United States
Environmental Protection

United States                                   744F08008
Environmental Protection                          June 2008
Agency                      www.epa.gov/greenchemistry
Office of Pollution Prevention and Toxics (7406M)

The Presidential
Green Chemistry Challenge
Award Recipients


2008 Winners
  Academic Award:
      Professors Robert E. Maleczkajr. and
      Milton R. Smith, III,
        Michigan State University ............................................. 2
  Small Business Award:
      SlGNa Chemistry, Inc. [[[ 4
  Greener Synthetic Pathways Award:
      Battelle [[[ 6
  Greener Reaction Conditions Award:
      'Nalco Company [[[ 8
  Designing Greener Chemicals Award:
      Dow AgroSciences LLC [[[ 10

2007 Winners
  Academic Award:
      Professor Michael J. Krische,
        University of Texas at Austin ....................................... 12
  Small Business Award:
      NovaSterilis Inc. [[[ 74
  Greener Synthetic Pathways Award:

        2006 Winners
         Academic Award:
             Professor Galen J. Suppes,
                University of Missouri-Columbia	22
         Small Business Award:
             Arkon Consultants, NuPro Technologies, Inc.  	24
         Greener Synthetic Pathways Award-.
             Merck & Co., Inc.  	26
         Greener Reaction Conditions Award:
             Codexls, Inc. 	28
         Designing Greener Chemicals Award:
             S.C. Johnson & Son, Inc. 	JO

        2005 Winners
         Academic Award:
             Professor Robin D. Rogers,
                The University of Alabama 	32
         Small Business Award:
             Metabolix, Inc.  	34
         Greener Synthetic Pathways Awards:
             Archer Daniels Midland Company, Novozymes 	36
             Merck & Co., Inc.  	38
         Greener Reaction Conditions Award:
             BASF Corporation 	40
         Designing Greener Chemicals Award:
             Archer Daniels Midland Company	42

        2004 Winnets
         Academic Award:
             Professors Charles A. Eckert and Charles L Liotta,
                Georgia Institute ofTechnology	44
         Small Business Award:
             Jeneil Biosurfactant Company	46
         Greener Synthetic Pathways Award:
             Bristol-Myers Squibb Company	48

iv  Contents

  Greener Reaction Conditions Award:
      Buck/nan Laboratories International, Inc. 	50
  Designing Greener Chemicals Award:
      Engelhard Corporation (now BASF Corporation) 	52

?00:i VYinncis
  Academic Award:
      Professor Richard A. Gross,
        Polytechnic University	54
  Small Business Award:
      AgraQuest, Inc.  	56
  Greener Synthetic Pathways Award:
      Sud-Chemle Inc.	58
  Greener Reaction Conditions Award:
      DuPont	60
  Designing Greener Chemicals Award:
      Shaw Industries, Inc.	62

"002 dinners
  Academic Award:
      Professor Eric]. Beckman,
        University of Pittsburgh  	64
  Small Business Award:
      SC Fluids, Inc. 	66
  Greener Synthetic Pathways Award:
      Pfizer, Inc. 	68
  Greener Reaction Conditions Award:
      Cargill Dow LLC (nowNatureWorks LLC) 	70
  Designing Greener Chemicals Award:
      Chemical Specialties, Inc. (nowViance)	72
                                                     Contents  v

        2001  Winners
         Academic Award:
             Professor Chao-JunLi,
                Tulane University	74
         Small Business Award:
             EDEN Bioscience Corporation	76
         Greener Synthetic Pathways Award-.
             Bayer Corporation, Bayer AC 	78
         Greener Reaction Conditions Award:
             Novozymes North America, Inc. 	80
         Designing Greener Chemicals Award:
             PPG Industries	82

        2000 Winners
         Academic Award:
             Professor Chi-Huey Wong,
                The Scrlpps Research Institute	84
         Small Business Award:
             RevTech, Inc. 	86
         Greener Synthetic Pathways Award:
             Roche Colorado Corporation 	88
         Greener Reaction Conditions Award:
             Bayer Corporation, Bayer AC 	90
         Designing Greener Chemicals Award:
             DowAgroSclencesLLC	92

        1999  Winners
         Academic Award:
             Professor Terry Collins,
                Carnegie Mellon University	94
         Small Business Award:
             Biofine, Inc. (nowBioMetics, Inc.)  	96
         Greener Synthetic Pathways Award:
             Lilly Research Laboratories	98
vi  Contents

  Greener Reaction Conditions Award:
      Nalco Chemical Company	 700
  Designing Greener Chemicals Award:
      DowAgroSciencesLLC	 70?

1998 Winners
  Academic Awards:
      Professor Barry M. Frost
        Stanford University	 704
      Dr. Karen M. Draths and Professor John W. Frost,
        Michigan State University	 706
  Small Business Award:
      PYROCOOL Technologies, Inc.  	 108
  Greener Synthetic Pathways Award:
      FlexsysAmerica L.P.  	770
  Greener Reaction Conditions Award:
      Argonne National Laboratory	772
  Designing Greener Chemicals Award:
      Rohm and Haas Company	774

1997 \\inners
  Academic Award:
      Professor Joseph M. DeSimone,
        University of North Carolina at Chapel Hill and
        North  Carolina State University	776
  Small Business Award:
      Legacy Systems, Inc.  	118
  Greener Synthetic Pathways Award:
      BHC Company (now BASF Corporation) 	 720
  Greener Reaction Conditions Award:
      Imation	 722
  Designing Greener Chemicals Award:
      Albright & Wilson Americas (now Rhodia)	724
                                                    Contents  vii

        1996 Winners
          Academic Award:
              Professor Mark Holtzapple,
                TexasA&M University  	 126
          Small Business Award:
              Donlar Corporation (nowNanoChem
                Solutions, Inc.) 	 728
          Greener Synthetic Pathways Award:
              Monsanto Company  	 130
          Greener Reaction Conditions Award:
              The Dow Chemical Company	 132
          Designing Greener Chemicals Award:
              Rohm and Haas Company	 134
        Proorarn Information 	

viii  Contents

The Presidential Green Chemistry Challenge Awards Program is an opportunity for
individuals, groups, and organizations to compete for annual awards in recognition of
innovations in cleaner, cheaper, smarter chemistry. The Program provides national
recognition for outstanding chemical technologies that incorporate the principles of green
chemistry into chemical design, manufacture, and use. In addition, winning technologies
have been or can be used by industry to achieve its pollution prevention goals. The U.S.
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 feed-
 stocks (e.g., biomass, natural oils); novel reagents or catalysts including biocatalysts
 and microorganisms; natural processes including fermentation and biomimetic
 syntheses; atom-economical syntheses; or 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; or 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,- or chemicals safer for the atmosphere (e.g., do
 not deplete ozone or form smog)

                               Award Winners
This booklet presents the 1996 through 2008 Presidential Green Chemistry Challenge
Award recipients and describes their award-winning technologies. Each winner demon-
stratesa 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.

                            Environmental  Results
Collectively, these award-winning technologies have:
•  Eliminated morethan 1.1 billion pounds of hazardous chemicals and solvents,
•  Saved over 21 billion gallons of water, and
•  Eliminated nearly 400 million pounds of carbon dioxide releases to air.

The Presidential Green Chemistry Challenge Program is looking forward to adding future
years' winners to the growing list of scientists and companies who are on the cutting
edge of pollution prevention.

                        2008 Winners
                      Academic Award
Professors Robert t. Mateczka, jr. and Milton R. Smith, III
Michigan Stale University
Green Chemistry for Preparing Boronic Esters
                       Innovation and Benefits
   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.
"Coupling" 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.
2 2008 Award

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., mete-
substituted) products, even when both the 1- and  3-substituents are
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

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 3

                   Small Business Award
SiGMd Chemistry, Inc.
New Stabilized Alkali Metals for Safer, Sustainable Syntheses
                        Innovation and Benefits
   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
Alkali 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 environ-
mental  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 alterna-
tive 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  elimi-
nate 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 activa-

4  2008 Award

tion that can be adapted to a variety of industry needs. By enabling
practical chemical shortcuts and continuous flow processes, the encap-
sulated alkali metals create efficiencies in storage, supply chain,
manpower, and waste disposal.

For the pharmaceutical,  petrochemical, and general synthesis indus-
tries, 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 effec-
tive 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 environ-
mental safety and in enabling new chemical technologies has helped it
attract more than  50 major global pharmaceutical,  chemical, and
energy companies as customers.
                                              2008 Small Business Award 5

                     Greener Synthetic
Development and Commercialization of Biobased Toners
                       Innovation and Benefits
   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 loner 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
More 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. Conven-
tional 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

6 2008 Award

and processing, with the de-inking process in mind. By incorporating
chemical groups that are susceptible to degradation during the stan-
dard 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 CO3
emissions per year.

Overall, soy toner provides a cost-effective, systems-oriented, environ-
mentally 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.
                                     2006' Qeenei Synthetic Pathways Award  7

        Greener Reactions Conditions Award

Nalco Company
3DTRASAR® Technology
                       innovation and Benefits
   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 3D TRASAR*
   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.
Most 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

S  2008 Award

replace the blowdown. Traditionally, antiscalants and antimicrobials are
added at regular intervals or, at best, after manual or indirect measure-
ments show scale or microbial buildup.

In 2004, Nalco commercialized  its 3D TRASAR® Cooling System Chemis-
try 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 forma-
tion 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 Itom  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.
                                    2008 Greener Reaction Conditions Award 9

        Designing Greener Chemicals Award

Dow AgroSciences LLC
Spinetoram: Enhancing a Natural Product for Insect Control
                       Innovation ant! Benefits
   Spinosad biopesticlde 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 splnetoram.
   Spinetoram retains the favorable environmental benefits of spinosad
   while replacing organophosphate pesticides for tree fruits, tree nuts,
   small fruits, and vegetables.
Spinosad  biopesticide won the Presidential Green Chemistry Challenge
Award for Designing Greener Chemicals in 1999. Spinosad, a combina-
tion 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 quanti-
tative structure-activity relationships of spinosyns and to predict ana-
logues 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 exten-
70 2008 Award

sively 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 mam-
malian 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 through-
out 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 insecti-
cides. 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
                                  2008 Designing Greener Chemicals Award  11

                        2007 Winners
                      Academic Award
Professor Michael j.  Krische
University of Texas at Austin
Hydrogen-Mediated Carbon-Carbon Bond Formation

                       Innovation and Benefits
  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.

Reductions 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 forma-
tions 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
12 2007 Award

systematic research to develop related C-C bond-forming hydrogena-
tions. 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 Oilman
reagents, in carbonyl and imine addition reactions. Such organometallic
reagents are highly reactive, typically moisture-sensitive, and some-
times 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.
                                                7007 Academic Award  13

                   Small Business Award
NovaSterilis Inc.
Environmentally Benign Medical Sterilization Using Supercritical Carbon

                        Innovation and Benefit?
   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. NovaSterllis 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

None 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 (COJ. 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

14 2007 Award

supercritical CO, 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) biodegrad-
able polymers and related materials used in medical devices, instru-
ments, and  drugs,- (c) drug delivery systems; and (d) whole-cell vaccines
that retain high antigenicity. Besides being  a  green chemical technol-
ogy, supercritical CO, 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.
                                             200/ Small Business Award  75

         Greener Synthetic Pathways Award

Professor Kaichanq Li, Oregon State University; Columbia Forest
Products; Hercules Incorporated
Development and Commercial Application of Environmentally Friendly
Adhesives for Wood Composites

                       innovation and Benefits
  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 Ihe new, soy-
  based adhesive to replace more than 47 million pounds of conventional
  formaldehyde-based adhesives.

Since the 1940s, the wood composites industry has been using syn-
thetic adhesive resins to  bind wood pieces into composites, such as
plywood, partideboard, 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

Inspired by the superior properties of the protein that mussels use to
adhere to rocks, FJrofessor  Fi and his group at Oregon State University
invented environmentally friendly wood  adhesives based on abundant,
renewable soy flour. Professor  Fi 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.
76 2007 Award

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 manufac-
turers 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 tech-
nology provides economic benefits for soybean farmers.
                                   2007 Qeener Synthetic Pathways Award  77

         Greener Reaction Conditions Award

Headwaters l'echnolog\: Innovation
Direct Synthesis of Hydrogen Peroxide by Selective  Nanocatalyst

                       Innovation and Benefits
   Hydrogen peroxide Is an environmentally friendly alternative to chlorine
   and chlorine-containing bleaches and oxldants. 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 AC to build plants to produce
   hydrogen peroxide.

Hydrogen peroxide (H-O,) 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 H,OJs 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 H-,O-. The H.,O-; is removed from the
solution with an energy-intensive stripping column and then concen-
trated 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

Headwaters Technology Innovation (HTI) has  produced a robust catalyst
technology that enables the synthesis of K.d, directly from hydrogen
and oxygen. This breakthrough technology, called NxCat™, is a palla-
dium-platinum catalyst that eliminates all the  hazardous reaction
conditions and chemicals of the existing process, along with its undesir-

78 2007 Award

able byproducts. It produces H,O, 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 H,O, up to 100 percent.

The NxCat™ technology enables a simple, commercially viable fi,O-,
manufacturing process.  In partnership with  Degussa AC (a major H,O2
manufacturer),  HTI successfully demonstrated the NxCat™ technology
and, in 2006, completed  construction of a demonstration  plant. This
demonstration plant will allow the partners to colled 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 H,O-, signifi-
cantly, generating a more competitively priced supply of H2O, and
increasing its market acceptance as an industrial oxidant. Except for its
historically higher price,  H.,O-;  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, environ-
mentally preferable oxidant (H:,O,) without the waste or high cost
associated with the traditional process.
                                   2007 Greener Reaction Conditions Award  79

        Designing Greener Chemicals Award

Car gill, incorporated
BiOH™ Polyols

                       Innovation and Benefits
   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.

Polyols are 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 polyure-
thane 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
20 2007 Award

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 photo-
synthesis. 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.
                                  2007 Designing Greener Chemicals Award  21

                        2006 Winners
                      Academic Award
Professor Galen j. Suppes
i iniversiiy of Missouri-Columbia
Biobased Propylene Glycol and Monomers from Natural Glycerin

                       innovation and Benefits
   Professor Suppes developed an inexpensive method to convert waste
   glycerin, a byproduct of blodiesel 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.

Glycerin 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.  Approxi-
mately 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 anti-
freeze, 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 mono-
mer 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 50d 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 commer-
cial 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  23

                  Small  Business Award
••\rkon Consultants
NuPm Technologies,  Inc.
Environmentally Safe Solvents and Reclamation in the Flexographic
Printing Industry

                       innovation and Benefits
   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 [he flexographic
   printing industry.

Flexographic  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
24 2006 Award

toxiclty, 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 mainte-
nance, and reduces waste. The waste is a solid, nonhazardous poly-
meric 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 cur-
rently 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,  reduc-
ing 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.
                                            2006 Small Business Award  25

          Greener Synthetic Pathways Award

.Merck A Co., Inc.
Novel Green Synthesis for p-Amino Acids Produces the Active
Ingredient in Januvia™

                       Innovation and Benefit?
   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-tips. 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 unpro-
tected  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 com-
pletely novel way: using it in the final synthetic step to maximize the

26 2006 Award

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 forma-
tion 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 Qeener Synthetic Pathways Award 27

         Greener Reaction  Conditions Award

Codexis, Inc.
Directed Evolution of Three Biocatalysts to Produce the Key Chiral
Building Block for Atorvastatin, the Active Ingredient in Lipitor®

                       Innovation and Benefits
   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'61, one of the
   world's best-selling drugs. The new enzymatic process reduces waste,
   uses less solvent, and requires less processing equipment - marked im-
   provements over processes used in the past: The process also increases
   yield and improves worker safety.

Atorvastatin 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 hydroxynitrile (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

28 2006 Award

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 cata-
lyzes the novel biocatalytic cyanation of the chlorohydrin to the cyano-
hydrin  under neutral conditions (aqueous, pH ~7, 77-104 °F, atmo-
spheric 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 approxi-
mately 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 increas-
ing yield, reducing the formation  of byproducts, reducing the genera-
tion 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 Lonza to manufacture HN
for Pfizer's production of atorvastatin calcium.
                                   2006 Greener Reaction Conditions Award  29

        Designing Greener Chemicals Award

S.C Johnson & Son, Inc.
Greenlist™ Process to Reformulate Consumer Products

                       Innovation and Benefits
   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 polyvlnylldene
   chloride (PVDC) annually after its "Greenlist" review of Saran Wrap'8
   revealed opportunities for changes.

Sc 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

Starting in 2001, SCJ developed Greenlist™1 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, biodegrad-
ability,  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

30 2006 Award

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, preserva-
tives, 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

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 poly-
vinylidene 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 31

                        2005 Winners
                      Academic Award
Professor Robin D. Rogers
The University of Alabama
A Platform Strategy Using Ionic Liquids to Dissolve and Process
Cellulose for Advanced New Materials

                       Innovation and Benefit?
   Professor Rogers developed methods that allow cellulose from wood,
   cloth, or even paper to be chemically modified to make new biorenew-
   able 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.

Major 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 success-
fully 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]CD, by gentle
heating (especially with microwaves). IL-dissolved cellulose can easily
be reconstituted in water in controlled architectures (fibers, mem-
branes, 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 dissolu-
tion 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]Q, studies of the IL 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  polyethyl-
ene-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
                                                2005 Academic Award 33

                  Small Business Award
Metaholix, Inc.
Producing Nature's Plastics Using Biotechnology

                       Innovation and Benefits
   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 biodegrade to 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.

Metabolix is  commercializing polyhydroxyalkanoates (PHAs), a broadly
useful family  of natural, environmentally friendly, high-performing,
biobased 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, demon-
strating 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 accomplish-
ments 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.
34 2005 Award

These new natural PHA plastics are highly versatile, have a broad range
of physical properties, and are practical alternatives to synthetic petro-
chemical 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 applica-
tions 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 ecosys-
tems. 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  35

         Greener Synthetic Pathways Award

Archer Daniels Midland Company
NovaLipid™: Low Trans Fats and Oils Produced by Enzymatic
Interesterification of Vegetable Oils Using Lipozyme®

                       Innovation and Benefits
  Archer Daniels Midland Company and Novozymes developed a way to
  make edible fats and oils that contain no fransfatty acids. The improved
  "interesterlficatlon" 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.

Iwo 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 enzy-
matic interesterification, a technology that not only has a tremendous
positive impact on public health by reducing tens fatty acids in Ameri-
can diet, but also offers  great environmental benefits by eliminating
the waste streams generated by the chemical interesterification

Triglycerides consist  of one glycerol plus three fatty acids. Triglycerides
that contain mostly unsaturated fatty acids are liquid at room tempera-
ture. Manufacturers  partially hydrogenate these  fatty acids  to make
them solids at room temperature. Trans fatly acids form during the
hydrogenation process; Ihey are found al 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 trans
fats in the American diet as much as possible, the FDA is requiring
labeling of tens fats on all nutrilional fad panels by January 1, 2006. In
response, the  U.S. food  and  ingredient induslry has been  investigat-
ing methods to reduce tens fats  in food.

36 2005 Award

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 ex-
change one or two of their fatty acids with triglycerides containing
unsaturated fatty acids, resulting in triglycerides that do not contain any
trans 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 fransfat 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. produclion  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 enzy-
matic process also contributes to improved public health by replacing
partially hydrogenated oils with interesterified oils that contain no  trans
fatty acids and have increased polyunsaturated  fatty acids.
                                   2005 Qeener Synthetic Pathways Award  37

         Greener Synthetic Pathways Award

Merck & Co., Inc.
A Redesigned, Efficient Synthesis of Aprepitant, the Active Ingredient
in Emend®: A New Therapy for Chemotherapy-Induced Emesis

                      Innovation and Benefit?
  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 [he
  original process. With its new method, Merck eliminates approximately
  41,000 gallons of" waste per 1,000 pounds ofthe drug that it produces.

Emend® is  a new therapy for chemotherapy-induced nausea and
vomiting, the most common side effects associated with  the chemo-
therapeutic 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

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

Merck's  new route to aprepitant demonstrates several important green
chemistry principles. This innovative and convergent synthesis as-
sembles 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 asymmet-

38  2005 Award

rlc 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 subse-
quent 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 environmen-
tal 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 imple-
mented 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 Qeener Synthetic Pathways Award  39

         Greener Reaction Conditions Award

BASF Corporation
A UV-Curable, One-Component, Low-VOC Refinish Primer:
Driving Eco-Efficiency Improvements

                      innovation and Benefits
   BASF developed a new automobile paint primer that contains less than
   half the amount of volatile organic compounds (VOCs) used in conven-
   tional 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.

The 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  refinishers and coating manufac-
turers 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.
VVaterborne 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

40 2005 Award

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® line as 151-70.

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

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.
                                  2005 Greener Reaction Conditions Award  41

        Designing Greener Chemicals Award

-\rcher Daniels Midland Company
Archer RC™: A Nonvolatile, Reactive Coalescent for the Reduction of
VOCs in Latex Paints

                      Innovation and Benefits
   Latex paints require coalescents to help the paint particles flow together
   and cover surfaces well. Archer Daniels Midland developed Archer RC™, a
   new blobased coalescent to replace traditional coalescents that are
   volatile organic compounds (VOCs). This new coalescent has other per-
   formance advantages as well, such as lower odor, Increased scrub
   resistance, and better opacity.

Since the 1980s, vvaterborne 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  commer-
cialize. Without a coalescent, the latex coating may crack and  may not
adhere to the substrate surface when dry at ambient temperatures.

42 2005 Award

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 commer-
cial use since March 2004.
                                  2005 Designing Greener Chemicals Award  43

                        2004 Winners
                      Academic Award
professors Charles A. Eckert and Charles L Liona
Georgia Institute of Technology
Benign Tunable Solvents Coupling Reaction and Separation Processes

                       Innovation and Benefits
   Professors Eckert and flotta found ways to replace conventional organic
   solvents with benign solvents, such as supercritical C02 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.

hor any chemical process, there must be both a reaction and a separa-
tion. 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

Supercritical CO,, nearcritical water, and CQ,-expanded liquids are
tunable benign solvents that offer exceptional opportunities as re-
placement 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 CO, to tune reaction equilib-
ria and rates, improve selectivities, and eliminate waste. They were the
first to use supercritical CO, with phase transfer catalysts to separate
products cleanly and economically. Their method allows them to
recycle their catalysts effectively. They have demonstrated the feasibil-
ity 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 subse-
quent neutralization and salt disposal. They have used CO, 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.
                                                2004 Academic Award  45

                  Small  Business Award
Jeneil Biosurfactant Company
Rhamnolipid Biosurfactant: A Natural, Low-Toxicity Alternative to
Synthetic Surfactants

                       Innovation and Benefits
   Billions of pounds of surfactants are used each year to lubricate, clean, or
   reduce undeslred foaming in Industrial applications. Jeneil Biosurfactant
   Company developed biobased surfactants that are less toxic and more
   biodegradable than conventional surfactants. Jeneil makes its biosur-
   factants 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 environ-
mental 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 avail-
able 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 supe-
rior 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 biosurfac-
tant  commercially in controlled, aerobic fermentations using particular

46 2004 Award

strains of the soil bacterium, Pseudomonas aeruQinosa. The
biosurfactant is recovered from the fermentation broth after steriliza-
tion and centrifugation, then purified to various levels to fit intended

Rhamnolipid biosurfactants are a much less toxic and more environ-
mentally 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 compo-

Although rhamnolipid biosurfactants have been the subject of consider-
able 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 47

          Greener Synthetic Pathways Award

Bristol-Myers Squibb Company
Development of a Green Synthesis for Taxol® Manufacture via Plant
Cell Fermentation and Extraction

                       Innovation and Benefits
   Bristol-Myers Squibb manufactures paclitaxel, the active Ingredient In the
   antlcancer 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.

Paclitaxel, the active ingredient in the anticancer drug Taxol®, was first
isolated and identified from the bark of the Pacific yew tree, Taxus
brevifo/ia, 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  re-
quired stripping the bark from the yew trees, killing them in the
process. Yews take 200 years to mature and are part of a sensitive

The complexity of the paclitaxel molecule makes commercial produc-
tion by chemical synthesis from simple compounds impractical. Pub-
lished syntheses involve about 40 steps with an overall yield of approxi-
mately 2  percent. In 1991,  NCI signed a Collaborative  Research  and
Development Agreement yvith 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).
48 2004 Award

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 environmen-
tal 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 condi-
tions 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 crystalli-
zation. 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 transfor-
mations, 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.
                                   2004 Qeener Synthetic Pathways Award  49

         Greener  Reaction Conditions Award

Buckman Laboratories International, Inc.
Optimyze®: A New Enzyme Technology to Improve Paper Recycling

                       Innovation and Benefits
   Paper mills traditionally use hazardous solvents, such as mineral spirits, to
   remove sticky contaminants (stickles) from machinery. Optimyze® technol-
   ogy 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 ils production by more lhan 6 percent,
   and save up to $1 million per year.

Recycling 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 numer-
ous 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 contami-
nants, called "stickies"  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 produc-
tion 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  re-
sources, 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.

50 2004 Award

Optimyze® technology from Buckman Laboratories is a completely
new way to control the problems associated with stickies. It uses a
novel enzyme to eliminate common  problems in the manufacture of
paper from recycled papers. A major  component of the sticky contami-
nants in paper is poly(vinyl acetate) and similar materials. Optimyze*1
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 effi-
ciency 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 57

        Designing Greener Chemicals Award

Engelhard Corporation (now BASF Corporation.)
Engelhard Rightfit™ Organic Pigments: Environmental  Impact,
Performance, and Value

                      Innovation and Benefits
  Rightfit™ azo pigments contain calcium, strontium, or barium,- they
  replace conventional heavy-metal-based pigments containing lead, hexa-
  valent 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 pigmenls with Rightfit™ pigments.

Historically, pigments based on lead,  chromium(VI), and cadmium
have served  the red, orange, and yellow color market. When the U.S.
EPA began regulating heavy metals,  however, color formulators typi-
cally 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 follow-
ing: (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 phos-
phates 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 transitioning to Rightfit™ azo
pigments. In 2002, Engelhard produced only 1.2 million pounds of

52 2004 Award

heavy-metal pigments,- they expect to phase them out completely in

Rightfit™ pigments eliminate the risk to human health and the envi-
ronment from exposure to heavy metals such as cadmium, chromi-
um^!), 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 inter-
mediates and organic solvents associated with the manufacture of
traditional high-performance pigments.

Rightfit™ pigments have additional benefits, such as good dispers-
ibility, 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.
                                  2004 Designing Greener Chemicals Award  53

                        2003 Winners
                      Academic Award
Professor Richard A. Cross
Polytechnic Univei'sily
New Options for Mild and Selective Polymerizations Using Upases

                       Innovation and Benefits
   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 lipases, 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 polymeriza-
tions and, thus, to decrease process energy consumption.  Further, the
regioselectivity of lipases has  been used to polymerize polyols directly.
Alternative synthetic pathways for such polymerizations require protec-
tion-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 lipases for polymerization
chemistry. Selected examples  include: (1) lipases catalyze trans-
esterification  reactions between high-molecular-weight chains in melt
conditions; (2) lipases will  use non-natural nudeophiles such as carbo-
hydrates and  monohydroxyl polybutadiene (/V1n 19,000) in place of
water; (3) the catalysis of ring-opening polymerization occurs in a con-
trolled  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 polyokontaining 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 (A/1W 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 carbo-
hydrates, such as sugars, into  polyesters without protection-
deprotection steps.

Professor Gross's laboratory discovered that certain lipases catalyze
transesterification reactions between high-molecular-weight chains that
contain intrachain esters or have functional end-groups. Thus, lipases,
such as Lipase B from Candida antarctica, catalyze intrachain exchange
reactions between polymer chains as well as  transesterification reac-
tions  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 A/1n values in excess of
40,000 grams per mole. In addition  to catalyzing metal-free transesteri-
fications at remarkably low temperatures, lipases endow transesteri-
fication reactions with remarkable selectivity. This feature allows the
preparation of block copolymers that have  selected block lengths.
                                                2003 Academic Award 55

                  Small  Business Award
-\QiaQuesi  Inc.
Serenade"51:  An Effective, Environmentally Friendly Biofungicide

                       Innovation and Benefits
   Serenade*1 Is a new blofungicide for fruits and vegetables based on a
   naturally occurring strain of bacteria. Serenade® Is nontoxlc to beneficial
   and other nontarget organisms, does not generate any hazardous chemi-
   cal residues, and is safe for workers and groundwater. It is well-sulled 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 suM//sQST-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 mani-
fested  both by  the physiology of the bacteria  and through the action
of secondary metabolites produced by the bacteria. Serenade® pre-
vents 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/

56 2003 Award

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 com-
pounds 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 friendli-
ness, 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 fungi-
cides. 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.
                                             2003 Small Business Award  57

          Greener Synthetic Pathways Award

SLid-Chemie Inc.
A Wastewater-Free Process for Synthesis of Solid Oxide Catalysts

                       Innovation and Benefits
  Sud-Chemie's new process to synthesize solid oxide catalysts used In
  producing hydrogen and clean fuel has virtually zero wastewater dis-
  charge, zero nitrate discharge, and no or little NOX emissions. Each
  10 million pounds of oxide catalyst produced by the new pathway elimi-
  nates 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.

Some 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, SO.,,  and halogens.

As a result of their commitment to continuously develop and invest in
new and improved catalyst synthesis technologies, Sud-Chemie suc-
cessfully developed and  demonstrated a new synthetic pathway that is
able to achieve virtually zero wastewater discharge, zero nitrate dis-
charge, 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 NO, 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 economi-
cally available in commercial  quantities. The synthesis proceeds by
58 2003 Award

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 con-
sumption 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 CO, 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 approxi-
mately $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.
                                    200.? Qeener Synthetic Pathways Award  59

         Greener  Reaction Conditions Award

Microbial Production of 1,3-Propanediol

                       Innovation and Benefits
   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

DuPont is integrating  biology in the manufacture of its newest poly-
mer platform, DuPont  Sorona® polymer. Combining metabolic engi-
neering 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, compris-
ing biocatalytic production of 1,3-propanediol from  renewable re-
sources, 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

Scientists and engineers from DuPont and  Genencor  International,
Inc. redesigned a living microbe to produce 1,3-propanediol. Inserting

60 2003 Award

biosynthetic pathways from several microorganisms into an industrial
host cell line allows the direct conversion of glucose to 1,3-propane-
diol, 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-pro-
panediol while minimizing its ability to produce biomass and un-
wanted 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 feedstock
and 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 produc-
tion 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.
                                   2003 Greener Reaction Conditions Award  67

        Designing Greener Chemicals Award
Shaw Industries, Inc.
EcoWorx™ Carpet Tile:  A Cradle-to-Cradle Product

                       Innovation and Benefits
   Conventional backings for carpet tiles contain bitumen, polyvlnyl chloride
   (PVC), or polyurethane. EcoWorx™ carpet tiles have a novel backing that
   uses less toxic materials and has superior adhesion and dimensional sta-
   bility. Because EcoWorx™ carpet tiles can be readily separated inio carpet
   fiber and backing, each component can be easily recycled.

Historically, carpet  tile backings  have  been manufactured using
bitumen, polyvinyl chloride (PVC), or polyurethane (PU). While these
backing systems  have  performed satisfactorily, there are several  inher-
ently 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 phtha-
late 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 U.S. 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 ex-
tremely 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
62 2003 Award

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 depolymer-
ization methods. PVC interferes with those processes. Nylon-6 chemis-
try 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 compo-
nents, 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  63

                       2002 Winners
                     Academic Award
Professor ['tic j. Beckman
University of Pittsburgh
Design of Non-Fluorous, Highly CO .-Soluble Materials

                       innovation and Benefits
  Carbon dioxide (C03) is a nontoxic chemical that can be used as a solvent
  In many Industrial processes. Professor Beckman  developed new deter-
  gents that allow a broad range of substances to dissolve In CO,. Any
  process that can now use CO, may reduce or eliminate the use of hazard-
  ous solvents.

Carbon dioxide (CO,), 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 CO,'s solvent power was similar to  that of n-alkanes,
leading to hopes that the chemical industry could use CO, 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 CO, and
that CO,  is actually a rather feeble solvent compared to alkanes. As the
1980s drew to a close, a number of research groups  began to explore
the design of CO,-philic materials, that is, compounds that dissolve in
CO, at significantly lower pressures than do their alkyl analogs. These
new CO,-philes, primarily fluoropolymers, opened up a host of new
applications for CO, including  heterogeneous polymerization, protein
extraction, and homogeneous catalysis.

Although fluorinated amphiphiles allow new applications  for CO,, their
cost (approximately $1 per gram) reduces the economic viability of CO,
processes, particularly given that the  use of CO, 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 CO,, and the full
promise of CO,-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 miscibil-
ity pressures in CO, that are comparable or lower than fluorinated
analogs and yet contain no fluorine.

Drawing from  recent studies of the thermodynamics of CO, mixtures,
Professor Beckman  hypothesized that CO,-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 CO-, (or any solvent). A low
cohesive energy density is primarily a result of weak solute-solute
interactions, a necessary feature given that CO-, is a rather  feeble
solvent. Finally, because CO,, is a Lewis acid,  the presence of Lewis
base groups should create sites for specific favorable interactions with
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 CO, than perfluoropolyethers, yet
are biodegradable and 100 times less expensive to prepare. Other
families of non-fluorous CO,-philes will inevitably be discovered using
this model, further broadening the applicability of CO, as a greener
process solvent.
                                                2002 Academic Award  65

                  Small Business Award
SC Fluids, Inc.
SCORR-Supercritical CO, Resist Remover

                       Innovation and Benefits
   SCORR (Supercritical CO., 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.

 1 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 (paniculate) 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 compat-
ibility, and cost. The key to the effectiveness of SCORR is the use of
supercritical CO., in place of hazardous solvents and corrosive chemi-
cals. Neat CO, 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, CO, returns to a gaseous phase
upon depressurization,  leaving the silicon wafer dry and free of resi-
66  2002 Award

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 simpli-
fying and streamlining the manufacturing process. It eliminates the
need for ultrapure deionized water, thus reducing time, energy, and
cost. Supercritical CO., costs less than traditional solvents and is recy-

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, there-
fore, can clean features  less than 100 nm. The low viscosity  of super-
critical fluids 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, ATM I, and Shipley, are participating in
the development of this innovative technology.
                                             2002 Small Business Award  67

          Greener Synthetic Pathways Award

Pfizer, Inc.
Green Chemistry in the Redesign  of the Sertraline Process

                       innovation and Benefits
   Pfizer dramatically Improved its manufacturing process for sertraline, the
   active Ingredient in its popular drug, Zoloft®. The new process doubles
   overall product yield, reduces rayy material use by 20-60 percent, elimi-
   nates the use or generation of approximately 1.8 million pounds of hazard-
   ous 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 imple-
mented 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 monomethylamlne
with a tetralone, followed by reduction of the imine function  and in
situ resolution of the diastereomeric salts of mandelic  acid to provide
chirally pure sertraline in much higher yield and with greater selectivity.

68 2002 Award

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,

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, tetrahydro-
furan, 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.
                                   2002 Qeener Synthetic Pathways Award  69

         Greener Reaction Conditions Award
Cargill Dow LLC {now NatureWorks LLO
NatureWorks™  PLA Process

                       Innovation and Benefits
  The NatureWorks™ process makes biobased, compostable, and recyclable
  polylactic acid  (PLA) polymers using 20-50 percent less fossil fuel re-
  sources 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.

NatureWorks™ 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 applica-
tions, 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
70 2002 Award

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. Addition-
ally, the lactic acid is derived from annually renewable resources, PLA
requires 20-50 percent less fossil resources than comparable petro-
leum-based plastics, and PLA is fully biodegradable or readily hydro-
lyzed 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, eliminat-
ing 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
                                   2002 Greener Reaction Conditions Award  77

        Designing Greener Chemicals Award
Chemical Specialties,  Inc. (now Viance)
ACQ Preserve®: The Environmentally Advanced Wood Preservative

                       Innovation and Benefits
  ACQ Preserve® is an environmentally advanced wood preservative de-
  signed to replace chromated copper arsenate (CCA) wood preservatives,
  which have been phased out because of their toxlcity. 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 associ-
  ated with producing, transporting, using, and disposing of CCA wood
  preservatives and CCA-treated wood.

I 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 con-
cern 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 quater-
nary (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
72  2002 Award

either ethanolamine or ammonia. Carbon dioxide (CO,) is added to the
formulation to improve stability and to aid in solubilization of the

Replacing CCA with ACQ is one of the most dramatic pollution preven-
tion 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,  transporta-
tion, 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 transi-
tion away from arsenic-based wood preservatives to a new generation
of preservative  systems.
                                    2002 Designing Safer Chemicals Award 73

                        2001 Winners
                      Academic Award
Professor Chao-jun Li
Julane University
Quasi-Mature Catalysis:  Developing Transition Metal Catalysis in Air
and Water

                       Innovation and Benefits
   Professor fl 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.

The 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,  petrochemi-
cals, agricultural chemicals, polymers, and plastics. Of particular impor-
tance 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 atmo-

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 carbocydes 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 com-
pounds. 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 macrocydic compounds, yields shorter reaction sequences.

Transition-metal-catalyzed reactions in water and air offer many advan-
tages. Water is readily available and inexpensive,- it is not flammable,
explosive, or toxic. Consequently, aqueous-based production pro-
cesses 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 75

                  Small  Business Award
EDEN Bioscience Corporation
Messenger"51: A Green Chemistry Revolution in Plant Production and
Food Safety

                       Innovation and Benefits
   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 mini-
   mizing 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 maxi-
mize crop productivity by enhancing yield and minimizing crop losses.
The Food and Agriculture Organization of the United Nations esti-
mates 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 world-
wide including environmental  groups, government regulators, con-
sumers, 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, natu-
rally occurring proteins called harpins, which were first discovered by
Dr. Zhongmin Wei,  EDEN's Vice President of Research, and his col-
leagues 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

76 2001 Award

plant biomass, photosynthesis, nutrient uptake,  and root develop-
ment, and, ultimately, lead to greater crop yield  and quality.

Unlike  most agricultural chemicals, harpin-based products are pro-
duced  in a water-based fermentation system that uses no harsh
solvents or reagents, requires only modest energy inputs, and gener-
ates 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

The result of this technology is a U.S. 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, Messen-
ger® has been shown through an extensive safety evaluation to have
virtually no adverse effect on any of the organisms 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 contami-
nate 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  77

          Greener Synthetic Pathways Award

Baver Corporation
Bayer AC
Baypure™ CX (Sodium Iminodisuccinate): An  Environmentally Friendly
and Readily Biodegradable Chelating Agent

                       innovation and Benefits
  Chelating agents are Ingredients In a variety of products, such as deter-
  gents, fertilizers, and household and Industrial cleaners. Most traditional
  chelating agents do not break down readily In the environment. Bayer
  Corporation and Bayer AC 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.

Chelating 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
wastevvater 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

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 toxico-
logical  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"

78 2001 Award

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  environ-
mentally friendly manufacturing process. Bayer AC 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 hydrox-
ide, 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 proper-
ties of the eight billion pounds of these products that are used annu-
ally. Specifically, sodium iminodisuccinate chelates calcium to soften
water and improve the cleaning function of the surfactant. In  photo-
graphic 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, environmen-
tally friendly chelating  agent that is also manufactured in a waste-free

                                   2007 Qeener Synthetic Pathways Award  79

         Greener  Reaction Conditions Award

Novozymes North America, Inc.
BioPreparation™ of Cotton Textiles: A Cost-Effective, Environmentally
Compatible Preparation Process

                       Innovation and Benefits
   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).
SO 2001 Award

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 charac-
teristics 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 prepara-
tions (amylases, cellulases) used to improve the performance proper-
ties 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 estab-
lished 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 alterna-
tive to alkaline scour systems currently used in the textile industry.
                                   200 / Greener Reaction Conditions Award  81

        Designing Greener Chemicals Award

PPG industries
Yttrium as a Lead Substitute in Cationic Electrodeposition Coatings

                       Innovation and Benefits
   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.

PPG 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 prop-
erty of electrocoat has always been dependent on the presence of
small amounts of lead salts or lead pigments in the product. As regula-
tory 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 100 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 sacri-

82 2001 Award

fice in corrosion performance. Yttrium is a common element in the
environment, being widely distributed in low concentrations through-
out 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 avail-
able 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 LDC[)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 produc-
tion, 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 chro-
mium- 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 perfor-
mance, 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 applica-
tions of PPG automotive customers.
                                  2001 Designing Greener Chemicals Award 83

                        2000 Winners
                      Academic Award
Professor Chi-Huey Wong
The Scripps Research Institute
Enzymes in  Large-Scale Organic Synthesis

                        innovation and Benefits
   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.

Organic 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, cata-
lysts, 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 stoichiomet-
ric 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 becom-
ing 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 environmen-
tally 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 pio-
neered 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 synthe-
sis. 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 enantio-
selective transformation of alcohols in  pharmaceutical development.
The multi-enzyme system based on genetically engineered glycosyl-
transferases coupled with in situ regeneration of sugar nudeotides
developed by Professor Wong has revolutionized the field of carbohy-
drate 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 repre-
sents a new field of green chemistry suitable for large-scale synthesis
that is impossible or impractical to achieve  by nonenzymatic means.

                                               2000 Academic Award  85

                  Small  Business Award
RevTech,  Inc.
Envirogluv™: A Technology for Decorating Glass and Ceramicware with
Radiation-Curable,  Environmentally Compliant Inks

                       Innovation and Benefits
   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 technol-
   ogy 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 inexpen-
sive 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

86 2000 Award

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 expo-
sure 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-tem-
perature  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 87

         Greener Synthetic Pathways Award

/?oc/7e Colorado Coi'poralion
An Efficient Process for the Production of Cytovene®, a Potent Antiviral

                       Innovation and Benefits
  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.

The  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 develop-
ment 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 immuno-
compromised 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, signifi-

SS  2000 Award

cant improvements were demonstrated in the second-generation
Guanine Triester (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, elimi-
nated 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 incorpo-
rated 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 reac-
tions. 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 environ-
mentally 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*1 and  other potent
antiviral agents. It is registered with the U.S. Food and Drug Adminis-
tration (FDA) as the current manufacturing process for the world's
supply of Cytovene111.
                                   2000 Qeener Synthetic Pathways Award  89

        Greener Reaction Conditions Awards

Bayer Corporation
Bayer AG
Two-Component Waterborne Polyurethane Coatings

                       innovation and Benefits
   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.

Iwo-component (2K) waterborne polyurethane coatings are an out-
standing 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  2Ksolventborne 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 polyure-
thane, 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 polyure-
thanes and aqueous polyurethane dispersions is a reactive 2K polyure-

90  2000 Award

thane 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 polyure-
thane 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  91

        Designing Greener Chemicals Award
               ces LLC
Sentricon™ Termite Colony Elimination System, A New Paradigm for
Termite Control

                       Innovation and Benefits
   Dovv's Sentricon™ System eliminates lermlle colonies wllh highly specific
   bait applied only where termites are active; It replaces widespread appli-
   cations of pesticide In the soil around houses and other structures. The
   U.S. 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 latel 999, Sentricon™
   was used for over 300,000 structures in the United States.

The 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 seek a control option, from the
1940s until  1995, the  nearly universal treatment approach for subterra-
nean 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 chemi-
cal 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
92 2000 Award

collaboration with Dr. Su, was launched commercially in 1995 after
receiving U.S. 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 re-
duced 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 applica-
bility 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 develop-
ment 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.
                                  2000 Designing Greener Chemicals Award  93

                        1999 Winners
                      Academic Award
Professor Tein Collins
Carnegie Mellon University
TAML™ Oxidant Activators: General Activation of Hydrogen  Peroxide
for Green Oxidation Technologies

                       Innovation and Benefit?
  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  paper-
  making 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 wide-
spread applications. TAML™ activators  (tetraamido-macrocydic 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 yvhite fibrous polysaccharides,  cellulose,  and hemicellulose. Wood
pulp delignification has traditionally relied on chlorine-based processes
that  produce chlorinated pollutants. Professor Collins has demon-
strated that TAML™ activators effectively catalyze hydrogen peroxide
in the selective delignification of yvood pulp. This is the first low-
temperature peroxide oxidation technique for treating yvood pulp,

which translates to energy savings for the industry. Environmental
compliance costs may be expected to decrease with this new ap-
proach 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 com-
mercial dyes are unaffected by the TAML™-activated  peroxide.  How-
ever, 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. Environ-
mental 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.
                                                7999 Academic Award  95

                  Small  Business Award
Biofine, Inc.  {now BioMe tics.. Inc.)
Conversion of Low-Cost Biomass Wastes to Levulinic Acid and

                       Innovation and Benefits
   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 levulinicacid (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 alterna-
tives to traditional feedstocks, attention often focuses on plant-based
materials. Renewable biomass conserves our dwindling supplies of
fossil  fuels and contributes no net  CO, 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 fur-
fural,  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.

96 1999 Award

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

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 commer-
cialization 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
                                             / 999 Small Business Award 97

          Greener Synthetic Pathways Award

Lilly Research Laboratories
Practical Application of a Biocatalyst in Pharmaceutical Manufacturing

                       Innovation and Benefits
   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.

The synthesis of a pharmaceutical agent is frequently accompanied by
the generation of a large amount of waste. This should not be surpris-
ing, 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 anticonvul-
sant drug candidate, LY300164. This pharmaceutical agent is being
developed for the treatment of epilepsy and neurodegenerative

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 environ-
mental 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 yvere iso-
lated, limiting worker exposure and decreasing  processing costs. The
synthetic scheme proved more efficient as well, with percent  yield
climbing  from 16 to 55 percent.
98 1999 Award

The new synthesis begins with the biocatalytic reduction of a ketone to
an optically pure alcohol. The yeast Zygosaccharomyces rouxii demon-
strated 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,  permit-
ting 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  5H-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 manufactur-
ing sector.
                                   1999 Greener Synthetic Pathways Award 99

         Greener Reaction Conditions Award

Nalco Chemical Company
The Development and Commercialization of U[TIMER®: The First of a
New Family of Water-Soluble Polymer Dispersions

                       Innovation and Benefits
  The Nalco Chemical Company developed a novel way to synthesize the
  polymers used to treat water In a variety of Industrial and municipal opera-
  tions. 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.

High-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,

700  1999 Award

homogeneous, polymer solution. This technology has been success-
fully 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 manufac-
ture of emulsion  polymers. Dispersion polymers produce no VOCs and
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 compo-
nent 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 byproduct 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.
                                  7999 Greener Reaction Conditions Award  707

        Designing Greener Chemicals Award

Dow --\QmSciences LLC
Spinosad: A New Natural Product for Insect Control

                       Innovation and Benefits
   Dow developed splnosad, 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
   lowtoxicityto mammals and birds.

Controlling insect pests is  essential to  maintaining high agricultural
productivity and minimizing monetary  losses. Synthetic organic pesti-
cides, 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 regula-
tions. 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 macrocydic lactones, containing a tetracydic 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 neurotox-
icity: lack of coordination, prostration, tremors, and other involuntary
muscle contractions leading to paralysis and death. Although the mode
of adion  of spinosad is not fully understood, it appears to affect

102 1999 Award

nicotinic and y-aminobutyric acid receptor function through a novel

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 molecu-
lar 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.
                                  /999 Designing Greener Chemicals Award  103

                        1998 Winners
                      Academic Award
Professor Banv M.  imst
Stanford University
The Development of the Concept of Atom Economy

                       innovation and Benefits
   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, minimiz-
   ing the amount of waste, and reducing the number of steps used to
   synthesize chemicals. Atom economy is one of the fundamental corner-
   stones of green chemistry. This concept is widely used by those who are
   working to improve the efficiency of chemical  reactions.

The 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, Pharma-
ceuticals, 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 prod-
uct."  In considering the question of what constitutes synthetic effi-
ciency, 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 stoichi-

ometry of a reaction or as a result of minimizing competing undesir-
able 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 consider-
ations. In too many cases, however, efforts to achieve the goal of
selectivity led to reactions requiring multiple components in stoichio-
metric 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 conse-
quence. Today, all of the  chemical industry explicitly acknowledges the
importance of atom economy.

Achieving the objectives of selectivity and atom economy encom-
passes 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 Pharmaceuti-
cals, which, in general, utilize very  atom-uneconomical reactions.
Professor Trost's research involves catalysis, largely focused on transi-
tion 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 luture.  However,
even today, there are applications for which such methodology may
offer more efficient syntheses.

                                               1998 Academic Award 105

                      Academic Award
Df.  Karen At Draths and Professor John W. Frost
Michigan State University
Use of Microbes as Environmentally Benign Synthetic Catalysts

                       Innovation and Benefits
  Adiplc add, 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.

Fundamental change in chemical synthesis can be achieved by
elaboration of new, environmentally benign routes to existing chemi-
cals. Alternatively, fundamental change can follow from characteriza-
tion 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 manipu-
lated microbes as synthetic catalysts. Nontoxic glucose is employed as
a starting material, which, in turn, is derived from renewable carbohy-
drate 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 em-
706  1998 Award

ploys 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 os,c/s-muconic acid using a single, geneti-
cally 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  Klebsie/la pneumoniae,  Acinetobacter calcoace-
ticus, and Escherichia coll. 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 cat-
echol 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 polymer-
ization 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,  carbohy-
drate starting materials,  and microbial biocatalysis. As the world moves
to national limits on carbon dioxide (CO-,) 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 synthe-
ses to use water as a reaction solvent, near-ambient pressures, and
temperatures that typically do not exceed human body temperature.
                                                1998 Academic Award  107

                  Small Business Award
PYROCOOL Technologies, Inc.
Technology for the Third Millennium: The Development and
Commercial Introduction of an Environmentally Responsible Fire
Extinguishment and Cooling Agent

                       innovation and Benefits
   PYROCOOL Technologies developed PYROCOOL F.E.F., a fire extinguishing
   foam that is nontoxic and highly biodegradable. PYROCOOL F.E.F. replaces
   ozone-depleting gases and aqueous foams that release toxic and per-
   sistent chemicals to the environment during use. PYROCOOL F.E.F. is
   effective at approximately one-tenth the concentration of conventional
   fire extinguishing chemicals.

Advances 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 formula-
tion 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 fluorocar-
bons when used. The fluorosurfactant compounds that make these
agents so effective against certain types of fires render them resistant
W8  1998 Award

to microbial degradation, often leading to contamination of ground-
water supplies and failure of wastevvater treatment systems.

In 1993, PYROCOOL Technologies initiated a project to create a fire
extinguishment and cooling agent that would be effective in extin-
guishing fires and that would greatly reduce the potential long-term
environmental and health problems associated with traditional prod-
ucts. To achieve this objective, PYROCOOL Technologies first deter-
mined 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 formula-
tion 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  effec-
tive 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 em-
ployment 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.
                                            / 998 Small Business A ward  109

          Greener Synthetic Pathways Award

flexsvs America L.P.
Elimination of Chlorine in the Synthesis of 4-Aminodiphenylamine:
A New Process That Utilizes Nucleophilic Aromatic Substitution
for Hydrogen

                        innovation and Benefits
  Flexsys developed a new method to eliminate waste from a critically impor-
  tant 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 Flexsvs process would
  reduce chemical waste by 74 million pounds per year and wastewater by
  1.4 billion pounds per year.

The  development of new environmentally favorable routes for the
production of chemical intermediates and products is an area of consid-
erable 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 innova-
tive processes that would focus on the elimination of waste at the
source. In view of these emerging requirements, Monsanto's Rubber
Chemicals Division (now Elexsys), in collaboration with Monsanto Corpo-
rate 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

770  1998 Award

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 contami-
nated with  organics that are difficult and  expensive to treat. Further-
more, 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 hydro-
gen (NASH). Through a series of experiments designed to probe the
mechanism of NASH reactions, Flexsys realized a breaklhrough 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 con-
verted 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 im-
plemented into innovative and environmentally safe chemical  processes.
                                   1998 Greener Synthetic Pathways Award   111

         Greener Reaction Conditions Award

Argonne National Laboratory
Novel Membrane-Based Process for Producing Lactate Esters—
Nontoxic Replacements for Halogenated and Toxic Solvents

                       Innovation and Benefits
  Argonne developed a novel process to synthesize organic solvents from
  sugars. These solvents can replace a wide variety of more hazardous sol-
  vents, 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.

Argonne 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 conven-
tional 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 fermen-
tation 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 eco-
nomically 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

Ethyl lactate has a good temperature performance range (boiling
point: 309 °F, melting point: 104 °F), is compatible with both  aqueous

772  1998 Award

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 demonstra-
tion 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.
                                   1998 Greener Reaction Conditions Award  113

        Designing Greener Chemicals Award

Rohm and Haas Company
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

                      Innovation and Benefits
   Rohm and Haas developed CONFIRM™, a novel insecticide for control-
   ling 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. U.S. EPA has classified CON FIRM™ as a
   reduced-risk pesticide.

The 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  the U.S.  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 "trig-
ger" that induces molting and regulates development in insects.
Because of this "ecdysonoid" mode of action, CONFIRM™ powerfully

114  1998 Award

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 insecti-
cides and  reduce the overall chemical load  on both the target crop
and the local  environment.

CONFIRM™ has low toxicity to mammals by ingestion,  inhalation, and
topical application and has been shown to be completely non-onco-
genic, 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.
                                 /998 Designing Greener Chemicals Award 115

                        1997 Winners
                      Academic Award
Professor Joseph M. DeSiinone
University of North Carolina at Chapel Hill (UNO
and Morth Carolina Stale University (MCSU)
Design and Application of Surfactants for Carbon Dioxide

                       Innovation and Benefit?
   Professor DeSimone developed new detergents that allow carbon dioxide
   (CO-,), a nontoxlc gas, to be used as a solvent in many Industrial applica-
   tions. Using CO, 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 (COJ,
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 alterna-
tives that can reduce or eliminate the negative impact that solvent
emissions can have in the workplace and in the environment. CO, in a
solution state has long been recognized as an ideal solvent,  extract-
ant, and separation aid. CO, 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
CO,, in both its  liquid and supercritical states. With the discovery of  CO,
surfactant systems, Professor Joseph  M.  DeSimone and his students
have dramatically advanced the solubility performance characteristics of
CO, systems for several industries.

The design of broadly applicable surfactants for CO, relies on the
identification of "CO-,-philic" materials from which to build amphiphiles.
Although CO-, 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
CO-,, he and his  researchers exploited the high solubility  of a select
few CO,-philic polymeric segments to develop nonionic surfactants
capable of dispersing high-solids polymer latexes in both liquid and
supercritical CO,  phases. The design criteria they developed for
surfactants, which were capable of stabilizing heterogeneous polymer-
izations in CO7, have been expanded to include CO:,-insoluble com-
pounds in general.

This development lays the foundation by which surfactant-modified
CO, can 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.
                                               7 997 Academic Award  117

                  Small Business Award
L egacy Sys'teins, Inc.
Coldstrip™, A Revolutionary Organic Removal and Wet Cleaning

                       Innovation and Benefits
   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.

For 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.

m  1997 Award

Using oxygen and water as raw materials replacing the Piranha solu-
tions significantly benefits the environment. One benefit is the elimi-
nation 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.
                                             / 997 Small Business Award  119

         Greener Synthetic Pathways Award

BHC Company (now BASF Corporation)
BHC Company Ibuprofen  Process

                      Innovation and Benefits
   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.

Bl-IC Company has developed a new synthetic process to manufac-
ture ibuprofen, a well-known nonsteroidal anti-inflammatory painkiller
marketed under brand names such as Advil™ and Motrin™. Commer-
cialized  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 approxi-
mately 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 U.S. EPA's  waste management hierarchy.
Virtually all starting materials are either converted to product or re-
claimed byproduct or are  completely recovered  and recycled in the
process. The generation of waste is practically eliminated.
UO  7997 Award

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 com-
plete atom utilization  of this streamlined  process truly makes it a
waste-minimizing, environmentally friendly technology.
                                    799/ Greener Synthetic Pathways Award  121

         Greener Reaction  Conditions Award

DryVievv™ Imaging Systems

                       Innovation and Benefits
   Imation's DryVlew™ 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 [he 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.

Photothermography 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. Photo-
thermographic 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™

122  7997 Award

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 reconnais-
sance.  DryView™ is valued by these industries because it supports
pollution prevention through  source reduction.
                                   1997 Greenei Reaction Conditions Award  123

        Designing Greener Chemicals Award

Albright & Wilson American (now Rhodia)
THPS Biocides: A New Class of Antimicrobial Chemistry

                       innovation and Benefits
  Albright & Wilson discovered the antimicrobial properties of THPS and
  developed it into a safer biocide that can be used to control [he growth of
  bacteria and algae in industrial water systems. THPS, or tetrakislhydroxy-
  methyDphosphonium 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.

Conventional biocides used to control the growth of bacteria, algae,
and fungi in industrial cooling systems, oil fields, and process applica-
tions 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, tetrakisihy-
droxymethyDphosphonium 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 break-
down 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 recom-
mended 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,
124  7997 Award

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 treat-
ment 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.
                                  7997 Designing Qeener Chemicals Award 125

                        1996 Winners
                      Academic Award
Professor Mark Holfzapple
Texas AMI  University
Conversion of Waste Biomass to Animal Feed, Chemicals, and Fuels

                       Innovation and Benefits
   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 technol-
   ogy 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.

A 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, releas-
ing 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 hydro-
genated to their corresponding alcohols such as isopropanol, isobu-
tanol, 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 exacer-
bates soil erosion and requires intensive inputs of fertilizers, herbi-
cides, and pesticides, all of which contaminate ground water.

Chemicals (e.g., organic acids and ketones) may be produced eco-
nomically 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 con-
served 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 warm-
                                               7996 Academic Award  127

                  Small Business Award
Donlat Cot potation (nowNanoChem Solutions, Inc.)
Production and Use of Thermal Polyaspartic Acid

                       Innovation and Benefits
   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.

Millions 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 manufac-
ture TPA for which patents have either been granted  or allowed.  The
first process involves a dry and solid polymerization converting aspartic
acid to polysucdnimide. 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 rou-
tinely achieved. The second step in this  process, the  base hydrolysis of
polysuccinimide to polyaspartate,  is also extremely efficient and waste-

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 characteris-
tics, lower color, and biodegradability. The catalyst can be recovered
from the process, thus minimizing waste.
    7996 Award

Independent toxicity studies of commercially produced TPA have been
conducted using mammalian and environmental models. Results
indicate that TPA is nontoxlc and environmentally safe. TPA biodegrad-
ability 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 protect-
ing the ecology of agricultural lands. TPA can also be used for water
treatment, as well as in the detergent, oil, and gas industries.
                                            1996 Small Business Award  129

         Greener Synthetic Pathways Award

Monsanto Company
Catalytic Dehydrogenation  of Diethanolamine

                       Innovation and Benefits
   DSIDA is a key building block for the herbicide Roundllp®. 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.

Disodium iminodiacetate (DSIDA) is a key intermediate in the produc-
tion of Monsanto's Roundup'1' 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 possibil-
ity 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 subse-
quent use in the manufacture of Roundup®. The new technology
represents a major breakthrough in the production of DSIDA,  because
130  7996 Award

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.
                                   7996 Greener Synthetic Pathways Award  131

         Greener Reaction  Conditions Award

The Dow Chemical Company
100 Percent Carbon Dioxide as a Blowing Agent for the Polystyrene
Foam Sheet  Packaging Market

                       Innovation and Benefits
   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 C02 only from existing commercial and nalural sources
   that generate it as a byproduct, so this process will not contribute to
   global CG, 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 (CO,). 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 CO., offers optimal environmental performance
because CQ, does not deplete the ozone layer, does not contribute to
ground-level smog, and will not contribute to global warming because
CO, will be used from existing byproduct commercial  and natural
sources. The use of CO, byproduct from  existing commercial and
natural sources, such as ammonia plants and  natural gas wells, will
ensure that no net increase in global CO, results from the use  of this

132 7996 Award

technology. CO-, is also nonflammable, providing increased worker
safety. It is cost-effective and readily available in food-grade quality. CO,
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 commer-
cial 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).
                                  7996 Greener Reaction Conditions Award  133

         Designing Greener Chemicals Award

Rohm and Haas Company
Designing an Environmentally Safe Marine Antifoulant

                       Innovation and Benefits
   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 con-
   sumption. Sea-Nine™ replaces environmentally persistent and loxic tin-
   containing antifoulants.

Fouling,  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 a
U.S. 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 the U.S. 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-/>octyl-4-
isothiazolin-3-one  (Sea-Nine™ antifoulant) was chosen as the candi-
date for commercial development.
134  1996 Award

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 organ-
isms, 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 U.S. EPA
registration for the use of Sea-Nine™ antifoulant, the first new
antifoulant registration in over a decade.
                                 /996 Designing Greener Chemicals Award  135

                  Program Information
Additional information on the Presidential Green Chemistry Challenge
program is available from:
• The Green Chemistry Program Web site at
• The Industrial Chemistry Branch of EPA by e-mail at
  greenchemistry@epa.gov or by telephone at 202-564-8740 and
• EPA's Pollution Prevention Information Clearinghouse by e-mail  at
  ppic@epa.gov or by telephone at 202-566-0799.
Note: The summaries provided in this document were obtained from
the entries received for the 1996-2008 Presidential Green Chemistry
Challenge Awards. They were edited for space, stylistic consistency,
and clarity, but they were neither written nor officially endorsed by the
U.S. 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.