycol and Monomers from Natural Glycerin
Professor Suppes developed an inexpensive method to convert waste glycerin, a byproduct of biodiesel fuel
production, into propylene glycol, which can replace ethylene glycol in automotive antifreeze. This high-value use of
the glycerin byproduct can keep production costs down and help biodiesel become a cost-effective, viable alternative
fuel, thereby reducing emissions and conserving fossil fuels.
I (lycerin is a coproduct of biodiesel production. The U.S. biodiesel industry is expected to introduce one billion
pounds of additional glycerin into a market that is currently only 600 million pounds. The economics of biodiesel
depend heavily on using its glycerin coproduct. A high-value use for glycerin could reduce the cost of biodiesel
by as much as 40C per gallon. There is simply not enough demand for glycerin, however, to make use of all the
waste glycerin expected.
One solution is to convert the glycerin to propylene glycol. Approximately 2.4 billion pounds of propylene glycol
are currently made each year, almost exclusively from petroleum-based propylene oxide. Propylene glycol is a less
toxic alternative to ethylene glycol in antifreeze, but is currently more expensive and, as a result, has a very small
market share. Professor Galen J. Suppes has developed a catalytic process that efficiently converts crude glycerin
to propylene glycol.
Professor Suppes's system couples a new copper-chromite catalyst with a reactive distillation. This system has
a number of advantages over previous systems that perform this conversion. The new process uses a lower
temperature and lower pressure than do previous systems (428 °F versus 500 °F and <145 psi versus >2,170 psi),
converts glycerin to propylene glycol more efficiently, and produces less byproduct than do similar catalysts.
Propylene glycol made from glycerin by Professor Suppes's method is also significantly cheaper than propylene
glycol made from petroleum.
Another solution is to convert glycerin to acetol (i.e., 1-hydroxy-2-propanone or hydroxyacetone), a well-known
intermediate and monomer used to make polyols. When made from petroleum, acetol costs approximately $5 per
pound, prohibiting its wide use. Professor Suppes's technology can be used to make acetol from glycerin at a cost
of approximately 50C per pound, opening up even more potential applications and markets for products made
from glycerin.
Professor Suppes initiated this project in June 2003. The first commercial facility, with a capacity of
50 million pounds per year, is under construction and is expected to be in operation by October 2006.
2006 Academic Award 33
-------
Environmentally Safe Solvents and Reclamation in the Flexographic Printing Industry
Flexographic printing is used in a wide array of print jobs such as food wrappers and boxes, but the process uses
millions of gallons of solvents each year. Arkon and NuPro developed a safer chemical processing system that reduces
the amounts of solvents needed for printing. The new system eliminates hazardous solvents, reduces explosion
potential and emissions during solvent recycling, and increases worker safety in the flexographic printing industry.
I lexographic printing is used on everything from food wrappers to secondary containers such as cereal boxes
to shipping cartons. The photopolymerizable material on a flexographic printing plate cross-links when exposed
to light and captures an image. After exposure, flexographic printing plates are immersed in a solvent to remove
the unpolymerized material. The developing, or washout, solvent is typically a mixture of chloro, saturated cyclic,
or acyclic hydrocarbons. Xylene is the most common solvent. Most traditional washout solvents are hazardous
air pollutants (HAPs) subject to stringent reporting requirements; they also raise worker safety issues and create
problems with recycling and disposal. North America alone uses 2 million gallons of washout solvents each year
with a market value of $20 million. Many small printing plants use these solvents.
Together, Arkon Consultants and NuPro Technologies have developed a safer chemical processing system,
including washout solvents and reclamation/recycling machinery for the flexographic printing industry. NuPro/
Arkon have developed several new classes of washout solvents with methyl esters, terpene derivatives, and
highly substituted cyclic hydrocarbons. The advantages include higher flash points and lower toxicity, which
reduce explosion potential, worker exposure, and regulatory reporting. The methyl esters and terpene derivatives
are biodegradable and can be manufactured from renewable sources. All of their solvents are designed to
be recycled in their Cold Reclaim System™. In contrast to traditional vacuum distillation, this combination of
filtration and centrifugation lowers exposures, decreases maintenance, and reduces waste. The waste is a solid,
nonhazardous polymeric material.
In the U.S. market, NuPro/Arkon are currently selling washout solvents that are terpene ether- and ester-based or
made with low-hazard cyclics. They are marketing their methyl ester-based solvent in China and Japan. Their first
filtration-based Cold Recovery System™ is currently in use in Menesha, Wl and is being marketed to larger U.S.
users. Their centrifugation reclamation system for smaller users is in the final stages of development.
Use of these solvents and systems benefits both human health and the environment by lowering exposure
to hazardous materials, reducing explosion potential, reducing emissions, and, in the case of the terpene
and methyl ester-based solvents, using renewable resources. These solvents and the reclamation equipment
represent major innovations in the safety of handling, exposure, and recovery. The reduced explosion potential,
reduced emissions, decreased worker exposure, and reduced transport and maintenance costs translate into
decreased cost and improved safety in all aspects of flexographic printing processes.
34 2006 Small Business Award
-------
Novel Green Synthesis for p-Amino Acids Produces the Active Ingredient in Januvia™
innsA,;•;)(;•!'; ,;IV' i ;Y; n >": H hv
Merck discovered a highly innovative and efficient catalytic synthesis for sitagliptin, which is the active ingredient in
Januvia™, the company's new treatment for type 2 diabetes. This revolutionary synthesis creates
220 pounds less waste for each pound of sitagliptin manufactured and increases the overall yield by nearly 50 percent.
Over the lifetime of Januvia™, Merck expects to eliminate the formation of at least 330 million pounds of waste,
including nearly 110 million pounds of aqueous waste.
Januvia™ is a new treatment for type 2 diabetes; Merck filed for regulatory approval in December 2005. Sitagliptin,
a chiral p-amino acid derivative, is the active ingredient in Januvia™. Merck used a first-generation synthesis of
sitagliptin to prepare over 200 pounds for clinical trials. With modifications, this synthesis could have been a viable
manufacturing process, but it required eight steps including a number of aqueous work-ups. It also required
several high-molecular-weight reagents that were not incorporated into the final molecule and, therefore, ended
up as waste.
While developing a highly efficient second-generation synthesis for sitagliptin, Merck researchers discovered a
completely unprecedented transformation: the asymmetric catalytic hydrogenation of unprotected enamines. In
collaboration with Solvias, a company with expertise in this area, Merck scientists discovered that hydrogenation
of unprotected enamines using rhodium salts of a ferrocenyl-based ligand as the catalyst gives p-amino acid
derivatives of high optical purity and yield. This new method provides a general synthesis of p-amino acids, a
class of molecules well-known for interesting biological properties. Merck scientists and engineers applied this
new method in a completely novel way: using it in the final synthetic step to maximize the yield in terms of the
valuable chiral catalyst. The dehydro precursor to sitagliptin used in the asymmetric hydrogenation is prepared in
an essentially one-pot procedure. Following the hydrogenation, Merck recovers and recycles over 95 percent of
the valuable rhodium. The reactive amino group of sitagliptin is only revealed in the final step; as a result, there is
no need for protecting groups. The new synthesis has only three steps and increases the overall yield by nearly
50 percent.
This strategy is broadly applicable to other pharmaceutical syntheses; Merck has used it to make several
exploratory drug candidates. Implementing the new route on a manufacturing scale has reduced the amount of
waste by over 80 percent and completely eliminated aqueous waste streams. This second-generation synthesis
will create 220 pounds less waste for each pound of sitagliptin manufactured. Over the lifetime of the drug,
Merck expects to eliminate the formation of 330 million pounds or more of waste, including nearly 110 million
pounds of aqueous waste. Because Merck's new synthesis has reduced the amount of raw materials, processing
time, energy, and waste, it is a more cost-effective option than the first-generation synthesis. The technology
discovered, developed, and implemented by Merck for the manufacture of Januvia™ is an excellent example of
scientific innovation resulting in benefits to the environment.
2006 Greener Synthetic Pathways Award 35
-------
Directed Evolution of Three Biocatalysts to Produce the Key Chiral Building Block for Atorvastatin, the Active
Ingredient in Lipitor®
lnnff\.-Vif;..i; >;no j:v i ,..••. I i.hv
Codexis developed cutting-edge genetic methods to create "designer enzymes". Codexis applied its methods to
produce enzymes that greatly improve the manufacture of the key building block for Lipitor®, one of the world's best-
selling drugs. The new enzymatic process reduces waste, uses less solvent, and requires less processing equipment-
marked improvements over processes used in the past. The process also increases yield and improves worker safety.
\torvastatin calcium is the active ingredient of Lipitor®, a drug that lowers cholesterol by blocking its synthesis
in the liver. Lipitor® is the first drug in the world with annual sales exceeding $10 billion. The key chiral building
block in the synthesis of atorvastatin is ethyl (£)-4-cyano-3-hydroxybutyrate, known as hydroxy nit rile (HN). Annual
demand for HN is estimated to be about 440,000 pounds. Traditional commercial processes for HN require
a resolution step with 50 percent maximum yield or syntheses from chiral pool precursors; they also require
hydrogen bromide to generate a bromohydrin for cyanation. All previous commercial HN processes ultimately
substitute cyanide for halide under heated alkaline conditions, forming extensive byproducts. They require a
difficult high-vacuum fractional distillation to purify the final product, which decreases the yield even further.
Codexis designed a green HN process around the exquisite selectivity of enzymes and their ability to catalyze
reactions under mild, neutral conditions to yield high-quality products. Codexis developed three specific enzymes
using state-of-the-art, recombinant-based, directed evolution technologies to provide the activity, selectivity, and
stability required for a practical and economic process. The bioengineered enzymes are so active and stable that
Codexis can recover high-quality product by extracting the reaction mixture. In the first step, two of the enzymes
catalyze the enantioselective reduction of a prochiral chloroketone (ethyl 4-chloroacetoacetate) by glucose to
form an enantiopure chlorohydrin. In the second step, a third enzyme catalyzes the novel biocatalytic cyanation
of the chlorohydrin to the cyanohydrin under neutral conditions (aqueous, pH ~7, 77-104 °F, atmospheric
pressure). On a biocatalyst basis, the three enzymes have improved the volumetric productivity of the reduction
reaction by approximately 100-fold and that of the cyanation reaction by approximately 4,000-fold.
The process involves fewer unit operations than earlier processes, most notably obviating the fractional distillation
of the product. The process provides environmental and human health benefits by increasing yield, reducing
the formation of byproducts, reducing the generation of waste, avoiding hydrogen gas, reducing the need
for solvents, reducing the use of purification equipment, and increasing worker safety. The Codexis process is
operated by Lonzato manufacture HN for Pfizer's production of atorvastatin calcium.
36 2006 Greener Reaction Conditions Award
-------
Greenlist™ Process to Reformulate Consumer Products
innsA,;•;)(;•!'; ,;IV' i ;Y; n >": H hv
SC Johnson developed Greenlist™, a system that rates the environmental and health effects of the ingredients in its
products. SC Johnson is now using Greenlist™ to reformulate many of its products. For example, SC Johnson eliminated
the use of nearly 4 million pounds of polyvinylidene chloride (PVDC) annually after its "Greenlist" review of Saran Wrap®
revealed opportunities for changes.
5C Johnson (SCJ) formulates and manufactures consumer products including a wide variety of products for
home cleaning, air care, personal care, insect control, and home storage. For more than a century, SCJ has
been guided by the belief that, because it is a family business, it must consider the next generation when
it makes current product decisions, not merely the next fiscal quarter. The most recent initiative in SCJ's long
history of commitment to environmentally preferable products is its Greenlist™ process, a system that rates
the environmental footprint of the ingredients in its products. Through Greenlist™, SCJ chemists and product
formulators around the globe have instant access to environmental ratings of potential product ingredients.
Starting in 2001, SCJ developed Greenlist™ according to the rigorous standards of scientific best practices.
Greenlist™ uses four to seven specific criteria to rate ingredients within 17 functional categories. SCJ enlisted
the help of suppliers, university scientists, government agencies, and nongovernmental organizations
(NGOs) to ensure that the rating criteria were meaningful, objective, and valid. These criteria include vapor
pressure, octanol/water partition coefficient, biodegradability, aquatic toxicity, human toxicity, European Union
Classification, source/supply, and others, as appropriate. The Greenlist™ process assigns an environmental
classification (EC) score to each ingredient by averaging its scores for the criteria in its category. EC scores range
from Best (3) to Restricted Use Material (0). SCJ lowers the EC score for chemicals with other significant concerns
including PBT (persistence, bioaccumulation, and toxicity), endocrine disruption, carcinogenicity, and reproductive
toxicity. Today, Greenlist™ provides ratings for more than 90 percent of the raw materials SCJ uses, including
solvents, surfactants, inorganic acids and bases, chelants, propellants, preservatives, insecticides, fragrances,
waxes, resins, nonwoven fabrics, and packaging. Company scientists have also developed criteria for dyes,
colorants, and thickeners and are working on additional categories as well.
During fiscal 2000-2001, the baseline year, SCJ's EC average was 1.12. Their goal was to reach an average EC of
1.40 during fiscal 2007-2008. The company reached this goal three years early, with an average EC of
1.41 covering almost 1.4 billion pounds of raw materials.
In recent years, SCJ has used Greenlist™ to reformulate multiple products to make them safer and more
environmentally responsible. In one example, SCJ used the Greenlist™ process to replace polyvinylidene chloride
(PVDC) with polyethylene in Saran Wrap®. In another example, SCJ applied Greenlist™ to remove a particular
volatile organic compound (VOC) from Windex®. They developed a novel new formula containing amphoteric
and anionic surfactants, a solvent system with fewer than 4 percent VOCs, and a polymer for superior wetting.
Their formula cleans 30 percent better and eliminates over 1.8 million pounds of VOCs per year.
2006 Designing Greener Chemicals Award 37
-------
2005 Winners
A Platform Strategy Using Ionic Liquids to Dissolve and Process Cellulose for Advanced New Materials
Professor Rogers developed methods that allow cellulose from wood, cloth, or even paper to be chemically modified
to make new biorenewable or biocompatible materials. His methods also allow cellulose to be mixed with other
substances, such as dyes, or simply to be processed directly from solution into a formed shape. Together, these
methods can potentially save resources, time, and energy.
\ \ajor chemical companies are currently making tremendous strides towards using renewable resources in
biorefineries. In a typical biorefinery, the complexity of natural polymers, such as cellulose, is first broken down
into simple building blocks (e.g., ethanol, lactic acid), then built up into complex polymers. If one could use the
biocomplexity of natural polymers to form new materials directly, however, one could eliminate many destructive
and constructive synthetic steps. Professor Robin D. Rogers and his group have successfully demonstrated
a platform strategy to efficiently exploit the biocomplexity afforded by one of Nature's renewable polymers,
cellulose, potentially reducing society's dependence on nonrenewable petroleum-based feedstocks for synthetic
polymers. No one had exploited the full potential of cellulose previously, due in part to the shift towards
petroleum-based polymers since the 1940s, difficulty in modifying the cellulose polymer properties, and the
limited number of common solvents for cellulose.
Professor Rogers's technology combines two major principles of green chemistry: developing environmentally
preferable solvents and using biorenewable feedstocks to form advanced materials. Professor Rogers has found
that cellulose from virtually any source (fibrous, amorphous, pulp, cotton, bacterial, filter paper, etc.) can be
dissolved readily and rapidly, without derivatization, in a low-melting ionic liquid (IL), 1-butyl-3-
methylimidazolium chloride ([C4mim]CI), by gentle heating (especially with microwaves). IL-dissolved cellulose
can easily be reconstituted in water in controlled architectures (fibers, membranes, beads, floes, etc.) using
conventional extrusion spinning or forming techniques. By incorporating functional additives into the solution
before reconstitution, Professor Rogers can prepare blended or composite materials. The incorporated functional
additives can be either dissolved (e.g., dyes, complexants, other polymers) or dispersed (e.g., nanoparticles,
clays, enzymes) in the IL before or after dissolution of the cellulose. With this simple, noncovalent approach,
Professor Rogers can readily prepare encapsulated cellulose composites of tunable architecture, functionality, and
rheology. The IL can be recycled by a novel salting-out step or by common cation exchange, both of which save
energy compared to recycling by distillation. Professor Rogers's current work is aimed at improved, more efficient,
and economical syntheses of [C4mim]CI, studies of the I L toxicology, engineering process development, and
commercialization.
Professor Rogers and his group are currently doing market research and business planning leading to the
commercialization of targeted materials, either through joint development agreements with existing chemical
companies or through the creation of small businesses. Green chemistry principles will guide the development
work and product selection, for example, targeting polypropylene- and polyethylene-derived thermoplastic
materials for the automotive industry could result in materials with lower cost, greater flexibility, lower weight,
lower abrasion, lower toxicity, and improved biodegradability, as well as significant reductions in the use of
petroleum-derived plastics.
Professor Rogers's work allows the novel use of ILs to dissolve and reconstitute cellulose and similar polymers.
Using green chemistry principles to guide development and commercialization, he envisions that his platform
strategy can lead to a variety of commercially viable advanced materials that will obviate or reduce the use of
synthetic polymers.
38 2005 Academic Award
-------
Producing Nature's Plastics Using Biotechnology
!nns;\,;•;)(;•!'; .;nr'' !:Y:n::l ihv
Metabolix used new biotechnology methods to develop microorganisms that produce polyhydroxyalkanoates
(PHAs) directly. PHAs are natural plastics with a range of environmental benefits, including reduced reliance on fossil
carbon, reduced solid waste, and reduced greenhouse gas emissions. PHAs biodegradeto harmless products in the
environment, reducing the burden of plastic waste on landfills and the environment. Metabolix hopes to develop
plants that produce PHAs as well.
etabolix is commercializing polyhydroxyalkanoates (PHAs), a broadly useful family of natural, environmentally
friendly, high-performing, bio-based plastics. PHAs are based on a biocatalytic process that uses renewable
feedstocks, such as cornstarch, cane sugar, cellulose hydrolysate, and vegetable oils. PHAs can provide a
sustainable alternative to petrochemical plastics in a wide variety of applications.
Metabolix uses biotechnology to introduce entire enzyme-catalyzed reaction pathways into microbes, which then
produce PHAs, in effect creating living biocatalysts. The performance of these engineered microbes has been
fully validated in commercial equipment, demonstrating reliable production of a wide range of PHA copolymers
at high yield and reproducibility. A highly efficient commercial process to recover PHAs has also been developed
and demonstrated. The routine expression of exogenous, chromosomally integrated genes coding for the
enzymes used in a non-native metabolic pathway is a tour de force in the application of biotechnology. These
accomplishments have led Metabolix to form an alliance with Archer Daniels Midland Company, announced in
November 2004, to produce PHAs commercially, starting with a 100-million-pound-per-year plant to be sited in the
U.S. Midwest.
These new natural PHA plastics are highly versatile, have a broad range of physical properties, and are practical
alternatives to synthetic petrochemical plastics. PHAs range from rigid to highly elastic, have very good barrier
properties, and are resistant to hot water and greases. Metabolix has developed PHA formulations suitable for
processing on existing equipment and demonstrated them in key end-use applications such as injection molding,
thermoforming, blown film, and extrusion melt casting including film, sheet, and paper coating.
Metabolix's PHA natural plastics will bring a range of environmental benefits, including reduced reliance on
fossil carbon and reduced greenhouse gas emissions. PHAs are now made from renewable raw materials,
such as sugar and vegetable oils. In the future, they will be produced directly in plants. In addition, PHAs will
reduce the burden of plastic waste on solid waste systems, municipal waste treatment systems, and marine and
wetland ecosystems: they will biodegrade to harmless products in a wide variety of both aerobic and anaerobic
environments, including soil, river and ocean water, septic systems, anaerobic digesters, and compost.
Metabolix's PHA technology is the first commercialization of plastics based on renewable resources that
employs living biocatalysts in microbial fermentation to convert renewable raw materials all the way to the
finished copolymer product. PHAs are also the first family of plastics that combine broadly useful properties with
biodegradability in a wide range of environments, including marine and wetlands ecosystems. Replacement of
petrochemical plastics with PHAs will also have significant economic benefits. Producing 50 billion pounds of
PHA natural plastics to replace about half of the petrochemical plastics currently used in the United States would
reduce oil imports by over 200-230 million barrels per year, improving the U.S. trade balance by $6-9 billion per
year, assuming oil at $30-40 per barrel.
2005 Small Business Award 39
-------
NovaLipid™: Low Trans Fats and Oils Produced by Enzymatic Interesterification of Vegetable Oils Using Lipozyme'1
Archer Daniels Midland Company and Novozymes developed a way to make edible fats and oils that contain no trans
fatty acids. The improved "interesterification" process they developed uses less resources. Potential savings include
hundreds of millions of pounds of soybean and other vegetable oils, processing chemicals, and water resources each
year.
I wo major challenges facing the food and ingredient industry are providing health-conscious products to the
public and developing environmentally responsible production technology. Archer Daniels Midland Company
(ADM) and Novozymes are commercializing enzymatic interesterification, a technology that not only has a
tremendous positive impact on public health by reducing trans fatty acids in American diet, but also offers great
environmental benefits by eliminating the waste streams generated by the chemical interesterification process.
Triglycerides consist of one glycerol plus three fatty acids. Triglycerides that contain mostly unsaturated fatty acids
are liquid at room temperature. Manufacturers partially hydrogenate these fatty acids to make them solids at room
temperature. Trans fatty acids form during the hydrogenation process; they are found at high concentrations in
a wide variety of processed foods. Unfortunately, consumption of trans fatty acids is also a strong risk factor for
heart disease. To reduce tens fats in the American diet as much as possible, the FDA is requiring labeling of trans
fats on all nutritional fact panels by January 1, 2006. In response, the U.S. food and ingredient industry has been
investigating methods to reduce tens fats in food.
Of the available strategies, interesterification is the most effective way to decrease the tens fat content in
foods without sacrificing the functionality of partially hydrogenated vegetable oils. During interesterification,
triglycerides containing saturated fatty acids exchange one or two of their fatty acids with triglycerides
containing unsaturated fatty acids, resulting in triglycerides that do not contain any tens fatty acids. Enzymatic
interesterification processes have many benefits over chemical methods, but the high cost of the enzymatic
process and poor enzyme stability had prevented its adoption in the bulk fat industry.
Extensive research and development work by both Novozymes and ADM has led to the commercialization of an
enzymatic interesterification process. Novozymes developed a cost-effective immobilized enzyme, and ADM
developed a process to stabilize the immobilized enzyme enough for successful commercial production. The
interesterified oil provides food companies with broad options for zero and reduced tens fat food products. Since
the first commercial production in 2002, ADM has produced more than 15 million pounds of interesterified oils.
ADM is currently expanding the enzyme process at two of its U.S. production facilities.
Enzymatic interesterification positively affects both environmental and human health. Environmental benefits
include eliminating the use of several harsh chemicals, eliminating byproducts and waste streams (solid and
water), and improving the use of edible oil resources. As one example, margarines and shortenings currently
consume 10 billion pounds of hydrogenated soybean oil each year. Compared to partial hydrogenation, the
ADM/Novozymes process has the potential to save 400 million pounds of soybean oil and eliminate 20 million
pounds of sodium methoxide, 116 million pounds of soaps, 50 million pounds of bleaching clay, and 60 million
gallons of water each year. The enzymatic process also contributes to improved public health by replacing partially
hydrogenated oils with interesterified oils that contain no tens fatty acids and have increased polyunsaturated
fatty acids.
40 2005 Greener Synthetic Pathways Award
-------
A Redesigned, Efficient Synthesis of Aprepitant, the Active Ingredient in Emend®: A New Therapy for
Chemotherapy-Induced Emesis
Emend® is a drug that combats the nausea and vomiting often resulting from chemotherapy treatment. Merck now
makes Emend® using a new process that requires much less energy, raw materials, and water than the original process.
With its new method, Merck eliminates approximately 41,000 gallons of waste per 1,000 pounds of the drug that it
produces.
I mend® is a new therapy for chemotherapy-induced nausea and vomiting, the most common side effects
associated with the chemotherapeutic treatment of cancer. Emend® has been clinically shown to reduce
nausea and vomiting when used during and shortly after chemotherapy. Aprepitant is the active pharmaceutical
ingredient in Emend®.
Aprepitant, which has two heterocyclic rings and three stereogenic centers, is a challenging synthetic target.
Merck's first-generation commercial synthesis required six synthetic steps and was based on the discovery
synthesis. The raw material and environmental costs of this route, however, along with operational safety issues
compelled Merck to discover, develop, and implement a completely new route to aprepitant.
Merck's new route to aprepitant demonstrates several important green chemistry principles. This innovative and
convergent synthesis assembles the complex target in three highly atom-economical steps using four fragments
of comparable size and complexity. The first-generation synthesis required stoichiometric amounts of an
expensive, complex chiral acid as a reagent to set the absolute stereochemistry of aprepitant. In contrast, the new
synthesis incorporates a chiral alcohol as a feedstock; this alcohol is itself synthesized in a catalytic asymmetric
reaction. Merck uses the stereochemistry of this alcohol feedstock in a practical crystallization-induced
asymmetric transformation to set the remaining stereogenic centers of the molecule during two subsequent
transformations. The new process nearly doubles the yield of the first-generation synthesis. Much of the
chemistry developed for the new route is novel and has wider applications. In particular, the use of a stereogenic
center that is an integral part of the final target molecule to set new stereocenters with high selectivity is
applicable to the large-scale synthesis of other chiral molecules, especially drug substances.
Implementing the new route has drastically improved the environmental impact of aprepitant production. Merck's
new route eliminates all of the operational hazards associated with the first-generation synthesis, including
those of sodium cyanide, dimethyl titanocene, and gaseous ammonia. The shorter synthesis and milder reaction
conditions have also reduced the energy requirements significantly. Most important, the new synthesis requires
only 20 percent of the raw materials and water used by the original one. By adopting this new route, Merck has
eliminated approximately 41,000 gallons of waste per 1,000 pounds of aprepitant that it produces.
The alternative synthetic pathway for the synthesis of aprepitant as discovered and implemented by Merck is an
excellent example of minimizing environmental impact while greatly reducing production costs by employing
the principles of green chemistry. Merck implemented the new synthesis during its first year of production of
Emend®; as a result, Merck will realize the benefits of this route for virtually the entire lifetime of this product. The
choice to implement the new route at the outset of production has led to a huge reduction in the cost to produce
aprepitant, demonstrating quite clearly that green chemistry solutions can be aligned with cost-effective ones.
2005 Greener Synthetic Pathways Award 41
-------
A UV-Curable, One-Component, Low-VOC Refinish Primer:
Driving Eco-Efficiency Improvements
lnnff\.-Vif;..i; >;no j:v i ,..••. I i.hv
BASF developed a new automobile paint primer that contains less than half the amount of volatile organic compounds
(VOCs) used in conventional primers. The new primer is also free of diisocyanates, a major source of occupational
asthma. Use in repair facilities has shown that only one-third as much of this primer is needed compared to
conventional primer and that waste is reduced from 20 percent to nearly zero.
I he market for automotive refinish coatings in North America exceeds $2 billion for both collision repairs and
commercial vehicle applications. Over 50,000 body shops in North America use these products. For more than
a decade, automotive refinishersand coating manufacturers have dealt with increasing regulation of emissions
of volatile organic compounds (VOCs). At first, coating manufacturers were able to meet VOC maximums with
high-performance products such as two-component reactive urethanes, which require solvents as carriers for
their high-molecular-weight resins. As thresholds for VOCs became lower, however, manufacturers had to
reformulate their reactive coatings, and the resulting reformulations were slow to set a film. Waterborne coatings
are also available, but their utility has been limited by the time it takes the water to evaporate. Continuing market
pressures demanded faster film setting without compromising either quality or emissions.
Through intense research and development, BASF has invented a new urethane acrylate oligomer primer system.
The resin cross-links with monomer (added to reduce viscosity) into a film when the acrylate double bonds
are broken by radical propagation. The oligomers and monomers react into the film's cross-linked structure,
improving adhesion, water resistance, solvent resistance, hardness, flexibility, and cure speed. The primer cures
in minutes by visible or near-ultraviolet (UV) light from inexpensive UV-A lamps or even sunlight. BASF's UV-cured
primer eliminates the need for bake ovens that cure the current primers, greatly reducing energy consumption.
BASF's primer performs better than the current conventional urethane technologies: it cures ten times faster,
requires fewer preparation steps, has a lower application rate, is more durable, controls corrosion better, and has
an unlimited shelf life. BASF is currently offering its UV-cured primers in its R-M® line as Flash Fill™ VP126 and in its
Glasurit®lineas151-70.
BASF's primer contains only 1.7 pounds of VOCs per gallon, in contrast to 3.5-4.8 pounds of VOCs per gallon of
conventional primers, a reduction of over 50 percent. The primer meets even the stringent requirements of South
Coast California, whereas its superior properties ensure its acceptance throughout the U.S. market. The one-
component nature of the product reduces hazardous waste and cleaning of equipment, which typically requires
solvents. Applications in repair facilities over the past year have shown that only one-third as much primer is
needed and that waste is reduced from 20 percent to nearly zero. The BASF acrylate-based technology requires
less complex, less costly personal protective equipment (PPE) than the traditional isocyanate-based coatings; this,
in turn, increases the probability that small body shops will purchase and use the PPE, increasing worker safety.
This eco-efficient product is the first step in an automobile refinishing coating system for which BASF plans to
include the globally accepted waterborne basecoat from BASF (sold under the Glasurit® brand as line 90). In the
near future, this system can be finished with the application of a one-component, UV-A-curable clearcoat. The
system will deliver quality, energy efficiency, economy, and speed for the small businessperson operating a local
body shop, while respecting the health and safety of the workers in this establishment and the environment in
which these products are manufactured and used. To fully support these claims, BASF has conducted an eco-
efficiency study with an independent evaluation.
42 2005 Greener Reaction Conditions Award
-------
Archer RC™: A Nonvolatile, Reactive Coalescent for the Reduction of VOCs in Latex Paints
Latex paints require coalescents to help the paint particles flow together and cover surfaces well. Archer Daniels
Midland developed Archer RC™, a new biobased coalescent to replace traditional coalescents that are volatile organic
compounds (VOCs). This new coalescent has other performance advantages as well, such as lower odor, increased
scrub resistance, and better opacity.
':>ince the 1980s, waterborne latex coatings have found increasingly broad acceptance in architectural and
industrial applications. Traditional latex coatings are based on small-particle emulsions of a synthetic resin, such
as acrylate- and styrene-based polymers. They require substantial quantities of a coalescent to facilitate the
formation of a coating film as water evaporates after the coating is applied. The coalescent softens (plasticizes)
the latex particles, allowing them to flow together to form a continuous film with optimal performance properties.
After film formation, traditional coalescents slowly diffuse out of the film into the atmosphere. The glass transition
temperature of the latex polymer increases as the coalescent molecules evaporate and the film hardens. Alcohol
esters and ether alcohols, such as ethylene glycol monobutyl ether (EGBE) and Texanol® (2,2,4-trimethyl-1,3-
pentanediol monoisobutyrate), are commonly used as coalescents. They are also volatile organic compounds
(VOCs). Both environmental concerns and economics continue to drive the trend to reduce the VOCs in coating
formulations. Inventing new latex polymers that do not require a coalescent is another option, but these polymers
often produce soft films and are expensive to synthesize, test, and commercialize. Without a coalescent, the latex
coating may crack and may not adhere to the substrate surface when dry at ambient temperatures.
Archer RC™ provides the same function as traditional coalescing agents but eliminates the unwanted VOC
emissions. Instead of evaporating into the air, the unsaturated fatty acid component of Archer RC™ oxidizes
and even cross-links into the coating. Archer RC™ is produced by interesterifying vegetable oil fatty acid esters
with propylene glycol to make the propylene glycol monoesters of the fatty acids. Corn and sunflower oils are
preferred feedstocks for Archer RC™ because they have a high level of unsaturated fatty acids and tend to
resist the yellowing associated with linolenic acid, found at higher levels in soybean and linseed oils. Because
Archer RC™ remains in the coating after film formation, it adds to the overall solids of a latex paint, providing an
economic advantage over volatile coalescents.
The largest commercial category for latex paint, the architectural market, was 618 million gallons in the United
States in 2001. Typically, coalescing solvents constitute 2-3 percent of the finished paint by volume; this
corresponds to an estimated 120 million pounds of coalescing solvents in the United States and perhaps three
times that amount globally. Currently, nearly all of these solvents are lost into the atmosphere each year.
Archer Daniels Midland Company has developed and tested a number of paint formulations using Archer
RC™ in place of conventional coalescing solvents. In these tests, Archer RC™ performed as well as commercial
coalescents such as Texanol®. Archer RC™ often had other advantages as well, such as lower odor, increased
scrub resistance, and better opacity. Paint companies and other raw material suppliers have demonstrated
success formulating paints with Archer RC™ and their existing commercial polymers. Archer RC™ has been in
commercial use since March 2004.
2005 Designing Greener Chemicals Award 43
-------
2004 Winners
Benign Tunable Solvents Coupling Reaction and Separation Processes
Professors Eckert and Liotta found ways to replace conventional organic solvents with benign solvents, such as
supercritical CO2 or water "tuned" by carefully selecting both temperature and pressure. These methods combine
reactions and separations, improving efficiency and reducing waste in a variety of industrial applications.
1 or any chemical process, there must be both a reaction and a separation. Generally, the same solvent is used
for both but is optimized only for the reaction. The separation typically involves 60-80 percent of the cost,
however, and almost always has a large environmental impact. Conventional reactions and separations are often
designed separately, but Professors Charles A. Eckert and Charles L. Liotta have combined them with a series of
novel, benign, tunable solvents to create a paradigm for sustainable development: benign solvents and improved
performance.
Supercritical CO2, nearcritical water, and CO2-expanded liquids are tunable benign solvents that offer exceptional
opportunities as replacement solvents. They generally exhibit better solvent properties than gases and better
transport properties than liquids. They offer substantial property changes with small variations in thermodynamic
conditions, such as temperature, pressure, and composition. They also provide wide-ranging environmental
advantages, from human health to pollution prevention and waste minimization. Professors Eckert, Liotta, and
their team have combined reactions with separations in a synergistic manner to use benign solvents, minimize
waste, and improve performance.
These researchers have used supercritical CO2 to tune reaction equilibria and rates, improve selectivities,
and eliminate waste. They were the first to use supercritical CO2 with phase transfer catalysts to separate
products cleanly and economically. Their method allows them to recycle their catalysts effectively. They have
demonstrated the feasibility of a variety of phase transfer catalysts on reactions of importance in the chemical
and pharmaceutical industries, including chiral syntheses. They have carried out a wide variety of synthetic
reactions in nearcritical water, replacing conventional organic solvents. This includes acid- and base-catalysis using
the enhanced dissociation of nearcritical water, negating the need for any added acid or base and eliminating
subsequent neutralization and salt disposal. They have used CO2 to expand organic fluids to make it easier to
recycle homogeneous catalysts, including phase transfer catalysts, chiral catalysts, and enzymes. Finally, they have
used tunable benign solvents to design syntheses that minimize waste by recycling and demonstrate commercial
feasibility by process economics.
The team of Eckert and Liotta has combined state-of-the-art chemistry with engineering know-how, generating
support from industrial sponsors to facilitate technology transfer. They have worked with a wide variety of
government and industrial partners to identify the environmental and commercial opportunities available with
these novel solvents; their interactions have facilitated the technology transfer necessary to implement their
advances.
44 2004 Academic Award
-------
Rhamnolipid Biosurfactant: A Natural, Low-Toxicity Alternative to Synthetic Surfactants
!nns;\,;•;)(;•!'; .;nr'' !:Y:n::l ihv
Billions of pounds of surfactants are used each year to lubricate, clean, or reduce undesired foaming in industrial
applications. Jeneil Biosurfactant Company developed biobased surfactants that are less toxic and more biodegradable
than conventional surfactants. Jeneil makes its biosurfactants using a simple fermentation.
Surfactants are chemicals that reduce the surface tension of water. Surfactants are widely used in soaps, laundry
detergents, dishwashing liquids, and many personal care products, such as shampoos. Other important uses are
in lubricants, emulsion polymerization, textile processing, mining flocculates, petroleum recovery, and wastewater
treatment. Most currently used surfactants are derived from petroleum feedstocks. The total worldwide chemical
surfactant consumption in the year 2000 has been estimated to be approximately 36 billion pounds. Many of
these chemical surfactants pose significant environmental risks because they form harmful compounds from
incomplete biodegradation in water or soil.
Jeneil Biosurfactant Company has successfully produced a series of rhamnolipid biosurfactant products, making
them commercially available and economical for the first time. These biosurfactant products provide good
emulsification, wetting, detergency, and foaming properties, along with very low toxicity. They are readily
biodegradable and leave no harmful or persistent degradation products. Their superior qualities make them
suitable for many diverse applications.
Rhamnolipid biosurfactant is a naturally occurring extracellular glycolipid that is found in the soil and on plants.
Jeneil produces this biosurfactant commercially in controlled, aerobic fermentations using particular strains of
the soil bacterium, Pseudomonas aeruginosa. The biosurfactant is recovered from the fermentation broth after
sterilization and centrifugation, then purified to various levels to fit intended applications.
Rhamnolipid biosurfactants are a much less toxic and more environmentally friendly alternative to traditional
synthetic or petroleum-derived surfactants. Rhamnolipid biosurfactants are also "greener" throughout their life
cycle. Biosurfactant production uses feedstocks that are innocuous and renewable compared to those used
for synthetic or petroleum-derived surfactants. In addition, their production requires less resources, employs
processes that are less complex and less capital- and energy-intensive, and does not require the use and disposal
of hazardous substances.
Some current uses of rhamnolipid biosurfactant are in consumer cleaning products, in solutions to clean
contact lenses, and in an agricultural fungicide as the active ingredient. These biosurfactants are also extremely
effective in precluding harmful environmental impacts and remediating environmental pollution, for example,
rhamnolipid biosurfactants can facilitate removal of hydrocarbons or heavy metals from soil, clean crude oil
tanks, and remediate sludge; often they can facilitate recovery of a significant amount of the hydrocarbons. In
many applications, these biosurfactants can replace less environmentally friendly synthetic or petroleum-derived
surfactants, further, these biosurfactants have excellent synergistic activity with many synthetic surfactants and,
when formulated together in a cosurfactant system, can allow a substantial reduction in the synthetic surfactant
component.
Although rhamnolipid biosurfactants have been the subject of considerable research, they had previously been
produced only on a small scale in laboratories. Jeneil Biosurfactant Company, in conjunction with its associated
company, Jeneil Biotech, Inc., has commercialized the rhamnolipid technology by developing efficient bacterial
strains, as well as cost-effective processes and equipment for commercial-scale production. Jeneil's facility in
Saukville, Wl produces the surfactants.
2004 Small Business Award 45
-------
Development of a Green Synthesis forTaxol® Manufacture via Plant Cell Fermentation and Extraction
Bristol-Myers Squibb manufactures paclitaxel, the active ingredient in the anticancer drug, Taxol®, using plant cell
fermentation (PCF) technology. PCF replaces the conventional process that extracts a paclitaxel building block from
leaves and twigs of the European yew. During the first five years of commercialization, PCF technology will eliminate an
estimated 71,000 pounds of hazardous chemicals and materials, eliminate 10 solvents and 6 drying steps, and save a
significant amount of energy.
i 'aclitaxel, the active ingredient in the anticancer drug Taxol®, was first isolated and identified from the bark of
the Pacific yew tree, Taxus brevifolia, in the late 1960s by Wall and Wani under the auspices of the National Cancer
Institute (NCI). The utility of paclitaxel to treat ovarian cancer was demonstrated in clinical trials in the 1980s.
The continuity of supply was not guaranteed, however, because yew bark contains only about 0.0004 percent
paclitaxel. In addition, isolating paclitaxel required stripping the bark from the yew trees, killing them in the
process. Yews take 200 years to mature and are part of a sensitive ecosystem.
The complexity of the paclitaxel molecule makes commercial production by chemical synthesis from simple
compounds impractical. Published syntheses involve about 40 steps with an overall yield of approximately
2 percent. In 1991, NCI signed a Collaborative Research and Development Agreement with Bristol-Myers Squibb
(BMS) in which BMS agreed to ensure supply of paclitaxel from yew bark while it developed a semisynthetic route
(semisynthesis) to paclitaxel from the naturally occurring compound 10-deacetylbaccatin III (10-DAB).
10-DAB contains most of the structural complexity (8 chiral centers) of the paclitaxel molecule. It is present in
the leaves and twigs of the European yew, Taxus baccata, at approximately 0.1 percent by dry weight and can be
isolated without harm to the trees. Taxus baccata is cultivated throughout Europe, providing a renewable supply
that does not adversely impact any sensitive ecosystem. The semisynthetic process is complex, however, requiring
11 chemical transformations and 7 isolations. The semisynthetic process also presents environmental concerns,
requiring 13 solvents along with 13 organic reagents and other materials.
BMS developed a more sustainable process using the latest plant cell fermentation (PCF) technology. In the
cell fermentation stage of the process, calluses of a specific taxus cell line are propagated in a wholly aqueous
medium in large fermentation tanks under controlled conditions at ambient temperature and pressure. The
feedstock for the cell growth consists of renewable nutrients: sugars, amino acids, vitamins, and trace elements.
BMS extracts paclitaxel directly from plant cell cultures, then purifies it by chromatography and isolates it by
crystallization. By replacing leaves and twigs with plant cell cultures, BMS improves the sustainability of the
paclitaxel supply, allows year-round harvest, and eliminates solid biomass waste. Compared to the semisynthesis
from 10-DAB, the PCF process has no chemical transformations, thereby eliminating six intermediates. During
its first five years, the PCF process will eliminate an estimated 71,000 pounds of hazardous chemicals and other
materials. In addition, the PCF process eliminates 10 solvents and 6 drying steps, saving a considerable amount of
energy. BMS is now manufacturing paclitaxel using only plant cell cultures.
46 2004 Greener Synthetic Pathways Award
-------
Optimyze®: A New Enzyme Technology to Improve Paper Recycling
Paper mills traditionally use hazardous solvents, such as mineral spirits, to remove sticky contaminants (stickles) from
machinery. Optimyze® technology uses a novel enzyme to remove stickles from paper products prior to recycling,
increasing the percentage of paper that can be recycled. Each paper mill that switches to Optimyze® can reduce its
hazardous solvent use by 200 gallons daily, reduce its chemical use by approximately 600,000 pounds yearly, increase
its production by more than 6 percent, and save up to $1 million per year.
Kecycling paper products is an important part of maintaining our environment. Although produced from
renewable resources, paper is a major contributor to landfilled waste. Paper can be recycled numerous times,
and much progress has been made: about one-half of the paper and paperboard currently used in the United
States is collected and reused. Some papers, however, contain adhesives, coatings, plastics, and other materials
that form sticky contaminants, creating serious problems during the paper recycling process. These contaminants,
called "stickles" by the paper industry, can produce spots and holes in paper goods made from recycled materials,
ruining their appearance and lowering their quality.
Stickles also waste significant manufacturing resources when production must stop to clean the equipment. One
source estimates the cost to the industry from production downtime alone to be more than $500 million annually.
Further, this cleaning is traditionally done with chemical solvents, typically mineral spirits, which can have health
and safety problems, are obtained from nonrenewable, petroleum resources, and are not readily recycled. These
solvents are volatile organic compounds (VOCs) that contribute to air pollution. As a result, some paper grades
cannot be recycled into reusable products.
Optimyze® technology from Buckman Laboratories is a completely new way to control the problems associated
with stickles. It uses a novel enzyme to eliminate common problems in the manufacture of paper from recycled
papers. A major component of the sticky contaminants in paper is poly(vinyl acetate) and similar materials.
Optimyze® contains an esterase enzyme that catalyzes the hydrolysis of this type of polymer to poly(vinyl
alcohol), which is not sticky and is water-soluble. A bacterial species produces large amounts of the Optimyze®
enzyme by fermentation. As a protein, the enzyme is completely biodegradable, much less toxic than alternatives,
and much safer. Only renewable resources are required to manufacture Optimyze®.
Optimyze® has been commercially available since May 2002. In that short time, more than 40 paper mills have
converted to Optimyze® for manufacturing paper goods from recycled papers. In one U.S. mill, conversion to
Optimyze® reduced solvent use by 200 gallons per day and chemical use by about 600,000 pounds per year.
Production increased by more than 6 percent, which amounted to a $1 million benefit per year for this mill alone.
This new enzyme technology has improved production of a broad range of paper products, including tissue,
paper toweling, corrugated cartons, and many other materials. It improves the quality and efficiency of
papermaking, dramatically reducing downtime to clean equipment. As a result, more paper is being recycled and
grades of paper that were not recyclable earlier are now being recycled. Paper mills adopting Optimyze® have
been able to greatly reduce the use of hazardous solvents.
In summary, Optimyze® makes it possible to recycle more grades of paper, allows more efficient processing of
recycled papers, and produces higher-quality paper goods from recycled materials. The Optimyze®technology
comes from renewable resources, is safe to use, and is itself completely recyclable.
2004 Greener Reaction Conditions Award 47
-------
Engelhard Rightfit™ Organic Pigments: Environmental Impact, Performance, and Value
lnnff\.-Vif;..i; >;no j:v i ,..••. I i.hv
Rightfit™ azo pigments contain calcium, strontium, or barium; they replace conventional heavy-metal-based pigments
containing lead, hexavalent chromium, or cadmium. Because of their low potential toxicity and very low migration,
most of the Rightfit™ azo pigments have received U.S. Food and Drug Administration (FDA) and Canadian Health
Protection Branch (HPB) approval for indirect food contact applications. By 2004, Engelhard expects to have replaced all
6.5 million pounds of its heavy-metal-based pigments with Rightfit™ pigments.
; 'istorically, pigments based on lead, chromium(VI), and cadmium have served the red, orange, and yellow
color market. When EPA began regulating heavy metals, however, color formulators typically turned to high-
performance organic pigments to replace heavy-metal-based pigments. Although high-performance pigments
meet performance requirements, they do so at the expense of the following: (1) their higher cost often acts
as a deterrent to reformulation; (2) their production uses large volumes of organic solvents; (3) some require
large quantities of polyphosphoric acid, resulting in phosphates in the effluent; and (4) some are based on
dichlorobenzidine or polychlorinated phenyls.
Engelhard has developed a wide range of environmentally friendly Rightfit™ azo pigments that contain calcium,
strontium, or sometimes barium instead of heavy metals. True to their name, the Rightfit™ pigments have the
right environmental impact, right color space, right performance characteristics, and right cost-to-performance
value. Since 1995, when Engelhard produced 6.5 million pounds of pigments containing heavy metals, it has
been transitioningto Rightfit™ azo pigments. In 2002, Engelhard produced only 1.2 million pounds of heavy-
metal pigments; they expect to phase them out completely in 2004.
Rightfit™ pigments eliminate the risk to human health and the environment from exposure to heavy metals
such as cadmium, chromium(VI), and lead used in the manufacture of cadmium and chrome yellow pigments.
They are expected to have very low potential toxicity based on toxicity studies, physical properties, and structural
similarities to many widely used food colorants. Because they have low potential toxicity and very low migration,
most of the Rightfit™ pigments have been approved both by the U.S. Food and Drug Administration (FDA) and
the Canadian Health Protection Branch (HPB) for indirect food contact applications. In addition, these pigments
are manufactured in aqueous medium, eliminating exposure to the polychlorinated intermediates and organic
solvents associated with the manufacture of traditional high-performance pigments.
Rightfit™ pigments have additional benefits, such as good dispersibility, improved dimensional stability, improved
heat stability, and improved color strength. Their higher color strength achieves the same color values using less
pigment. Rightfit™ pigments also cover a wide color range from purple to green-shade yellow color. Being closely
related chemically, these pigments are mutually compatible, so two or more can combine to achieve any desired
intermediate color shade.
Rightfit™ pigments meet the essential performance characteristics at significantly lower cost than high-
performance organic pigments. Thus, formulators get the right performance properties at the right cost, resulting
in a steadily increasing market for these pigments. Rightfit™ pigments provide environmentally friendly, value-
added color to packaging used in the food, beverage, petroleum product, detergent, and other household
durable goods markets.
48 2004 Designing Greener Chemicals Award
-------
2003 Winners
New Options for Mild and Selective Polymerizations Using Lipases
Professor Gross developed a highly selective, more efficient way to make polyesters using enzymes. This technique
requires less energy and toxic substances than conventional methods that typically use heavy metal catalysts and
hazardous solvents. This innovation also makes it possible to manufacture new types of polyesters.
Isolated Upases, harvested from living organisms, have been used as catalysts for polymer synthesis in vitro.
Professor Richard A. Gross's developments on lipase-catalyzed polymer synthesis have relied on the ability of
enzymes to reduce the activation energy of polymerizations and, thus, to decrease process energy consumption.
further, the regioselectivity of Upases has been used to polymerize polyols directly. Alternative synthetic pathways
for such polymerizations require protection-deprotection chemical steps. The mild reaction conditions allow
polymerization of chemically and thermally sensitive molecules. Current alternative chemical routes require
coupling agents (e.g., carbodiimides) that would be consumed in stoichiometric quantities relative to the
reactants. fundamental studies of these polymerizations have uncovered remarkable capabilities of Upases
for polymerization chemistry. Selected examples include: (1) Upases catalyze transesterification reactions
between high-molecular-weight chains in melt conditions; (2) Upases will use non-natural nucleophiles such as
carbohydrates and monohydroxyl polybutadiene (Mn 19,000) in place of water; (3) the catalysis of ring-opening
polymerization occurs in a controlled manner without termination reactions and with predictable molecular
weights; and (4) the selectivity of lipase-catalyzed step-condensation polymerizations leads to nonstatistical
molecular weight distributions (polydispersities well below 2.0). These accomplishments are elaborated on the
next page.
A series of polyol-containing polyesters was synthesized via a one-pot lipase-catalyzed condensation
polymerization. By using various mixtures of polyols (e.g., glycerol, sorbitol) with other diacid and diol
building blocks, the polyols are partially or completely solubilized, resulting in highly reactive condensation
polymerizations. By this method, organic solvents and activated acids (e.g., divinyl esters) are not needed. The
polymerization reactions give high-molecular-weight products (/Ww up to 200,000) with narrow polydispersities
(as low as 1.3). further, the condensation reactions with glycerol and sorbitol building blocks proceed with
high regioselectivity. Although the polyols used have three or more hydroxyl groups, only two of these hydroxyl
groups are highly reactive in the polymerization. Thus, instead of obtaining highly cross-linked products, the
regioselectivity provided by the lipase leads to lightly branched polymers where the degree of branching
varies with the reaction time and monomer stoichiometry. By using lipase as the catalyst, highly versatile
polymerizations result that can simultaneously polymerize lactones, hydroxyacids, cyclic carbonates, cyclic
anhydrides, amino alcohols, and hydroxylthiols. The method developed offers simplicity, mild reaction conditions,
and the ability to incorporate carbohydrates, such as sugars, into polyesters without protection-deprotection steps.
Professor Gross's laboratory discovered that certain Upases catalyze transesterification reactions between high-
molecular-weight chains that contain intrachain esters or have functional end-groups. Thus, Upases, such as
Lipase B from Candida antarctica, catalyze intrachain exchange reactions between polymer chains as well as
transesterification reactions between a monomer and a polymer, for polymers that have melting points below
100 °C, the reactions can be conducted in bulk. Transacylation reactions occur because the lipase has the ability
to accommodate large-molecular-weight substrates and to catalyze the breaking of ester bonds within chains.
Immobilized Candida antarctica Lipase B (Novozyme-435) catalyzed transesterification reactions between
aliphatic polyesters that had Mn values in excess of 40,000 grams per mole. In addition to catalyzing metal-free
transesterifications at remarkably low temperatures, Upases endow transesterification reactions with remarkable
selectivity. This feature allows the preparation of block copolymers that have selected block lengths.
2003 Academic Award 49
-------
Serenade®: An Effective, Environmentally Friendly Biofungicide
!nns;\,;•;)(;•!'; .;nr'' !:Y:n::l ihv
Serenade® is a new biofungicide for fruits and vegetables based on a naturally occurring strain of bacteria. Serenade®
is nontoxicto beneficial and other nontarget organisms, does not generate any hazardous chemical residues, and is
safe for workers and groundwater. It is well-suited for use in integrated pest management (IPM) programs and is listed
with the Organic Materials Review Institute (OMRI) for use in organic agriculture.
Serenade® Biofungicide is based on a naturally occurring strain of Bacillus subtilis QST-713, discovered in a
California orchard by AgraQuest scientists. Serenade® has been registered for sale as a microbial pesticide in
the United States since July 2000. It is also registered for use in Chile, Mexico, Costa Rica, and New Zealand.
Registration is pending in the Philippines, Europe, Japan, and several other countries. The product is formulated
as a wettable powder, wettable granule, and liquid aqueous suspension. Serenade® has been tested on 30 crops
in 20 countries and is registered for use in the United States on blueberries, cherries, cucurbits, grape vines,
greenhouse vegetables, green beans, hops, leafy vegetables, mint, peanuts, peppers, pome fruit, potatoes,
tomatoes, and walnuts. It is also registered for home and garden use. AgraQuest has been issued four U.S.
patents; several international patents are pending on the QST-713 strain, associated antifungal lipopeptides,
formulations, and combinations with other pesticides.
Serenade® works through a complex mode of action that is manifested both by the physiology of the bacteria
and through the action of secondary metabolites produced by the bacteria. Serenade® prevents plant diseases
first by covering the leaf surface and physically preventing attachment and penetration of the pathogens. In
addition, Serenade® produces three groups of lipopeptides (iturins, agrastatins/plipastatins, and surfactins) that
act in concert to destroy germ tubes and mycelium. The iturins and plipastatins have been reported to have
antifungal properties. Strain QST-713 is the first strain reported to produce iturins, plipastatins, and surfactins, as
well as two new compounds with a novel cyclic peptide moiety, the agrastatins. The surfactins have no activity on
their own, but low levels (25 ppm or less) in combination with the iturins or the agrastatin/plipastatin group cause
significant inhibition of spores and germ tubes. In addition, the agrastatins and iturins have synergistic activities
towards inhibition of plant pathogen spores.
The Serenade® formulation is available as a wettable powder, wettable granule, and aqueous suspension that is
applied just like any other foliar fungicide. It can be applied alone or tank mixed; it can also be alternated with
traditional chemical pesticides. Serenade® is not toxic to beneficial and nontarget organisms, such as trout, quail,
lady beetles, lacewings, parasitic wasps, earthworms, and honey bees. Serenade® is exempt from tolerance
because there are no synthetic chemical residues and it is safe to workers and ground water.
Serenade®'s wettable granule formulation is listed with the Organic Materials Review Institute (OMRI) for use in
organic agriculture and will continue to be listed under the National Organic Standards, which were enacted in
the United States in October 2002.
Serenade®'s novel, complex mode of action, environmental friendliness, and broad spectrum control make
it well-suited for use in integrated pest management (IPM) programs that utilize many tools, such as cultural
practices, classical biological control, and other fungicides. Serenade® can be applied right up until harvest,
providing needed pre-and post-harvest protection when there is weather conducive to disease development
around harvest time.
50 2003 Small Business Award
-------
A Wastewater-Free Process for Synthesis of Solid Oxide Catalysts
Sud-Chemie's new process to synthesize solid oxide catalysts used in producing hydrogen and clean fuel has virtually
zero wastewater discharge, zero nitrate discharge, and no or little NOX emissions. Each 10 million pounds of oxide cata-
lyst produced by the new pathway eliminates approximately 760 million pounds of wastewater discharges, 29 million
pounds of nitrate discharges, and 7.6 million pounds of NOX emissions. The process also saves water and energy.
borne major achievements in pollution reduction have been made recently through advancement of catalytic
technologies. One such effort is in the area of hydrogen and clean fuel production. However, the synthesis of
catalysts for such reactions is often accompanied by the discharge of large amounts of wastewater and other
pollutants, such as NOX, SOX, and halogens.
As a result of their commitment to continuously develop and invest in new and improved catalyst synthesis
technologies, Sud-Chemie successfully developed and demonstrated a new synthetic pathway that is able to
achieve virtually zero wastewater discharge, zero nitrate discharge, and no or little NOX emissions. Meantime, it
substantially reduces the consumption of water and energy, for example, it is estimated that about
760 million pounds of wastewater discharges, about 29 million pounds of nitrate discharges, and about
7.6 million pounds of NOX emissions can be eliminated for every 10 million pounds of oxide catalyst produced.
The new synthetic pathway is based on very simple chemistry. Instead of acid-base precipitation typically using
metal nitrate as raw material, the new process starts with a clean metal that is readily and economically available
in commercial quantities. The synthesis proceeds by reaction of the metal with a mild organic acid in the
presence of an oxidation agent. The function of the acid is to activate the metal and extract electrons to form the
oxide precursor. With assistance of the oxidation agent (typically air), a porous solid oxide is synthesized in one
step at ambient temperature without any wastewater discharge. The other active ingredients of the catalyst can
be incorporated using the concept of wet-agglomeration. In contrast, the precipitation process requires intensive
washing and filtration to remove nitrate and the other salts, further, the new process substantially reduces
the consumption of water and energy for production of solid oxide catalysts over conventional methods. The
emission in the entire process is only pure water vapor and a small amount of CO2 that is generated during spray-
drying and afterburning of hydrogen.
This wastewater-free process for making solid oxide catalysts has been demonstrated, and more than
300 kilograms of the metal oxide catalysts have been produced. Patent protection is being sought for the
development. The catalysts made by the green process give superior performance in the synthesis of clean fuels
and chemicals. The market for such solid oxide catalysts is estimated to be approximately $100 million. Sud-
Chemie is the first in the industry to use the green process for making a catalyst for the synthesis of "green" fuels
and chemicals.
2003 Greener Synthetic Pathways Award
-------
Microbial Production of 1,3-Propanediol
DuPont and Genencor International jointly developed a genetically engineered microorganism to manufacture the key
building block for DuPont's Sorona® polyester. The process uses renewable cornstarch instead of petroleum to make
environmentally friendly, cost-competitive textiles.
•'uPont is integrating biology in the manufacture of its newest polymer platform, DuPont Sorona® polymer.
Combining metabolic engineering with polymer science, researchers are introducing a microbial process
in a business that, historically, has relied solely on traditional chemistry and petrochemical feedstocks. This
achievement, comprising biocatalytic production of 1,3-propanediol from renewable resources, offers economic
as well as environmental advantages. The key to the novel biological process is an engineered microorganism
that incorporates several enzyme reactions, obtained from naturally occurring bacteria and yeast, into an
industrial host cell line. For the first time, a highly engineered microorganism will be used to convert a renewable
resource into a chemical at high volume.
The catalytic efficiency of the engineered microorganism allows replacement of a petroleum feedstock,
reducing the amount of energy needed in manufacturing steps and improving process safety. The microbial
process is environmentally green, less expensive, and more productive than the chemical operations it replaces.
1,3-Propanediol, a key ingredient in the Sorona® polymers, provides advantageous attributes for apparel,
upholstery, resins, and nonwoven applications.
Scientists and engineers from DuPont and Genencor International, Inc. redesigned a living microbe to produce
1,3-propanediol. Inserting biosynthetic pathways from several microorganisms into an industrial host cell
line allows the direct conversion of glucose to 1,3-propanediol, a route not previously available in a single
microorganism. Genes from a yeast strain with the ability to convert glucose, derived from cornstarch, to glycerol
were inserted into the host. Genes from a bacterium with the ability to transform glycerol to 1,3-propanediol
were also incorporated. Additionally, the reactions present naturally in the host were altered to optimize product
formation. The modifications maximize the ability of the organism to convert glucose to 1,3-propanediol while
minimizing its ability to produce biomass and unwanted byproducts. Coalescing enzyme reactions from multiple
organisms expands the range of materials that can be economically produced by biological means.
For more than 50 years, scientists have recognized the performance benefits of polyesters produced with
1,3-propanediol; however, the high cost of manufacturing the ingredient using petroleum feedstockand
traditional chemistry kept it from the marketplace. The biological process using glucose as starting material
will enable cost-effective manufacture of Sorona® polymer, which will offer consumer fabrics with softness,
stretch and recovery, easy care, stain resistance, and colorfastness. A unique kink in the structure of the polymer
containing 1,3-propanediol allows recovery at a high rate when it is stretched. As a result, Sorona® improves fit
and comfort because the fabric quickly recovers its original shape when stretched, for example, in knees or
elbows. The resilience of Sorona® also adds beneficial features to automotive upholstery and home textiles. In
resin applications, Sorona®'s barrier characteristics protect moisture, taste, and odor.
Biology offers chemical manufacturers attractive options for the production of chemicals while adhering to the
principles of green chemistry. This microbial production of a key polymer ingredient from renewable sources is
one example. By integrating biology with chemistry, physics, and engineering, DuPont develops new solutions
that enhance the environment and improve upon existing materials.
52 2003 Greener Reaction Conditions Award
-------
EcoWorx™ Carpet Tile: A Cradle-to-Cradle Product
Conventional backings for carpet tiles contain bitumen, polyvinyl chloride (PVC), or polyurethane. EcoWorx™ carpet
tiles have a novel backing that uses less toxic materials and has superior adhesion and dimensional stability. Because
EcoWorx™ carpet tiles can be readily separated into carpet fiber and backing, each component can be easily recycled.
' 'istorically, carpet tile backings have been manufactured using bitumen, polyvinyl chloride (PVC), or
polyurethane (PU). While these backing systems have performed satisfactorily, there are several inherently
negative attributes due to their feedstocks or their ability to be recycled. Although PVC has, to date, held the
largest market share of carpet tile backing systems, it was Shaw's intent to design around PVC due to the health
and environmental concerns around vinyl chloride monomer, chlorine-based products, plasticized PVC-containing
phthalate esters, and toxic byproducts of combustion of PVC, such as dioxin and hydrochloric acid. While some
claims are accepted by the Agency for Toxic Substances and Disease Registry (ATSDR) and the EPA, those resulting
from publicly debated consumer perceptions provide ample justification for finding a PVC alternative.
Due to the thermoset cross-linking of polyurethanes, they are extremely difficult to recycle and are typically
downcycled or landfilled at the end of their useful life. Bitumen provides some advantages in recycling, but the
modified bitumen backings offered in Europe have failed to gain market acceptance in the United States and are
unlikely to do so.
Shaw selected a combination of polyolefin resins from Dow Chemical as the base polymer of choice for
EcoWorx™ due to the low toxicity of its feedstocks, superior adhesion properties, dimensional stability, and its
ability to be recycled. The EcoWorx™ compound also had to be designed to be compatible with nylon carpet
fiber. Although EcoWorx™ may be recovered from any fiber type, nylon-6 provides a significant advantage.
Polyolefins are compatible with known nylon-6 depolymerization methods. PVC interferes with those processes.
Nylon-6 chemistry is well-known and not addressed in first-generation production.
From its inception, EcoWorx™ met all of the design criteria necessary to satisfy the needs of the marketplace
from a performance, health, and environmental standpoint. Research indicated that separation of the fiber
and backing through elutriation, grinding, and air separation proved to be the best way to recover the face and
backing components, but an infrastructure for returning postconsumer EcoWorx™ to the elutriation process was
necessary. Research also indicated that the postconsumer carpet tile had a positive economic value at the end of
its useful life. The cost of collection, transportation, elutriation, and return to the respective nylon and EcoWorx™
manufacturing processes is less than the cost of using virgin raw materials.
With introduction in 1999 and an anticipated lifetime often to fifteen years on the floor, significant quantities of
EcoWorx™ will not flow back to Shaw until 2006 to 2007. An expandable elutriation unit is now operating at Shaw,
typically dealing with industrial EcoWorx™ waste. Recovered EcoWorx™ is flowing back to the backing extrusion
unit. Caprolactam recovered from the elutriated nylon-6 is flowing back into nylon compounding. EcoWorx™ will
soon displace all PVC at Shaw.
2003 Designing Greener Chemicals Award 53
-------
2002 Winners
Design of Non-Fluorous, Highly CCh-Soluble Materials
Carbon dioxide (CO ) is a nontoxic chemical that can be used as a solvent in many industrial processes. Professor
Beckman developed new detergents that allow a broad range of substances to dissolve in CO Any process that can
now use CO2 may reduce or eliminate the use of hazardous solvents.
Larbon dioxide (CO2), an environmentally benign and nonflammable solvent, has been investigated extensively
in both academic and industrial settings. Solubility studies performed during the 1980s had suggested that CO2's
solvent power was similar to that of n-alkanes, leading to hopes that the chemical industry could use CO2 as a
"drop-in" replacement for a wide variety of organic solvents. It was learned that these solubility studies inflated
the solvent power value by as much as 20 percent due to the strong quadrupole moment of CO2 and that CO2 is
actually a rather feeble solvent compared toalkanes. As the 1980s drew to a close, a number of research groups
began to explore the design of CO2-philic materials, that is, compounds that dissolve in CO2 at significantly lower
pressures than do their alkyl analogs. These new CO2-philes, primarily fluoropolymers, opened up a host of new
applications for CO2 including heterogeneous polymerization, protein extraction, and homogeneous catalysis.
Although fluorinated amphiphiles allow new applications for CO2, their cost (approximately $1 per gram) reduces
the economic viability of CO2 processes, particularly given that the use of CO2 requires high-pressure equipment.
Furthermore, data have recently shown that fluoroalkyl materials persist in the environment, leading to the
withdrawal of certain consumer products from the market. The drawbacks inherent to the use of fluorinated
precursors, therefore, have inhibited the commercialization of many new applications for CO2, and the full
promise of CO2-based technologies has yet to be realized. To address this need, Professor Eric J. Beckman and his
group at the University of Pittsburgh have developed materials that work well, exhibiting miscibility pressures in
CO2 that are comparable or lower than fluorinated analogs and yet contain no fluorine.
Drawing from recent studies of the thermodynamics of CO2 mixtures, Professor Beckman hypothesized that CO2-
philic materials should contain three primary features: (1) a relatively low glass transition temperature;
(2) a relatively low cohesive energy density; and (3) a number of Lewis base groups. Low glass transition
temperature correlates to high free volume and high molecular flexibility, which imparts a high entropy of mixing
with CO2 (or any solvent). A low cohesive energy density is primarily a result of weak solute-solute interactions,
a necessary feature given that CO2 is a rather feeble solvent. Finally, because CO2 is a Lewis acid, the presence of
Lewis base groups should create sites for specific favorable interactions with CO2.
Professor Beckman's simple heuristic model was demonstrated on three sets of materials: functional silicones;
poly(ether-carbonates); and acetate-functional polyethers. Poly(ether-carbonates) were found to exhibit lower
miscibility pressures in CO2 than perfluoropolyethers, yet are biodegradable and 100 times less expensive
to prepare. Other families of non-fluorous CO2-philes will inevitably be discovered using this model, further
broadening the applicability of CO2 as a greener process solvent.
54 2002 Academic Award
-------
SCORR—Supercritical CO2 Resist Remover
SCORR (Supercritical CO2 Resist Remover) technology cleans residues from semiconductor wafers during their
manufacture. SCORR improves on conventional techniques: it minimizes hazardous solvents and waste, is safer for
workers, costs less, and uses less water and energy. SCORR also eliminates rinsing with ultrapure water and subsequent
drying.
\ he semiconductor industry is the most successful growth industry in history, with sales totaling over
$170 billion in the year 2000. The fabrication of integrated circuits (ICs) relies heavily on photolithography to define
the shape and pattern of individual components. Current manufacturing practices use hazardous chemicals and
enormous amounts of purified water during this intermediate step, which may be repeated up to 30 times for
a single wafer. It is estimated that a typical chip-fabrication plant generates 4 million gallons of wastewater and
consumes thousands of gallons of corrosive chemicals and hazardous solvents each day.
SC Fluids, in partnership with Los Alamos National Laboratory, has developed a new process, SCORR, that
removes photoresist and post-ash, -etch, and -CMP (particulate) residue from semiconductor wafers. The SCORR
technology outperforms conventional photoresist removal techniques in the areas of waste minimization,
water use, energy consumption, worker safety, feature size compatibility, material compatibility, and cost. The
key to the effectiveness of SCORR is the use of supercritical CO2 in place of hazardous solvents and corrosive
chemicals. Neat CO2 is also utilized for the rinse step, thereby eliminating the need for a deionized water rinse
and an isopropyl alcohol drying step. In the closed-loop SCORR process, CO2 returns to a gaseous phase upon
depressurization, leaving the silicon wafer dry and free of residue.
SCORR is cost-effective for five principal reasons. It minimizes the use of hazardous solvents, thereby minimizing
costs required for disposal and discharge permits. It thoroughly strips photoresists from the wafer surface in less
than half the time required for wet-stripping and far outperforms plasma, resulting in increased throughput.
It eliminates rinsing and drying steps during the fabrication process, thereby simplifying and streamlining the
manufacturing process. It eliminates the need for ultrapure deionized water, thus reducing time, energy, and
cost. Supercritical CO2 costs less than traditional solvents and is recyclable.
SCORR will meet future, as well as current technology demands. To continue its astounding growth, the
semiconductor industry must develop ICs that are smaller, faster, and cheaper. Due to their high viscosity,
traditional wet chemistries cannot clean small feature sizes. Vapor cleaning technologies are available, but viable
methods for particle removal in the gas phase have not yet been developed. Using SCORR, the smallest features
present no barriers because supercritical fluids have zero surface tension and a "gaslike" viscosity and, therefore,
can clean features less than 100 nm.The low viscosity of super-critical flu ids also allows particles less than
100 nm to be removed. The end result is a technically enabling "green" process that has been accepted by
leading semiconductor manufacturers and equipment and material suppliers.
SCORR technology is being driven by industry in pursuit of its own accelerated technical and manufacturing
goals. SCORR was initially developed through a technical request from Hewlett Packard (now Agilent). A joint
Cooperative Research and Development Agreement between Los Alamos National Laboratory and SC Fluids has
led to the development of commercial units (SC Fluids's Arroyo™ System). Other industry leaders, such as IBM,
ATMI, and Shipley, are participating in the development of this innovative technology.
2002 Small Business Award 55
-------
Green Chemistry in the Redesign of the Sertraline Process
Pfizer dramatically improved its manufacturing process for sertraline, the active ingredient in its popular drug, Zoloft®.
The new process doubles overall product yield, reduces raw material use by 20-60 percent, eliminates the use or
generation of approximately 1.8 million pounds of hazardous materials, reduces energy and water use, and increases
worker safety.
Sertraline is the active ingredient in the important pharmaceutical, Zoloft®. Zoloft® is the most prescribed agent
of its kind and is used to treat an illness (depression) that each year strikes 20 million adults in the United States,
and that costs society $43.7 billion (1990 dollars). As of february 2000, more than 115 million Zoloft® prescriptions
had been written in the United States.
Applying the principles of green chemistry, Pfizer has dramatically improved the commercial manufacturing
process of sertraline. After meticulously investigating each of the chemical steps, Pfizer implemented a
substantive green chemistry technology for a complex commercial process requiring extremely pure product. As a
result, Pfizer significantly improved both worker and environmental safety. The new commercial process (referred
to as the "combined" process) offers substantial pollution prevention benefits including improved safety and
material handling, reduced energy and water use, and doubled overall product yield.
Specifically, a three-step sequence in the original manufacturing process was streamlined to a single step in the
new sertraline process. The new process consists of imine formation of monomethylamine with a tetralone,
followed by reduction of the imine function and in situ resolution of the diastereomeric salts of mandelicacid
to provide chirally pure sertraline in much higher yield and with greater selectivity. A more selective palladium
catalyst was implemented in the reduction step, which reduced the formation of impurities and the need
for reprocessing. Raw material use was cut by 60 percent, 45 percent, and 20 percent for monomethylamine,
tetralone, and mandelic acid, respectively.
Pfizer also optimized its process using the more benign solvent ethanol for the combined process. This change
eliminated the need to use, distill, and recover four solvents (methylene chloride, tetrahydrofuran, toluene,
and hexane) from the original synthesis. Pfizer's innovative use of solubility differences to drive the equilibrium
toward imine formation in the first reaction of the combined steps eliminated approximately 310,000 pounds per
year of the problematic reagent titanium tetrachloride. This process change eliminates 220,000 pounds of
50 percent sodium hydroxide, 330,000 pounds of 35 percent hydrochloric acid waste, and 970,000 pounds of solid
titanium dioxide waste per year.
By eliminating waste, reducing solvents, and maximizing the yield of key intermediates, Pfizer has demonstrated
significant green chemistry innovation in the manufacture of an important pharmaceutical agent.
56 2002 Greener Synthetic Pathways Award
-------
Natureworks™ PLA Process
The NatureWorks™ process makes biobased, compostable, and recyclable polylactic acid (PLA) polymers using
20-50 percent less fossil fuel resources than comparable petroleum-based polymers. The synthesis of PLA polymers
eliminates organic solvents and other hazardous materials, completely recycles product and byproduct streams, and
efficiently uses catalysts to reduce energy consumption and improve yield.
..atureWorks™ polylactic acid (PLA) is the first family of polymers derived entirely from annually renewable
resources that can compete head-to-head with traditional fibers and plastic packaging materials on a cost and
performance basis, for fiber consumers, this will mean a new option for apparel and carpeting applications: a
material that bridges the gap in performance between conventional synthetic fibers and natural fibers such as
silk, wool, and cotton. Clothing made with NatureWorks™ fibers features a unique combination of desirable
attributes such as superior hand, touch, and drape, wrinkle resistance, excellent moisture management, and
resilience. In packaging applications, consumers will have the opportunity to use a material that is natural,
compostable, and recyclable without experiencing any tradeoffs in product performance.
The NatureWorks™ PLA process offers significant environmental benefits in addition to the outstanding
performance attributes of the polymer. NatureWorks™ PLA products are made in a revolutionary new process
developed by Cargill Dow LLC that incorporates all 12 green chemistry principles. The process consists of three
separate and distinct steps that lead to the production of lactic acid, lactide, and PLA high polymer. Each of the
process steps is free of organic solvent: water is used in the fermentation while molten lactide and polymer serve
as the reaction media in monomer and polymer production. Each step not only has exceptionally high yields
(over 95 percent) but also utilizes internal recycle streams to eliminate waste. Small (ppm) amounts of catalyst
are used in both the lactide synthesis and polymerization to further enhance efficiency and reduce energy
consumption. Additionally, the lactic acid is derived from annually renewable resources, PLA requires
20-50 percent less fossil resources than comparable petroleum-based plastics, and PLA is fully biodegradable or
readily hydrolyzed into lactic acid for recycling back into the process.
While the technology to create PLA in the laboratory has been known for many years, previous attempts at large-
scale production were targeted solely at niche biodegradable applications and were not commercially viable. Only
now has Cargill Dow been able to perfect the NatureWorks™ process and enhance the physical properties of
PLA resins to compete successfully with commodity petroleum-based plastics. Cargill Dow is currently producing
approximately 8.8 million pounds of PLA per year to meet immediate market development needs. Production in
the first world-scale 310-million-pound-per-year plant began November 1, 2001.
The NatureWorks™ process embodies the well-known principles of green chemistry by preventing pollution
at the source through the use of a natural fermentation process to produce lactic acid, substituting annually
renewable materials for petroleum-based feedstock, eliminating the use of solvents and other hazardous
materials, completely recycling product and byproduct streams, and efficiently using catalysts to reduce energy
consumption and improve yield. In addition, NatureWorks™ PLA products can be either recycled or composted
after use.
2002 Greener Reaction Conditions Award 57
-------
ACQ Preserve®: The Environmentally Advanced Wood Preservative
ACQ Preserve® is an environmentally advanced wood preservative designed to replace chromated copper arsenate
(CCA) wood preservatives, which have been phased out because of their toxicity. ACQ Preserve® will eliminate the use
of 40 million pounds of arsenic and 64 million pounds of hexavalent chromium each year. It also avoids the potential
risks associated with producing, transporting, using, and disposing of CCA wood preservatives and CCA-treated wood.
\ he pressure-treated wood industry is a $4 billion industry, producing approximately 7 billion board feet of
preserved wood per year. More than 95 percent of the pressure-treated wood used in the United States is
currently preserved with chromated copper arsenate (CCA). Approximately 150 million pounds of CCA wood
preservatives were used in the production of pressure-treated wood in 2001, enough wood to build
435,000 homes. About 40 million pounds of arsenic and 64 million pounds of chromium(VI) were used to
manufacture these CCA wood preservatives.
Over the past few years, scientists, environmentalists, and regulators have raised concerns regarding the risks
posed by the arsenic that is either dislodged or leached from CCA-treated wood. A principal concern is the risk
to children from contact with CCA-treated wood in playground equipment, picnic tables, and decks. This concern
has led to increased demand for and use of alternatives to CCA.
Chemical Specialties, Inc. (CSI) developed its alkaline copper quaternary (ACQ) wood preservative as an
environmentally advanced formula designed to replace the CCA industry standard. ACQ formulations combine
a bivalent copper complex and a quaternary ammonium compound in a 2:1 ratio. The copper complex may
be dissolved in either ethanolamine or ammonia. Carbon dioxide (CO2) is added to the formulation to improve
stability and to aid in solubilization of the copper.
Replacing CCA with ACQ is one of the most dramatic pollution prevention advancements in recent history.
Because more than 90 percent of the 44 million pounds of arsenic used in the United States each year is used
to make CCA, replacing CCA with ACQ will virtually eliminate the use of arsenic in the United States. In addition,
ACQ Preserve® will eliminate the use of 64 million pounds of chromium(VI). Further, ACQ avoids the potential
risks associated with the production, transportation, use, and disposal of the arsenic and chromium(VI) contained
in CCA wood preservatives and CCA-treated wood. In fact, ACQ does not generate any RCRA (i.e., Resource
Conservation and Recovery Act) hazardous waste from production and treating facilities. The disposal issues
associated with CCA-treated wood and ash residues associated with the burning of treated wood will also be
avoided.
In 1996, CSI commercialized ACQ Preserve® in the United States. More than one million active pounds of ACQ
wood preservatives were sold in the United States in 2001 for use by 13 wood treaters to produce over
100 million board feet of ACQ-preserved wood. In 2002, CSI plans to spend approximately $20 million to increase
its production capacity for ACQ to over 50 million active pounds. By investing in ACQ technology, CSI has
positioned itself and the wood preservation industry to transition away from arsenic-based wood preservatives to
a new generation of preservative systems.
58 2002 Designing Greener Chemicals Award
-------
2001 Winners
Quasi-Mature Catalysis: Developing Transition Metal Catalysis in Air
and Water
Professor Li developed a novel method to carry out a variety of important chemical reactions that had previously
required both an oxygen-free atmosphere and hazardous organic solvents. His reactions use metal catalysts and run in
open containers of water. His method is inherently safer, requires fewer process steps, operates at lower temperatures,
and generates less waste.
I he use of transition metals for catalyzing reactions is of growing importance in modern organic chemistry.
These catalyses are widely used in the synthesis of Pharmaceuticals, fine chemicals, petrochemicals, agricultural
chemicals, polymers, and plastics. Of particular importance is the formation of C-C, C-O, C-N, and C-H bonds.
Traditionally, the use of an inert gas atmosphere and the exclusion of moisture have been essential in both
organometallic chemistry and transition-metal catalysis. The catalytic actions of transition metals in ambient
atmosphere have played key roles in various enzymatic reactions including biocatalysis, biodegradation,
photosynthesis, nitrogen fixation, and digestions, as well as the evolution of bioorganisms. Unlike traditionally
used transition-metal catalysts, these "natural" catalytic reactions occur under aqueous conditions in an air
atmosphere.
The research of Professor Chao-Jun Li has focused on the development of numerous transition-metal-catalyzed
reactions both in air and water. Specifically, Professor Li has developed a novel [3+2] cycloaddition reaction to
generate 5-membered carbocycles in water; a synthesis of p-hydroxyl esters in water; a chemoselective alkylation
and pinacol coupling reaction mediated by manganese in water; and a novel alkylation of 1,3-dicarbonyl-
type compounds in water. His work has enabled rhodium-catalyzed carbonyl addition and rhodium-catalyzed
conjugate addition reactions to be carried out in air and water for the first time. A highly efficient, zinc-mediated
Ullman-type coupling reaction catalyzed by palladium in water has also been designed. This reaction is conducted
at room temperature under an atmosphere of air. In addition, a number of Barbier-Grignard-type reactions in
water have been developed; these novel synthetic methodologies are applicable to the synthesis of a variety
of useful chemicals and compounds. Some of these reactions demonstrate unprecedented chemoselectivity
that eliminates byproduct formation and product separation. Application of these new methodologies to natural
product synthesis, including polyhydroxylated natural products, medium-sized rings, and macrocyclic compounds,
yields shorter reaction sequences.
Transition-metal-catalyzed reactions in water and air offer many advantages. Water is readily available and
inexpensive; it is not flammable, explosive, or toxic. Consequently, aqueous-based production processes are
inherently safer with regard to accident potential. Using water as a reaction solvent can save synthetic steps by
avoiding protection and deprotection processes that affect overall synthetic efficiency and contribute to solvent
emission. Product isolation may be facilitated by simple phase separation rather than energy-intensive and
organic-emitting processes involving distillation of organic solvent. The temperature of reactions performed in
aqueous media is also easier to control since water has such a high heat capacity. The open-air feature offers
convenience in operations of chemical synthesis involving small-scale combinatorial synthesis, large-scale
manufacturing, and catalyst recycling. As such, Professor Li's work in developing transition-metal-mediated and
-catalyzed reactions in air and water offers an attractive alternative to the inert atmosphere and organic solvents
traditionally used in synthesis.
2001 Academic Award 59
-------
Messenger®: A Green Chemistry Revolution in Plant Production and Food Safety
EDEN Bioscience Corporation discovered and commercialized harpins, a new class of nontoxic, naturally occurring,
biodegradable proteins, as an alternative to traditional pesticides. Harpins activate a plant's defense and growth
mechanisms, thereby increasing crop yield and quality, and minimizing crop losses. EDEN manufactures Messenger®,
its commercially available, harpin-containing, EPA-approved product, using a water-based fermentation system.
In today's competitive agricultural environment, growers must maximize crop productivity by enhancing yield and
minimizing crop losses. The Food and Agriculture Organization of the United Nations estimates that annual losses
to growers from pests reach $300 billion worldwide. In addition to basic agronomic practices, growers generally
have two alternatives to limit these economic losses and increase yields: (1) use traditional chemical pesticides;
or (2) grow crops that are genetically engineered for pest resistance. Each of these approaches has come under
increasing criticism from a variety of sources worldwide including environmental groups, government regulators,
consumers, and labor advocacy groups. Harpin technology, developed by EDEN Bioscience Corporation, provides
growers with a highly effective alternative approach to crop production that addresses these concerns.
EDEN's harpin technology is based on a new class of nontoxic, naturally occurring proteins called harpins, which
were first discovered by Dr. Zhongmin Wei, EDEN's Vice President of Research, and his colleagues during his
tenure at Cornell University. Harpin proteins trigger a plant's natural defense systems to protect against disease
and pests and simultaneously activate certain plant growth systems without altering the plant's DNA. When
applied to crops, harpins increase plant biomass, photosynthesis, nutrient uptake, and root development, and,
ultimately, lead to greater crop yield and quality.
Unlike most agricultural chemicals, harpin-based products are produced in a water-based fermentation system
that uses no harsh solvents or reagents, requires only modest energy inputs, and generates no hazardous
chemical wastes. Fermentation byproducts are fully biodegradable and safely disposable. In addition, EDEN uses
low-risk ingredients to formulate the harpin protein-based end product. Approximately 70 percent of the dried
finished product consists of an innocuous, food-grade substance that is used as a carrier for harpin protein.
The result of this technology is an EPA-approved product called Messenger® that has been demonstrated on
more than 40 crops to effectively stimulate plants to defend themselves against a broad spectrum of viral,
fungal, and bacterial diseases, including some for which there currently is no effective treatment. In addition,
Messenger® has been shown through an extensive safety evaluation to have virtually no adverse effect on any of
the organ isms tested, including mammals, birds, honey bees, plants, fish, aquatic invertebrates, and algae. Only
0.004-0.14 pounds of harpin protein per acre per season is necessary to protect crops and enhance yields. As with
most proteins, harpin is a fragile molecule that is degraded rapidly by UV and natural microorganisms and has no
potential to bioaccumulate or to contaminate surface or groundwater resources.
Deployment of harpin technology conserves resources and protects the environment by reducing total
agricultural inputs and partially replacing many higher-risk products. Using environmentally benign harpin protein
technology, growers for the first time in the history of modern agriculture will be able to harness the innate
defense and growth systems of crops to substantially enhance yields, improve crop quality, and reduce reliance
on conventional agricultural chemicals.
2001 Small Business Award
-------
Baypure™ CX (Sodium Iminodisuccinate): An Environmentally Friendly and Readily Biodegradable Chelating Agent
Chelating agents are ingredients in a variety of products, such as detergents, fertilizers, and household and industrial
cleaners. Most traditional chelating agents do not break down readily in the environment. Bayer Corporation and
Bayer AG developed a waste-free, environmentally friendly manufacturing process for a new, biodegradable, nontoxic
chelating agent. This new process eliminates the use of formaldehyde and hydrogen cyanide.
(.relating agents are used in a variety of applications, including detergents, agricultural nutrients, and household
and industrial cleaners. Most traditional chelating agents, however, are poorly biodegradable. Some are actually
quite persistent and do not adsorb at the surface of soils in the environment or at activated sludge in wastewater
treatment plants. Because of this poor biodegradability combined with high water solubility, traditional chelators
are readily released into the environment and have been detected in the surface waters of rivers and lakes and in
make-up water processed for drinking water.
As part of its commitment to Responsible Care®, Bayer Corporation manufactures a readily biodegradable and
environmentally friendly chelating agent, D,L-aspartic-/V-(1,2-dicarboxyethyl) tetrasodium salt, also known as
sodium iminodisuccinate. This agent is characterized by excellent chelation capabilities, especially for iron(lll),
copper(ll), and calcium, and is both readily biodegradable and benign from a toxicological and ecotoxicological
standpoint. Sodium iminodisuccinate is also an innovation in the design of chemicals that favorably impact the
environment. This accomplishment was realized not by "simple" modification of molecular structures of currently
used chelating agents, but instead by the development of a wholly new molecule. Sodium iminodisuccinate is
produced by a 100 percent waste-free and environmentally friendly manufacturing process. Bayer AG was the
first to establish an environmentally friendly, patented manufacturing process to provide this innovative chelant
commercially.
Sodium iminodisuccinate belongs to the aminocarboxylate class of chelating agents. Nearly all aminocarboxylates
in use today are acetic acid derivatives produced from amines, formaldehyde, sodium hydroxide, and hydrogen
cyanide. The industrial use of thousands of tons of hydrogen cyanide is an extreme toxicity hazard. In contrast,
Bayer's sodium iminodisuccinate is produced from maleic anhydride (a raw material also produced by Bayer),
water, sodium hydroxide, and ammonia. The only solvent used in the production process is water, and the only
side product formed, ammonia dissolved in water, is recycled back into sodium iminodisuccinate production or
used in other Bayer processes.
Because sodium iminodisuccinate is a readily biodegradable, nontoxic, and nonpolluting alternative to other
chelating agents, it can be used in a variety of applications that employ chelating agents, for example, it can
be used as a builder and bleach stabilizer in laundry and dishwashing detergents to extend and improve the
cleaning properties of the eight billion pounds of these products that are used annually. Specifically, sodium
iminodisuccinate chelates calcium to soften water and improve the cleaning function of the surfactant. In
photographic film processing, sodium iminodisuccinate complexes metal ions and helps to eliminate precipitation
onto the film surface. In agriculture, chelated metal ions help to prevent, correct, and minimize crop mineral
deficiencies. Using sodium iminodisuccinate as the chelating agent in agricultural applications eliminates the
problem of environmental persistence common with other synthetic chelating agents. In summary, Bayer's
sodium iminodisuccinate chelating agent offers the dual benefits of producing a biodegradable, environmentally
friendly chelating agent that is also manufactured in a waste-free process.
2001 Greener Synthetic Pathways Award
-------
BioPreparation™ of Cotton Textiles: A Cost-Effective, Environmentally Compatible Preparation Process
innsA,;•;)(;•!'; ,;IV' i ;Y; n >": H hv
Novozymes North America developed BioPreparation™, a technology to separate natural waxes, oils, and
contaminants from cotton before it is made into fabric. This technology uses enzymes instead of corrosive chemicals
and could save 7-12 billion gallons of water each year.
In textiles, the source of one of the most negative impacts on the environment originates from traditional
processes used to prepare cotton fiber, yarn, and fabric. Fabric preparation consists of a series of various
treatments and rinsing steps critical to obtaining good results in subsequent textile finishing processes. These
water-intensive, wet processing steps generate large volumes of wastes, particularly from alkaline scouring and
continuous/batch dyeing. These wastes include large amounts of salts, acids, and alkali. In view of the
40 billion pounds of cotton fiber that are prepared annually on a global scale, it becomes clear that the
preparation process is a major source of environmentally harsh chemical contribution to the environment.
Cotton wax, a natural component in the outer layer of cotton fibers, is a major obstacle in processing textiles; it
must be removed to prepare the textile for dyeing and finishing. Conventional chemical preparation processes
involve treatment of the cotton substrate with hot solutions of sodium hydroxide, chelating agents, and surface
active agents, often followed by a neutralization step with acetic acid. The scouring process is designed to break
down or release natural waxes, oils, and contaminants and emulsify or suspend these impurities in the scouring
bath. Typically, scouring wastes contribute high biological oxygen demand (BOD) loads during cotton textile
preparation (as much as 50 percent).
Novozymes's BioPreparation™ technology is an alternative to sodium hydroxide that offers many advantages for
textile wet processing, including reduced biological and chemical oxygen demand (BOD/COD) and decreased
water use. BioPreparation™ is an enzymatic process for treating cotton textiles that meets the performance
characteristics of alkaline scour systems while reducing chemical and effluent load. Pectate lyase is the main
scouring agent that degrades pectin to release the entangled waxes and other components from the cotton
surface. The enzyme is also compatible with other enzymatic preparations (amylases, cellulases) used to improve
the performance properties of cotton fabrics.
The practical implications that BioPreparation™ technology has on the textile industry are realized in terms of
conservation of chemicals, water, energy, and time. Based on field trials, textile mills may save as much as
30-50 percent in water costs by replacing caustic scours or by combining the usually separate scouring and
dyeing steps into one. This water savings results because BioPreparation™ uses fewer rinsing steps than required
during a traditional caustic scour. Significant time savings were also demonstrated by combining treatment steps.
A recent statistical survey determined that 162 knitting mills typically use 24 billion gallons per year of water in
processing goods from scouring to finishing; the BioPreparation™ approach would save from
7-12 billion gallons per year of water. In addition, field trials established that BOD and COD loads are decreased
by 25 and 40 percent, respectively, when compared to conventional sodium hydroxide treatments. Furthermore,
these conservation measures translate directly into cost savings of 30 percent or more. As such, this patented
process provides an economical and environmentally friendly alternative to alkaline scour systems currently used
in the textile industry.
62 2001 Greener Reaction Conditions Award
-------
Yttrium as a Lead Substitute in Cationic Electrodeposition Coatings
PPG Industries developed a novel metal primer that uses yttrium instead of lead to resist corrosion in automobiles. The
metal yttrium is far less toxic to human health and the environment than is lead and is more effective in preventing
corrosion. PPG's primer should eliminate one million pounds of lead from automobile manufacture over the next few
years. In addition, this primer does not require chromium- or nickel-based pretreatments, potentially eliminating the
use of 25,000 pounds of chromium and 50,000 pounds of nickel each year.
I 'PG Industries introduced the first cationic electrodeposition primer to the automotive industry in 1976. During
the succeeding years, this coating technology became very widely used in the industry such that today essentially
all automobiles are given a primer coat using the chemistry and processing methods developed by PPG. The
major benefits of this technology are corrosion resistance, high transfer efficiency (low waste), reliable automated
application, and very low organic emissions. Unfortunately, the high corrosion resistance property of electrocoat
has always been dependent on the presence of small amounts of lead salts or lead pigments in the product.
As regulatory pressure on lead increased and consumer demand for improved corrosion resistance grew, lead
was regularly exempted from regulation in electrocoat because there were no cost-effective substitutes. This is
especially important in moderately priced cars and trucks where the high cost of using 1 00 percent zinc-coated
(galvanized) steel could not be tolerated. Lead is very effective for protecting cold-rolled steel, which is still a
common material of construction in automobiles.
For more than 20 years, PPG and other paint companies have sought a substitute for lead in this application. This
search led to PPG's discovery that yttrium can replace lead in cationic electrocoat without any sacrifice in corrosion
performance. Yttrium is a common element in the environment, being widely distributed in low concentrations
throughout the earth's crust and more plentiful in the earth's crust than lead and silver. Although yttrium is much
less studied than lead, the available data on yttrium indicate orders of magnitude lower hazard. As a dust hazard,
yttrium is 100 times safer than lead at typical levels of use.
Numerous other benefits are realized when yttrium is used in electrocoat applications. Yttrium is twice as
effective as lead on a weight basis, allowing the formulation of commercial coatings that contain half the yttrium
by weight relative to lead in comparably performing lead-containing products. In addition, it has been found that
as yttrium is deposited in an electrocoat film, it deposits as the hydroxide. The hydroxide is converted to yttrium
oxide during normal baking of the electrocoat. The oxide is extraordinarily nontoxic by ingestion as indicated by
the LD50 of over 10 grams per kilogram in rats, which is in stark contrast to lead. The ubiquitous nature of yttrium
in the environment and the insoluble ceramic-like nature of the oxide combine to make it an unlikely cause of
future environmental or health problems.
An environmental side benefit of yttrium is its performance over low-nickel and chrome-free metal pretreatments.
In automotive production, a metal pretreatment is always applied to the body prior to electrocoat, which is
designed to assist in adhesion and corrosion performance. This process generates significant quantities of
chromium- and nickel-containing waste and, like lead, is also a concern to recyclers of the finished vehicle. By
using yttrium in the electrocoat step, chrome can be completely eliminated using standard chrome-free rinses
and low-nickel or possibly nickel-free pretreatments, both of which are commercially available today. This should
be possible without concern of compromising long-term vehicle corrosion performance. For PPG pretreatment
customers, this should result in the elimination of up to 25,000 pounds of chrome and 50,000 pounds of nickel
annually from PPG products. As PPG customers implement yttrium over the next several years, approximately
one million pounds of lead (as lead metal) will be removed from the electrocoat applications of PPG automotive
customers.
2001 Designing Greener Chemicals Award 63
-------
2000 Winners
Enzymes in Large-Scale Organic Synthesis
Professor Wong developed methods to replace traditional reactions requiring toxic metals and hazardous solvents. His
methods use enzymes, environmentally acceptable solvents, and mild reaction conditions. His methods also enable novel
reactions that were otherwise impossible or impractical on an industrial scale. Professor Wong's methods hold promise for
applications in a wide variety of chemical industries.
1 ;rganic synthesis has been one of the most successful of scientific disciplines and has contributed significantly to
the development of the pharmaceutical and chemical industries. New synthetic reagents, catalysts, and processes
have made possible the synthesis of molecules with varying degrees of complexity. The types of problems at which
nonbiological organic synthesis has excelled, ranging from stoichiometric reactions to catalysis with acids, bases,
and metals, will continue to be very important. New synthetic and catalytic methods are, however, necessary to deal
with the new classes of compounds that are becoming the key targets of molecular research and development.
Compounds with polyfunctional groups such as carbohydrates and related structures pose particular challenges to
nonbiological synthetic methods but are natural targets for biological methods. In addition, biological methods are
necessary to deal with increasing environmental concerns. Transition metals, heavy elements, and toxic organic
solvents are often used in nonbiological processes. When these materials are used with great care and efficiency,
they may still be environmentally acceptable, but their handling and disposal pose problems. The ability to use
recombinant and engineered enzymes to carry out environmentally acceptable synthetic transformations that
are otherwise impossible or impractical offers one of the best opportunities now available to chemistry and the
pharmaceutical industry.
Professor Chi-Huey Wong at the Scripps Research Institute has pioneered work on the development of effective
enzymes and the design of novel substrates and processes for large-scale organic synthesis. The methods and
strategies that Professor Wong has developed have made possible synthetic transformations that are otherwise
impossible or impractical, especially in areas vitally important in biology and medicine, and have pointed the way
toward new green methodologies for use in large-scale chemistry. A recent study by the Institute for Scientific
Information ranked Professor Wong in the top 15 of the most-cited chemists in the world for the period 1994 to 1996.
According to this study, he is also the most-cited chemist worldwide working in the area of enzymes.
Some of the strategies and methods developed by Professor Wong are breakthrough achievements that laid the
framework for much of the current use of enzymes as catalysts in large-scale organic synthesis. The techniques
and reagents developed in this body of pioneering work are used widely today for research and development. The
scope of contributions ranges from relatively simple enzymatic processes (e.g., chiral resolutions and stereoselective
syntheses) to complex, multistep enzymatic reactions (e.g., oligosaccharide synthesis). For example, the irreversible
enzymatic transesterification reaction using enol esters in environmentally acceptable organic solvents invented
by Professor Wong represents the most widely used method for enantioselective transformation of alcohols in
pharmaceutical development. The multi-enzyme system based on genetically engineered glycosyltransferases
coupled with in situ regeneration of sugar nucleotides developed by Professor Wong has revolutionized the field of
carbohydrate chemistry and enabled the large-scale synthesis of complex oligosaccharides for clinical evaluation.
All of these new enzymatic reactions are carried out in environmentally acceptable solvents, under mild reaction
conditions, at ambient temperature, and with minimum protection of functional groups. The work of Professor
Wong represents a new field of green chemistry suitable for large-scale synthesis that is impossible or impractical to
achieve by nonenzymatic means.
64 2000 Academic Award
-------
Envirogluv™: A Technology for Decorating Glass and Ceramicware with Radiation-Curable, Environmentally
Compliant Inks
RevTech developed the Envirogluv™ process to print top-quality labels directly on glass, replacing paper labels,
decals, or applied ceramic labeling. Envirogluv™ inks do not contain heavy metals, contain little to no volatile organic
compounds (VOCs), and are biodegradable. This technology saves energy by replacing high-temperature ovens with
ultraviolet light, saves raw materials, wastes no ink, and produces decorated glass that is completely recyclable.
Billions of products are sold in glass containers in the United States every year. Most, if not all, of these glass
containers are labeled in some fashion. Typically, decorative indicia are applied to glass using paper labels, decals,
or a process known as applied ceramic labeling (ACL). ACL involves first printing the glass with an ink composition
that contains various heavy metals such as lead, cadmium, and chromium, then bonding the ink to the glass by
baking in an oven known as a lehr at temperatures of 1,000 °F or more for several hours.
All of these processes have disadvantages. Paper labels are inexpensive but can be easily removed if the
container is exposed to water or abrasion. In addition, paper labels do not provide the aesthetics desired by
decorators who want rich, expensive-looking containers. Decals are expensive and difficult to apply at the high
line speeds that are required in the decoration of most commercial containers. More important, decals are made
from materials that are not biodegradable, which causes serious problems in the recycling of glass containers
that are decorated by this method. The use and disposal of the heavy metals required in ACL presents serious
environmental concerns. Moreover, the high-temperature lehr ovens required in ACL decorating utilize substantial
amounts of energy and raise safety issues with respect to workers and plant facilities that use this equipment. The
inks used in ACL decorating also tend to contain high levels of volatile organic compounds (VOCs) that can lead
to undesirable emissions.
Clearly, there has been a need in the glass decorating industry for a decorated glass container that is aesthetically
pleasing, durable, and obtained in a cost-effective, environmentally friendly, and energy-efficient manner.
Envirogluv™ technology fills that need. Envirogluv™ is a glass decorating technology that directly silk-screens
radiation-curable inks onto glass, then cures the ink almost instantly by exposure to UV light. The result is a crisp,
clean label that is environmentally sound, with a unit cost that is about half that of traditional labeling.
Envirogluv™ technology offers many human health and environmental benefits. The ink compositions used in
the Envirogluv™ process do not contain any heavy metals and contain little to no VOCs. All Envirogluv™ pigments
are biodegradable. The Envirogluv™ inks are cured directly on the glass by exposure to UV radiation, eliminating
the high-temperature baking in a lehr oven that is associated with the ACL process. This provides additional
safety and environmental benefits, such as reduced energy consumption and reduced chance of worker injury.
In addition, the process uses less raw materials and does not generate any waste ink. Furthermore, Envirogluv™
decorated glass containers eliminate the need for extra packaging and are completely recyclable. Applications
suitable for the Envirogluv™ process include tableware, cosmetics containers, and plate glass.
2000 Small Business Award 65
-------
An Efficient Process for the Production of Cytovene®, a Potent Antiviral Agent
Roche Colorado developed an environmentally friendly way to synthesize Cytovene®, a potent antiviral drug. Their
process eliminates nearly 2.5 million pounds of hazardous liquid waste and over 55,000 pounds of hazardous solid
waste each year. This process also increases the overall yield more than 25 percent and doubles the production
throughput.
I he design, development, and implementation of environmentally friendly processes for the large-scale
production of pharmaceutical products is one of the most technically challenging aspects of business
operations in the pharmaceutical industry. Roche Colorado Corporation (RCC), in establishing management and
operational systems for the continuous improvement of environmental quality in its business activities, has, in
essence, adopted the Presidential Green Chemistry Challenge Program's basic principles of green chemistry:
the development of environmentally friendly processes for the manufacture of pharmaceutical products. In
particular, RCC has successfully applied these principles to the manufacture of ganciclovir, the active ingredient
in Cytovene®, a potent antiviral agent. Cytovene® is used in the treatment of cytomegalovirus (CMV) retinitis
infections in immunocompromised patients, including patients with AIDS, and also used for the prevention of
CMV disease in transplant recipients at risk for CMV.
In the early 1990s, Roche Colorado Corporation developed the first commercially viable process for the production
of Cytovene®. By 1993, chemists at RCC's Boulder Technology Center designed a new and expedient process for
the production of Cytovene®, which at the time had an estimated commercial demand of approximately
110,000 pounds per year. Leveraging the basic principles of green chemistry and molecular conservation into
the design process, significant improvements were demonstrated in the second-generation GuanineTriester
(GTE) Process. Compared to the first-generation commercial manufacturing process, the GTE Process reduced the
number of chemical reagents and intermediates from 22 to 11, eliminated the (only) two hazardous solid waste
streams, eliminated 11 different chemicals from the hazardous liquid waste streams, and efficiently recycled
and reused four of the five ingredients not incorporated into the final product. Inherent within the process
improvements demonstrated was the complete elimination of the need for operating and monitoring three
different potentially hazardous chemical reactions. Overall, the GTE Process provided an expedient method for
the production of Cytovene®, demonstrating a procedure that provided an overall yield increase of more than
25 percent and a production throughput increase of 100 percent.
In summary, the new GTE Process for the commercial production of Cytovene® clearly demonstrates the
successful implementation of the general principles of green chemistry: the development of environmentally
friendly syntheses, including the development of alternative syntheses utilizing nonhazardous and nontoxic
feedstocks, reagents, and solvents; elimination of waste at the source (liquid waste: 2.5 million pounds per year
and solid waste: 56,000 pounds per year); and elimination of the production of toxic wastes and byproducts. The
process establishes new and innovative technology for a general and efficient method for the preparation of
Cytovene® and other potent antiviral agents. It is registered with the U.S. Food and Drug Administration (FDA) as
the current manufacturing process for the world's supply of Cytovene®.
66 2000 Greener Synthetic Pathways Award
-------
Two-Component Waterborne Polyurethane Coatings
Bayer developed a series of high-performance, water-based, two-component polyurethane coatings that eliminate
most or all of the organic solvents used in conventional polyurethane coatings. Bayer's water-based polyurethane
coatings reduce volatile organic compound (VOC) and hazardous air pollutant (HAP) emissions by 50-90 percent.
I wo-component (2K) waterborne polyurethane coatings are an outstanding example of the use of alternative
reaction conditions for green chemistry. This technology is achieved by replacing most or all of the volatile organic
compounds (VOCs) and hazardous air pollutants (HAPs) used in conventional 2K solventborne polyurethane
coatings with water as the carrier, without significant reduction in performance of the resulting coatings. This may
seem an obvious substitution, but, due to the particular chemistry of the reactive components of polyurethane, it
is not that straightforward.
Two-component solventborne polyurethane coatings have long been considered in many application areas to be
the benchmark for high-performance coatings systems. The attributes that make these systems so attractive are
fast cure under ambient or bake conditions, high-gloss and mirror-like finishes, hardness or flexibility as desired,
chemical and solvent resistance, and excellent weathering. The traditional carrier, however, has been organic
solvent that, upon cure, is freed to the atmosphere as VOC and HAP material. High-solids systems and aqueous
polyurethane dispersions ameliorate this problem but do not go far enough.
An obvious solution to the deficiencies of 2K solventborne polyurethanes and aqueous polyurethane dispersions
is a reactive 2K polyurethane system with water as the carrier. In order to bring 2K waterborne polyurethane
coatings to the U.S. market, new waterborne and water-reducible resins had to be developed. To overcome
some application difficulties, new mixing/spraying equipment was also developed. For the technology to be
commercially viable, an undesired reaction of a polyisocyanate cross-linker with water had to be addressed, as
well as problems with the chemical and film appearance resulting from this side reaction. The work done on the
2K waterborne polyurethanes over the past several years has resulted in a technology that will provide several
health and environmental benefits. VOCs will be reduced by 50-90 percent and HAPs by 50-99 percent. The
amount of chemical byproducts evolved from films in interior applications will also be reduced, and rugged
interior coatings with no solvent smell will now be available.
Today, 2K waterborne polyurethane is being applied on industrial lines where good properties and fast cure rates
are required for such varied products as metal containers and shelving, sporting equipment, metal- and fiberglass-
reinforced utility poles, agricultural equipment, and paper products. In flooring coatings applications where the
market-driving force is elimination of solvent odor, 2K waterborne polyurethane floor coatings provide a quick dry,
high abrasion resistance, and lack of solvent smell (<0.1 pound organic solvent per gallon). In wood applications,
2K waterborne polyurethane coatings meet the high-performance wood finishes requirements for kitchen
cabinet, office, and laboratory furniture manufacturers while releasing minimal organic solvents in the workplace
or to the atmosphere. In the United States, the greatest market acceptance of 2K waterborne polyurethane is in
the area of special-effect coatings in automotive applications. These coatings provide the soft, luxurious look
and feel of leather to hard plastic interior automobile surfaces, such as instrument panels and air bag covers.
Finally, in military applications, 2K waterborne polyurethane coatings are being selected because they meet the
demanding military performance criteria that include flat coatings with camouflage requirements, corrosion
protection, chemical and chemical agent protection, flexibility, and exterior durability, along with VOC reductions
of approximately 50 percent.
2000 Greener Reaction Conditions Award 67
-------
Sentricon™ Termite Colony Elimination System, A New Paradigm for Termite Control
Dow's Sentricon™ System eliminates termite colonies with highly specific bait applied only where termites are active;
it replaces widespread applications of pesticide in the soil around houses and other structures. EPA has registered
Sentricon™ as a reduced-risk pesticide. Dow's system reduces the use of hazardous materials and reduces potential
impacts on human health and the environment. By Iate1999, Sentricon™ was used for over 300,000 structures in the
United States.
I he annual cost of termite treatments to the U.S. consumer is about $1.5 billion, and each year as many as
1.5 million homeowners will experience a termite problem and seeka control option. From the 1940s until 1995,
the nearly universal treatment approach for subterranean termite control involved the placement of large volumes
of insecticide dilutions into the soil surrounding a structure to create a chemical barrier through which termites
could not penetrate. Problems with this approach include difficulty in establishing an uninterrupted barrier in
the vast array of soil and structural conditions, use of large volumes of insecticide dilution, and potential hazards
associated with accidental misapplications, spills, off-target applications, and worker exposure. These inherent
problems associated with the use of chemical barrier approaches for subterranean termite control created a
need for a better method. The search for a baiting alternative was the focus of a research program established
by Dr. Nan-Yao Su of the University of Florida who, in the 1980s, had identified the characteristics needed for a
successful termite bait toxicant.
The unique properties of hexaflumuron made it an excellent choice for use in controlling subterranean termite
colonies. The Sentricon™Termite Colony Elimination System, developed by Dow AgroSciences in collaboration
with Dr. Su, was launched commercially in 1995 after receiving EPA registration as a reduced-risk pesticide.
Sentricon™ represents truly novel technology employing an Integrated Pest Management approach using
monitoring and targeted delivery of a highly specific bait. Because it eliminates termite colonies threatening
structures using a targeted approach, Sentricon™ delivers unmatched technical performance, environmental
compatibility, and reduced human risk. The properties of hexaflumuron as a termite control agent are attractive
from an environmental and human risk perspective, but more important, the potential for adverse effects is
dramatically reduced because it is present only in very small quantities in stations with termite activity. The
comparisons to barrier methods show significant reduction in the use of hazardous materials and substantial
reduction in potential impacts on human health and the environment.
The discovery of hexaflumuron's activity with its unique fit and applicability for use as a termite bait was a key
milestone for the structural pest control industry and Dow AgroSciences. The development and commercial
launch of Sentricon™ changed the paradigm for protecting structures from damage caused by subterranean
termites. The development of novel research methodologies, new delivery systems, and the establishment of
an approach that integrates monitoring and baiting typify the innovation that has been a hallmark of the project.
More than 300,000 structures across the United States are now being safeguarded through application of this
revolutionary technology, and adoption is growing rapidly.
68 2000 Designing Greener Chemicals Award
-------
1999 Winners
TAML™ Oxidant Activators: General Activation of Hydrogen Peroxide
for Green Oxidation Technologies
Professor Collins developed a series of activator chemicals that work with hydrogen peroxide to replace chlorine
bleaches. His TAML™ activators have many potential uses that include preparing wood pulp for papermaking and
removing stains from laundry. This novel, environmentally benign technology eliminates chlorinated byproducts from
wastewater streams and saves both energy and water.
In nature, selectivity is achieved through complex mechanisms using a limited set of elements available in the
environment. In the laboratory, chemists prefer a simpler design that utilizes the full range of the periodic table.
The problem of persistent pollutants in the environment can be minimized by employing reagents and processes
that mimic those found in nature. By developing a series of activators effective with the natural oxidant, hydrogen
peroxide, Professor Terry Collins has devised an environmentally-benign oxidation technique with widespread
applications. TAML™ activators (tetraamido-macrocyclic ligand activators) are iron-based and contain no toxic
functional groups. These activators offer significant technology breakthroughs in the pulp and paper industry and
the laundry field.
The key to quality papermaking is the selective removal of lignin from the white fibrous polysaccharides, cellulose,
and hemicellulose. Wood pulp delignification has traditionally relied on chlorine-based processes that produce
chlorinated pollutants. Professor Collins has demonstrated that TAML™ activators effectively catalyze hydrogen
peroxide in the selective delignification of wood pulp. This is the first low-temperature peroxide oxidation
technique for treating wood pulp, which translates to energy savings for the industry. Environmental compliance
costs may be expected to decrease with this new approach because chlorinated organics are not generated in
this totally chlorine-free process.
TAML™ activators may also be applied to the laundry field, where most bleaches are based on peroxide. When
bound to fabric, most commercial dyes are unaffected by the TAML™-activated peroxide. However, random dye
molecules that "escape" the fabric during laundering are intercepted and destroyed by the activated peroxide
before they have a chance to transfer to other articles of clothing. This technology prevents dye-transfer accidents
while offering improved stain-removal capabilities. Washing machines that require less water will be practical
when the possibility of dye-transfer is eliminated.
An active area of investigation is the use of TAML™ peroxide activators for water disinfection. Ideally, the activators
would first kill pathogens in the water sample, then destroy themselves in the presence of a small excess of
peroxide. This protocol could have global applications, from developing nations to individual households.
The versatility of the TAML™ activators in catalyzing peroxide has been demonstrated in the pulp and paper and
laundry industries. Environmental benefits include decreased energy requirements, elimination of chlorinated
organics from the waste stream, and decreased water use. The development of new activators and new
technologies will provide environmental advantages in future applications.
1999 Academic Award 69
-------
Conversion of Low-Cost Biomass Wastes to Levulinic Acid and Derivatives
Biofine developed a process to convert the waste cellulose in paper mill sludge, municipal solid waste, unrecyclable
waste paper, waste wood, and agricultural residues into levulinic acid (LA). LA can be used as a building block for many
other useful chemicals. LA made from waste cellulose reduces the use of fossil fuels and reduces the overall cost of LA
from $4-6 per pound to as little as $0.32 per pound.
Replacing petroleum-based feedstocks with renewable ones is a crucial step toward achieving sustainability.
When considering alternatives to traditional feedstocks, attention often focuses on plant-based materials.
Renewable biomass conserves our dwindling supplies of fossil fuels and contributes no net CO2 to the
atmosphere. Biofine has developed a high-temperature, dilute-acid hydrolysis process that converts cellulosic
biomass to levulinic acid (LA) and derivatives. Cellulose is initially converted to soluble sugars, which are then
transformed to levulinic acid. Byproducts in the process include furfural, formic acid, and condensed tar, all of
which have commercial value as commodities or fuel, feedstocks used include paper mill sludge, municipal solid
waste, unrecyclable waste paper, waste wood, and agricultural residues.
Levulinic acid serves as a building block in the synthesis of useful chemical products. Markets already exist
for tetrahydrofuran, succinic acid, and diphenolic acid, all of which are levulinic acid derivatives. The use of
diphenolic acid (DPA) as a monomer for polycarbonates and epoxy resins is currently under investigation. An
industry/government consortium has conducted research on two additional derivatives with commercial value:
methyltetrahydrofuran (MTHF), a fuel additive, and 5-amino levulinic acid (DALA), a pesticide.
The conversion of levulinic acid to MTHF is accomplished at elevated temperature and pressure using a catalytic
hydrogenation process. MTHF is a fuel additive that is miscible with gasoline and hydrophobic, allowing it to be
blended at the refinery rather than later in the distribution process. Using MTHF as a fuel additive increases the
oxygenate level in gasoline without adversely affecting engine performance. MTHF also boasts a high octane
rating (87) and a lower vapor pressure, thereby reducing fuel evaporation and improving air quality.
DALA can be obtained from levulinic acid in high yield using a three-step process. DALA is a broad-spectrum
pesticide that is nontoxic and biodegradable. Its activity is triggered by light, selectively killing weeds while leaving
most major crops unaffected. DALA also shows potential as an insecticide.
Diphenolic acid is synthesized by reacting levulinic acid with phenol. DPA has the potential to displace
bisphenol-A, a possible endocrine disrupter, in polymer applications. Brominated DPA shows promise as an
environmentally-acceptable marine coating, while dibrominated DPA may find use as a fire retardant.
Currently, levulinic acid has a worldwide market of about one million pounds per year at a price of $4-6 per
pound. Large-scale commercialization of the Biofine process could produce levulinic acid for as little as
$0.32 per pound, spurring increased demand for LA and its derivatives. Using the Biofine process, waste biomass
can be transformed into valuable chemical products. The ability to produce levulinic acid economically from waste
biomass and renewable feedstocks is the key to increased commercialization of LA and its derivatives.
70 1999 Small Business Award
-------
Practical Application of a Biocatalyst in Pharmaceutical Manufacturing
innsA,;•;)(;•!'; ,;IV' i ;Y; n >": H hv
Lilly Research Laboratories developed a novel, low-waste process for drug synthesis. One key aspect uses yeast to
replace a chemical reaction. Applying its process, Lilly eliminates approximately 41 gallons of solvent and 3 pounds of
chromium waste for every pound of a drug candidate that it manufactures. Lilly's process also improves worker safety
and increases product yield from 16 to 55 percent.
I he synthesis of a pharmaceutical agent is frequently accompanied by the generation of a large amount of
waste. This should not be surprising, as numerous steps are commonly necessary, each of which may require
feedstocks, reagents, solvents, and separation agents. Lilly Research Laboratories has redesigned its synthesis of
an anticonvulsant drug candidate, LY300164. This pharmaceutical agent is being developed for the treatment of
epilepsy and neurodegenerative disorders.
The synthesis used to support clinical development of the drug candidate proved to be an economically viable
process, although several steps proved problematic. A large amount of chromium waste was generated,
an additional activation step was required, and the overall process required a large volume of solvent. Significant
environmental improvements were realized upon implementing the new synthetic strategy. Roughly 9,000 gallons
of solvent and 660 pounds of chromium waste were eliminated for every 220 pounds of LY300164 produced. Only
three of the six intermediates generated were isolated, limiting worker exposure and decreasing processing costs.
The synthetic scheme proved more efficient as well, with percent yield climbing from 16 to 55 percent.
The new synthesis begins with the biocatalytic reduction of a ketone to an optically pure alcohol. The
yeast Zygosaccharomyces rouxii demonstrated good reductase activity but was sensitive to high product
concentrations. To circumvent this problem, a novel three-phase reaction design was employed. The starting
ketone was charged to an aqueous slurry containing a polymeric resin, buffer, and glucose, with most of the
ketone adsorbed on the surface of the resin. The yeast reacted with the equilibrium concentration of ketone
remaining in the aqueous phase. The resulting product was adsorbed onto the surface of the resin, simplifying
product recovery. All of the organic reaction components were removed from the aqueous waste stream,
permitting the use of conventional wastewater treatments.
A second key step in the synthesis was selective oxidation to eliminate the unproductive redox cycle present
in the original route. The reaction was carried out using dimethylsulfoxide, sodium hydroxide, and compressed
air, eliminating the use of chromium oxide, a possible carcinogen, and preventing the generation of chromium
waste. The new protocol was developed by combining innovations from chemistry, microbiology, and
engineering. Minimizing the number of changes to the oxidation state improved the efficiency of the process
while reducing the amount of waste generated. The alternative synthesis presents a novel strategy for producing
5/-/-2,3-benzodiazepines. The approach is general and has been applied to the production of other anticonvulsant
drug candidates. The technology is low-cost and easily implemented; it should have broad applications within the
manufacturing sector.
1999 Greener Synthetic Pathways Award
-------
The Development and Commercialization of ULTIMER®: The First of a New Family of Water-Soluble Polymer
Dispersions
The Nalco Chemical Company developed a novel way to synthesize the polymers used to treat water in a variety of
industrial and municipal operations. Nalco now manufactures these polymers in water, replacing the traditional water-
in-oil mixtures and preventing the release of organic solvents and other chemicals into the environment.
1 ligh-molecular-weight polyacrylamides are commonly used as process aids and water treatment agents in
various industrial and municipal operations. Annually, at least 200 million pounds of water-soluble, acrylamide-
based polymers are used to condition and purify water. These water-soluble polymers assist in removing
suspended solids and contaminants and effecting separations. Traditionally, these polymers are produced
as water-in-oil emulsions. Emulsions are prepared by combining the monomer, water, and a hydrocarbon
oil-surfactant mixture in approximately equal parts. Although the oil and surfactant are required for processing,
they do not contribute to the performance of the polymer. Consequently, approximately 90 million pounds of oil
and surfactant are released to the environment each year. Nalco has developed a new technology that permits
production of the polymers as stable colloids in water, eliminating the introduction of oil and surfactants into the
environment.
The Nalco process uses a homogeneous dispersion polymerization technique. The water-soluble monomers are
dissolved in an aqueous salt solution of ammonium sulfate then polymerized using a water-soluble, free-radical
initiator. A low-molecular-weight dispersant polymer is added to prevent aggregation of the growing polymer
chains. For end-use applications, the dispersion is simply added to water, thereby diluting the salt and allowing
the polymer to dissolve into a clear, homogeneous, polymer solution. This technology has been successfully
demonstrated with cationic copolymers of acrylamide, anionic copolymers of acrylamide, and non-ionic
polymers.
Development of water-based dispersion polymers provides three important environmental benefits. First,
the new process eliminates the use of hydrocarbon solvents and surfactants required in the manufacture of
emulsion polymers. Dispersion polymers produce noVOCsand exhibit lower biological oxygen demand (BOD)
and chemical oxygen demand (COD) than do emulsion polymers. Second, the salt used, ammonium sulfate, is a
waste byproduct from another industrial process, the production of caprolactam. Caprolactam is the precursor in
the manufacture of nylon; 2.5-4.5 million pounds of ammonium sulfate are produced for every million pounds
of caprolactam, providing a ready supply of feedstock. Finally, dispersion polymers eliminate the need for costly
equipment and inverter surfactants needed for mixing emulsion polymers. This technological advantage will
make wastewater treatment more affordable for small- and medium-sized operations.
Nalco's dispersion polymers contain the same active polymer component as traditional emulsion polymers
without employing oil and surfactant carrier systems. The polymers are produced as stable colloids in water,
retaining ease and safety of handling while eliminating the release of oil and surfactants into the environment.
By adopting this new technology, Nalco has conserved over one million pounds of hydrocarbon solvent and
surfactants since 1997 on two polymers alone. In 1998, the water-based dispersions used 3.2 million pounds of
ammonium sulfate, a by-product from caprolactam synthesis that would otherwise be treated as waste. Additional
environmental benefits will be realized as the dispersion polymerization process is extended to the manufacture
of other polymers.
72 1999 Greener Reaction Conditions Award
-------
Spinosad: A New Natural Product for Insect Control
Dow developed spinosad, a highly selective, environmentally friendly insecticide made by a soil microorganism.
It controls many chewing insect pests in cotton, trees, fruits, vegetables, turf, and ornamentals. Unlike traditional
pesticides, it does not persist in the environment; it also has lowtoxicity to mammals and birds.
'«, ontrolling insect pests is essential to maintaining high agricultural productivity and minimizing monetary
losses. Synthetic organic pesticides, from a relatively small number of chemical classes, play a leading role in pest
control. The development of new and improved pesticides is necessitated by increased pest resistance to existing
products, along with stricter environmental and toxicological regulations. To meet this need, Dow AgroSciences
has designed spinosad, a highly selective, environmentally friendly insecticide.
High-volume testing of fermentation isolates in agricultural screens produced numerous leads, including the
extracts of a Caribbean soil sample found to be active on mosquito larvae. The microorganism, Saccharopolyspora
spinosa, was isolated from the soil sample, and the insecticidal activity of the spinosyns was identified. Spinosyns
are unique macrocyclic lactones, containing a tetracyclic core to which two sugars are attached. Most of the
insecticidal activity is due to a mixture of spinosyns A and D, commonly referred to as spinosad. Products such as
Tracer® Naturalyte® Insect Control and Precise® contain spinosad as the active ingredient.
Insects exposed to spinosad exhibit classical symptoms of neurotoxicity: lack of coordination, prostration, tremors,
and other involuntary muscle contractions leading to paralysis and death. Although the mode of action of
spinosad is not fully understood, it appears to affect nicotinic and y-aminobutyric acid receptor function through a
novel mechanism.
Spinosad presents a favorable environmental profile. It does not leach, bioaccumulate, volatilize, or persist in
the environment. Spinosad will degrade photochemically when exposed to light after application. Because
spinosad strongly adsorbs to most soils, it does not leach through soil to groundwater. Spinosad demonstrates
low mammalian and avian toxicity. No long-term health problems were noted in mammals, and a low potential
for acute toxicity exists due to low oral, dermal, and inhalation toxicity. This is advantageous, because low
mammalian toxicity imparts reduced risk to those who handle, mix, and apply the product. Although spinosad
is moderately toxic to fish, this toxicity represents a reduced risk to fish when compared with many synthetic
insecticides currently in use.
Spinosad has proven effective in controlling many chewing insect pests in cotton, trees, fruits, vegetables, turf,
and ornamentals. High selectivity is also observed: 70-90 percent of beneficial insects and predatory wasps are
left unharmed. Spinosad features a novel molecular structure and mode of action that provide the excellent
crop protection associated with synthetic products coupled with the low human and environmental risk found
in biological products. The selectivity and low toxicity of spinosad make it a promising tool for integrated pest
management.
1999 Designing Greener Chemicals Award
-------
1998 Winners
The Development of the Concept of Atom Economy
Professor Trost developed the concept of atom economy: chemical reactions that do not waste atoms. Professor
Trost's concept of atom economy includes reducing the use of nonrenewable resources, minimizing the amount of
waste, and reducing the number of steps used to synthesize chemicals. Atom economy is one of the fundamental
cornerstones of green chemistry. This concept is widely used by those who are working to improve the efficiency of
chemical reactions.
\ he general area of chemical synthesis covers virtually all segments of the chemical industry—oil refining, bulk
or commodity chemicals, and fine chemicals, including agrochemicals, flavors, fragrances, Pharmaceuticals,
etc. Economics generally dictates the feasibility of processes that are "practical". A criterion that traditionally has
not been explicitly recognized relates to the total quantity of raw materials required for the process compared
to the quantity of product produced or, simply put, "how much of what you put into your pot ends up in your
product." In considering the question of what constitutes synthetic efficiency, Professor Barry M. Trost has
explicitly enunciated a new set of criteria by which chemical processes should be evaluated. They fall under two
categories—selectivity and atom economy.
Selectivity and atom economy evolve from two basic considerations. First, the vast majority of the synthetic
organic chemicals in production derive from nonrenewable resources. It is self-evident that such resources should
be used as sparingly as possible. Second, all waste streams should be minimized. This requires employment of
reactions that produce minimal byproducts, either through the intrinsic stoichiometry of a reaction or as a result of
minimizing competing undesirable reactions (i.e., making reactions more selective).
The issues of selectivity can be categorized under four headings—chemoselectivity (differentiation among various
functional groups in a molecule), regioselectivity (locational), diastereoselectivity (relative stereochemistry),
and enantioselectivity (absolute stereochemistry). The chemical community at large has readily accepted
these considerations. In too many cases, however, efforts to achieve the goal of selectivity led to reactions
requiring multiple components in stoichiometric quantities that are not incorporated into the product, thus
creating significant amounts of waste. How much of the reactants end up in the product (i.e., atom economy)
traditionally has been ignored. When Professor Trost's first paper on atom economy appeared in the literature,
the idea generally was not adopted by either academia or industry. Many in industry, however, were practicing
this concept without explicitly enunciating it. Others in industry did not consider the concept because it did
not appear to have any economic consequence. Today, all of the chemical industry explicitly acknowledges the
importance of atom economy.
Achieving the objectives of selectivity and atom economy encompasses the entire spectrum of chemical
activities—from basic research to commercial processes. In enunciating these principles, Professor Trost has set
a challenge for those involved in basic research to create new chemical processes that meet the objectives.
Professor Trost's efforts to meet this challenge involve the rational invention of new chemical reactions that are
either simple additions or, at most, produce low-molecular-weight innocuous byproducts. A major application of
these reactions is in the synthesis of fine chemicals and Pharmaceuticals, which, in general, utilize very atom-
uneconomical reactions. Professor Trost's research involves catalysis, largely focused on transition metal catalysis
but also main group catalysis. The major purpose of his research is to increase the toolbox of available reactions
to serve these industries for problems they encounter in the future. However, even today, there are applications
for which such methodology may offer more efficient syntheses.
74 1998 Academic Award
-------
Use of Microbes as Environmentally Benign Synthetic Catalysts
Adipic acid, a building block for nylon, and catechol, a building block for Pharmaceuticals and pesticides, are two
chemicals of major industrial importance. Using environmentally benign, genetically engineered microbes, Dr. Draths
and Professor Frost synthesized adipic acid and catechol from sugars. These two chemicals are traditionally made from
benzene, a petroleum product; they can now be made with less risk to human health and the environment.
I undamental change in chemical synthesis can be achieved by elaboration of new, environmentally
benign routes to existing chemicals. Alternatively, fundamental change can follow from characterization and
environmentally benign synthesis of chemicals that can replace those chemicals currently manufactured by
environmentally problematic routes. Examples of these design principles are illustrated by the syntheses of adipic
acid and catechol developed by Dr. Karen M. Draths and Professor John W. Frost. The Draths-Frost syntheses
of adipic acid and catechol use biocatalysis and renewable feedstocks to create alternative synthetic routes to
chemicals of major industrial importance. These syntheses rely on the use of genetically manipulated microbes as
synthetic catalysts. Nontoxic glucose is employed as a starting material, which, in turn, is derived from renewable
carbohydrate feedstocks, such as starch, hemicellulose, and cellulose. In addition, water is the primary reaction
solvent, and the generation of toxic intermediates and environment-damaging byproducts is avoided.
In excess of 4.2 billion pounds of adipic acid are produced annually and used in the manufacture of nylon 6,6.
Most commercial syntheses of adipic acid use benzene, derived from the benzene-toluene-xylene (BTX) fraction
of petroleum refining, as the starting material. In addition, the last step in the current manufacture of adipic acid
employs a nitric acid oxidation resulting in the formation of nitrous oxide as a byproduct. Due to the massive
scale on which it is industrially synthesized, adipic acid manufacture has been estimated to account for some
10 percent of the annual increase in atmospheric nitrous oxide levels. The Draths-Frost synthesis of adipic acid
begins with the conversion of glucose into c/s,c/s-muconic acid using a single, genetically engineered microbe
expressing a biosynthetic pathway that does not exist in nature. This novel biosynthetic pathway was assembled
by isolating and amplifying the expression of genes from different microbes including Klebsiella pneumoniae,
Acinetobacter calcoaceticus, and Escherichia coli. The c/s,c/s-muconic acid, which accumulates extracellularly, is
hydrogenated to afford adipic acid.
Yet another example of the Draths-Frost strategy for synthesizing industrial chemicals using biocatalysis and
renewable feedstocks is their synthesis of catechol. Approximately 46 million pounds of catechol are produced
globally each year. Catechol is an important chemical building block used to synthesize flavors (e.g., vanillin,
eugenol, isoeugenol), Pharmaceuticals (e.g., L-DOPA, adrenaline, papaverine), agrochemicals(e.g., carbofuran,
propoxur), and polymerization inhibitors and antioxidants (e.g., 4-f-butylcatechol, veratrol). Although some
catechol is distilled from coal tar, petroleum-derived benzene is the starting material for most catechol
production. The Draths-Frost synthesis of catechol uses a single, genetically engineered microbe to catalyze the
conversion of glucose into catechol, which accumulates extracellularly. As mentioned previously, plant-derived
starch, hemicellulose, and cellulose can serve as the renewable feedstocks from which the glucose starting
material is derived.
In contrast to the traditional syntheses of adipic acid and catechol, the Draths-Frost syntheses are based on
renewable feedstocks, carbohydrate starting materials, and microbial biocatalysis. As the world moves to national
limits on carbon dioxide (CO2) emissions, each molecule of a chemical made from a carbohydrate may well
be counted as a credit due to the CO2 that is fixed by plants to form the carbohydrate. Biocatalysis using intact
microbes also allows the Draths-Frost syntheses to use water as a reaction solvent, near-ambient pressures, and
temperatures that typically do not exceed human body temperature.
1998 Academic Award 75
-------
Technology for the Third Millennium: The Development and Commercial Introduction of an Environmentally
Responsible Fire Extinguishment and Cooling Agent
PYROCOOL Technologies developed PYROCOOL F.E.F., a Fire extinguishing Foam that is nontoxic and highly
biodegradable. PYROCOOF F.E.F. replaces ozone-depleting gases and aqueous Foams that release toxic and persistent
chemicals to the environment during use. PYROCOOF F.E.F. is eFFective at approximately one-tenth the concentration oF
conventional Fire extinguishing chemicals.
Vdvances in chemical technology have greatly benefited firefighting in this century. From the limitation of having
only local water supplies at their disposal, firefighters have been presented over the years with a wide variety of
chemical agents, as additives or alternatives to water, to assist them. These advances in chemical extinguishment
agents, however, have themselves created, in actual use, potential long-term environmental and health problems
that tend to outweigh their firefighting benefits. PYROCOOL Technologies, Inc. developed PYROCOOL F.E.F. (Fire
Extinguishing Foam) as an alternative formulation of highly biodegradable surfactants designed for use in very
small quantities as a universal fire extinguishment and cooling agent.
Halon gases, hailed as a tremendous advance when introduced, have since proven to be particularly destructive
to the ozone layer, having an ozone depletion potential (OOP) value of 10-16 times that of common refrigerants.
Aqueous film-forming foams (AFFFs) developed by the U.S. Navy in the 1960s to combat pooled-surface, volatile,
hydrocarbon fires release both toxic hydrofluoric acid and fluorocarbons when used. The fluorosurfactant
compounds that make these agents so effective against certain types of fires render them resistant to microbial
degradation, often leading to contamination of groundwater supplies and failure of wastewater treatment
systems.
In 1993, PYROCOOL Technologies initiated a project to create a fire extinguishment and cooling agent that would
be effective in extinguishing fires and that would greatly reduce the potential long-term environmental and
health problems associated with traditional products. To achieve this objective, PYROCOOL Technologies first
determined that the product (when finally developed) would contain no glycol ethers or fluorosurfactants. In
addition, it decided that the ultimate formulation must be an effective fire extinguishment and cooling agent at
very low mixing ratios. PYROCOOL F.E.F. is a formulation of highly biodegradable nonionic surfactants, anionic
surfactants, and amphoteric surfactants with a mixing ratio (with water) of 0.4 percent. In initial fire tests at the
world's largest fire-testing facility in the Netherlands, PYROCOOL F.E.F. was demonstrated to be effective against a
broad range of combustibles.
Since its development in 1993, PYROCOOL F.E.F. has been employed successfully against numerous fires both
in America and abroad. PYROCOOL F.E.F. carries the distinction of extinguishing the last large oil tanker fire at
sea (a fire estimated by Lloyd's of London to require 10 days to extinguish) on board the Nassia tanker in the
Bosphorous Straits in just 12.5 minutes, saving 80 percent of the ship's cargo and preventing 160 million pounds
of crude oil from spilling into the sea.
As demonstrated by the PYROCOOL F.E.F. technology, selective employment of rapidly biodegradable substances
dramatically enhances the effectiveness of simple water, while eliminating the environmental and toxic impact
of other traditional fire extinguishment agents. Because PYROCOOL F.E.F. is mixed with water at only 0.4 percent,
an 87-93 percent reduction in product use is realized compared to conventional extinguishment agents typically
used at 3-6 percent. Fire affects all elements of industry and society, and no one is immune from its dangers.
PYROCOOL F.E.F. provides an innovative, highly effective, and green alternative for firefighters.
76 1998 Small Business Award
-------
Elimination of Chlorine in the Synthesis of 4-Aminodiphenylamine:
A New Process That Utilizes Nucleophilic Aromatic Substitution
for Hydrogen
Flexsys developed a new method to eliminate waste from a critically important reaction used to manufacture a wide range
of chemical products. They are using this method to manufacture 4-ADPA, a key, high-volume building block for a rubber
preservative. Converting just 30 percent of the world's production capacity of this key building block to the Flexsys process
would reduce chemical waste by 74 million pounds per year and wastewater by 1.4 billion pounds per year.
I he development of new environmentally favorable routes for the production of chemical intermediates and
products is an area of considerable interest to the chemical processing industry. Recently, the use of chlorine
in large-scale chemical syntheses has come under intense scrutiny. Solutia, Inc. (formerly Monsanto Chemical
Company), one of the world's largest producers of chlorinated aromatics, has funded research over the years to
explore alternative synthetic reactions for manufacturing processes that do not require the use of chlorine. It was
clear that replacing chlorine in a process would require the discovery of new atom-efficient chemical reactions.
Ultimately, it was Monsanto's goal to incorporate fundamentally new chemical reactions into innovative processes
that would focus on the elimination of waste at the source. In view of these emerging requirements, Monsanto's
Rubber Chemicals Division (now flexsys), in collaboration with Monsanto Corporate Research, began to explore
new routes to a variety of aromatic amines that would not rely on the use of halogenated intermediates or reagents.
Of particular interest was the identification of novel synthetic strategies to 4-aminodiphenylamine (4-ADPA), a key
intermediate in the Rubber Chemicals family of antidegradants. The total world volume of antidegradants based on
4-ADPA and related materials is approximately 300 million pounds per year, of which flexsys is the world's largest
producer, (flexsys is a joint venture of the rubber chemicals operations of Monsanto and Akzo Nobel.)
flexsys's current process to 4-ADPA is based on the chlorination of benzene. Since none of the chlorine used in the
process ultimately resides in the final product, the pounds of waste generated in the process per pound of product
produced from the process are highly unfavorable. A significant portion of the waste is in the form of an aqueous
stream that contains high levels of inorganic salts contaminated with organics that are difficult and expensive to
treat, furthermore, the process also requires the storage and handling of large quantities of chlorine gas. flexsys
found a solution to this problem in a class of reactions known as nucleophilic aromatic substitution of hydrogen
(NASH). Through a series of experiments designed to probe the mechanism of NASH reactions, flexsys realized
a breakthrough in understanding this chemistry that has led to the development of a new process to 4-ADPA that
utilizes the base-promoted, direct coupling of aniline and nitrobenzene.
The environmental benefits of this process are significant and include a dramatic reduction in waste generated. In
comparison to the process traditionally used to synthesize 4-ADPA, the flexsys process generates 74 percent less
organic waste, 99 percent less inorganic waste, and 97 percent less wastewater. In global terms, if just
30 percent of the world's capacity to produce 4-ADPA and related materials were converted to the flexsys process,
74 million pounds less chemical waste would be generated per year and 1.4 billion pounds less wastewater would
be generated per year. The discovery of the new route to 4-ADPA and the elucidation of the mechanism of the
reaction between aniline and nitrobenzene have been recognized throughout the scientific community as a
breakthrough in the area of nucleophilic aromatic substitution chemistry.
This new process for the production of 4-ADPA has achieved the goal for which all green chemistry endeavors strive:
the elimination of waste at the source via the discovery of new chemical reactions that can be implemented into
innovative and environmentally safe chemical processes.
1998 Greener Synthetic Pathways Award 77
-------
Novel Membrane-Based Process for Producing Lactate Esters—
Nontoxic Replacements for Halogenated and Toxic Solvents
lnnff\.-Vif;..i; >;no j:v i ,..••. I i.hv
Argonne developed a novel process to synthesize organic solvents from sugars. These solvents can replace a wide
variety of more hazardous solvents, such as methylene chloride. Argonne's process requires little energy, is highly
efficient, eliminates large volumes of salt waste, and reduces pollution and emissions. These solvents can potentially
replace 7.6 billion pounds of toxic solvents used annually by industry, commerce, and households.
\rgonne National Laboratory (AND has developed a process based on selective membranes that permits low-
cost synthesis of high-purity ethyl lactate and other lactate esters from carbohydrate feedstock. The process
requires little energy input, is highly efficient and selective, and eliminates the large volumes of salt waste
produced by conventional processes. ANL's novel process uses pervaporation membranes and catalysts. In the
process, ammonium lactate is thermally and catalytically cracked to produce the acid, which, with the addition
of alcohol, is converted to the ester. The selective membranes pass the ammonia and water with high efficiency
while retaining the alcohol, acid, and ester. The ammonia is recovered and reused in the fermentation to make
ammonium lactate, eliminating the formation of waste salt. The innovation overcomes major technical hurdles
that had made current production processes for lactate esters technically and economically noncompetitive. The
innovation will enable the replacement of toxic solvents widely used by industry and consumers, expand the use
of renewable carbohydrate feedstocks, and reduce pollution and emissions.
Ethyl lactate has a good temperature performance range (boiling point: 309 °F, melting point: 104 °F), is
compatible with both aqueous and organic systems, is easily biodegradable, and has been approved for food by
the U.S. Food and Drug Administration (FDA). Lactate esters (primarily ethyl lactate) can replace most halogenated
solvents (including ozone-depleting chlorofluorocarbons (CFCs), carcinogenic methylene chloride, toxic ethylene
glycol ethers, perchloroethylene, and chloroform) on a 1:1 basis. At 1998 prices ($1.60-2.00 per pound), the
market for ethyl lactate is about 20 million pounds per year for a wide variety of specialty applications. The novel
and efficient ANL membrane process will reduce the selling price of ethyl lactate to $0.85-1.00 per pound and
enable ethyl lactate to compete directly with the petroleum-derived toxic solvents currently in use. The favorable
economics of the ANL membrane process, therefore, can lead to the widespread substitution of petroleum-
derived toxic solvents by ethyl lactate in electronics manufacturing, paints and coatings, textiles, cleaners and
degreasers, adhesives, printing, de-inking, and many other industrial, commercial, and household applications.
More than 80 percent of the applications requiring the use of more than 7.6 billion pounds of solvents in the
United States each year are suitable for reformulation with environmentally friendly lactate esters.
The ANL process has been patented for producing esters from all fermentation-derived organic acids and their
salts. Organic acids and their esters, at the purity achieved by this process, offer great potential as intermediates
for synthesizing polymers, biodegradable plastics, oxygenated chemicals (e.g., propylene glycol and acrylic acid),
and specialty products. By improving purity and lowering costs, the ANL process promises to make fermentation-
derived organic acids an economically viable alternative to many chemicals and products derived from petroleum
feedstocks.
A U.S. patent on this technology has been allowed, and international patents have been filed. NTEC, Inc. has
licensed the technology for lactate esters and provided the resources for a pilot-scale demonstration of the
integrated process at ANL. The pilot-scale demonstration has produced a high-purity ethyl lactate product that
meets or exceeds all the process performance objectives. A 10-million-pound-per-year demonstration plant is
being planned for early 1999, followed by a 100-million-pound-per-year, full-scale plant.
78 1998 Greener Reaction Conditions Award
-------
Invention and Commercialization of a New Chemical Family of Insecticides Exemplified by CONFIRM™ Selective
Caterpillar Control Agent and the Related Selective Insect Control Agents MACH 2™ and INTREPID™
Rohm and Haas developed CONFIRM™, a novel insecticide for controlling caterpillar pests in turf and a variety of
crops. CONFIRM™ is less toxic than other insecticides to a wide range of nontarget organisms, poses no significant
hazard to farm workers or the food chain, and does not present a significant spill hazard. EPA has classified
CONFIRM™ as a reduced-risk pesticide.
\ he value of crops destroyed worldwide by insects exceeds tens of billions of dollars. Over the past fifty years,
only a handful of classes of insecticides have been discovered to combat this destruction. Rohm and Haas
Company has discovered a new class of chemistry, the diacylhydrazines, that offers farmers, consumers, and
society a safer, effective technology for insect control in turf and a variety of agronomic crops. One member of
this family, CONFIRM™, is a breakthrough in caterpillar control. It is chemically, biologically, and mechanistically
novel. It effectively and selectively controls important caterpillar pests in agriculture without posing significant
risk to the applicator, the consumer, or the ecosystem. It will replace many older, less effective, more hazardous
insecticides and has been classified by EPA as a reduced-risk pesticide.
CONFIRM™ controls target insects through an entirely new mode of action that is inherently safer than current
insecticides. The product acts by strongly mimicking a natural substance found within the insect's body called
20-hydroxy ecdysone, which is the natural "trigger" that induces molting and regulates development in insects.
Because of this "ecdy-sonoid" mode of action, CONFIRM™ powerfully disrupts the molting process in target
insects, causing them to stop feeding shortly after exposure and to die soon thereafter.
Since 20-hydroxy ecdysone neither occurs nor has any biological function in most nonarthropods, CONFIRM™
is inherently safer than other insecticides to a wide range of nontarget organisms such as mammals, birds,
earthworms, plants, and various aquatic organisms. CONFIRM™ is also remarkably safe to a wide range of
key beneficial, predatory, and parasitic insects such as honeybees, lady beetles, parasitic wasps, predatory
bugs, beetles, flies, and lacewings, as well as other predatory arthropods such as spiders and predatory mites.
Because of this unusual level of safety, the use of these products will not create an outbreak of target or
secondary pests due to destruction of key natural predators or parasites in the local ecosystem. This should
reduce the need for repeat applications of additional insecticides and reduce the overall chemical load on both
the target crop and the local environment.
CONFIRM™ has lowtoxicity to mammals by ingestion, inhalation, and topical application and has been shown
to be completely non-oncogenic, nonmutagenic, and without adverse reproductive effects. Because of its high
apparent safety and relatively low use rates, CONFIRM™ poses no significant hazard to the applicator or the
food chain and does not present a significant spill hazard. CONFIRM™ has proven to be an outstanding tool for
control of caterpillar pests in many integrated pest management (IPM) and resistance management situations.
All of these attributes make CONFIRM™ among the safest, most selective, and most useful insect control
agents ever discovered.
1998 Designing Greener Chemicals Award 79
-------
1997 Winners
Design and Application of Surfactants for Carbon Dioxide
Professor DeSimone developed new detergents that allow carbon dioxide (CO2), a nontoxic gas, to be used as a
solvent in many industrial applications. Using CO2 as a solvent allows manufacturers to replace traditional, often
hazardous chemical solvents and processes, conserve energy, and reduce worker exposure to hazardous substances.
It has been a dilemma of modern industrial technology that the solvents required to dissolve the environment's
worst contaminants themselves have a contaminating effect. Now, new technologies for the design and
application of surfactants for carbon dioxide (CO2), developed at UNC, promise to resolve this dilemma.
Over 30 billion pounds of organic and halogenated solvents are used worldwide each year as solvents,
processing aids, cleaning agents, and dispersants. Solvent-intensive industries are considering alternatives
that can reduce or eliminate the negative impact that solvent emissions can have in the workplace and in the
environment. CO2 in a solution state has long been recognized as an ideal solvent, extractant, and separation
aid. CO2 solutions are nontoxic, nonflammable, energy-efficient, cost-effective, waste-minimizing, reusable, and
safe to work with. Historically, the prime factor inhibiting the use of this solvent replacement has been the low
solubility of most materials in CO2, in both its liquid and supercritical states. With the discovery of CO2 surfactant
systems, Professor Joseph M. DeSimone and his students have dramatically advanced the solubility performance
characteristics of CO2 systems for several industries.
The design of broadly applicable surfactants for CO2 relies on the identification of "CO2-philic" materials from
which to build amphiphiles. Although CO2 in both its liquid and supercritical states dissolves many small
molecules readily, it is a very poor solvent for many substances at easily accessible conditions (T< 212 °F and
P< 4,350 psi). As an offshoot of Professor DeSimone's research program on polymer synthesis in CO2, he and
his researchers exploited the high solubility of a select few CO2-philic polymeric segments to develop nonionic
surfactants capable of dispersing high-solids polymer latexes in both liquid and supercritical CO2 phases. The
design criteria they developed for surfactants, which were capable of stabilizing heterogeneous polymerizations
in CO2, have been expanded to include CO2-insoluble compounds in general.
This development lays the foundation by which surfactant-modified CO2can be used to replace conventional
(halogenated) organic solvent systems currently used in manufacturing and service industries such as precision
cleaning, medical device fabrication, and garment care, as well as in the chemical manufacturing and coating
industries.
1997 Academic Award
-------
Coldstrip™, A Revolutionary Organic Removal and Wet Cleaning Technology
During manufacture, silicon-based semiconductors and flat-panel displays require cleaning to remove manufacturing
residues, usually with corrosive acid solutions. Legacy Systems developed the Coldstrip™ process, which uses only
water and oxygen to clean silicon semiconductors. Coldstrip™ has the potential to cut the use of corrosive solutions by
hundreds of thousands of gallons and also save millions of gallons of water each year.
I or over 30 years, the removal of photoresists with Piranha solutions (sulfuric acid, hydrogen peroxide, or
ashers) has been the standard in the semiconductor, flat panel display, and micromachining industries. Use of
Piranha solutions has been associated with atmospheric, ground, and water pollution. Legacy Systems, Inc. (LSI)
has developed a revolutionary wet processing technology, Coldstrip™, which removes photoresist and organic
contaminants for the semiconductor, flat panel display, and micromachining industries.
LSI's Coldstrip™ process is a chilled-ozone process that uses only oxygen and water as raw materials. The active
product is ozone, which safely decomposes to oxygen in the presence of photoresist. Carbon dioxide, carbon
monoxide, oxygen, and water are formed. There are no high temperatures, no hydrogen peroxide, and no nitric
acid, all of which cause environmental issues.
The equipment required for the chilled-ozone process consists of a gas diffuser, an ozone generator, a
recirculating pump, a water chiller, and a process vessel. The water solution remains clear and colorless
throughout the entire process sequence. There are no particles or resist flakes shed from the wafer into the
water,- therefore, there are no requirements for particle filtration.
Using oxygen and water as raw materials replacing the Piranha solutions significantly benefits the environment.
One benefit is the elimination of over 8,400 gallons of Piranha solutions used per year per silicon wet station
and over 25,200 gallons used per year per flat panel display station. Additionally, the overall water consumption
is reduced by over 3,355,800 gallons per year per silicon wafer wet station and over 5,033,700 gallons per year
per flat panel display station. The corresponding water consumption in LSI's process is 4,200 gallons per year and
there is no Piranha use.
In 1995, the U.S. Patent Office granted LSI Patent 5,464,480 covering this technology. The system has the lowest
environmental impact of any wet-resist-strip process, eliminating the need for thousands of gallons of Piranha
chemicals and millions of gallons of water a year.
1997 Small Business Award 81
-------
BHC Company Ibuprofen Process
BHC Company developed an efficient method to make ibuprofen, a commonly used painkiller, using only three
steps instead of six. BHC recovers and recycles the waste byproduct from the manufacturing process and has virtually
eliminated large volumes of aqueous salt wastes. BASF Corporation, one of the BHC partners, uses this process in one
of the largest ibuprofen production plants in the world.
HHC Company has developed a new synthetic process to manufacture ibuprofen, a well-known nonsteroidal
anti-inflammatory painkiller marketed under brand names such as Advil™ and Motrin™. Commercialized since
1992 in BHC's 7.7-million-pound-per-year facility in Bishop, TX, the new process has been cited as an industry
model of environmental excellence in chemical processing technology. For its innovation, BHC was the recipient
of the Kirkpatrick Achievement Award for "outstanding advances in chemical engineering technology" in 1993.
The new technology involves only three catalytic steps with approximately 80 percent atom utilization (virtually
99 percent including the recovered byproduct acetic acid) and replaces technology with six stoichiometric steps
and less than 40 percent atom utilization. The use of anhydrous hydrogen fluoride as both catalyst and solvent
offers important advantages in reaction selectivity and waste reduction. As such, this chemistry is a model of
source reduction, the method of waste minimization that tops EPA's waste management hierarchy. Virtually
all starting materials are either converted to product or reclaimed byproduct or are completely recovered and
recycled in the process. The generation of waste is practically eliminated.
The BHC ibuprofen process is an innovative, efficient technology that has revolutionized bulk pharmaceutical
manufacturing. The process provides an elegant solution to a prevalent problem encountered in bulk
pharmaceutical synthesis (i.e., how to avoid the large quantities of solvents and wastes associated with the
traditional stoichiometric use of auxiliary chemicals for chemical conversions). Large volumes of aqueous wastes
(salts) normally associated with such manufacturing are virtually eliminated. The anhydrous hydrogen fluoride
catalyst/solvent is recovered and recycled with greater than 99.9 percent efficiency. No other solvent is needed in
the process, simplifying product recovery and minimizing fugitive emissions. The nearly complete atom utilization
of this streamlined process truly makes it a waste-minimizing, environmentally friendly technology.
82 1997 Greener Synthetic Pathways Award
-------
DryView™ Imaging Systems
Imation's DryView™ Imaging Systems use a new type of photographic film for medical imaging that uses heat instead
of hazardous developer chemicals. During 1996, Imation delivered more than 1,500 DryView™ Imaging Systems
worldwide. These units alone eliminate the annual disposal of over half a million gallons of developer chemicals and
54.5 million gallons of contaminated water and reduce workers' exposure to chemicals.
i hotothermography is an imaging technology whereby a latent image, created by exposing a sensitized
emulsion to appropriate light energy, is processed by the application of thermal energy. Photothermographic
films are easily imaged by laser diode imaging systems, with the resultant exposed film processed by passing it
over a heat roll. A heat roll operating at 250 °F in contact with the film will produce diagnostic-quality images in
approximately 15 seconds. Based on photothermography technology, Imation's DryView™ Imaging Systems use
no wet chemistry, create no effluent, and require no additional postprocess steps such as drying.
In contrast, silver halide photographic films are processed by being bathed in a chemical developer, soaked in a
fix solution, washed with clean water, and finally dried. The developer and fix solutions contain toxic chemicals
such as hydroquinone, silver, and acetic acid. In the wash cycle, these chemicals, along with silver compounds,
are flushed from the film and become part of the waste stream. The resulting effluent amounts to billions of
gallons of liquid waste each year.
Significant developments in photothermographic image quality have been achieved that allow it to compete
successfully with silver halide technology. During 1996, Imation placed more than 1,500 DryView™ medical laser
imagers, which represent 6 percent of the world's installed base. These units alone have eliminated the annual
disposal of 192,000 gallons of developer, 330,000 gallons of fixer, and 54.5 million gallons of contaminated water
into the waste stream. As future systems are placed, the reductions will be even more dramatic.
DryView™ technology is applicable to all industries that process panchromatic film products. The largest of these
industries are medical radiography, printing, industrial radiography, and military reconnaissance. DryView™ is
valued by these industries because it supports pollution prevention through source reduction.
1997 Greener Reaction Conditions Award 83
-------
THPS Biocides: A New Class of Antimicrobial Chemistry
Albright & Wilson discovered the antimicrobial properties of THPS and developed it into a safer biocide that can
be used to control the growth of bacteria and algae in industrial water systems. THPS, or tetrakis(hydroxymethyl)
phosphonium sulfate, offers many advantages over other, traditional biocides because, for example, it is significantly
less toxic to nontarget organisms, is effective at much lower concentrations, and is more biodegradable than other
biocides.
Lonventional biocides used to control the growth of bacteria, algae, and fungi in industrial cooling systems, oil
fields, and process applications are highly toxic to humans and aquatic life and often persist in the environment,
leading to long-term damage. To address this problem, a new and relatively benign class of biocides, tetrakis
(hydroxymethyl)phosphonium sulfate (THPS), has been discovered by Albright & Wilson Americas. THPS biocides
represent a completely new class of antimicrobial chemistry that combines superior antimicrobial activity with
a relatively benign toxicology profile. THPS's benefits include low toxicity, low recommended treatment level,
rapid breakdown in the environment, and no bioaccumulation. When substituted for more toxic biocides, THPS
biocides provide reduced risks to both human health and the environment.
THPS is so effective as a biocide that, in most cases, the recommended treatment level is below that which
would be toxic to fish. In addition, THPS rapidly breaks down in the environment through hydrolysis, oxidation,
photodegradation, and biodegradation. In many cases, it has already substantially broken down before the
treated water enters the environment. The degradation products have been shown to possess a relatively benign
toxicology profile, furthermore, THPS does not bioaccumulate and, therefore, offers a much-reduced risk to
higher life forms.
THPS biocides are aqueous solutions and do not contain volatile organic compounds (VOCs). Because THPS is
halogen-free, it does not contribute to the formation of dioxin or absorbable organic halides (AOX). Because of its
low overall toxicity and easier handling compared to alternative products, THPS provides an opportunity to reduce
the risk of health and safety incidents.
THPS has been applied to a range of industrial water systems for the successful control of microorganisms.
The U.S. industrial water treatment market for nonoxidizing biocides alone is 42 million pounds per year and
growing at 6-8 percent annually. There are over 500,000 individual user sites in this industry category. Because
of its excellent environmental profile, THPS has already been approved for use in environmentally sensitive areas
around the world and is being used as a replacement for higher risk alternatives.
84 1997 Designing Greener Chemicals Award
-------
1996 Winners
Conversion of Waste Biomassto Animal Feed, Chemicals, and Fuels
Professor Holtzapple developed a family of technologies that convert waste biomass, such as sewage sludge and
agricultural wastes, into animal feed products, industrial chemicals, or fuels, depending on the technology used.
Because these technologies convert waste biomass into useful products, other types of basic resources, such as
petroleum, can be conserved. Also, the technologies can reduce the amount of biomass waste going to landfills or
incinerators.
\ family of technologies has been developed by Professor Mark Holzapple at Texas A&M University that converts
waste biomass into animal feed, industrial chemicals, and fuels. Waste biomass includes such resources as
municipal solid waste, sewage sludge, manure, and agricultural residues. Waste biomass is treated with lime to
improve digestibility. Lime-treated agricultural residues (e.g., straw, stover, and bagasse) may be used as ruminant
animal feeds. Alternatively, the lime-treated biomass can be fed into a large anaerobic fermentor in which rumen
microorganisms convert the biomass into volatile fatty acid (VFA) salts, such as calcium acetate, propionate, and
butyrate. The VFA salts are concentrated and may be converted into chemicals or fuels via three routes. In one
route, the VFA salts are acidified, releasing acetic, propionic, and butyric acids. In a second route, the VFA salts are
thermally converted to ketones, such as acetone, methyl ethyl ketone, and diethyl ketone. In a third route, the
ketones are hydrogenated to their corresponding alcohols such as isopropanol, isobutanol, and isopentanol.
The technologies above offer many benefits for human health and the environment. Lime-treated animal feed
can replace feed corn, which is approximately 88 percent of corn production. Growing corn exacerbates soil
erosion and requires intensive inputs of fertilizers, herbicides, and pesticides, all of which contaminate ground
water.
Chemicals (e.g., organic acids and ketones) may be produced economically from waste biomass. Typically, waste
biomass is landfilled or incinerated, which incurs a disposal cost and contributes to land or air pollution. Through
the production of chemicals from biomass, non-renewable resources, such as petroleum and natural gas, are
conserved for later generations. Because 50 percent of U.S. petroleum consumption is now imported, displacing
foreign oil will help reduce the U.S. trade deficit.
Fuels (e.g., alcohols) produced from waste biomass have the benefits cited above (i.e., reduced environmental
impact from waste disposal and reduced trade deficit). In addition, oxygenated fuels derived from biomass are
cleaner-burning and do not add net carbon dioxide to the environment, thereby reducing factors that contribute
to global warming.
1996 Academic Award 85
-------
Production and Use of Thermal Polyaspartic Acid
Donlar developed TPA, a nontoxic, environmentally safe, biodegradable polymer for use in agriculture, water treatment,
and other industries. Donlar manufactures TPA using a highly efficient process that eliminates use of organic solvents,
cuts waste, and uses less energy. TPA has been used successfully in a variety of applications, such as improving
fertilizer uptake in plants, and improving the efficiency of oil and gas production.
'• 'illions of pounds of anionic polymers are used each year in many industrial applications. Polyacrylic acid (PAC)
is one important class of such polymers, but the disposal of PAC is problematic because it is not biodegradable.
An economically viable, effective, and biodegradable alternative to PAC is thermal polyaspartate (TPA).
Donlar Corporation invented two highly efficient processes to manufacture TPA for which patents have either
been granted or allowed. The first process involves a dry and solid polymerization converting aspartic acid to
polysuccinimide. No organic solvents are involved during the conversion and the only byproduct is water. The
process is extremely efficient—a yield of more than 97 percent of polysuccinimide is routinely achieved. The
second step in this process, the base hydrolysis of polysuccinimide to polyaspartate, is also extremely efficient
and waste-free.
The second TPA production process involves using a catalyst during the polymerization, which allows a lower
heating temperature to be used. The resulting product has improvements in performance characteristics, lower
color, and biodegradability. The catalyst can be recovered from the process, thus minimizing waste.
Independent toxicity studies of commercially produced TPA have been conducted using mammalian and
environmental models. Results indicate that TPA is nontoxic and environmentally safe. TPA biodegradability
has also been tested by an independent lab using established Organization for Economic Cooperation and
Development (OECD) methodology. Results indicate that TPA meets OECD guidelines for Intrinsic Biodegradability.
PAC cannot be classified as biodegradable when tested under these same conditions.
Many end-uses of TPA have been discovered, such as in agriculture to improve fertilizer or nutrient management.
TPA increases the efficiency of plant nutrient uptake, thereby increasing crop yields while protecting the ecology
of agricultural lands. TPA can also be used for water treatment, as well as in the detergent, oil, and gas industries.
86 1996 Small Business Award
-------
Catalytic Dehydrogenation of Diethanolamine
DSIDA is a key building block for the herbicide RoundUp®. Monsanto's novel synthesis of DSIDA eliminates most of
the manufacturing hazards associated with the previous synthesis; it uses no ammonia, cyanide, or formaldehyde. This
synthesis is safer to operate, has a higher overall yield, and has fewer process steps.
Uisodium iminodiacetate (DSIDA) is a key intermediate in the production of Monsanto's Roundup® herbicide,
an environmentally friendly, nonselective herbicide. Traditionally, Monsanto and others have manufactured
DSIDA using the Strecker process requiring ammonia, formaldehyde, hydrochloric acid, and hydrogen cyanide.
Hydrogen cyanide is acutely toxic and requires special handling to minimize risk to workers, the community,
and the environment, furthermore, the chemistry involves the exothermic generation of potentially unstable
intermediates, and special care must be taken to preclude the possibility of a runaway reaction. The overall
process also generates up to 1 pound of waste for every 7 pounds of product, and this waste must be treated
prior to safe disposal.
Monsanto has developed and implemented an alternative DSIDA process that relies on the copper-catalyzed
dehydrogenation of diethanolamine. The raw materials have low volatility and are less toxic. Process operation
is inherently safer, because the dehydrogenation reaction is endothermic and, therefore, does not present the
danger of a runaway reaction. Moreover, this zero-waste route to DSIDA produces a product stream that, after
filtration of the catalyst, is of such high quality that no purification or waste cut is necessary for subsequent use in
the manufacture of Roundup®. The new technology represents a major breakthrough in the production of DSIDA,
because it avoids the use of cyanide and formaldehyde, is safer to operate, produces higher overall yield, and has
fewer process steps.
The metal-catalyzed conversion of amino-alcohols to amino acid salts has been known since 1945. Commercial
application, however, was not known until Monsanto developed a series of proprietary catalysts that made the
chemistry commercially feasible. Monsanto's patented improvements on metallic copper catalysts afford an
active, easily recoverable, highly selective, and physically durable catalyst that has proven itself in large-scale use.
This catalysis technology also can be used in the production of other amino acids, such as glycine. Moreover, it
is a general method for conversion of primary alcohols to carboxylic acid salts; it is potentially applicable to the
preparation of many other agricultural, commodity, specialty, and pharmaceutical chemicals.
1996 Greener Synthetic Pathways Award 87
-------
100 Percent Carbon Dioxide as a Blowing Agent for the Polystyrene Foam Sheet Packaging Market
Dow developed a process for manufacturing polystyrene foam sheets that uses carbon dioxide (CO ) as a blowing
agent, eliminating 3.5 million pounds per year of traditional blowing agents. Traditional blowing agents deplete the
ozone layer or contribute to ground-level smog. In addition, Dow will obtain CO2 only from existing commercial and
natural sources that generate it as a byproduct, so this process will not contribute to global CO2 levels.
In recent years the chlorofluorocarbon (CFC) blowing agents used to manufacture polystyrene foam sheet have
been associated with environmental concerns such as ozone depletion, global warming, and ground-level smog.
Due to these environmental concerns, The Dow Chemical Company has developed a novel process for the
use of 100 percent carbon dioxide (CO2). Polystyrene foam sheet is a useful packaging material offering a high
stiffness-to-weight ratio, good thermal insulation value, moisture resistance, and recyclability. This combination of
desirable properties has resulted in the growth of the polystyrene foam sheet market in the United States to over
700 million pounds in 1995. Current applications for polystyrene foam include thermoformed meat, poultry, and
produce trays; fast food containers; egg cartons; and serviceware.
The use of 100 percent CO2 offers optimal environmental performance because CO2 does not deplete the
ozone layer, does not contribute to ground-level smog, and will not contribute to global warming because CO2
will be used from existing byproduct commercial and natural sources. The use of CO2 byproduct from existing
commercial and natural sources, such as ammonia plants and natural gas wells, will ensure that no net increase in
global CO2 results from the use of this technology. CO2 is also nonflammable, providing increased worker safety. It
is cost-effective and readily available in food-grade quality. CO2 also is used in such common applications as soft
drink carbonation and food chilling and freezing.
The Dow 100 percent CO2 technology eliminates the use of 3.5 million pounds per year of hard CFC-12 and soft
HCFC-22. This technology has been scaled from pilot-line to full-scale commercial facilities. Dow has made the
technology available through a commercial license covering both patented and know-how technology. The U.S.
Patent Office granted Dow two patents for this technology (5,250,577 and 5,266,605).
1996 Greener Reaction Conditions Award
-------
Designing an Environmentally Safe Marine Antifoulant
!nns;\,;•;)(;•!'; .;nr'' !:Y:n::l ihv
Rohm and Haas developed Sea-Nine™, a novel antifoulant to control the growth of plants and animals on the hulls of
ships. In 1995, fouling cost the shipping industry approximately $3 billion a year in increased fuel consumption. Sea-
Nine™ replaces environmentally persistent and toxic tin-containing antifoulants.
I ouling, the unwanted growth of plants and animals on a ship's surface, costs the shipping industry
approximately $3 billion a year, largely due to increased fuel consumption to overcome hydrodynamic drag.
Increased fuel consumption contributes to pollution, global warming, and acid rain.
The main compounds used worldwide to control fouling are the organotin antifoulants, such as tributyltin
oxide (TBTO). While effective, they persist in the environment and cause toxic effects, including acute toxicity,
bioaccumulation, decreased reproductive viability, and increased shell thickness in shellfish. These harmful
effects led to an EPA special review and to the Organotin Antifoulant Paint Control Act of 1988. This act mandated
restrictions on the use of tin in the United States, and charged EPA and the U.S. Navy with conducting research on
alternatives to organotins.
Rohm and Haas Company searched for an environmentally safe alternative to organotin compounds. Compounds
from the 3-isothiazolone class were chosen as likely candidates and over 140 were screened for antifouling
activity. The 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one (Sea-Nine™ antifoulant) was chosen as the candidate for
commercial development.
Extensive environmental testing compared Sea-Nine™ antifoulant to TBTO, the current industry standard. Sea-
Nine™ antifoulant degraded extremely rapidly with a half-life of one day in seawater and one hour in sediment.
Tin had bioaccumulation factors as high as 10,000-fold, whereas Sea-Nine™ antifoulant's bioaccumulation was
essentially zero. Both TBTO and Sea-Nine™ were acutely toxic to marine organisms, but TBTO had widespread
chronic toxicity, whereas Sea-Nine™ antifoulant showed no chronic toxicity. Thus, the maximum allowable
environmental concentration (MAEC) for Sea-Nine™ antifoulant was 0.63 parts per billion (ppb) whereas the
MAEC for TBTO was 0.002 ppb.
Hundreds of ships have been painted with coatings containing Sea-Nine™ worldwide. Rohm and Haas Company
obtained EPA registration for the use of Sea-Nine™ antifoulant, the first new antifoulant registration in over a
decade.
1996 Designing Greener Chemicals Award
-------
Additional information on the Presidential Green Chemistry Challenge program is available from:
• The Green Chemistry Web site at
http://www.epa.gov/greenchemistryand
• The Industrial Chemistry Branch of EPA by e-mail at greenchemistry@epa.gov or by telephone at 202-564-8740.
Note: The summaries provided in this document were obtained from the entries received for the 1996-2009
Presidential Green Chemistry Challenge Awards. They were edited for space, stylistic consistency, and clarity,
but they were neither written nor officially endorsed by EPA. These summaries represent only a fraction of the
information that was provided in the entries received and, as such, are intended to highlight the nominated
projects, not describe them fully. These summaries were not used in the judging process; judging was conducted
on all information contained in the entries.
90
-------
AgraQuest, Inc., 50
Albright & Wilson Americas (now Rhodia), 84
Archer Daniels Midland Company (ADM), 40, 43
Argonne National Laboratory (AND, 78
Arkon Consultants, 34
Ashland Inc, 30
BASF Corporation, 15, 42, 48, 82
Battelle, 25
Bayer AC, 61, 67
Bayer Corporation, 61, 67
Beckman, EricJ., 54
BHC Company (now BASF Corporation), 82
BioAmber, Inc., 9
Biofine, Inc., (now BioMetics, Inc.), 70
BioMetics, Inc., 70
Bristol-Myers Squibb Company (BMS), 46
Buckman International, Inc. 7
Buckman Laboratories International, Inc., 47
Cargill Dow LLC (now NatureWorks LLC), 57
Cargill, Incorporated, 32
Carnegie Mellon University, 18, 69
CEM Corporation, 21
Chemical Specialties, Inc. (CSI) (nowViance), 58
Clarke, 17
Coates, Geoffrey W., 2
Codexis, Inc., 5, 16, 36
Collins, Terry, 69
Columbia Forest Products, 30
Cornell University, 2
Cook Composites and Polymers Company, 22
Cytec Industries Inc. 6
DeSimone, Joseph M., 80
Donlar Corporation (now NanoChem Solutions, Inc.!
Dow AgroSciences LLC, 27, 68, 73
Dow Chemical Company, The, 15, 79, 88, 89
Draths, Karen M., 75
DuPont, 51
Easel Biotechnologies, LLC, 13
Eastman Chemical Company, 20
Eastman Kodak Company, 34, 83
Eckert, Charles A., 44
EDEN Bioscience Corporation, 60
Elevance Renewable Sciences, Inc. 4
Engelhard Corporation (now BASF Corporation), 48
Flexsys America L.P., 77
Frost, John W., 75
Genomatica, 10
Georgia Institute of Technology, 44
Gross, Richard A., 49
Headwaters Technology Innovation, 31
Hedrick, James L, 3
Hercules Incorporated (now Ashland Inc.), 30
Holtzapple, Mark, 85
IBM Aim ad en Research Center, 3
Imation, 83
Jeneil Biosurfactant Company, 45
Kraton Performance Polymers, Inc., 11
Krische, Michael J., 28
Legacy Systems, Inc.(LSI), 81
Li, Chao-Jun, 59
Li, Kaichang, 30
Liao, James C, 13
Lilly Research Laboratories, 71
Liotta, Charles L., 44
Lipshutz, Bruce H., 8
LS9, Inc. 14
Maleczka, Robert E., Jr., 23
Matyjaszewski, Krzysztof, 18
Merck & Co, Inc., 16, 35, 41
Metabolix, Inc., 39
Michigan State University, 23, 75
Monsanto Company, 87
Nalco Company, 26, 73
NanoChem Solutions, Inc., 86
NatureWorks LLC, 57
North Carolina State University (NCSU), 80
NovaSterilis Inc., 29
Novozymes, 40
Novozymes North America, Inc., 62
NuPro Technologies, Inc. (now Eastman Kodak Company), 34
Oregon State University, 30
Pfizer, Inc., 56
Polytechnic University, 49
PPG Industries, 63
Procter & Gamble Company, The, 22
PYROCOOL Technologies, Inc., 76
Index 91
-------
RevTech, Inc., 65
Rhodia, 84
Roche Colorado Corporation, 66
Rogers, Robin D., 38
Rohm and Haas Company (nowThe Dow Chemical
Company), 79, 89
SC Fluids, Inc., 55
S.C.Johnson &Son, Inc., 31Scripps Research
Institute, The, 64
Shaw Industries, Inc. 53
The Sherwin-Williams Company, 12
SiGNa Chemistry, Inc., 24
Smith, Milton R., Ill, 23
Stanford University, 3, 74
Sud-Chemie Inc., 51
Suppes, Galen J., 33
Tang, Yi, 5
Texas A&M University, 85
Trost, Barry M., 73
Tulane University, 59
University of Alabama, The, 37
University of California, Los Angeles, 5, 13
University of California, Santa Barbara, 8
University of Missouri-Columbia, 33
University of North Carolina at Chapel Hill (UNO, 80
University of Pittsburgh, 54
University of Texas at Austin, 28
Viance, 58
Virent Energy Systems, Inc., 19
Waymouth, Robert M. 3
Wong, Chi-Huey, 64
Index 92
-------
-------
-------
Office of Pollution 744F12001
Prevention and June 2012
Toxics (7406M) www.epa.gov
------- |