EPA/600/R-94/125
Proceedings October 1994
WORKSHOP ON GREEN SYNTHESES AND PROCESSING
IN CHEMICAL MANUFACTURING
Omni Netherland Plaza
Cincinnati, Ohio
July 12-13, 1994
Sponsored by the U.S. Environmental Protection Agency:
Office of Research & Development
Risk Reduction Engineering Laboratory
Cincinnati, Ohio 45268
Office of Prevention, Pesticides and Toxic Substances
Washington, D.C. 20460
Co-sponsored by:
National Science Foundation
Arlington, Virginia 22230
Contract No. 68-CO-0068
Coordinated by:
Eastern Research Group, Inc.
Lexington, Massachusetts 02173-3198
Project Officer:
Randy Revetta
CENTER FOR ENVIRONMENTAL RESEARCH INFORMATION
Work Assignment Manager:
Thomas J. Powers
RISK REDUCTION ENGINEERING LABORATORY
OFFICE OF RESEARCH AND DEVELOPMENT
U.S. ENVIRONMENTAL PROTECTION AGENCY
CINCINNATI, OHIO 45268
^.9 Printed on Recycled Paper
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NOTICE
These Proceedings have been reviewed in accordance with the U.S.
Environmental Protection Agency's peer and administrative review policies and
approved for presentation and publication. Mention of trade names or
commercial products does not constitute endorsement or recommendation for
use.
n
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CONTENTS
Foreword v
Abstract vj
Figures ^i
Tables x
I. Introduction j
II. Presentations - Opening Plenary Session 4
Next Generation Manufacturing Systems and the
Environment: The Federal Agenda
Joseph Bordogna, National Science Foundation 4
Benign Organic Synthesis
James Bashkin, Washington University 12
Benign Biosynthesis
Jerome Schultz, University of Pittsburgh 28
Benign Engineering Approaches
C. Thomas Sciance, DuPont Experimental Station 47
Computer-Based Methods for Finding Green Synthesis
Pathways and Industrial Processes for Manufacturing
Chemicals: A View From 10,000 Feet
Peter P. Radecki, Michigan Technological University 66
III. Breakout Sessions 79
IV. Presentations - Closing Plenary Session 81
Workgroup on Benign Engineering Approaches 81
Workgroup on Biosynthesis 39
Workgroup on Chemical Synthesis 95
Workgroup on Computer-Based Methods 101
V. Closing Remarks 110
111
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CONTENTS (continued)
Appendices
Appendix A: List of Workshop Participants A-l
Appendix B: Workshop Agenda B-l
Appendix C: Minutes of Individual Breakout Groups C-l
IV
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FOREWORD
Today's rapidly developing and changing technologies and industrial products
and practices frequently carry with them the increased generation of materials
that, if improperly dealt with, can threaten both public health and the
environment. The U.S. Environmental Protection Agency is charged by Congress
with protecting the Nation's land, air, and water resources. Under a mandate of
national environmental laws, the Agency strives to formulate and implement
actions leading to a compatible balance between human activities and the ability
of natural systems to support and nurture life. These laws direct the EPA to
perform research to define our environmental problems, measure the impacts,
and search for solutions.
The Risk Reduction Engineering Laboratory is responsible for planning,
implementing, and managing research, development, and demonstration programs.
These provide an authoritative defensible engineering basis in support of the
policies, programs, and regulations of the EPA with respect to drinking water,
wastewater, pesticides, toxic substances, solid and hazardous wastes, and
Superfund-related activities. This publication is one of the products of that
research and provides a vital communication link between researchers and users.
The Workshop on Green Syntheses and Processing in Chemical Manufacturing
was designed to provide an insight into the state of the art of environmentally
benign chemical manufacturing. The recommendations of the workshop are
summarized in these proceedings. The perspectives and recommendations coming
out of this Workshop will help federal research directors make decisions regarding
the support of research and development related to benign synthesis and
manufacturing.
E. Timothy Oppelt, Director
Risk Reduction Engineering Laboratory
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ABSTRACT
The Workshop on Green Syntheses and Processing in Chemical
Manufacturing was held in Cincinnati, Ohio, on July 12 and 13, 1994. The
purpose of the workshop was to solicit information from industry, academia, and
government regarding research related to the advancement of environmentally
benign chemical manufacturing processes.
Keynote addresses in Organic Synthesis, Biosynthesis, Engineering
Approaches, and Computer-Based Methods specifically related to benign
technology were presented by leading experts. The workshop attendees were
subdivided into smaller groups addressing each of these four key areas. Proposed
research topics were ranked according to their overall priority; the time frame
within which an impact of the proposed research would be felt; what combination
of industrial, academic, and government efforts is appropriate; and the need and
justification for Federal funding.
VI
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FIGURES
Number
Figure 1.
Figure 2.
Figure 3.
Figure 4.
Figure 5.
Figure 6.
Figure 7.
Figure 8.
Figure 9.
Figure 10.
Figure 11.
Figure 12.
Figure 13.
Figure 14.
Figure 15.
Figure 16.
R&D Issues in a Changed World
Concurrent Integration of Innovation and Wealth Creation
Organization of the National Science and Technology
Council (NSTC)
Page
4
5
7
Organization of the NSTC Committee on the Environment 9
and Natural Resources
Chemical Structure of Taxol 13
Helton's Synthesis of Taxol 14
Traditional versus Environmentally Benign Methods of 17
Synthesizing Water
Traditional Cholorine-Based Oxidation Reactions 18
Oxygen and Hydrogen Peroxide as Clean Oxidizing Agents 19
Preparation of Murray's Dimethyldioxirane as a Clean 20
Oxidizing Agent
Conventional Pathway for Synthesizing para- 22
Nitrodiphenylamine
Generation of a Meisenheimer Intermediate via 23
Chlorobenzeneversus Direct Nucleophilic Attack
Synthesis of para-Nitrodiphenylamine Without Using 25
Chlorobenzene
Overall Stoichiometry of the Tetramethyl-ammonmm 26
Hydroxide-Catalyzed Synthesis of para-Nitrosodiphenylamine
Percent Yield of Nitro and Nitroso Diphenylamine
Products with Varying Aniline: Nitrobenzene Ratios
26
Production of Organic Chemicals in the United States, 1993 29
Vll
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Number
FIGURES (continued)
Page
Figure 17. Current and Potential Biomass Feedstocks in the 31
United States
Figure 18. A Total-System Perspective on Bioprocessing 32
Figure 19. A Biparticle Fluidized Bed Operating in 33
Countercurrent Mode
Figure 20. Process Flowsheet for the Biological Production of 34
Ethanol from Wastepaper
Figure 21. Breakdown of Ethanol Production Costs by Process Area 35
Figure 22. Sensitivity of Ethanol Selling Price to Major Process 36
Parameters
Figure 23. Typical Concentrations of Products Leaving Fermenters 37
Figure 24. Relationship Between Product Concentration and Selling 38
Price
Figure 25. Relationship Between Selling Price and Worldwide 38
Production of Various Fermentation Products
Figure 26. Production of High-Fructose Corn Syrup by Enzymatic 39
Methods
Figure 27. Economics of High-Fructose Corn Syrup Production 40
Figure 28. Potential Applications of Enzymes in Environmentally 41
Benign Chemical Processing
Figure 29. Enzymatic Enhancement of Chemical Reaction Rates 42
Figure 30. Lipase-Catalyzed Polymerization Reaction 43
Figure 31. Relationship Between Pressure and Degree of Polymer- 45
ization in a Supercritical Solvent System
Figure 32. Enzymatic Catalysis in the Gas Phase 46
Figure 33. Enzymatic Catalysis in Pure Reactants 46
vm
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Number
Figure 34.
Figure 35.
Figure 36.
Figure 37.
Figure 38.
Figure 39.
Figure 40.
Figure 41.
Figure 42.
Figure 43.
Figure 44.
Figure 45.
Figure 46.
Figure 47.
Figure 48.
Figure 49.
Figure 50.
Figure 51.
FIGURES (continued)
Evolution of Engineering Paradigms
Predicted Time Course for Developing Sustainable
Technologies
Pollution Prevention Ideas
Limitations Inherent to the Production of Maleic Acid
via a Fixed Bed Reactor
Innovations Required for the New Synthetic Pathway
The Role of Lattice Oxygen Chemistry in the New
Synthetic Pathway
Riser Reactor Developed for the New Synthetic Pathway
Riser versus Fluid Bed Oxidation
Alternative Processes for HCN Production
Effect of Feed Purity and Conversion
Homogeneous versus Heterogeneous Catalysts
Process Concept: Acid-Catalyzed Hydrolysis of Biosludge
Clean Technology Targets
Stages of Process Development and Implementation
Computer-Based Tools for Use in the Early Planning
Stages of Process Design
Computer-Based Tools for Use in Industrial-Scale Process
Design
Computer-Based Tools for Use During the Industrial
Production Stage
Object-Oriented Programming and Concurrent Software
Page
48
50
53
56
56
57
58
59
61
63
64
65
66
69
70
72
74
77
Development
IX
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TABLES
Number
Table 1.
Table 2.
Table 3.
Table 4.
Recommendations of the Workgroup on Benign Engineering
Approaches
Recommendations of the Workgroup on Benign Biosynthesis
Recommendations of the Workgroup on Chemical Synthesis
Recommendations of the Workgroup on Computer-Based
Methods
Page
82
90
97
102
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I. INTRODUCTION
In recent years, efforts have intensified to identify alternative chemical or
biochemical processes that are both environmentally friendly and economically
attractive. The chemical and allied industries, broadly defined as those industries
employing processes involving chemical reactions that have the potential to cause
the formation of undesirable by-products or the emission of toxic compounds, are
responsible for the bulk of the environmental pollution associated with
manufacturing activities.
To explore issues related to environmentally benign synthesis, a two-day
workshop was organized under the joint sponsorship of the U.S. Environmental
Protection Agency's (EPA's) Office and Research and Development (ORD),
EPA's Office of Prevention, Pesticides and Toxic Substances (OPPTS), and the
National Science Foundation (NSF). This meeting, entitled "Workshop on Green
Syntheses and Processing in Chemical Manufacturing," was held in Cincinnati,
Ohio, on July 12 and 13, 1994. At this workshop, more than 50 chemists,
biochemists, and chemical engineering experts representing industrial, academic,
and government institutions met to discuss the research needed to advance the
development and adoption of environmentally benign chemical manufacturing
processes (see Appendix A).
An overview of the background and goals of the workshop was provided by
Thomas Powers of ORD's Water and Hazardous Waste Research Treatment
Division, who chaired the opening session. Following several administrative
announcements, T. Powers introduced Subhas Sikdar, Director of the Water and
Hazardous Waste Treatment Research Division. After welcoming participants to
Cincinnati, Dr. Sikdar described the workshop as part of an ongoing joint effort
through which EPA and NSF are attempting to develop an integrated program in
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support of environmentally benign chemical manufacturing. As stated by Dr.
Sikdar, the specific goal of the workshop was to identify critical areas of research
and development (R&D) in which government assistance and/or partnerships with
industry and academia could be expected to offer the greatest benefit in meeting
the dual goal of maintaining the economic vitality of the chemical manufacturing
industry while at the same time reducing the industry's disproportionate
contribution to environmental pollution. The case for so-called green chemistry
has attracted a great deal of attention in the past year, beginning with a white
paper entitled "Chemistry for a Clean World," published by the European
Community's Chemistry Council in June, 1993. More recently, green chemistry
has been the subject of articles in professional journals such as Science and
Chemical and Engineering News. The scope of this workshop would be somewhat
broader, moving beyond chemical processes per se to include chemical engineering
and economic feasibility issues.
Dr. Sikdar concluded his introductory presentation by reviewing the
proposed agenda for the two-day meeting (Appendix B). The first afternoon of
the workshop would be devoted to an overview of issues in advanced
manufacturing as seen from the perspective of the National Science and
Technology Council, followed by a series of formal presentations on issues related
to green syntheses and manufacturing processes. The following morning, the
workshop would break into smaller workgroups that would attempt to answer four
questions related to general areas covered in the plenary speakers' presentations:
• Question #1: What research and development must be exploited to
accelerate the development of benign organic synthesis?
• Question #2: What research and development must be exploited to
accelerate the development of benign biosynthesis?
• Question #3: What engineering methods must be developed to aid in the
cost-effective manufacturing of chemicals by benign routes?
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• Question #4: What models, databases, and algorithms must be developed
to make benign, manufacturing more facile?
At the end of the second day of the meeting, the group was scheduled to
reconvene as a whole to discuss the conclusions and recommendations reached by
the workgroups, particularly as those conclusions related to the need for short-,
medium-, and long-term government assistance. These recommendations will be
helpful to both EPA and NSF in their decision-making process for federal funding
in this area.
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II. PRESENTATIONS - OPENING PLENARY SESSION
Next Generation Manufacturing Systems and the Environment:
The Federal Agenda
Joseph Bordogna, National Science Foundation
A schematic representation of the variety of issues that currently impinge
on thinking about research and development priorities at the federal level is
depicted in Figure 1. Much effort is being invested in issues related to
manufacturing and the environment. With the establishment of the National
Science and Technology Council (NSTC) in November, 1993, there is a
centralized structure for decisions about how to allocate the $70 billion the
federal government spends on research and development each year. The
Cognitive
Revolution
Diverse
Workforce
Defense
Conversion
Data
Explosion
Global
Economy
Shared
Wealth
Dual
Use
International
Partnerships
Finite
Resources
Environmental
Imperatives
Demographic
Shifts
Figure 1. R&D Issues in a Changed World
4
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proceedings of this workshop will be very useful to guide the decisions of NSTC,
particularly to the extent that workshop participants could address the full
spectrum of issues from discovery to regulation that fall under the combined aegis
of the EPA and NSF.
Decisions concerning the allocation of federal R&D funding are presently
being evaluated by two main criteria: the extent to which proposed efforts
promote innovation and the extent to which these efforts contribute to the
creation of wealth in the United States (see Figure 2). In this regard, a
distinction is to be made between innovation, defined as new knowledge applied
to things you did not know how to do before, and productivity, new knowledge
that helps you do better things you already know how to do. In the context of
ANALYSIS
REDUCTION
DISCOVKRY OF
NKW KNOWLEDGE,
HASIC LAWS
INNOVATION
&
WEALTH
CREATION
PROCESSES
SYSTEMS
T
E
C
H
N
O
L
O
G
Y
DEVICES
IDEAS
SYNTHESIS
INTEGRATION
DESIGN
MANUFACTURE
MAINTENANCE
CAIMTAI.
FORMATION/
INVESTMENT
Figure 2. Concurrent Integration of Innovation and Wealth Creation
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wealth creation, innovation is key, for innovation and wealth creation to go hand-
in-hand. However, it is not sufficient just to have the science and engineering
elements in place; for wealth creation to occur, it is also necessary for the
resulting technology to fill a need in terms of prevailing economic and policy
contexts. Moreover, for a process to realize its wealth-creating potential, all five
aspects of the process (i.e., the science, engineering, technology, policy context,
and economic context) must develop in parallel.
To illustrate the changing economic and political context for manufacturing
in the United States, the change in demands on industry over the past several
decades are described. For much of the 20th century, it was sufficient for
manufacturers to pick two of three desirable attributes: good, fast, and cheap.
Beginning in the 1980s, it became necessary for manufacturers to assure that
processes met all three of these criteria. For the 1990s and beyond, a fourth
criterion - clean - has been added to the list. From this point forward,
environmental considerations must become part of the front-end design process
for any manufacturing interest.
Perhaps the best indication of the federal government's increasing
awareness of the importance of science and technology to the overall well-being
of the United States was the November 1993, Executive Order, which established
the National Science and Technology Council within the Executive Office of the
President. The NSTC was organized to offer advice directly to the President in a
manner similar to that previously provided only by the National Security Council
and the National Economic Council. The most important undertaking of the
NSTC is to decide how the federal R&D budget allocation should be used. In
the past, federal R&D expenditures have been summarized on a single page in
the budget, where R&D outlays were divided into four general categories: basic
research, applied research, development, and facilities. In lieu of this somewhat
"fuzzy" breakdown, one goal of the NSTC is to look at federal R&D expenditures
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in terms of their impact on functions that the government exists to fulfill. Thus,
the NSTC has organized itself into nine committees, one dedicated to each of
these priority functions (see Figure 3). Each of these Committees is chaired by
an Executive Branch member.
National Science & Technology Council
(NSTC)
Education
& training
Health,
Safety &
Pood
Civilian
Industrial
Technology
National
Security
Resources
Figure 3. Organization of the National Science and Technology Council (NSTC)
Manufacturing issues fall within the purview of the NSTC Committee on
Civilian Industrial Technology. The Civilian Industrial Technology Committee is
an extremely important one, because it is the only committee in government that
has representatives from both the private and public sectors working together.
One initiative, the Partnership for a New Generation of Vehicles, involves
executive vice presidents from the "Big Three" automobile manufacturers as well
as representatives from seven government agencies.
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The Subcommittee on Manufacturing Infrastructure has five working
groups, each dedicated to an area the Subcommittee views as particularly worthy
of federal support:
Manufacturing Systems, dedicated to the advancement of next-
generation manufacturing systems (e.g., agile/flexible manufacturing,
intelligent manufacturing systems, quality initiatives)
Engineering Tools for Design and Manufacturing, which will attempt to
answer the question of how best to deal with the decline in the machine
tool industry (e.g., concurrent engineering, virtual prototyping)
Manufacturing Processes and Equipment, the working group that will
promote the development of environmentally benign processes; rapid
physical prototyping; and intelligent sensors, controls, and actuators
Manufacturing Education and Training (e.g., TRP projects, teaching
factories)
Manufacturing Technology Deployment (e.g., MTCs, TRP projects)
An NSTC Committee of relevance to the issues being discussed at the
workshop is the Committee on the Environment and Natural Resources, the
organizational structure of which is illustrated in Figure 4. This committee has a
Subcommittee on Technology and Engineering Research, the purview of which
cuts across numerous areas of environmental concern, including air quality, toxic
substances, and others. Currently, this subcommittee's efforts are focused in two
main areas. The first, determining how to facilitate the commercialization of
extant environmental technologies that for various reasons have not yet reached
the market, is probably about a $100 million effort.
The other main interest of this subcommittee - long-term environmental
technology research and development needs - is also the subject of a document
entitled "Technology for a Sustainable Future." This document outlines the three
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Committee on the Environment
and Natural Resources
Executive Council
Social & Economic
Sciences Research
Subcommittee
Technology &
Engineering Research
Subcommittee
Global Change
Research
Subcommittee
Biodiversity &
Ecosystem
Research
Science and Policy
Assessment
Federal Policy
Formulation
Resource Use &
Management
Research
Subcommittee
Water Resources/
Coastal & Marine
Environment
Research
Air Quality
Research
Subcommittee
Toxic Substances &
Hazardous and
Solid Waste Research
Subcommittee
Natural
Disasters
Research
Committee
Figure 4. Organization of the NSTC Committee on the Environment and Natural Resources
main goals that will guide the Administration's efforts to develop an integrated,
long-term environmental technology strategy:
• Encourage development of avoidance technologies and adoption of the
low-waste/no-waste tenets of industrial ecology
• Forge stronger public-private partnerships to foster rapid diffusion of
research results to environmental technology users
• Foster use of environmentally sound and socially appropriate
technologies worldwide
The definition of sustainable development set forth by the Bruntland Commission
in 1987 ("development that meets the needs of the present without compromising
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the ability of future generations to meet their own needs"), was used as a basis for
environmental technology as "technology that advances sustainable development
by reducing risk, enhancing cost-effectiveness, improving process efficiency, and
creating products and processes that are environmentally beneficial or benign."
In this context, technology includes hardware, software, systems, and services.
With a vision of long-term economic growth that creates jobs while improving and
sustaining the environment, the overall thrust of the contemplated program is to
move the environmental technology paradigm from one of cleanup and control to
one of anticipation, avoidance, and assessment.
The "Technology for a Sustainable Future" document is expected to be the
focus of extensive interaction among representatives from industry, academia, and
government over the next year. Based on these interactions, the President will
enunciate an Environmental Technology Strategy for the U.S. on Earth Day,
1995.
Noting that it is common for people in government to think about
manufacturing primarily if not exclusively in terms of parts assembly, it will be
important for the chemical manufacturing community to make its R&D needs
known to policymakers. Among areas of research and development considered to
be at the leading edge of chemical technology and manufacturing are the
following:
• Environmental Technology
• Biotechnology
• Chemical Processes
• Process Design
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• Process Equipment, Analytic Devices and Sensors, and Materials of
Construction
• Microtechnology and Microsystems Technology
Given the stiff competition for federal research dollars, it will be important for
chemists and chemical engineers to make a case for environmental technologies
as a potential source of wealth creation. Toward this end, Robert Wellek of the
NSF has estimated that the global market for environmental technologies
amounted to nearly $300 billion in 1992 and that this market could grow to
roughly $425 billion per year by 1997.
Turning to the issue of pollution prevention, there remains considerable
debate regarding the potential of pollution prevention strategies as a catalyst for
innovation, new market opportunities, and wealth creation. On the one hand,
U.S. businesses spent $91 billion in 1989 for pollution control and abatement, and
it was recently estimated that cleanup of Superfund hazardous waste sites could
cost as much as $700 billion, much of which will also come from U.S. businesses.
In light of these and other costs, avoidance of problems through pollution
prevention has become an option of choice for many U.S. chemical
manufacturers. On the other hand, responding to environmental challenges has
almost always been a costly and complicated proposition in which "win-win"
solutions are rare. Because of this, some globally managed corporations have
elected to move their production facilities out of the U.S. to areas that place a
lower value on less polluting manufacturing. Given these conflicting viewpoints,
this emphasizes that there is a great deal of wealth that can be made through
green manufacturing, and an important part of that process is obtaining the
funding needed for research in this area.
It is important that the activities of the NSTC Committee on Environment
and Natural Resources mesh with NSF's ongoing Environment and Manufacturing
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Initiatives. Within the Environment Initiative, emphasis is placed on the
development of new products, materials, and processing methods to minimize
pollution, while the Manufacturing Initiative concentrates on environmentally
conscious means of scaling up production, actual plant processing and equipment
design, and reuse of by-products for reducing manufacturing costs. Often, the
same R&D skills are used in both research initiatives, leading to opportunities for
cooperative and synergistic planning.
Recently, a number of integrating themes have been developed as priority
areas for the NSF Environmental Initiative; these integrating themes include
Biodiversity, Water and Watersheds, Environmental Technology, and Resource
Use and Management. The Environmental Technology theme is that
fundamental research in environmentally conscious technologies, monitoring
technologies, and remediation technologies increases our capabilities with regard
to environmentally benign manufacturing, materials, water and energy
technologies, and the application of existing technologies to new environmental
problems. In support of this theme and in partnership with other agencies -
including EPA - NSF plans to initiate cooperative research efforts supporting the
design and development of new products and materials, especially those that
involve streamlining synthetic methods and enhancing product biodegradability.
Benign Organic Synthesis
James Bashkin, Washington University
The state of the art of synthetic organic chemistry is often equated with the
tremendous advances that are occurring in the synthesis of highly complex natural
products of known or potential pharmaceutical importance. An example of this
type of advance is the synthesis of Taxol, an anti-cancer agent derived from the
bark and needles of yew trees (Figure 5). Achieving total synthesis of Taxol is
12
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OAc 0
Taxol
Figure 5. Chemical Structure of Taxol
remarkable not only because of the complex structure of the target molecule, but
also because of the number and complexity of chemical transformations that make
up the synthetic process (see Figure 6).
While not disputing the importance of synthesizing compounds of
pharmaceutical value, the broadening of our view of state-of-the-art organic
synthesis to include the synthesis of commodity and specialty chemicals might
afford the opportunity to develop equally impressive advances in the form of new
versions of old reactions that do not carry the "environmental baggage" of
traditional industrial processes. Moreover, new organic synthetic techniques can
be brought to bear in the manufacturing of many materials that are prepared via
organic chemical reactions. Examples of the breadth of areas in which synthetic
organic chemistry and organic chemical reactions impact on manufacturing and
society are:
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OAc
OP
HO
TBSO
D
OTES
TBSO'
OTES
TBSO-
II
OTES
TBSO'
J. ,4m. Chem. Soc. 1994, 116, 1597-1598
J. Am. Chem. Soc. 1994, 116, 1599-1600
Figure 6. Holton 's Synthesis of Taxol
14
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• Natural, semisynthetic, and synthetic fibers used in clothing
• Paper pulp used to form paper
• Polyurethane coatings that protect automobiles
• Structural plastics used to build medical devices and other equipment
• Rubber chemicals used in the manufacture of automobile tires and other
products
• Specialty fluids necessary to the operation of the Space Shuttle
Chemical processes involved in the preparation of materials for these purposes
include the bleaching of paper pulp, the uv-stabilization and crosslinking of
polymers, protection of automobile tires from oxidative breakdown, and
modification of fibers to improve stain resistance and wear.
Given the wide-ranging importance of commodity and specialty chemicals
to society, another "leading edge" of organic synthesis is embodied in attempts to
replace traditional synthetic processes with environmentally benign alternatives. It
is possible to develop benign organic syntheses that eliminate the waste of the old
process while at the same time offering a more economically viable method of
producing the target molecule. Because of this, the economics of benign synthesis
can be very attractive even without considering costs related to the environmental
elements of the equation.
One important barrier to the development of environmentally benign
syntheses has been the tendency of organic chemists to focus exclusively on the
target molecule (product). Many organic chemists feel successful if they are able
to synthesize a target molecule - even if the yield is small and the synthetic
process requires a large number of intermediate steps. In almost every such
process, however, by-products other than the target molecule are also generated.
In the past, chemical manufacturers have typically viewed these by-products as
15
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annoying but not terribly important wastes. In academic pursuits, where even
very low-yield syntheses may represent important intellectual advances, reaction
by-products do not always receive much attention. As awareness of the
environmental impact of chemical processes has increased, it becomes clearer that
all of the by-products of chemical reactions must be taken into account.
Although many organic chemists are working on the synthesis of very complex
molecules, few people are engaged in the development of new synthetic methods
that replace traditional bond-making and bond-breaking reactions or oxidation
reactions with environmentally acceptable alternatives.
To promote the development of new organic reactions that meet
environmental criteria, the application of the concept "the conservation of useful
mass" could help. The key tenet of this concept is to incorporate all of the atoms
in the starting materials in the product to the extent possible. Where reaction by-
products are unavoidable, these by-products should themselves be benign
compounds.
To illustrate the conservation of useful mass concept in a simplistic
manner, two different methods of producing water were outlined in Figure 7.
Using traditional methods, a mixture of an acid and a base produces water; both
organic or inorganic reactants could be used in this process. Although this type
of reaction has the desired effect of producing water, it does not meet the criteria
of conserving useful mass, since one equivalent of salt is produced for each
equivalent of water. If the goal of the process is synthesizing water, salt is a
waste product that will have to be dealt with in some way. Alternatively, water
could be synthesized via a reaction between hydrogen and oxygen. This pathway
results in a full conservation of useful mass, since all of the atoms of the starting
materials are incorporated in the product.
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The Synthesis of Water. 1.
Acid 4- Base = Salt + Water
An Inorganic example:
HC1 + NaOH = NaCl + H2O
Using an Organic Acid:
MeCOOH + [NMe4+]OH- = [MeCO2-][NMe4+]
+ H2O
Water is produced, but so is an equivalent of
salt.
The Synthesis of Water. 2.
H2 + 1/2O2 = H20
There is no wasted mass. AH of the mass of the
starting materials is incorporated into the
product.
Figure 7. Traditional versus Environmentally Benign Methods of Synthesizing Water
17
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A more sophisticated example of environmentally benign alternatives to
traditional reaction processes could be the oxidation reactions such as those used
in the bleaching of paper pulp. Traditionally, these reactions have been carried
out using a variety of chlorine-based bleaches (Figure 8). In these reactions,
C12
oci-
C1O2
C1O3-
C1O4-
Examples:
C12 + 2e- = 2 Cl-
+ ci2
HCl
Figure 8. Traditional Cholorine-Based Oxidation Reactions
chlorine gas acts as an oxidizing agent by accepting two electrons, in the process
generating two equivalents of chloride ion. Although effective in achieving the
desired oxidation, the halogen-based bleaching process produces waste chloride
anion and chlorinated organics that will have to be dealt with in some manner.
Similarly, chlorine gas is commonly used in the functionalization of benzene,
generating starting materials for nucleophilic aromatic substitution reactions.
Waste products associated with these types of reactions include two equivalents
of chloride waste: one in the form of hydrochloric acid and the other in the form
18
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of chloride that will act as a leaving group during the nucleophilic displacement
step of the reaction.
To accomplish the same goal in a more environmentally benign way,
oxygen and hydrogen peroxide could be used as oxidizing agents in place of
halogen-based compounds. As Figure 9 illustrates, the only by-products of such
oxidations would be two equivalents of water. All of the atoms of the starting
materials are incorporated in the reaction products, so this process, too, satisfies
the criteria for conservation of useful mass.
O2 and H2O2 as Clean Oxidizing Agents
0 + 2e- + 2H
H,0
2^2
2H,0
Figure 9. Oxygen and Hydrogen Peroxide as Clean Oxidizing Agents
There are a number of difficulties in attempting to use oxygen and
hydrogen peroxide as oxidizing agents, most involving the problem of how to
control the oxidation reaction once it begins. Normally, such reactions require
the use of a catalyst that helps modify the reactivity and selectivity of oxygen. It
is extremely difficult to avoid overoxidation to carbon dioxide or carbon monoxide
in a methane-to-methanol conversion, for example, unless the reaction is carried
19
-------
out in the presence of methane monooxygenase, a metalloenzyme that acts to
control the rate and extent of the oxidation reaction. Development and industrial
exploitation of metal catalysts that can replace environmentally dangerous
oxidizing agents should be an area in which increased efforts have a great deal of
potential. In some cases, such catalysts have already been developed and need
only be exploited by industry. One example of such catalyst development is the
use of a manganese dimer to accelerate the decomposition of sodium perborate,
allowing the bleaching of fabrics to take place at low temperatures.
Another approach to modulating oxidation reactions involves the use of
highly-oxygenated reactive intermediates. The development of a distillable
oxidizing agent, dimethyldioxirane, by Murray and colleagues at the University of
Missouri, St. Louis, is shown in Figure 10. Because it is distillable, this oxidizing
0 H->O, NaHCO3
+ KHSO5 *-
acetone potassium ,. .... .
rL™,* dimethyldioxirane
Caroate
1. Murray, R. W.; Jeyaraman, R., /. Org. Chem. 1985,50, 2847.
2. Waldemar, A.; Hadjiarapoglou, L.; Top. Curr. Chem. 1993,164,
45-62.
Figure 10. Preparation of Murray's Dimethyldioxirane as a Clean Oxidizing Agent
agent can be readily separated from organic by-products, and because it uses a
regenerable acetone as the oxygen carrier, it can also be recycled. By providing
20
-------
an oxidation pathway that is totally devoid of inorganic by-products, this kind of
reagent is currently receiving very serious attention in industry.
An example of green chemistry, which can be economically as well as
environmentally rewarding, is an alternate pathway to 4-nitro dybenzylamine. A
precursor, 4-nitro dyphenylamine, used in making the additives that prevent the
oxidative breakdown of automobile tires by ozone, can be made by traditional
means (see Figure 11). In this process, benzene is functionalized via an oxidative
chlorination reaction. The resulting chlorobenzene is nitrated, producing water
and a para-chloronitrobenzene intermediate. Finally, aniline or formaniline is
added in the presence of a base, where it acts as a nucleophile to displace the
chloride leaving group and form the target product.
The traditional synthetic pathway is limited by the formation of an
equivalent of salt, also produced for each equivalent of para-nitrodiphenylamine
produced. Given that compounds based on para-nitrodiphenylamine are
produced on a scale of approximately 300 million pounds per year worldwide, the
associated salt waste stream represents a significant challenge. The problem is
complicated further by the fact that the waste salt is contaminated by aromatic
amine impurities that are structurally related to benzidine, a known human
carcinogen.
To evaluate the potential for environmental and human health risks
associated with conventional methods of producing para-nitrodiphenylamine, an
attempt was made to devise a synthetic pathway through which the target
compound could be produced without generating any salt. The major problem
that had to be overcome was finding a way to perform a nucleophilic substitution
reaction without a leaving group, or using hydride as a leaving group. Direct
nucleophilic attack of the nitrobenzene produces a Meisenheimer complex that is
21
-------
Cl
+ Cli
HC1 +
Cl
HNO3 H20
Cl
NH2
Cl
K2C03
HN
•O'^O
+ KC1
-o'NS
Figure 11. Conventional Pathway for Synthesizing para-Nitrodiphenylamine
22
-------
structurally similar to that produced in the chlorination reaction, except that the
structure does not include a good leaving group (Figure 12).
Conventional Nucleophilic Aromatic Substitution for Chloride
NOo
N02
NU'
Nu
Cl
=N
,o. cr
ci
Nu
Nucleophilic Aromatic Substitution for Hydrogen
NO2
NU"
Nu.
H' Y—/ ~ v
N
N
N02
Nu H
Nu
-H"
Nu
Figure 12. Generation of a Meisenheimer Intermediate via Chlorobenzene
versus Direct Nucleophilic Attack
23
-------
To achieve the desired product, a method had to be found to replace a
hydride - whether in the form of a proton plus two electrons, a hydrogen radical
and an electron, or a hydride ion - in order to aromatize the ring. The method
chosen was to use aniline as a starting material in the presence of a catalytic base,
tetramethylammonium hydroxide (see Figure 13). In this system, the catalytic
base deprotonates aniline, generating an anilide nucleophile. This nucleophile
attacks the nitrobenzene molecule, forming a Meisenheimer complex in which the
no-longer aromatic nitro group can act as a hydride acceptor. Depending on the
concentration of nitrobenzene present, the reaction yields varying combinations of
para-nitrosodiphenylamine, para-nitrodiphenylamine, and azobenzene. The nitro
and nitroso compounds are readily hydrogenated, generating more of the desired
para-nitrodiphenylamine product. Azobenzene can be hydrogenated to produce
aniline, which can be recycled in the reaction. Thus, the only by-product of the
reaction is distilled water.
The overall stoichiometry of the catalyzed reaction is summarized in Figure
14. In this reaction, nitrobenzene plus anilide in the presence of a catalytic base
yields para-nitrosodiphenylamine plus water. This reaction avoids both the
chlorination of nitrobenzene and the subsequent removal of the chloride ion
during the nucleophilic substitution step, and the only by-product of the process is
distilled water. The oxygen atom in the water comes from the nitro group, one
hydrogen comes from the aniline, and the other comes from the Meisenheimer
intermediate.
The overall synthetic yield of the nitro and nitroso compounds is 90% or
greater, depending on the anilinemitrobenzene ratio of the reaction mixture
(Figure 15). Since nitrobenzene is much cheaper than para-chloronitrobenzene,
this route not only avoids environmental clean-up problems but is actually more
cost-effective than the conventional process for synthesizing para-
24
-------
TMA+
+ TMA(OH)
+ H20
tfTTMA* N02
Ortho Attack
Phenazine
Intramolecular
Pathway
N02
N
Intermolecular
Pathway
Azobenzene
13. Synthesis of para-Nitrodiphenylamine Without Using Chlorobenzene
25
-------
catalytic
base
Figure 14. Overall Stoichiometty of the Tetramethylammonium Hydroxide-Catalyzed
Synthesis of para-Nitrosodiphenylamine
Mole Ratio
Aniline :Nitrobenzene
Yield*
1.32
11.9
51.5
15
55
86
30
35
9
^Reverse phase HPLC was used to analyze the reaction mixtures. The external standard metr.od
was used to quanntaie reaction yields using a Vydac 210HS54 ( 4.6 X 250 mm) column and t"V
detection at 254 run. Yields are normalized to total moles of 4-NODPA and 4-NDPA produced it
each AN:MB ratio.
Figure 15. Percent Yield of Nitro and Nitroso Diphenylamine Products
with Varying Aniline: Nitrobenzene Ratios
26
-------
nitrodiphenylamine. Monsanto has taken this alternative mode of synthesis to a
pilot plant stage, and the economics of the process thus far look very promising.
There are a number of nucleophiles other than aniline that can be used in
aromatic substitution reactions designed to avoid the use of chlorobenzenes. For
those interested in more information, the following references are offered:
• "Methods of Preparing Anti-ozonants for Rubber Chemicals," M.K.
Stern and J.K. Bashkin, U.S. Patent 5,117,063.
• "The Direct Coupling of Aniline and Nitrobenzene: A New Example of
Nucleophilic Aromatic Substitution for Hydrogen," M.K. Stern, F.D.
Hileman, J.K. Bashkin, /. Am. Chem. Soc., 1992, 114, 9237-9238.
• "Process for preparing/7-nitroaromatic amides and products thereof,"
J.K. Bashkin, M.K. Stern, U.S. Patent 5,331,099.
• "Animation of Nitrobenzene via Nucleophilic Aromatic Substitution for
Hydrogen: Direct Formation of Aromatic Amide Bonds," M.K. Stern,
B.K. Cheng, /. Org. Chem., 1993, 58, 6883-6888.
There is information relating to green processes currently sitting on shelves
in universities and industry. The main obstacle to commercial application of
some processes is the difficulty of raising the capital needed to build new
chemical plants. Federal assistance in this area - perhaps in the form of new
guidelines regarding the tax treatment of capital expenditures - would provide a
useful counterbalance to penalties that are rightly imposed for chemical processes
that pollute. In addition, federal funding should play an important role in
educating academic scientists about and supporting research on the standard
bond-making and bond-breaking reactions that need to be re-examined from the
perspective of environmentally benign organic synthesis.
27
-------
Benign Biosynthesis
Jerome Schultz, University of Pittsburgh
Since the term benign biosynthesis is a relatively new one, the area may be
approached from two distinct points of view. First, benign biosynthesis can be
defined in terms of utilizing what might otherwise be considered waste; included
within this definition would be efforts involving the use of biotechnology to
convert agricultural wastes to chemical feedstocks (e.g., lignocellulose to ethanol)
or to treat conventional feedstocks in ways that reduce their potential to pollute
(e.g., desulfurization of coal). Second, it is important to keep in mind that most
of conventional biotechnology is based in aqueous systems, which could pose
problems for large-scale manufacturing in that most of these systems are relatively
dilute. Another definition of benign biosynthesis, therefore, involves exploring
ways in which enzymes and other biotechnologic approaches to chemical synthesis
might be applied to non-aqueous systems.
To set a general framework for the discussion, a table from the July, 1994
issue of Chemical and Engineering News lists most of the organic chemicals
currently produced in the United States (see Figure 16). This table raises two
important issues regarding biosynthetic approaches to organic chemistry. First,
most of the chemicals on the list are produced in the range of millions to billions
of pounds. One question, therefore, is whether biotechnologic techniques can
realistically be expected to achieve production levels in this range. Second, most
chemicals on the list are low molecular weight compounds, whereas the efforts of
the biotechnology industry have been focused mainly on production of large
pharmaceutical compounds. Thus, a second question concerns how adaptable
existing biotechnologic techniques will be to the production of smaller molecules.
28
-------
Acetic Acid, synthetic
Acetone
Acrylonitrile
Aniline
Benzene
Bisphenol A
1,3-Butadiene
1-Butanol
Caprolactam
Chloroform
Cumene
Cyclohexane
Dioctyl phthalate
Ethanol, synthetic
Ethanolamines
Ethylbenzene
Ethylene
Ethylene dichloride
Ethylene glycol
Ethylene oxide
2-Ethylhexanol
Formaldehyde
Isobutylene
Isopropyl alcohol
Maleic anhydride
Methanol, synthetic
Methyl tert-butyl ether
Methyl chloride
Methyl ethyl ketone
Methyl methacrylate
Methy (chloroform
Methylene chloride
Perchloroethylene
Phenol, synthetic
Phthalic anhydride
Propylene
Propylene glycol
Styrene
Terephthalic acid
Toluene
Vinyl acetate
Vinyl chloride
o-Xylene
p-Xylene
- — — -•-— >*• gams, wnviii^iai rTOOUCtlon
Chem and Eng News - July 1994
Millions
Pounds
3656
2462
2508
1011
13416
1286
3092
1328
1359
476
4489
2000
245
740
706
11758
41244
17945
5228
5684
688
3041
1146
1236
424
10542
24053
849
556
1088
452
354
271
3718
854
22398
885
10063
7837
6664
2827
13746
884
5757
Total 240966
% change
(1983-1993)
23
£m W
24
•»~
19
34
27
50
24
37
28
24
25
17
-18
-31
34
33
30
36
w w
15
I w
3
44
28
34
2
29
24
97
52
4
22
-23
-39
-50
29
2
38
45
32
28
6
31
50
ww
12
29
Figure 16. Production of Organic Chemicals in the United States, 1993
29
-------
To address the issue of biomass feedstocks, Figure 17 shows data
developed by Charles Scott and colleagues at the Oak Ridge National Laboratory.
These data indicate that millions of tons of waste materials could potentially be
used to replace petroleum as a feedstock for chemical production. With potential
feedstocks in the 3 trillion ton range, the volume of biomass resources is large
enough to have a significant impact on the production of industrial organic
chemicals. Altogether, chemicals that could be synthesized from agricultural
feedstocks have a total value of approximately $110 billion per year. Most
promising in this regard, 25% of these chemicals that represent oxidation
products could potentially be produced by microorganisms.
The potential use of wastepaper as a chemical feedstock offers another
example of an evolving biotechnology. Because wastepaper is already being
"harvested," raw material costs should be vanishingly small. At the same time,
the amount of wastepaper currently processed is enough to produce on the order
of 4 million gallons of ethanol per year, and at a competitive price (i.e., less than
$ I/gallon). As such, use of wastepaper as a feed material for the production of
ethanol may well represent the first entry into the industrial market of a
lignocellulose-based commodity chemical.
For a chemical manufacturing plant to be built around a bioprocess, two
important criteria must be met. First, the proposed feedstock must be able to
compete with the fluctuating and currently low cost of fossil materials, and
secondly, an adequate supply of the feedstock must be assured. From this
perspective, waste materials may be the most useful feedstocks for initial market
penetration. Second, the manufacturer must have the advanced technology
required to process this material. In this regard, research directed toward
development of more effective biocatalysts and more advanced bioprocessing
systems may be especially useful.
30
-------
PRODUCTION
(Millions of Drv Tons/Yr)
FEEDSTOCK
CROPS:
LIGNOCELLULOSE
STARCH CROPS
FORAGE GRASSES
WASTE:
AGRICULTURAL
LIVESTOCK
INDUSTRIAL
MUNICIPAL
FORESTRY
TOTAL
Current
391
103
26
390
290
60
125
110
1495
Potential
1565*
1575*
414
390
325
60
160
140
3064*
'Since some of the same land area may be required by both lignocellulose
and starch crops, the quoted potential biomass for each could be mutually
exclusive. The total potential feedstock includes only one of these sources.
Figure 17. Current and Potential Biomass Feedstocks in the United States
(Source: "Production of Organic Chemicals via Byconversion,"
U.S. DOE Report EGG-2645, 1991.)
31
-------
From a biochemical engineering perspective, the most effective approach is
to consider the entire biosynthetic process (Figure 18). Particularly if benign
biosynthesis is the goal, it is no longer sufficient to think of the acquisition of
feedstocks and the disposal of waste products as separate processes; rather, it is
necessary to consider the system as a whole, from input to output. Not only must
chemical engineers consider the material balance around an entire plant, but it is
also becoming increasingly important to think of material balances around the
economy as a whole. From this broader perspective, it may well turn out that
waste materials produced by one industrial sector are ideal feedstocks for
another.
n
CARBOHYDRATE!
REFINING AND
CHCMICAL
•IOCHEMICAI
CONVERSION
REFINED Oil 3
CORN NEFHtENV
Figure 18. A Total-System Perspective on Bioprocessing
(Source: Dr. Charles Scott.)
32
-------
Another important consideration in biochemical processing is scale, since
catalyst-based processes often involve flow dynamics that are not easily scaled up
to the larger systems required for production in the millions of gallons or millions
of tons range. In the petrochemical industry, similar problems have been
overcome by development of fluidized bed technologies (Figure 19). Using the
FLJIDIZED-3ED
REACTOR •
?ART!CLE RETURN
(IF NECESSARY)
..QUID EFFLUENT
-EXPANSION SECTION
TO ENHANCE
DISENGAGEMENT OF
GAS PHASE AND
SECONDARY
PARTICLES
-BOTTOM TAPER TO
ENHANCE "ARTICLE
SEPARATION
SECONDARY PARTICLES
TO PRODUCT RECOVERY
_J
LIQUID FEED STREAM
(4 'NLETS)
MULTIVANE PARTICLE
lOVAL VALVE
Figure 19. A Biparticle Fluidized Bed Operating in Countercurrent Mode
(Source: Dr. Charles Scott.)
fluidized bed model, it is usually possible to construct very large systems that
behave very similarly to smaller, pilot-scale systems. If fluidized bed behavior can
be adapted to biochemical processing, it might be possible for advanced
separation systems such as adsorption to replace or augment less efficient
processes such as distillation. At the same time, it might also be possible to
combine two or more processing steps.
33
-------
Figure 20 illustrates how fluidized bed bioreactors could be incorporated
into a biochemical production process. In this case, ethanol is produced from
*
WATER
WASTEPAPER
MAKE-UP \_X
WAHR i}
I
SOLID WASH (OR
*" BOILER fflO
AnvAMrrn RECYCLED ENZYMES *v \ J
r » HYDROLYSIS
SYSTEM
GLUCOSE
PRODUCT STREAM
a
M WASTE STREA
u
o
2 OFF-GAS OFF-GAS CO-
o » » *
| FIUIOIZED BED f
v •* -"\ r
X \ E COOLING
rn rrp ENZYME ., '
RECOVERY ** REAGIHIS
REACIOR ;
* WITH UNREACTED SOLIDS
r-*- ETIIANOI Oil GAS
DILUTE f^\ I
ponnurr niSIIIIAllOH } ' WAIER fOR
•*^*~ foR nHAN"l ~*"^~ ' --••"• -' - "" ""'
PRODUCTION
• .» FIUIOIZED -BED «. •
''• . BIOREACTOR . cl
• * . FOR CELIUI ASE
.."„ PRODUCTION .". .
W \4/
f GLUCOSE f
NUTRIENTS
' . OR RLCYCLl
° • flUIDIZFD BIO
WASTE ' / FOR WASHWAHR
SOLIDS r- ••! TR(ATMINI
III MR
Figure 20. Process Flowsheet for the Biological Production of Ethanol from Wastepaper
(Source: Dr. Charles Scott.)
wastepaper feedstocks. The flow chart in Figure 20 illustrates the basic difference
in viewpoint between chemists and chemical engineers, in that chemical engineers
must consider both the energy and mass balances of industrial processes. Thus,
to gain a perspective on the process as a whole, a chemical engineer must
consider all streams coming into and going out of the plant. To a chemical
engineer, energy must be viewed as a cost in much the same way that materials
are a cost of the process as a whole.
34
-------
Another obstacle to the development of biochemical industrial processes
arises from the relative lack of in-house biochemical engineering expertise in the
chemical manufacturing industry. Although most manufacturing interests have
experts in chemical or petrochemical engineering on hand, relatively few employ
individuals with training in biochemical engineering. As a result, it is common for
engineers unfamiliar with biochemical unit processes to overestimate the costs of
biological elements of the process. Intuitively, chemical engineers are likely to
expect enzymes or microorganisms for biosynthetic processes to comprise a large
part of the total cost of the process. In fact, as Figure 21 illustrates, costs
50r
I Feedstock
| Capital
[Operating
I Energy
Figure 21. Breakdown of Ethanol Production Costs by Process Area
(Source: Chemical Engineering Progress.)
associated with biochemical elements comprise only a small fraction of total
process costs. In this particular process, which involves using hydrolytic enzymes
to produce ethanol from a cellulose feedstock, the costs associated with feedstock,
treatment, and utilities are significantly higher than those associated with
production of the enzyme. Thus, economics of the process are far more
35
-------
dependent on materials and energy costs than on the cost of the catalyst or other
biological components.
A sensitivity analysis of the same production process (Figure 22) confirms
that major benefits in terms of process improvements lie not in reducing the cost
o>
CTJ
o
c
JO
75
c
O
O
Yield Cone. Rate Enzyme Agitation
Figure 22. Sensitivity of Ethanol Selling Price to Major Process Parameters
(Source: Chemical Engineering Progress.)
of the enzyme but rather in increasing the yield of the conversion and/or
concentration of the product. These two parameters, which together comprise
recovery cost of the product, represent an especially important component of total
biosynthetic costs, since microorganisms used in aqueous biochemical processing
typically grow only in very dilute solutions. As a result, industrial processes
currently using microorganisms tend to have very low yields - in most cases lower
than 10% (Figure 23).
36
-------
Product
Acetone/butanol/ethanol mixture
Antibiotics by established processes (e.g.,
penicillin G)
Cyanocobalamin
Enzymes (e.g., serum protease)
Ethanol
Lipids
Organic acids (e.g., citric acid, lactic acid)
Riboflavia
Single-cell proteins (e.g., yeast where entire
dry biomass is product)
Concentration
(*!-')
18-20
10-30
0.02
2-5
70-120
10-30
40-100
10-15
30-50
Figure 23. Typical Concentrations of Products Leaving Fermenters
(Source: Handbook of Biochemical Engineering.)
The inverse relationship between product concentration and selling price is
illustrated in Figure 24. When the concentration of product is low, as is the case
with many pharmaceutical biotechnology products, the selling price tends to be
high. Conversely, only compounds that can readily be produced at high
concentrations can be marketed at low selling prices. By the same token, when
economies of scale can be achieved, biological products can be competitive on a
price per weight basis (Figure 25). The obvious conclusion is that efficient and
economical bioprocessing will require methods of producing materials at higher
concentrations than can be obtained using conventional biochemical processes.
37
-------
10"
10-
10»
10-i
10"
10
10-
•Water
Ethanol
Amino acids
.Citric acid, monosodium glutamate
, Penicillin
^.Threonine
Antibiotics
MicrobUi
proteases
AmyUses
Research/diafnostk
enzymes
Glycerophospate
dehydrogenase
Luciferase
I I
Urokinase-
Therapeutic enzynws^^^^
I I Jill
io-< jo- to* 10- io> IP 10* io> io» i 10*
Seilin«pnce($ kf)
Figure 24. Relationship Between Product Concentration and Selling Price
(Source: Handbook of Biochemical Engineering.)
10
10
13
10
Interferon
.Human Factor VIII
Human Growth Hormone
• Rennin
Insulin • "
Vitamin 8,2*
Benzyl Penicillin
Citric Acid*
Baker's Yeast'
• Cheese
•Beer
10'
r2
1 102 104 10s 108
10
,10
World Production (tons/annum)
Figure 25. Relationship Between Selling Price and Worldwide
Production of Various Fermentation Products
(Source: Handbook of Biochemical Engineering.)
38
-------
Production of high-fructose corn syrup through the enzymatic conversion
of glucose to fructose (Figure 26) represents an example of a successful large-
scale process using biochemical methods. Worldwide, the total market for high-
fructose corn syrup is about 6 million tons per year, which translates to roughly
CHO CH2OH
H-C-OH C = 0
HO — C — H Glucose HO — C — H
I ^ |
H — C — OH Isomerase H — C — OH
I I
H-C-OH ™°C H-C-OH
CH2OH CH2OH
D-Glucose D-Fructose
Figure 26. Production of High-Fructose Corn Syrup by Enzymatic Methods
$20 billion. As in the earlier example, analysis of the economics of high-fructose
corn syrup production indicates that the biological component - enzyme -
accounts for only a small fraction of the total production cost (Figure 27).
Turning to a different area of biochemical processing, consider the issue of
enzymes as tools in environmentally benign chemical processing. To illustrate the
broad variety of areas in which enzymes might play a role in benign processing,
Figure 28 shows a list of potential applications prepared by Alan Russell of the
University of Pittsburgh.
39
-------
Production cost of MFCS US (cents/lb)
a. Raw com cost (1980) 9^03
b. Return from by-products
Oil 1.38
Feed (Gluten) 2.79
Meal (Gluten) 0.75
c. Net raw material cost, a-b 4.11
d. Other costs
Enzyme 0.40
Operating Labor 2.00
Utilities 0.70
e. Total variable cost 7.31
f. Fixed overhead costs 2.00
Freight 1.75
g.Totil 11.06
h.Capital investment cost 2.40 - 4.50
i. Total (42% HFCS) 13.46 -15.56
j. Total (55% HFCS) + 15% 15.48 -17.89
Figure 27. Economics of High-Fructose Corn Syrup Production
(Source: Dr. Alan Russell.)
The remainder of this presentation focuses on four general areas:
• Enzymes as Catalysts
• Enzymes in Supercritical Fluids
• Enzymes in the Gas Phase
• Enzyme Catalysis in Pure Reactants
Regarding the use of enzymes as catalysts, Figure 29 presents data showing
the enhancement of chemical reaction rates possible with use of enzymes as
alternative to heavy metal catalysts. In one set of data, addition of a pig liver
40
-------
Enzymes in organic solvents
Bioluminescence Enhancement
for Chemical Detection
Specialty Monomer Synthesis
Specialty Polymer Synthesis
Enzymes in Reverse Micelles
Bioluminescence Enhancement
for Chemical Detection
Pesticide Degradation
Nerve Gas Degradation
Enzymes in Gas Phase
Oxidation/Reduction of volatile compounds
Nerve Gas degradation
Waste Gas Treatment
Thermophilic Enzymes
Sterilizable Biosensors
Self-Cleaning Membranes
Catalysis of viscous fluids
Contamination Resistant
Bioprocessing
Rapid Bioprocessing
Supercritical Fluids
Polymer Synthesis
Peptide Synthesis
Defined Sequence Polymers
Metal Extraction (Ur, Hg, Pb)
Environmentally Benign
Chemical Processing
Protein Purification
Chemical Waste
Extraction/Remediation
Stabilization of Thennolysin
Diabetes Treatment
Bioactive Membrane Synthesis
Bioactive Fiber Synthesis
Bioactive Bead Synthesis
Oil-Spill Clean-Up
Figure 28. Potential Applications of Enzymes in Environmentally Benign Chemical Processing
41
-------
Substrate Catalyst Rate Temperature
Constant
IVT sec
Ethyl Butyrate H20 1CT5 100
(Hydrolysis)
OH' KT1 25
Pig Liver 104 25
Esterase
Enzyme Substrate Product Enzyme Catalyzed Rate
Un-Catalyzed Rate
Hexokinase Glucose, ATP Glucose-6-P > 1010
Phosphorylase Glucose-P, Glycogenn+1 > 1011
Glycogenn
Alcohol Ethanol, NAD Acetaldehyde > 109
Figure 29. Enzymatic Enhancement of Chemical Reaction Rates
(Source: Dr. Alan Russell.)
esterase increased the rate of ethyl butyrate hydrolysis by 8 orders of magnitude
compared with a hydroxide catalyst. Other enzymes have been demonstrated to
increase reaction rates between 9 and 11 orders of magnitude in comparison
withuncatalyzed rates for a variety of other types of biochemical reactions,
including phosphorylation reactions, polymerizations, and acetaldehyde
production.
Next, supercritical fluids may be used as solvents to carry out biochemical
reactions. Thermodynamic properties of supercritical fluids, which are gases
compressed to a level at which they behave as fluids, offer more degrees of
freedom than can be obtained using conventional solvents. Although supercritical
42
-------
fluids have been used in extraction processes, their use as solvents for biochemical
reactions is relatively new. The advantage of supercritical fluids is that
separations can be made markedly more efficient and inexpensive by changing the
pressure at the end of a reaction to convert the solvent to a gas.
Figure 30 shows an example of the potential value of supercritical fluids as
solvents for enzyme-catalyzed reactions. A polymerization reaction that Alan
CC13CH2 -
0 Bis(2,2,2-trichloroethyl) Adipate
CH,CC13
HOCH,
"CH,OH
LJPASE
1,4-butanediol
HOHC,
FURTHER POLYMERIZATION
Figure 30. Lipase-Catalyzed Polymerization Reaction
(Source: Dr. Alan Russell.)
Russell has been exploring where an adipate and a butanediol are exposed to a
lipase that promotes the polymerization reaction is depicted. When using
supercritical fluoro-form as a solvent, it is possible to control the reaction to
43
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produce polymers of a defined molecular weight (Figure 31). In this system, the
polymer grows as a function of time, but changing pressure of the supercritical
fluid changes solubility of the polymer, eventually causing it to precipitate out of
solution. Thus, it is possible to generate polymers of any desired molecular
weight simply by adjusting the pressure under which the reaction is conducted.
A third example of potential biosynthetic applications of enzymes deals
with use of enzymes on solid supports as catalysts for gaseous substrates (Figure
32). This approach is especially useful for oxidation-reduction reactions, where a
proton acceptor or exchanger must be present. In a redox reaction, the enzyme is
supported on a solid matrix to which some type of solvent or fluid also adsorbs,
and the reactant is present in the gas phase. The advantage of this system is that
the nicotinamide cofactor stays with the enzyme and can be recovered for reuse.
As a result, this expensive cofactor can be recycled, whereas in an aqueous system
the cofactor would be lost.
A final example involves benign synthesis that does not use a catalyst at all
- i.e., a system in which the reactants themselves are the liquid phase. To
illustrate this concept, consider a reaction in which methyl methacrylate and
hexanol are mixed together as pure liquids (Figure 33). When the lipase catalyst
is added to the mixture, methacrylate can be separated out and the remaining
reactants can be recycled. Thus, in this system, a concentrated form of reactants
is used to generate a concentrated product without unwanted by-products.
In summary, this presentation has focused on three main ideas:
For biochemical engineering to have a significant impact on industrial
processes, it must function on a scale capable of generating products in
large volumes, which for most industrial chemicals is in the millions of
pounds range.
44
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* Enzyme
I Monomers
CHKHKH Soluble Polymer
Precipitated Polymer
INCREASING PRESSURE
a a
0»
Q»
D*O»O-BJ
MKMKOwO-fJ
Dw
Raactor after
completion of
biocAUlytic
polymerization
o»
0*0*
CHHHKrt
Molecular Weight Distribution ofSolubU (S) and Solid (P) Phtun
Pressure
(p«i)
900
1600
2400
3000
Molecular
Weight of the
Soluble
Polymer
•987
1424
2586
2849
Average
Molecular
Weight and
Diapenity of the
Soluble Polymer
"937 (1.07)
1037 (1.11)
1371 (1.18)
1762 (1.23)
Average Molecular
Weight and
Diipenity of the
Precipitated Polymer
•1020 (1.02)
1677 (1.03)
2774 (1.03)
3357 (1.05)
The alcoholyaia of bis<2,2,2-trichloroethyi) adipate by 1,4-butanediol catalyzed by
porcine pancreatic lipaae impended in fluorofonn at 50 "C. The error in
determination of polymer molecular weight* i« ±5 %. «The extraction* for the
biocatalysia experiment performed at 900 p*i wen performed in a supercritical fluid
extractor in which the minimum preMure achievable ia 1200 pai.
Figure 31. Relationship Between Pressure and Degree of Polymerization
in a Supercritical Solvent System
(Source: Dr. Alan Russell.)
45
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OH
3-methyl-2-butcn-1 -ol
NAD
3-methyl-2-butenal
Bakers yeast
alcohol
dehydrogenasc
NADH
Uopropanol
Conversion: Avg 8% over 150 hours
Figure 32. Enzymatic Catalysis in the Gas Phase
Methyl Methacrylate
2-Ethyl Hexanol
Upase (Candida cylindracea )
2-Ethylhexyl Methacrylate
$/#
Methanol
Figure 33. Enzymatic Catalysis in Pure Reactants
46
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• Problems with dilute aqueous chemistry remain to be resolved, but
promising methods for dealing with these problems have begun to be
developed.
• With development of new technologies, enzymes can be used as catalysts
in organic syntheses, but these applications will require new thinking on
the part of industrial chemists and chemical engineers.
Regarding the last point, the most likely scenario for broader use of enzymes as
catalysts involves joint efforts between the traditional organic chemistry industry
and the emerging biotechnology industry. In this scenario, the smaller
biotechnology companies could create and provide the needed catalysts to larger
chemical companies engaged in industrial-scale organic synthesis.
Benign Engineering Approaches
C. Thomas Sciance, DuPont Experimental Station
The concept of engineering paradigms was defined as "patterns that
determine the rules of the game." Since ideas and concepts outside the prevailing
paradigm usually remain invisible, behaviors that have been rewarded in the past
are reinforced even in the face of considerable evidence that the future will be
different.
Figure 34 outlines the paradigms that have defined the boundaries of
chemical engineering over the past several decades. For many years, chemical
engineering was dominated by a growth-centered paradigm in which rewards came
from increasing capacity and solving problems quickly. Under this paradigm, it
was often better to proceed simultaneously on several possible solutions to a
technical problem rather than to waste time attempting to determine which
solution was best. Technical mistakes were corrected during subsequent
expansions, and economies of scale dominated capital decisions.
47
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GROWTH
• Speed
• Expandability and flexibility
• Economies of scale
• Add capacity
EFFICIENCY
• Reduce fixed costs (people, physical plant)
• Reduce variable costs (materials, energy)
• Economies of scope
• Rationalize capacity
SUSTAINABLE ECONOMIC GROWTH
• Globalization (production, markets, labor)
• Life cycle thinking (materials, process, products)
• Strategic growth
• Minimal environmental impact
• Economies of balance
Figure 34. Evolution of Engineering Paradigms
In recent years, as the global chemical industry suffered hard times, the
growth-centered paradigm was supplanted by a new paradigm centered on
efficiency. This new paradigm emphasized differentiation of products through
quality and customer service, reducing costs, and various types of rationalization
such as disinvestment, mergers, and downsizing. Under the efficiency-centered
paradigm, excess capacity became a burden rather than an opportunity. At the
same time, rewards were more likely to come from cost-conscious management
than from economies of scale. As a result, technical options and innovations have
been studied more carefully and implemented more cautiously than in the past.
Chemical engineering is currently under-going another paradigm shift, this
time to a paradigm that has sustainable economic growth as its central organizing
48
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principle. Rewards in the next decade and beyond will come from strategic
thinking that leads to an economically viable compromise between business and
societal needs. Technology will play an essential role in this process, but it will
have to take into account many more variables than ever before. Under this
paradigm, effective management will consist of learning how to cooperate
effectively in order to compete more effectively. A multidisciplinary approach will
be required, not only because of the complexity of the technology but also
because of the variety of interests that must be considered. At the same time,
new tools and techniques will be needed to improve the selection and execution
of research and development programs.
To describe the situation, testimony to a Congressional committee by
Braden Allenby of AT&T in May of 1994 is quoted:
In leading industrial firms, we are moving conceptually beyond end-of-pipe
and emission control technologies, beyond even pollution prevention and
waste reduction programs. It is not that we are reducing such activities in
an absolute sense. Rather, we are recognizing that they are not, by
themselves, adequate to allow us to live in equilibrium with natural
systems. They are an important dimension of the solution, but by no
means the only one.
This understanding is leading to a fundamental change in the way the
environmental impacts of materials and products are being managed
around the world. Most importantly, it is now clear that any
environmental assessment of materials must include consideration of
impacts across the lifecycle of materials - from their mining or initial
production, to their use in commerce and products and return of the
components or materials to the economy. Fixating on any single lifecycle
state of a material runs the risk of failing to recognize more serious risks
posed at other stages.
The logical conclusion is that decisions in the future will have to take into account
a longer time horizon and a much broader scope than was ever necessary in the
past. This necessity may in turn lead to some reversal of the trend toward
49
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decision-making at lower and lower levels of industrial organizations. In the
future, it will be necessary for those in leadership positions to view a wider field
and operate in a longer time horizon than is currently the norm.
A graph from a report prepared by a Dutch government group studying
the time horizon likely to be involved in achieving the development of sustainable
technology is illustrated by Figure 35. This group found that, starting from a new
situation, it may take 10 years or more to progress to some form of sustainable
technology. From an existing situation, several decades may be required. Using
DuPont's five adipic acid plants as an example, it would cost billions of dollars
and take more than a decade to replace this investment, even if technologically
and economically attractive options were currently available.
bmlsslon
level
100
75
SO
25
'ENVIRONMENTAL PROTECTION'
curb
'END OF PIPE1
shift
'PROCESS-INTEGRATED'
adapt
'SUSTAINABLE TECHNOLOGY*
renewal
10
25
starting from the existing situations
starting from new situations
Figure 35. Predicted Time Course for Developing Sustainable Technologies
(Source: "Sustainable Development: a Challenge to Technology.r'
J.LA. Jansen and Ph. J. Vergragt, 6-92.
Ministry for Housing, Physical Planning and Environment.
Technical University of Delft, Netherlands.)
50
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It is important to keep in mind that not every good technical idea that
would improve the environment is economically viable. Without economic
viability a good technical idea is not a technology at all - it is merely a fact or a
bit of knowledge. Clearly there is room for technical improvements that are both
environmentally advanced and that meet the economic criteria necessary to
implement them. Economic growth and environmental protection are inextricably
linked, however, and competent engineers are going to have to learn how to deal
with both.
One area having a great deal of potential value is generic science related
to pollution prevention. The only example of truly generic research in this area
that a group of chemists and chemical engineers at a meeting several years ago of
the Council for Chemical Research (CCR) were able to cite, concerned work at
UCLA on avoiding making aerosols in the range of droplet sizes that are difficult
to collect. Concluding that most waste prevention or avoidance work is extremely
process-specific, and that prevention is both conceptually and intellectually a more
difficult problem than clean-up, the CCR and NSF jointly published a list of areas
in which basic pollution prevention research is needed. Items listed in the joint
program announcement included the following:
• New chemistries and methodologies for on-demand, on-site production
and consumption of toxic intermediates for use in manufacturing
• New, more highly selective catalysts to increase product yield and reduce
by-product formation in chemical manufacturing
• Low-energy separation technologies for feedstock purification and
recycling
• Improved membranes and membrane/molecular sieve technologies that
integrate transport and reaction to enhance specificity
• Alternative chemical syntheses that bypass toxic feedstocks and solvents
such as chloro- and nitrocarbons
51
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• New processing methods that eliminate production of hard-to-entrap
micron-sized aerosols
• Alternative chemical syntheses that eliminate or combine process steps,
resulting in a net reduction of pollutants
• Design of novel low-temperature or other energy-efficient methods for
chemical synthesis and processing
Approaching the same problem from a slightly different perspective, the
Chemical Manufacturers' Association (CMA) has published as part of its
Responsible Care™ series a book called Designing Pollution Prevention into the
Process. Whereas the CCR/NSF list begins from technologies and their possible
applications, the CMA document contains an appendix listing pollution prevention
ideas from a perspective that is more process-oriented (see Figure 36). This
appendix is another good source for stimulating thinking about waste prevention.
One of the most difficult tasks in process design is asking the right
questions to begin with. Three areas were presented in which asking the right
questions is particularly important:
Fundamental beliefs and assumptions (e.g., What business are we in?
Why are we making this product? Why do we use the materials we do?)
Factors that govern investment behavior (e.g., Is management willing to
innovate? Is capital available? What is the time scale? Is there an
investment hurdle rate?
What we "know" that may not be right (e.g., What were our past
"failures" and have the reasons for failure changed? Could cooperation
help? Could leveraging help?)
The Strategic Decisions Group (which attempts to apply mathematical methods
such as decision tree analysis to decisions about research and development)
advocates separating the probability of technical success from the probability of
52
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Pollution Prevention Ideas
Byproduct/Coproducts
Quantity and Quality
Uses and Outlets
Catalysts
Composition
Preparation and Handling
Effectiveness
Intermediate Products
Quantity and Quality
Properties
Process Conditions/Configuration
Temperature
Pressure
Corrosive Environment
Batch vs. Continuous Operations
Process Operations/Designs
Product
Process Chemistry
Product Formulation
Raw Materials
Purity
Vapor Pressure
Water Solubility
Toxicity
Regulatory
Form of Supply
Handling and Storage
Waste Streams
Quantity and Quality
Composition
Properties
Disposal
Figure 36. Pollution Prevention Ideas (Source: Chemical Manufacturers'
Association, Designing Pollution Prevention into the Process)
commercial success/given technical success. If the probability is low that a
technical success will be implemented in the industrial R&D community, it usually
makes more sense to look for something else to do.
An example of a situation in which benign engineering played a significant
role in process selection, is DuPont's experience in synthesizing adiponitrile, a
nylon intermediate. Thirty years ago, adiponitrile was made by chlorinating
butadiene and then reacting the product with sodium cyanide to make adiponitrile
and salt. The selection of butadiene as a feedstock got the process off to an
environmentally good start, since butadiene is a by-product of ethylene
manufacturing. On the other hand, buying caustic and chlorine, making salt, and
53
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then throwing it away is neither an especially cost-effective nor a very green thing
to do.
DuPont had been trying since 1939 to directly produce hydrocyanate
butadiene, but the company was unable to produce a linear isomer. It was not
until they tried a new type of catalysis which had not previously been industrially
applied that this problem was solved. This process, which was the first industrial
application of coordination catalysis, eliminated the use of chlorine and the salt
waste stream. As a result, this process at one time comprised the most valuable
set of patents in DuPont's possession. This invention led DuPont to embark on
the largest commercial process development on new chemistry in the company's
history. Over a short period of time, plants using the older technology fell off
one by one, and the new process was adopted throughout the company. As with
any entirely new process, of course, a whole host of other problems arose that
required a constant stream of further innovations over the next 25 years - but the
process remains a fine example of the fact that economic and environmental
concerns do not have to oppose one another. In fact, it is the continual stream of
innovation and creativity rather than the invention or catalyst per se that makes or
breaks such a process conversion.
The importance of thinking as far into the future as possible is illustrated
by the various catalysts and reactor types that have been used in the
hydrogenation of adiponitrile to produce hexamethylenedi-amine. DuPont had
concentrated on developing a cheap high-pressure catalyst that minimized the cost
of synthesis but, because of its slightly lower yield, required a large refining train.
One competitor used a very expensive high-pressure catalyst that had
exceptionally high yield and thus minimized the refining investment. Another
competitor used a slurry process that was intermediate in yield, minimizing energy
consumption and investment. Ah1 of these companies improved their processes
for years, and all became economically equivalent. From the perspective of 50
54
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years ago, all of these processes seemed about the same. From today's
perspective, however, the high-yield process that does not make impurities to
begin with would certainly be preferred. Because of their early investment
decisions and hard-won expertise in their own processes, however, all companies
are locked in to continuing their current methods. The point is that once a
company starts on a particular path of capital investment, the choices of
generations of successors may be significantly constrained. Minimizing such
constraints requires thinking as far into the future as possible before selecting a
process.
Another example of new process development is the process developed for
producing tetrahydrofuran (THF). Because the existing process required energy-
intensive and reactive starting materials and because it was expensive, DuPont
wanted to develop a new process for THF synthesis. This example is particularly
relevant to this workshop since the process selected required innovations in
engineering as well as in chemistry.
As Figure 37 illustrates, one intermediate in the THF pathway is maleic
anhydride. Using a fixed bed system, this compound can be made from readily
available hydrocarbons, but the fixed bed process has a number of limitations,
including the high cost of the fixed bed reactor. To address this problem, DuPont
engineers determined that three major new inventions or developments would be
required:
• A transport bed reactor that would allow the reaction to take place
while at the same time using a flywheel mechanism to regenerate the
catalyst
• An attrition-resistant catalyst (since the catalyst would be moving around
so much in the system)
• A hydrogenation catalyst for the final step of the reaction
55
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H
H,C'
H
H,(T H
T
l^-X^r
Fixed Bed Limitations
• 1-1.5% butane in air
• Single pass-high conversion
• 45-50% yield
• Expensive reactors
Figure 37. Limitations Inherent to the Production of Maleic Acid via a Fixed Bed Reactor
The relationship of these advances to the proposed synthetic pathway are
illustrated in Figure 38.
CH3CH2CH2CH3
1 VPO
HO2CCH=CHCO2H
H2 1 Pd/Re/C
Q
Three Major Inventions
Transport Bed Reactor
Attrition Resistant Catalyst
Hydrogenation Catalysts For
Aqueous Maleic Acid
Figure 38. Innovations Required for the New Synthetic Pathway
56
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Figure 39 illustrates the role of lattice oxygen chemistry in the new
synthetic pathway. In essence, the process involves pumping oxygen through an
Reaction
VxOy + C4H10 — VxOy_7 +
Regeneration
VxOy.7 + 3.5 02 VxOy
Metal oxide acts as oxygen source
Figure 39. The Role of Lattice Oxygen Chemistry in the New Synthetic Pathway
oxide catalyst and then regenerating it. That is, the metal oxide is used to pump
oxygen into the butane, and then separately - but in the same piece of equipment
- is regenerated. The reactor itself is illustrated in Figure 40. Conceptually, the
reactor is relatively simple; the reaction itself takes place in one part of the
reactor, while the catalyst is regenerated in another part of the reactor and fed
back into the reaction chamber.
Advantages of the riser reactor over fluidized bed oxidation reactions
include advances in both the safety and the greenness of the process. The
incorporation of separate catalyst redox zones offers independent control. In
addition, selectivity is better at higher conversion, and oxygen levels are lower
57
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Off-gas
Maleic Anhydride I
Stripper
Standpipe
Riser
Butane
Figure 40. Riser Reactor Developed for the New Synthetic Pathway
(see Figure 41). At the same time, the riser reactor offers a more concentrated
product stream, high throughput, a low catalyst inventory, and a reduced risk of
explosions. Its main limitations lie in the operational complexity of the system,
which is a problem only if the complexity precludes a solution, and in the need
for an attrition-resistant catalyst. To meet the latter need, DuPont has developed
a special encapsulated catalyst with an attrition-resistant shell that still permits
the mass transfer required.
At least at the pilot level, the new process clearly works better than the old
one. Getting everything to keep working as intended, however, is an enormous
engineering problem - particularly when it comes to scale-up. DuPont is
currently building a plant in Spain for industrial-scale testing of the new process.
58
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Figure 41. Riser versus Fluid Bed Oxidation
This exercise is expensive, but if the process works as envisioned it will offer an
important new option for engineers to apply in the design of other alternative
synthetic processes.
As a final example of process selection, the alternative methods of
manufacturing hydrogen cyanide (HCN) come to mind. The two methods that
are widely used in industry are the Andrussow process, which is the most
economical for large-scale production of HCN, and the Degussa process, which is
most appropriate for intermediate-scale production (see Figure 42). Although
DuPont uses the Andrussow process for its own HCN production, some of the
company's process development people have begun to think about the needs of
small-scale HCN users. Although HCN is a useful, reactive material, it is
poisonous and will explosively polymerize if allowed to become too acidic or too
59
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basic. If shipped, it must be inhibited, which may introduce problems related to
removing the inhibitor. In addition, HCN is difficult to make because it is a very
endothermic reaction carried out at high temperature. Thus, to accommodate the
needs of small-scale users, the ideal process would provide a controllable, safe
process for making small amounts of HCN at the point of use.
The process that DuPont engineers have proposed for this purpose is
depicted in the lower portion of Figure 42. The essence of the process is using
microwave energy to generate the necessary heat in situ. The idea is that if the
heat can be generated in a fixed bed, it should be possible to make HCN with no
waste streams and no need to recycle ammonia. The process should be relatively
easy to control, and should greatly reduce inventory. In fact, if the reaction is
done in a carbon bed, only ammonia need be fed to the system continuously.
Although it is not yet clear whether this process can be made economical, it is
another example of how thinking in terms of balance might lead to entirely new
synthetic pathways.
It is not usual for industrial engineers to be given the opportunity to
develop and commercialize completely new processes. It is far more common for
innovation to be required within the constraints of an existing system. For this
reason, a list of individual process improvements that might be expected to
broaden the range of environmentally attractive and economically viable choices
available to engineers confronted with this type of task follows:
• Improvements related to feedstocks
• Improvements related to ordinary chemical processes (e.g., mechanical
separations, optimum networks/model-based control)
• Improvements related to unusual reactions or reaction conditions (e.g.,
supercritical water oxidation, "Bioprocessing Plus")
60
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Degussa vs Andrussow HCN
Degussa (AH°298= -60 kcals/mole)
CH4 + NH3 ^ HCN + 3H2
• external heating and heat exchangers
• high yield and investment
• medium scale
Andrussow (AH°298= - -50 kcals/mole)
CH4 + NH3 + [CyN2] ^ HCN + [H2O]
• internal combustion for heat
• lower yield and investment
• high capacity but more waste
Microwave HCN Process
CH4 + NH3 ^ HCN + 3H2
1200° C, Pt/AI2O3
Advantages
»Quick startup and shutdown (rapid heating)
• On-site production and consumption
• Reduced potential for exposure
> High yield (>95%)
1 Essentially no waste stream
Figure 42. Alternative Processes for HCN Production
61
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Improvements related to unusual separations (e.g., pressure-recovery
desalination, solids transfer columns, melt crystallizations, physical and
physicochemical separations)
Methods of avoiding separations (e.g., heterogeneous versus
homogeneous catalysis, chemical reactions, avoiding or substituting
solvents, precise reaction control)
It is recommended that government and private industry select some of the more
promising of these possibilities for concerted joint efforts that in many cases
would need to be both long-term and multidisciplinary. Candidate projects
attractive in this regard include developing alternative methods of producing a
vacuum, producing better tools both for modeling and developing processes that
already have environmental considerations embedded in them, promoting
research into advanced oxidation treatment systems (particularly supercritical
water oxidation), developing chemically resistant polymeric membranes and
tailored asymmetric structures for unusual separations, and investigating the
applicability of solvent-free melting and freezing purifications to the chemical
industry.
Specific examples of process improvements that are already being
addressed are the effects of feed purity and conversion, the use of heterogeneous
catalysts, and process improvements related to the treatment of biosludge.
Figure 43 shows the effect of inert substances in feedstocks. In this case,
inert substances comprise 10% of the feedstock in a process that runs a 50%
conversion. The need to purge inert substances from the feedstock causes an
additional 10% loss of feedstock materials. Because of this, the reaction system is
three times as large as it might otherwise be, and a great deal of energy is
consumed merely circulating the impure feedstock through the system. Since low
feed purity increases losses, equipment costs, energy consumption, and waste, the
use of a purer feedstock might well be worth the extra cost. Similarly, since low
62
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100 IbF
10lbl
Purge® 50% Inert
90 100 100
P + F + I
90P
n Low conversion increases equipment cost
and energy consumption.
n Low feed purity increases losses, equipment
cost, energy consumption and waste.
Figure 43. Effect of Feed Purity and Conversion
conversion increases equipment costs and energy consumption, higher conversion
might be worth some loss of yield or investment in a different catalyst.
While homogeneous catalysts are often very selective, the need to recover
and recycle the catalyst and solvents can often outweigh the advantages of a
homogeneous system. Because of this, heterogeneous catalysts may be preferable
in some situations, particularly those involving acid-based conversions. Figure 44
shows a simple fixed bed system of the sort described earlier for small-scale
production of hydrogen cyanide. Although somewhat more complex, a slurry
system would provide many of the same benefits.
63
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HOMOGENEOUS CATALYSTS
Reactant
Catalyst
+ Solvent j i
Product to
Purification
Separation
Train
Purge
HETEROGENEOUS CATALYSTS
Catalyst
Reactant
Product to
Purification
Figure 44. Homogeneous versus Heterogeneous Catalysts
In the area of biosludge treatment, Figure 45 is a flow chart illustrating a
process currently being contemplated for the acid-catalyzed hydrolysis of
biosludge. As a step toward DuPont's corporate goal of zero-discharge
processing, this process could be used for the treatment within plant boundaries
of biosludge that may contain various industrial contaminants such as trace
metals. The goal is to eliminate the purge stream.
A good rule of thumb in new process design appears to be to seek
methods of solving problems that make the process simpler rather than more
complicated. It might be very fruitful to go back and take a second look at
processes that were developed but not exploited in the past because they were not
considered economically viable at the tune they were developed. Many of these
64
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ACID CATALYZED HYDROLYSIS OF BIOSLUDGE:
PROCESS CONCEPT
6500 T/rt WATER
45 T/d BOD'
66T/dCOD
RECYCLE
0.5 T/0 SOLIDS
3.0 T/d COD
132 T/d WATER
N2. C02 ?
CONCENTRATE AND
PURGE TO INCINERATION
OR LANDFILL
0.5 T/d SOLIDS
12 T/d WATER
MINERAL ACID
HYDROLYSIS REACTOR
COOLER
180 C. 5 MIN. MINERAL ACID
Figure 45. Process Concept: Acid-Catalyzed Hydrolysis ofBioshidge
processes may be much more appealing in the context of current goals and
priorities. Most important is the need to expand the scope of our thinking to
include larger, more complex systems, more disciplines, and a longer time scale.
Although attention to unit parts and unit operations will remain an important
part of chemical engineering, the demands of sustainable development will
increasingly require this broader view.
65
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Computer-Based Methods for Finding Green Synthesis
Pathways and Industrial Processes for Manufacturing Chemicals:
A View From 10.000 Feet
Peter P. Radecki, Center for Clean Industrial and Treatment
Technologies/Michigan Technological University
A graphic depicting the trade-offs between unit costs and pollution
prevention associated with various types of approaches to the problem of making
chemical manufacturing processes greener is shown in Figure 46. Most current
approaches fall into the general category of management practices. These
approaches, which include pollution audit activities such as inventory control,
materials management, and energy utilization analysis, may reduce unit
production costs in some instances but may increase these costs in others. At the
APPLICATION OF
EXISTING
TECHNOLOGIES
MANAGEMENT
PRACTICES
NEW
TECHNOLOGIES
AND INNOVATIVE
USES OF EXISTING
TECHNOLOGIES
Pollution Prevention
Figure 46. Clean Technology Targets
66
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same time, these approaches offer only modest improvements from the
perspective of pollution prevention.
The goals of the workshop are more closely related to the right side of the
diagram - that is, finding ways of applying existing technologies that will provide
large payoffs in pollution prevention while maintaining production costs at an
acceptable level. The ideal that we are moving toward is represented in the
lower-right quadrant of the diagram - a situation in which the development of
new technologies or the innovative use of existing technologies enhances pollution
prevention while at the same time decreasing the production costs of the material
in question. Thus, the ultimate goal of benign process development is to achieve
source reduction in such a way that unit production costs remain constant or go
down.
Current reality is far from this ideal. In many cases, for example, advances
in industrial process design are held as corporate secrets. As a result, what
scientists in academic or government laboratories consider state-of-the-art may
actually be quite different from what is already being implemented in industry. In
addition, the results of a Hoechst Celanese study in which 80% of about 200
pollution prevention projects spanning a whole range of chemical processes were
found to have a high cost impact. Thus, while maintaining or even reducing
production costs is a goal of green chemistry, the reality is that most of the
projects we are talking about are going to cost money. Processes described as
"the low-hanging fruit" have already been picked by the large chemical companies
who have been proactive in the area of process pollution prevention. Despite
impressive engineering capability, going beyond these projects is not likely to
occur on a large scale in the near future due to the combination of market forces,
structural barriers, political considerations, and emphasis on short-term funding
that all come to bear on the issue.
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Two of the main barriers to the sort of holistic development that is
necessary to attain the goal of environmentally benign manufacturing are the
"culture of verification" that currently pervades our thinking about environmental
issues, and the emphasis on highly quantitative, single-medium, chemical-by-
chemical measurements that characterize our thinking about monitoring and
regulation. These inhibit environmental impact-based approaches and favor low-
risk, end-of-pipe solutions to environmental problems. Some means of measuring
progress is needed, and the techniques needed to measure progress in pollution
prevention may be very different from those developed to measure progress in
areas related to chemical-by-chemical monitoring and regulation.
Another important barrier to holistic development has to do with
corporate realities in an age of compliance. In some ways this is related to the
issue of verification, in that monies spent on chemical-by-chemical monitoring and
reporting are not available for long-range research and development or other
types of green planning. This is true not only in industry, but also in the public
sector, since the tax dollars required to run federal and state environmental
agencies charged with establishing regulations and monitoring compliance are also
part of the financial equation. The focus on compliance also results in a
corporate structure that separates treatment and environmental expertise from
process design expertise. With the relevant individuals in different parts of a
company, it should not be surprising that environmental considerations are not
routinely incorporated in new process design. The costs of compliance induce
investment in oil producing countries and elsewhere to turn oil into chemicals.
Increasingly, overseas interests are providing the value added to basic resources
instead of this being done in the United States.
A series of diagrams outlining the major stages of new process
development and implementation are shown in Figure 47. It is estimated that
construction of entirely new plants, and therefore, the synthesis steps shown in
68
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SYNTHESIS STEPS
STATEMENT OF NEED
MOLECULAR
DESCRIPTION
SYNTHESIS
PATHWAY
IDENTIFICATION
SYNTHESIS
REACTOR
SCALE-UP
INDUSTRIAL PROCESS DESIGN
LARGE SCALE PLANNING
CONCEPTUAL
PROCESS
DESIGN
PRELIMINARY
DESIGN
DETAIL
DESIGN
CONSTRUCTION
INDUSTRIAL PRODUCTION
FEEDSTOCK
PRODUCTION
Figure 47. Stages of Process Development and Implementation
69
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this figure, account for about 5% of capital expenditures in any given year, while
industrial process design and production in plant revamps account for the bulk of
the remaining 95%. This distribution reflects the fact that it is not often the case
that one gets the opportunity to design a new process from the ground up. Much
more common are situations in which engineers are asked to modify an existing
system so that the system will fulfill more or different needs.
Figure 48 lists computer tools that might be of use during the preliminary
stages such as molecular description, synthesis pathway identification, and
synthesis reactor scale-up. Although in this diagram the computer-based
approaches and the development steps to which they apply generally correlate, a
direct, one-to-one relationship does not necessarily hold.
STATEMENT OF NEED
MOLECULAR
DESCRIPTION
SYNTHESIS
PATHWAY
IDENTIFICATION
SYNTHESIS
REACTOR
SCALE-UP
Molecular Structure Prediction
Chem/Phys/Bip Property Databases
Toxicity Modeling
Marketing Information Resources
Chem/Phys/Bio Property Prediction
Retrosynthetic Pathway Prediction
Synthetic Pathway Prediction
Catalyst Design Tools
Catalytic Pollutant Prediction (Rudd)
Kinetics Equation Solvers
Thermodynamic Modeling Tools
Metabolic Pathway Descriptors
Electrolyte System Modeling
"Generic" Reactor Modeling Tools
Neural Networks
Dynamic Modeling
Control System Design Tools
Figure 48. Computer-Based Tools for Use in the Earfy Planning Stages of Process Design
70
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In terms of the computer-based tools available for use in the early
planning stages of process design, there is a distinction between those that are
available for more or less generic application and those more likely to be
developed in-house and considered highly proprietary. Examples of the former
include molecular structure prediction packages and consortia-funded databases
of physical-chemical biological properties. When the development process
reaches the stage of catalyst design, design of the reactor itself, or design of
control systems, however, computer-based tools tend to be "home grown"
packages developed by academic or industrial researchers for use in a specific
manufacturing situation; as such, these tools are much less likely to be available
outside the sponsoring company. There is a fair amount of movement in the
direction of creating generic reactor modeling tools that would allow chemical
engineers to experiment with variables such as reaction conditions, the inclusion
of additives or inhibitors, and so on. With such tools, engineers could relatively
easily evaluate a half-dozen different types of reactors to determine which might
work best for a given synthetic pathway.
Computer-based tools that might be used during the industrial process
design stage are listed in Figure 49. For the most part, the goal of the large-scale
planning tools is to allow a means of taking a proactive look at potential impacts
over the 40- or 50- or 100-year lifetime of the contemplated process. This is an
important advance over existing programs most of which involve after-the-fact
analysis of problems only after it is too late to do anything about them.
As a specific example of the types of tools envisioned as particularly useful,
a project to develop a program which would enable corporate planners to view a
matrix of industrial processes used to manufacture a given feedstock from the
perspective of an environmental inventory has been proposed. This matrix would
allow planners, particularly those with multinational operations, to determine
where it might make economic sense to reduce output from one plant and
71
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LARGE SCALE PLANNING
CONCEPTUAL
PROCESS
DESIGN
PRELIMINARY
DESIGN
t
DETAIL
DESIGN
CONSTRUCTION
Land Use Planning Tools
GIS Data Presentations
Chem. Industry Planning (Rudd)
Regulatory Databases
Clean Process Advisory System
EPA/DOE P2 Module (planned)
Flowsheet Simulators
Batch Processing Tools
Separation Modeling
Technology Vendor Models
Stochastic Tools
Pinch Technology Modeling
Control System Design Tools
Construction Management Tools
Safety and Reporting Aids
Figure 49. Computer-Based Tools for Use in Industrial-Scale Process Design
increase output from another. Similarly, such a matrix would help identity areas
in which environmentally-motivated changes in process design are economically
viable versus areas in which they are not.
The Clean Process Advisory System is a program through which CenCITT
and two industrial consortia, the Center for Waste Reduction Technologies and
the National Center for Manufacturing Sciences, are attempting to assure that
information about process options is made more widely available to process
engineers. At present, the designer's awareness of options for achieving a
particular process goal are often limited to information that he or she happens to
hear about from other process designers. The goal of the Clean Process Advisory
System, which is currently about a year old, is to make available a comprehensive
72
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list of all the options that are available to achieve a specific goal - for example,
ways of separating materials which result in less environmental impact. Thus, for
example, if someone comes up with a new membrane separation process that
could be used to replace an energy-consuming distillation process, the Advisory
System would make this information available to process engineers who may be
confronted with a parallel situation in which distillation is not the best or most
desirable way of achieving the targeted separation.
Another example is a multi-million-dollar, multi-year program that the
Water and Wastewater Research Division of the Risk Reduction Engineering
Laboratory is trying to develop in conjunction with the Department of Energy.
This program which falls somewhere between conceptual process and preliminary
design, would attempt to develop a pollution prevention module that could be
tied to conventional process flow sheet simulators. The availability of such a
module would make it much easier for environmental considerations to be taken
into account during each step of the design process.
Regarding the potential of pinch technology in the context of
environmentally benign manufacturing, efforts are currently under way to develop
tools to look at mass exchange in much the same way that pinch technologies for
energy conservation look at heat exchange.
Turning to the industrial production stage, most existing computer-based
tools apply to this final segment of the development process as shown in Figure
50. Many gains have already been realized from tools available in the areas of
pollution auditing, total quality management, and safety assessments. In the area
of environmental impact, however, most existing packages focus on chronic
emissions and other problems from an after-the-fact perspective. An important
goal will be to get similar types of information made available for use earlier in
the design process.
73
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STARTUP
1
NORMAL
OPERATION
FEEDSTOCK
PRODUCTION
END-USE
PRODUCTION
i
REUSE
WASTE
Recycler Databases
Dynamic Simulation
Control & Shutdown Modeling
Pollution Audit Tools
Customized Process Simulators
Empirical Control Modeling
Safety, HAZOP Tools
Neural Networks
General Circulation Models
TQM Facilitators
Compliance Reporting Aids
Exposure-Related Databases
Inventory Management Tools
Solvent Substitution/Compatibility
Material Selection Aids
Design for Disassembly Tools
Concurrent Engineering Packages
Life Cycle Assessment Tools
Environmental Fate Modeling
Toxicity Modeling
Waste Inventory Databases
Remediation Techs Databases
Treatment Techs Databases
Figure 50. Computer-Based Tools for Use During the Industrial Production Stage
As an example of an area in which many tools are available but integration
is needed, the programs designed to facilitate decisions related to solvent
substitution and solvent compatibility are available. There are at least a half-
dozen different efforts under way in this area, including several at National Labs,
several at various industrial consortia, and at least one being funded by EPA.
Because these systems were developed in parallel, however, there may be overlap
among them as well as problems related to the fact that the various programs
cannot "talk" to one another. Currently, the National Center for Manufacturing
Sciences is trying to come up with a way to tie all of these systems together, but
this is a very costly undertaking. Better front-end planning might have resulted in
tremendous cost savings for everyone involved.
74
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A few more general observations about current computer-based tools can
be made. For the most part, existing programs are independent, stand-alone
tools, each of which can only offer limited benefits in terms of making process
design more environmentally friendly. In addition, commercial software
development is going to tend to focus on marketable products, whether or not
these products address the most important aspects of green process design. As a
result, federal funding should be earmarked for programs in areas in which
market forces alone cannot be expected to provoke sufficient interest on the part
of software developers.
New releases of commercially available programs generally tend to focus
on front-end features such as user interface, robustness, and speed. What is
really needed, however, is advancement of the "workhorse" databases that
underlie these programs. Data acquisition programs only rarely have significant
commercial potential; as a result, almost all currently available tools focus on
issues of treatment, liability, compliance, or management.
The greatest capability of existing chemical synthesis tools is in dealing
with high-purity systems. In these systems, it is sometimes possible to make
synthetic and retrosynthetic predictions .related to a single chemical. When it
comes to predicting the behavior of real-world chemical feedstocks, however, the
utility of these systems falls off dramatically, even for very standard feedstocks. It
has been only recently that a good surrogate for gasoline has appeared in the
literature, and that analysis received funding only because there was a great deal
of interest in leaking underground storage tanks at the time. The coarseness of
modeling tools for commodity chemicals is perhaps best reflected in the fact that
it is not at all uncommon for predictions about the physical properties of mixed-
species feedstock components to have errors on the order of 20-30%, and these
errors are compounded many times over when the predicted values are
propagated through an entire process. Therefore, while molecular modeling
75
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techniques and molecular-level surface chemistry tools may be useful in providing
conceptual insights, correlation with actual industrial experience is rare, and
meaningful stochastic analyses are virtually impossible.
In the area of data acquisition and management, these types of programs
are almost never profitable enough for commercial software houses to develop
and maintain. Those programs that do generate data are almost always consortia-
funded, but it is very difficult to arrange for long-term stewardship of these
programs. When funding is obtained, duplication of efforts is often a problem,
and projects that integrate data and methodologies are exceedingly rare.
Left to its own, the commercial software industry will continue to focus on
advances in numerical methods, user interfaces, computing power, and
communications and networking - despite the fact that information management
acquisition and retrieval is the area that offers the greatest potential for
meaningful advances in this field. The single biggest obstacle to improved
information management is in developing protocols for effective information
transfer from one unit operation to the next or even from one step to the next
within a single unit operation. The only such program he is aware of aware of,
Mr. Radecki said, is an effort by the Process Data Exchange Institute of AIChE,
which is supported at a level of about $100,000 per year. For comparison, Mr.
Radecki noted he has been told that Japanese spending in this area is currently
about $5 million per year. Advocating a long-term federal commitment to
environmental information acquisition and management, the current model of
support through short-term projects will not be adequate to maintain the edge the
U.S. has historically held in information management systems. Information
management strategies would benefit from a more object-oriented approach that
would allow parallel rather than stepwise development of the range of
components needed to address a given technologic problem (see Figure 51).
76
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Figure 51. Object-Oriented Programming and Concurrent Software Development
In the search to identify and fill critical R&D needs, the focus should be
on the industrial designer, who is in a far better position than government
regulators or academic scientists to know what type of information would be of
greatest practical benefit. At the same time, greenness should be measured on a
broad spectrum, so that movement in the right direction is valued over advances
that echo the "bean-counting" approach of monitoring and compliance.
A summary list of elements that should guide research and development in
the area of green process design follows:
77
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Facilitate the convergence of process design and environmental
understanding within the corporate structure
Make it easy to learn about the green synthesis and process design
options that are already available
Target those information needs not likely to be filled by the market
Emphasize long-term stewardship over short-duration projects
Promote the development of common R&D goals of multiple
organizations
78
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III. BREAKOUT SESSIONS
During the morning and early afternoon of the second day of the
workshop, participants met in four smaller breakout groups to discuss and make
recommendations regarding research needs in the four general areas addressed by
the plenary speakers:
• Benign Organic Synthesis
• Benign Biosynthesis
• Benign Engineering Approaches
• Computer-Based Methods
In addition to workshop attendees who had preregistered to participate, each
breakout group included a facilitator responsible for guiding the discussion and
making sure all participants got a chance to express their views, a chart writer
responsible for capturing the main points of discussion on a flip chart, and an
EPA writer responsible for taking detailed notes of the breakout group
proceedings. Minutes of the proceedings for each breakout group are contained
in Appendix C of this document.
In making recommendations about needed research and development
within their assigned area, breakout group members were asked to address four
main questions:
Whether the priority assigned to each area of recommended research
was high, medium, or low
79
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Whether the recommended research could be expected to produce an
impact within a long (>10 years), medium (5-10 years), or short (0-5
years) timeframe
Whether the research would most appropriately be undertaken by
industry (I), government (G), academia (A), or some combination of the
three
Whether and why government funding is or is not needed to support the
recommended research
In addition, workgroups were asked to using a voting procedure to assign relative
priority scores to each area of recommended research.
80
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IV. PRESENTATIONS - CLOSING PLENARY SESSION
Following the completion of individual breakout sessions, the workshop
reconvened as a whole. During this closing plenary session, representatives from
each of the workgroups made presentations summarizing the discussions that took
place and the recommendations reached in their respective groups.
Workgroup on Engineering Approaches
Facilitator: A. Ford, Lamar University
The recommendations of the workgroup are summarized in Table 1. Due
to its large size, this workgroup was divided into several smaller groups to address
the various areas of research initially identified by the workgroup. Summaries of
discussion and findings of each of these groups were presented by members of the
smaller workgroups.
P. Biswas presented recommendations regarding research needed in the
area of high temperature processes. Examples of synthetic routes that might be
good candidates for further investigation are fume silica and titanium pigments
(both involving gas phase/aerosol synthesis). The rationale for the group's
recommendation for fundamental study of high-temperature chemistry was the
need for a better understanding of the mechanisms of both product and pollutant
formation, which may permit better control of pollutants, despite the instance
where formation of these by-products cannot be totally avoided. Finally, an
emphasis on both research and development was deemed important to permit
control of processes within narrow operating windows and to trigger a shut-down
if the process falls outside the prescribed operating constraints.
81
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C. Sciance identified "front-end" issues that they considered important:
• Define benign technologies and "greenness" to help all parties develop
and enunciate a "green vision"
• Develop tools and technology to facilitate selection of environmental
alternatives (e.g., life cycle analysis, risk/benefit analysis, environmental
full-cost accounting, databases and heuristics, methods of quantifying
"greenness")
• Promote progress toward benign processing (e.g., programs addressing
the unique needs of small companies, programs addressing the common
needs of related industries, programs identifying suppliers of needed
equipment, services, and so on)
• Develop innovative ways to promote more effective cooperation, and
identify and prioritize research needs to serve industry; seek
complimentary roles and responsibilities and work with government to
secure funding
• Promote professional and public education and continuing workplace
training on values, ethics, and sustainability as well as benign
technologies
C. Nassaralla presented findings related to waste issues. By-products were
selected to mean solid wastes such as incinerator ash, tar, dust, biosolids, and any
other solid wastes produced during a synthetic process. The goals of the
recommended research were to avoid the formation of solid waste or to transform
the wastes into useful products. Recognizing that it is currently not economical to
recycle much of this material, the group felt that diminishing landfill space and
increasing government regulation were likely to change this situation.
E. Nauman presented the workgroup's findings related to containment
issues, noting that there was not universal agreement on this point, but a general
opinion among workgroup members that greenness ought to be judged on the
basis of what goes into and comes out of a plant, not on the basis of what might
87
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be within the boundaries of the plant itself. Research into ways of "keeping the
nasties locked up" should be part of an overall program that has zero- or near-
zero emissions as its goal.
T. Foust presented the recommendations in the area of catalysis. The
catalysis group believed work on separations and developing non-toxic catalysts
was rated as relatively high-risk, while research into methods of achieving higher
product concentrations and reducing catalyst attrition were rated as lower-risk
undertakings.
W. Schmeal presented the recommendations regarding research needs in
the area of process synthesis. Creative thinking about process synthesis using a
rationale for classifying these efforts as long-term should be promoted.
Attempting to apply pinch computational technologies to the issue of mass
transfer may be significantly more difficult than applying them to energy
conservation - which itself was not an easy or quick process. Instead of a single
commodity (energy), an environmentally-based pinch technology approach would
have to take substances of many different chemical compositions into account.
J. Watson presented the workgroup's recommendations in the area of unit
operations. Low-energy separations are particularly important in the context of
biotechnology products, which tend to be made in very dilute solutions. Examples
of the types of physical separations the group thought particularly worthy of
consideration were (1) removing toxic materials from wastes, (2) removing
impurities from feedstocks, and (3) various types of de-misting processes. The
objective of hybrid unit operations research should be to come up with novel
combinations of unit operations that lower operating costs, reduce energy
consumption, reduce capital requirements, and/or minimize product degradation.
88
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Following the presentations, one workshop participant (Bashkin) expressed
some confusion about the relationship between fundamental studies of high
temperature chemistry and benign processing. It was concluded that the products
of high-temperature chemistry often have very narrow or controlled properties, so
that even a slight change in processing conditions can significantly affect the
extent to which solid wastes or toxic emissions are created. A better
understanding of the chemistry would make it possible to minimize the formation
of these undesirable products.
Workgroup on Biosynthesis
Facilitators: J. Frost, Michigan State University and
P. Elankovan, Michigan Biotechnology Institute
The recommendations of the Workgroup on Benign Biosynthesis are
summarized in Table 2. The workgroup's findings were presented by D.
Cameron, who noted that there was a fair amount of overlap between the
recommendations of this and the Engineering Approaches workgroup. Cameron
said that this was encouraging, since it probably meant that there really is some
consensus about the types of projects that should be funded.
Regarding the group's recommendation that renewable feedstocks be
investigated, some of the examples discussed were carbohydrates, carbon dioxide,
methane, mixed organic wastes, and lipids. Already some companies have begun
efforts to design specialized starches and lipids for use as chemical feedstocks. In
addition, the group felt that more attention should be given to non-carbon-based
activities of biological systems. Nitrogen fixation, conversion of minerals into
unique materials like ceramics, and water-splitting reactions represent examples of
biological processes that might be relevant to feedstock selection.
89
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As discussed by the Biosynthesis group, pathway engineering was defined
as taking advantage of advances in molecular biology to modify the metabolism of
organisms, making them better producers of chemicals they already produce or
causing them to produce chemicals that they otherwise would not. The types of
work that need to be done in this area, the group felt, have to do with improving
the yield, selectivity, tolerance, productivity, titer, and robustness of these
biologically-based systems. Among tools that would help advance pathway
engineering, the group discussed databases providing information on enzymatic
activity and genes; models capable of integrating thermodynamics, kinetics, and
stoichiometry; and databases containing information about the thermodynamics of
various materials within the aqueous cellular environment.
In contrast with pathway engineering, which the group had defined to
include large, integrated systems of reactions, reaction engineering was defined as
having to do with modifying and improving single reaction sequences or enzymatic
reactions. Regarding the identified need for work on alternative methods of
electron transfer, the group thought that, in addition to cofactor regeneration,
research should focus on ways of coupling electron transfers with electrochemical
or photochemical reactions. Among the methods discussed to improve the
productivity and selectivity of biocatalytic conversions, the Biosynthesis group
listed phase transfer catalysis; use of non-aqueous media, including specialized
media such as supercritical fluids; catalyst immobilization; post-translational
modification, and substrate and product transport through the catalytic system.
The greatest area of overlap with the Engineering group was in the
Biosynthesis group's consideration of issues related to processing. Noting that
large databases are available only for the physical and chemical properties of
chemicals in organic systems, the group felt that comparable databases should be
developed for the behavior of chemicals in aqueous or mixed aqueous/organic
systems and for process alternatives in aqueous systems. In the area of
93
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monitoring, the group was particularly interested in methods of monitoring
substrate concentrations, product concentrations, and biomass or catalyst
concentration and activity on line. Regarding new methods of integrating
biosynthetic and traditional synthetic processes, the group was particularly
interested in comparative analyses of immobilized systems versus suspension
biocatalysts and of batch versus continuous processing. The group also felt that
integrations of organic and biological synthesis offer many unique opportunities in
process development. Examples of integrated reactions included the fermentative
production of lactic acid followed by chemical formation of an ester and chemical
hydrolysis of feedstocks and sugars followed by fermentation processes.
Following Cameron's presentation, a workshop participant (Bashkin) asked
about the group's inclusion of nitrogen fixation as a non-carbon-based reaction
that might be exploited biosynthetically. From the questioner's perspective,
biological nitrogen fixation is a poor competitor for standard chemical processes
of nitrogen fixation, since biological fixation consumes large amounts of ATP and
large numbers of protons and is associated with uncontrolled hydrogen
production. The only advantage of biological nitrogen fixation, this participant
suggested, is that it works at atmospheric pressure and room temperature.
Cameron indicated that the group had wanted to make sure that they did not
neglect non-carbon-based chemistry in their consideration of biosynthetic
processes, and that some members of the group thought that there might be some
interesting nitrogen-based chemistry that could be done with microorganisms.
While agreeing that nitrogen fixation might not be the best example of such a
process, large-scale nitrogen fixation by plants is, in fact, a pretty benign form of
chemical processing.
Another participant (Sciance) asked whether the group had discussed
sulfur, noting that a number of people in refining are interested in bioprocessing
as a way to remove sulfur from feedstocks. Cameron emphasized that the group
94
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had focused mainly on synthetic processes, but he agreed that biological
desulfurization of oil and coal is a very promising area. The questioner pointed
out that sulfate esters are an example of a biosynthetic process involving sulfur.
Another member of the workgroup (Bradford) noted that the group had talked
about both sulfur and phosphorus in terms of esterification reactions that could
be of value in organic synthesis. As an example, he said that it might be possible
to oxidize elemental sulfur or some other substrate in situ to generate a sulfate
ester, and then to use this ester in the manufacture of surfactin or other sulfur-
con taming compounds.
Another workshop participant (Lee) expressed interest in the group's call
for the development of new databases and asked what types of thermodynamic
information are needed. Cameron responded that the group had discussed two
different types of needs. First, there is a need for information about the nature
of thermodynamic equilibrium in a cellular environment, the concentration of
reaction intermediates within cells, and other types of similarly rudimentary
baseline information. Second, the group felt there to be a great need for more
information about the thermodynamic properties of various compounds in an
aqueous environment. Examples offered included octanol/water partition
coefficients and vapor pressure and equilibrium constants for organic acids in
water or in ionic media that more closely resemble the solutions found in living
systems.
The question was also posed (Radecki) whether the group had discussed
the use of organisms for extracting toxic materials out of various types of streams;
this questioner noted that bioaccumulation might be a very energy-efficient way to
detoxify various types of materials. Cameron related that the group had agreed
that microorganisms represent an important resource for clean-up and
remediation, but that they had decided to focus strictly on issues related to
biosynthesis.
95
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Workgroup on Chemical Synthesis
Facilitator: P. Anastas, U.S. Environmental Protection Agency
The technical recommendations of the Workgroup on Chemical Synthesis
are summarized in Table 3. The workgroup's findings were presented by T.
Collins, who noted that the group had decided to rename itself the Workgroup on
Environmentally Benign Synthesis, since there was general agreement that much
of the research needed in this area would also apply to inorganic syntheses.
Regarding the group's recommendation that robust and selective
homogeneous oxidants be developed, Collins noted that many of the species
currently used in oxidation reactions are metals that have the potential to
generate toxic by-products. Because of this, the group felt that high priority
should be placed on developing recyclable alternatives, especially for catalytic
purposes. The group's recommendation regarding the development of new
solvents and/or solventless systems reflected a consensus regarding the need to
find alternatives to chlorinated solvents and other solvents that represent health
hazards.
The group's recommendation regarding long-term research on oxide-based
catalysts for NOX abatement had to do with finding an alternative to the "lose-
lose" situation faced with existing internal combustion engines. If a rich mixture
is run through these engines, the exhaust contains an excessive amount of
hydrocarbon by-products. With the use of a lean mixture, production of nitrogen
oxides increases. Because of this dilemma, there is currently a great deal of
interest in the automobile industry in developing a solid catalyst for NO
abatement.
Some detail was presented about the group's recommendation related to
the development of functional models of enzymes. Enzymes are currently
96
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98
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receiving a great deal of attention from many different perspectives. Of particular
interest to the workgroup was the fact that in addition to optimizing reaction
rates, we are getting closer and closer to developing "smart" molecules - that is,
multifunctional molecules that are capable of carrying out a transformation
involving more than one reaction at more than one reaction site. The workgroup
felt that support of these types of efforts has a very great potential for advances
in our ability to make synthetic reactions more benign.
In addition to its technical recommendations, the workgroup offered a
number of broader suggestions for promoting the development of environmentally
benign syntheses. In the area of education and training, for example, the
workgroup identified a number of efforts that it felt had significant potential for
short-term impacts. These efforts included:
• Developing a list of 250 of the top processes that provide opportunities
for pollution prevention, so that academic chemists will better
understand which alternative pathways offer the greatest potential
benefit
• Including benign chemistry as a core tenet of the chemistry curriculum,
and teaching young chemists that responsible chemistry and creative
chemistry are not two different things
• Developing educational approaches to familiarize chemists with
separations and processes (physical/chemical isolation)
• Developing a database and/or information network on benign synthesis
• Promoting special issues of journals to disseminate information on
benign synthesis to scientists in many different disciplines
• Disseminating information on benign synthesis to the public and
promoting chemistry as a source of solutions to environmental problems
• Gaining a better understanding of industrial processes that could benefit
from environmentally benign synthesis
99
-------
The workgroup had also considered issues related to the implementation of
environmentally benign synthetic pathways, and it was here that the workgroup
felt that the government must play a major role. Elements of this effort might
include any or all of the following:
• Promoting the implementation of benign methods in industry
• Identifying barriers to the implementation of benign methods
• Clearly stating a stable commitment to long-term research in synthetic
chemistry
• Developing evaluative tools to assess the environmental and economic
impact of synthetic methods at both the bench and process scales
• Developing means of funding interdisciplinary teams of scientists who
can collaborate to address key problems in research and education
Like its recommendations related to education and training, the workgroup felt
that efforts in this area have a great deal of potential to impact the development
of benign synthesis over the short term. Particularly important in this regard is
the commitment to long-term research. The group felt strongly that moving in
and trying to find short-term projects to fund would retard rather than advance
progress in this area. They agreed that long-term funding, particularly in the
academic sector, is essential to building a solid research base for benign synthesis.
The workgroup had two general recommendations that it felt likely to
promote the development of many different types of benign products. First, they
suggested that a goal of benign synthesis should be to design target molecules that
preserve the desired function and then to mitigate the toxicity of these
compounds by modifying their physical and chemical properties. Second, the
group thought that it would be useful to develop a functional group
understanding of health and environmental hazards, since chemists are most
adept at learning and comprehending chemistry through a functional group
100
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approach. The working group felt that both of these general principles would
help pull together broad areas of knowledge and would give people a much-
needed intellectual framework for thinking about environmental problems.
Workgroup on Computer-Based Methods
Facilitator: C. Brunner, U.S. Environmental Protection Agency
The recommendations of the Workgroup on Computer-Based Methods are
summarized in Table 4. The workgroup's findings were presented by P. Radecki,
who began by noting that the group had a general concern about the
compartmentalization of knowledge related to environmentally benign syntheses.
People who understand process and synthesis design either do not have a good
grasp of environmental issues or they are unable to obtain the data they need to
implement that understanding in a quantifiable way. By addressing this problem
from a number of different perspectives, the group felt that all of the research
they recommended has the potential for significant impact at the application
stage over the next 5 years.
In assigning the various research tasks to industry, government, or
academia, the group had used fairly broad definitions of these terms. In addition
to universities, for example, the group included "think tanks" and various other
types of research institutions that may or may not be located at universities in its
assignment of specific tasks to academia. Similarly, the group had considered
industrial consortia to be the most appropriate sponsors for some of the tasks
assigned to industry.
Regarding the category of integrating activities, the sense of the group was
that there are some types of information needs that are not tied to a specific
model. Rather, these are areas in which it will be necessary to develop some sort
101
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of consensus regarding the best way to get information out to the people who
need it. Particularly important in this regard, the group thought, were efforts to
coordinate software packages and to provide long-term maintenance of databases
once they are developed.
In the area of decision-making tools, the workgroup had focused on
programs that would facilitate the process of comparing one process design with
another. Especially important in this regard is the development of tools that are
useful in the retrofitting approach that characterizes most process design in this
country. Unfortunately, many of the currently available programs assume that
process design is starting from scratch, when in fact most efforts have
considerably fewer degrees of freedom than these packages assume.
In its discussion of expanded process simulation, the group was concerned
about what they referred to as "small-customer modules." The group was
interested in promoting green processes in areas where financial backing for
research and development is not readily available. As a leading example,
membrane systems development was cited as almost exclusively the domain of
very small and highly specialized firms. Because of this, major process simulation
houses are unlikely to consider it cost-effective to build a generic membrane
module and include it in a larger process simulation package. The group felt that
federal funding in this area should be a very high priority, since it would go a long
way toward providing engineers with ways of looking at alternative processes.
Without small-customer modules, a process engineer has no way to evaluate the
membrane system in comparison with a distillation column, for example.
Similarly, the group had felt it important to promote the development of
dynamic process simulations to complement existing packages that focus on
steady-state conditions. Often a company's biggest pollution problems are
107
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associated with start-ups and shutdowns rather than steady-state operation of the
facility.
The workgroup spent a great deal of time discussing computer-based tools
for decision support, and a broad range of needs were identified. In particular,
the group's recommendation regarding the need to investigate ways of
incorporating life cycle assessment into process design was described. This is an
especially important area since legislative initiatives are increasingly including
language requiring life cycle assessments, yet there are very few tools that allow
these assessments to be done on any kind of consistent or large scale. In
addition, there is a fairly strong likelihood that the next round of amendments to
the General Agreement on Trade and Tariffs (GATT) will include language
similar to that which has begun to appear in domestic initiatives.
Regarding the need for tools that could be used in total cost assessment,
the group had been concerned about the tendency of existing packages to include
the costs of environmental compliance in the general category of overhead. More
useful, it was concluded, would be tools that enable managers to look at
environment-related expenses on a unit-by-unit or process-by-process basis, as
well as tools that would associate the costs of waste management with specific
streams instead of the facility as a whole. Using such tools, managers could then
make decisions about process improvements from the perspective of knowing
what cost savings could be expected from the adoption of specific benign
processes.
Most of the workgroup's recommendations related to reaction engineering,
and therefore echoed the needs expressed by other breakout workgroups. One
exception was the Computer-Based Methods group's focus on solvent substitution
within the reaction system rather than at the end-product production stage. By
exploring ways of modifying the reaction system itself, it might be possible to
108
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identify more benign or less energy-intensive alternatives earlier in the synthetic
pathway.
One workshop participant (Sciance) commented that in developing new
computer-based tools it will be important to assure that the packages developed
are not user-hostile programs that can be run on only one type of equipment.
While agreeing that computer-based tools are important and valuable, this
participant urged that the programmers keep the end user in mind throughout
their development efforts and that they define the universe of potential users as
broadly as possible.
109
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V. CLOSING REMARKS
At the conclusion of the workgroup presentations, Dr. Sikdar asked
Dr. Robert Wellek of the National Science Foundation to speak briefly about his
impressions of the workshop and the extent to which it had achieved the
organizers' goals.
Dr. Wellek began by noting that, like most of those present, he had
participated in quite a large number of workshops during his career. This
workshop, he said, was certainly among the most important, in that it represented
an attempt to actually build some of the partnerships among government,
industry, and academia that people so often talk about but so seldom actually
achieve.
Dr. Wellek commended workshop participants for the seriousness with
which they had addressed the issues before them, and he noted that the
Proceedings of the workshop would be very valuable to him and others at NSF.
He described the current environment for research as the best and worst of times
- the best of times in the sense that the Administration is focusing more on
civilian technologies, but the worst of times in the sense that limited resources
demand difficult tradeoffs among competing research needs. Dr. Wellek said that
the justifications for federal funding provided by this workshop would give NSF
and others important leads in preparing environmental research budgets for 1996
and 1997. He noted that the workshop had also provided him with contacts that
would be useful farther down the line, as some of the suggested programs began
to reach fruition.
Dr. Sikdar thanked Dr. Wellek for his Agency's support of the workshop
and said that he, too, had been very impressed by the seriousness with which
110
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participants had approached the task at hand. He noted that the Proceedings
would also be useful to EPA as the Agency begins to move more fully into the
area of environmental R&D in support of benign syntheses and manufacturing.
Following a few announcements regarding the review process for the Proceedings
document, the workshop was adjourned.
Ill
-------
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APPENDIX A—LIST OF WORKSHOP PARTICIPANTS
&EPA
U.S. Environmental Protection Agency and
The National Science Foundation
Workshop on Green Syntheses and Processing in
Chemical Manufacturing
Omni Netherland Plaza
Cincinnati, OH
July 12-13, 1994
Final Participant List
Madhu Anand
Air Products & Chemicals, Inc.
7201 Hamilton Boulevard (R4201)
Allentown, PA 18195
610-481-6561
Fax: 610-481-7923
Paul Anastas*
Office of Environmental
Engineering & Technology
Office of Pollution Prevention & Toxics
U.S. Environmental Protection Agency
401 M Street, SW (TS-779)
Washington, DC 20460
202-260-2257
Fax: 202-260-1661
April Applegate
Environmental Writer
Eastern Research Group, Inc.
110 Hartwell Avenue
Lexington, MA 02173-3198
617-674-7200
Fax: 617-674-2851
Stanley Barnett
Chair/Professor
Chemical Engineering Department
University of Rhode Island
Crawford Hall
Kingston, RI 02881
401-792-2443
Fax: 401-782-1180
*Hosts
James Bashkin
Assistant Professor
Department of Chemistry
Washington University
One Brookings Drive
P.O. Box 1134
St. Louis, MO 63130
314-935-4801
Fax: 314-935-4481
Dolloff Bishop*
Chief, Biosystems Branch
Water & Hazardous Waste
Treatment Research Division
Risk Reduction Engineering Laboratory
U.S. Environmental Protection Agency
26 West Martin Luther King Drive
Cincinnati, OH 45268
513-569-7629
Fax: 513-569-7501
Pratim Biswas
Professor
Department of Environmental Engineering
University of Cincinnati
(ML-71)
Cincinnati, OH 45221-0071
513-556-3697
Fax: 513-556-2599
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Joe Bordogna
National Science Foundation
4201 Wilson Boulevard - Suite 505
Arlington, VA 22230
703-306-1300
Fax: 703-306-0289
Harry Bostian
Chemical Engineer
U.S. Environmental Protection Agency
26 West Martin Luther King Drive
Cincinnati, OH 45268
513-569-7619
Fax: 513-569-7677
Marion Bradford
Research & Development Department
AE Staley Manufacturing Company
2200 East Eldorado Street
Decatur, IL 62525
217-421-3334
Fax: 217-421-2936
Richard Brenner*
Chief, Biosystems Engineering Section
Risk Reduction Engineering Laboratory
U.S. Environmental Protection Agency
26 West Martin Luther King Drive
(MS-420)
Cincinnati, OH 45268
513-569-7657
Fax: 513-569-7105
Gary Brown
Associate Director
Process Engineering Technology
Union Carbide
Technical Center - P.O. Box 8361
South Charleston, WV 25303
304-747-5473
Carl Brunner*
Risk Reduction Engineering Laboratory
U.S. Environmental Protection Agency
26 West Martin Luther King Drive
Cincinnati, OH 45268
513-569-7655
Fax: 513-569-7787
Carol Burns
Inorganic & Structural Chemistry Group
Chemical Science & Technology Division
Los Alamos National Laboratory
(MS-C346) (Group CST-3)
Los Alamos, NM 87545
505-665-1765
Fax: 505-665-3688
Douglas Cameron
Department of Chemical Engineering
University of Wisconsin at Madison
1415 Johnson Drive
Madison, WI 53706-1691
608-262-8931
Fax: 608-262-5434
Margaret Chu
U.S. Environmental Protection Agency
401 M Street, SW
Washington, DC 20460
202-260-5740
Fax: 202-260-3861
Terrance Collins
Department of Chemistry
Carnegie Mellon University
4400 Fifth Avenue
Pittsburgh, PA 15213
412-268-6335
Fax: 412-268-6897
Stephen DeVito*
U.S. Environmental Protection Agency
401 M Street, SW (MC-7406)
Washington, DC 20460
202-260-1748
Fax: 202-260-1661
Richard Dobbs*
Chief, Biosystems Development Section
Risk Reduction Engineering Laboratory
U.S. Environmental Protection Agency
26 West Martin Luther King Drive
Cincinnati, OH 45268
513-569-7649
Fax: 513-569-7501
A-2
*Hosts
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Ponnan Elankovan
Michigan Biotechnology Institute
P.O. Box 27609
Lansing, MI 48909-7609
517-336-4654
Fax: 517-337-2122
Thomas Evans
Research Associate
External Research & Development
The Dow Chemical Company
1776 Building
Midland, MI 48642
517-636-1547
Fax: 517-636-1705
Rod Fisher
Cargill, Inc.
P.O. Box 5698
Minneapolis, MN 55440
612-742-6470
Fax: 612-742-4707
Allan Ford
Director
Gulf Coast Hazardous
Substances Research Center
Lamar University
886 Georgia Avenue
Beaumont, TX 77705
409-880-8707
Fax: 409-880-2397
Sue Ford*
Office of Pollution Prevention & Toxics
U.S. Environmental Protection Agency
401 M Street, SW (MC-7406)
Washington, DC 20460
202-260-4153
Fax: 202-260-1661
Thomas Foust
U.S. Department of Energy
1000 Independence Avenue, SW
Washington, DC 20585
202-586-0198
Fax: 202-586-3237
John Frost
Professor
Department of Chemistry
Michigan State University
East Lansing, MI 48824-1322
517-355-9715 Extension: 115
Fax: 517-432-3873
John Glaser*
Team Leader for Soil Bioremediation
Risk Reduction Engineering Laboratory
U.S. Environmental Protection Agency
26 West Martin Luther King Drive
(MS-420)
Cincinnati, OH 45268
513-569-7568
Fax: 513-569-7105
Teresa Harten*
Risk Reduction Engineering Laboratory
U.S. Environmental Protection Agency
26 West Martin Luther King Drive
Cincinnati, OH 45268
513-569-7565
Fax: 513-569-7787
Trisha Hasch
Vice President/Manager
Conference Services
Eastern Research Group, Inc.
110 Hartwell Avenue
Lexington, MA 02173-3198
617-674-7384
Fax: 617-674-2906
Jon Herrmann*
Water & Hazardous Waste
Treatment Research Division
Risk Reduction Engineering Laboratory
U.S. Environmental Protection Agency
26 West Martin Luther King Drive
Cincinnati, OH 45268
513-569-7839
Fax: 513-569-7787
A-3
"Hosts
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S. Garry Howell*
Risk Reduction Engineering Laboratory
U.S. Environmental Protection Agency
26 West Martin Luther King Drive
Cincinnati, OH 45268
513-569-7756
Fax: 513-569-7111
David Huestis
Associate Director
Molecular Physics Laboratory
SRI International
333 Ravenswood Avenue
Menlo Park, CA 94025
415-859-3464
Fax: 415-859-6169
John Hunt
Acting Director, Chemistry Division
National Science Foundation
4201 Wilson Boulevard
Arlington, VA 22230
703-306-1857
Fax: 800-338-3128
Krishnendu Kar*
Fellow, American Association for
the Advancement of Science
Office of Pollution Prevention & Toxics
U.S. Environmental Protection Agency
401 M Street, SW (MC-7406)
Washington, DC 20460
202-260-7367
Fax: 202-260-1661
Prashant Kokitkar
Research Associate
Department of Chemistry
Michigan State University
East Lansing, MI 48824
517-355-9715
Fax: 517-353-1793
Dhinakar Kompala
Department of Chemical Engineering
University of Colorado at Boulder
Boulder, CO 80309-0424
303-492-6350
Fax: 303-492-4341
*Hosts
George Kraus
Chemistry Department
Iowa State University
Ames, IA 50011
515-294-7794
Fax: 515-294-0105
Albert Lee
Chemical Science &
Technology Laboratory
National Institute of
Standards & Technology
Building 221 - Room B312
Gaithersburg, MD 20899
301-975-5190
Fax: 301-869-5924
Marilyn Lehmkuhl*
Water & Hazardous Waste
Treatment Research Division
Risk Reduction Engineering Laboratory
U.S. Environmental Protection Agency
26 West Martin Luther King Drive
Cincinnati, OH 45268
513-569-7428
Fax: 513-569-7787
Terry Leib
Manager, Environmental
Technology Program
General Electric Research & Development
P.O. Box 8
Building K-l - Room 3B35
Schenectady, NY 12301
518-387-5563
Fax: 518-387-5604
Robert Mather
Hoechst Celanese Corporation
2300 Archdale Drive
Charlotte, NC 28210-6500
706-554-3191
Fax: 706-554-3533
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Henry McGee
Associate Provost for Engineering
Virginia Commonwealth University
827 West Franklin Street
P.O. Box 842041
Richmond, VA 23284-2041
804-828-3636
Fax: 804-828-8172
Don Meyer
Vice President, Process & Technology
Center for Waste
Reduction Technologies
The C.W. Nofsinger Company
4700 East 63rd Street
P.O. Box 419173
Kansas City, MO 64130-6173
816-822-3255
Fax: 816-822-3416
Claudia Nassaralla
Department of Metallurgical &
Materials Engineering
Michigan Technological University
1400 Townsend Drive
Houghton, MI 49931
906-487-3348
Fax: 906-487-2934
E. Bruce Nauman
Professor
Chemical Engineering Department
Rensselaer Polytechnic Institute
Troy, NY 12180
518-276-6726
Fax: 518-276-4030
Carl Potter*
Toxicologjst
Risk Reduction Engineering Laboratory
U.S. Environmental Protection Agency
26 West Martin Luther King Drive
Cincinnati, OH 45268
513-569-7231
Fax: 513-569-7105
Thomas Powers*
Water & Hazardous Waste
Treatment Research Division
Risk Reduction Engineering Laboratory
U.S. Environmental Protection Agency
26 West Martin Luther King Drive
Cincinnati, OH 45268
513-569-7550
Fax: 513-569-7787
Peter Radecki
Program Manager
Center for Clean Industrial &
Treatment Technologies
Michigan Technological University
1400 Townsend Drive
Houghton, MI 49931
906-487-3143
Fax: 906-487-3292
Paul Randall*
Chemical Engineer
Pollution Prevention Research Branch
Risk Reduction Engineering Laboratory
U.S. Environmental Protection Agency
26 West Martin Luther King Drive
Cincinnati, OH 45268
513-569-7673
Fax: 513-569-7111
Gregory Rosasco
Chief, Process Measurements Division
National Institute of
Standards & Technology
Building 221 - Room B312
Gaithersburg, MD 20899
301-975-2609
Fax: 301-869-5924
W. Richard Schmeal
Manager
Chemicals & Petroleum Office
Electric Power Research Institute
1775 St. James Place - Suite 105
Houston, TX 77056
713-963-9307
Fax: 713-963-8341
'Hosts
A-5
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Jerome Schultz
Center for Biotechnology & Bioengineering
University of Pittsburgh
300 Technology Drive
Pittsburgh, PA 15219
412-383-9700
Fax: 412-383-9710
Kathleen Schulz
Program Area Manager
Environmentally Conscious
Manufacturing Program Office
Sandia National Laboratories
P.O. Box 5800
Albuquerque, MM 87185-0738
505-845-9879
Fax: 505-844-8719
Tom Sciance
DuPont Experimental Station
P.O. Box 80304
Wilmington, DE 19880-0304
302-695-9486
Fax: 302-695-2214
Michael Seibert
Manager, Photoconversion Branch
National Renewable Energy Laboratory
1617 Cole Boulevard
Golden, CO 80401
303-384-6279
Fax: 303-384-6150
Subhas Sikdar*
Director
Water & Hazardous Waste
Treatment Research Division
Risk Reduction Engineering Laboratory
U.S. Environmental Protection Agency
26 West Martin Luther King Drive
Cincinnati, OH 45268
513-569-7528
Fax: 513-569-7787
Milagros Simmons*
Fellow, American Association for the
Advancement of Science
Office of Pollution Prevention & Toxics
U.S. Environmental Protection Agency
401 M Street, SW (MC-7406)
Washington, DC 20460
202-260-0957
Fax: 202-260-1661
Jordan Spooner*
Risk Reduction Engineering Laboratory
U.S. Environmental Protection Agency
26 West Martin Luther King Drive
Cincinnati, OH 45268
513-569-7422
Fax: 513-569-7111
Usha Srinivasan
Risk Reduction Engineering Laboratory
U.S. Environmental Protection Agency
26 West Martin Luther King Drive
Cincinnati, OH 45268
513-569-7618
Fax: 513-569-7105
F. Dee Stevenson
Program Manager
Division of Chemical Sciences
Office of Basic Energy Sciences
U.S. Department of Energy
1000 Independence Avenue, SW
Washington, DC 20585
301-903-5802
Fax: 301-904-4110
Dennis Timberlake*
U.S. Environmental Protection Agency
26 West Martin Luther King Drive
Cincinnati, OH 45268
513-569-7547
Fax: 513-569-7787
A-6
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Ronald Turner*
Chemical Engineer
Risk Reduction Engineering Laboratory
U.S. Environmental Protection Agency
26 West Martin Luther King Drive
Cincinnati, OH 45268
513-569-7775
Fax: 513-569-7677
Jim Tzeng
Research Fellow
Risk Reduction Engineering Laboratory
U.S. Environmental Protection Agency
26 West Martin Luther King Drive
Cincinnati, OH 45268
513-569-7618
Fax: 513-569-7105
Vincent Vilker
National Institute of
Standards & Technology
Gaithersburg, MD 20899
301-975-5066
Fax: 301-330-3447
Jack Watson
Deputy Coordinator
Chemical Technology Division
Oak Ridge National Laboratory
P.O. Box 2008
Oak Ridge, TN 32831-6227
615-574-6795
Fax: 615-576-7468
Leland Webster*
Fellow, American Association for the
Advancement of Science
Office of Pollution Prevention & Toxics
U.S. Environmental Protection Agency
401 M Street, SW (MC-7406)
Washington, DC 20460
202-260-5372
Fax: 202-260-1661
Steven Weiner
Battelle Pacific Northwest Laboratories
901 D Street, SW - Suite 900
Washington, DC 20024-2115
202-646-7870
Fax: 202-646-5020
Robert Wellek
Deputy Director
Chemical & Transport Systems
National Science Foundation
4201 Wilson Boulevard
Arlington, VA 22230
703-306-1370
Fax: 703-306-0319
A-7
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xvEPA
APPENDIX B—WORKSHOP AGENDA
U.S. Environmental Protection Agency and
The National Science Foundation
Workshop on Green Syntheses and Processing in
Chemical Manufacturing
Omni Netherland Plaza
Cincinnati, OH
July 12-13, 1994
Agenda
TUESDAY JULY 12
12:00 Noon Registration
1:OOPM Welcome Dr. Subhas Sikdar
U.S. EPA
1:15PM Advanced Manufacturing Dr. Joe Bordogna
National Science Foundation
1:30PM Benign Organic Synthesis Dr. James Bashkin
Washington University
2:15PM Benign Biosynthesis Dr. Jerome Schultz
University of Pittsburgh
3:OOPM BREAK
3:15PM Benign Engineering Approaches Dr. Tom Sciance
DuPont
4:OOPM Computer-Based Methods Dr. Peter Radecki
Michigan Technological University
4:45PM Guidance on Workgroups Ms. Trisha Hasch
Eastern Research Group, Inc.
5:OOPM ADJOURN
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WEDNESDAY
8:OOAM
10:00 AM
10:15AM
11:45AM
1:OOPM
2:30PM
2:45PM
4:30PM
JULY 13
Concurrent Breakout Sessions
BREAK
Concurrent Breakout Sessions (continued)
LUNCH
Concurrent Breakout Sessions (continued)
BREAK
Review and Wrap-up Session
ADJOURN
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APPENDIX C
MINUTES OF INDIVIDUAL BREAKOUT GROUPS
Minutes of the Workgroup on Benign Organic Synthesis
Minutes of the Workgroup on Benign Biosynthesis
Minutes of the Workgroup on Benign Engineering Approaches
Minutes of the Workgroup on Computer-Based Methods
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MINUTES OF THE
WORKGROUP ON BENIGN ORGANIC SYNTHESIS
The Workgroup on Benign Organic Synthesis was facilitated by
P. Anastas of the U.S. EPA. T. Hasch of Eastern Research Group served as
Chart Writer for the workgroup, while J. Glaser served as EPA Writer. Other
members of the workgroup were:
J. Bashkin D. Huestis
Washington University SRI International
C. Burns G. Kraus
Los Alamos National Laboratory Iowa State University
M. Chu M. Simmons
U.S. EPA U.S. EPA
T. Collins F. Stevenson
Carnegie Mellon University U.S. Department of Energy
S. DeVito
U.S. EPA
To begin the session, the group agreed on a general process for identifying
areas in which research to promote green synthesis is needed. During the first
stage of discussion, it was agreed that participants would raise as many issues as
occurred to them, including both very broad and very narrow topics. To promote
consideration of research in both organic and inorganic processes, the workgroup
elected to change its name to the Workgroup on Environmentally Benign
Synthesis. Following a brainstorming session during which individual group
members offered their suggestions for needed research, the group agreed to the
following master list of recommendations:
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• Provide academic scientists with a list of 250 chemical processes for
which alternatives are needed from the perspective of pollution
prevention and encourage academic scientists to identify additional
opportunities for pollution prevention
• Expose students to the ideas that chemistry is not only a source of
pollution but a source of pollution prevention and that responsible
chemistry is creative chemistry; incorporate benign chemistry as a core
tenet of academic curricula
• Develop robust homogeneous transition metal oxidants
• Clearly state a stable commitment to long-term research in synthetic
chemistry
• Develop safer solvents to replace those currently used, or develop
solventless systems
• Encourage selective clean oxidation based on molecular oxygen in
bond-making processes in order to reduce the use of substitution
reactions
• Investigate novel media and/or reaction systems to enhance the
selectivity of chemical reactions
• Develop and promote solid-acid catalysts (heterogenizing processes)
• Develop new separation techniques aimed toward enhanced recovery of
products
• Develop educational approaches to familiarize chemists with
separations and processes of physical/chemical isolation
• Develop evaluative tools to assess the environmental/economic impact
of synthetic methods at the bench and process scale
• Develop a means of long-term funding for programs in which scientists
from different disciplines can collaborate to address key issues in
research and education
• Develop databases or an information network on benign synthesis and
develop indexing techniques that are user-friendly
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• Conduct research on the synthesis of oxide-based catalysts for lean burn
processes (automotive emissions)
• Promote special issues of journals to disseminate information about
benign synthesis; promote the use of benign synthesis as a key word,
and work with editorial boards to promote publication in this area
• Promote research on small-molecule biomimetic catalysts
• Provide a venue that fosters communication among scientists from
different disciplines (e.g., societies, research-oriented workshops,
sessions at ACS meetings, etc.)
• Develop catalysts capable of carrying out difficult reactions by
employing multiple steps at a single site
• Develop functional models of enzymes
• Investigate methods of improving enantioselective synthetic methods,
especially in the area of catalysis
• Investigate biocatalysis, including the mechanisms of enzymatic and
microbiological transformations
• Promote the use of photochemistry and electrochemistry for benign
synthesis
• Investigate the use of supercritical fluids for chemical and biocatalytic
transformations
• Promote efforts in molecular design for advanced separation systems
• Design target molecules to preserve desired functions while mitigating
toxicity through structural modifications or modification of
physical/chemical properties
• Develop a functional-group understanding of health and environmental
hazards
• Develop in situ or more benign analytic sensors/monitors
• Promote the implementation of benign methods in industry
• Educate the general public about environmentally benign chemistry
and the importance of chemistry in solving environmental problems
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• Promote benign reactor designs
• Promote environmentally benign synthesis
• Learn more about industrial synthetic processes
• Gain a better understanding of industrial processes that could benefit
from environmentally benign alternatives
• Develop generic reagent-based benign strategies
• Use renewable feedstocks in place of non-renewable feedstocks
• Identify barriers to implementing environmentally benign processes
Once the master list of topics had been generated, workgroup members
were asked to vote for the topics they thought should be given highest priority.
Each workgroup member was given a total of 10 votes to spread among the
nominated research topics as he or she saw fit. The group was not satisfied with
the voting procedure, noting that some categories overlapped with one another
and others could easily be broken into two or more subcategories. One
workgroup member abstained from the voting process entirely, indicating that he
thought these issues deserved more thoughtful deliberation than such a voting
process could possibly allow.
Following this discussion, the group decided to divide its recommendations
into several general categories. All recommendations regarding specific reaction
steps or process improvements were grouped under the general category of
Benign Reaction Design. Two other general categories were established for
topics related to Education and Implementation. Two items that didn't seem to
fit into any of these categories were given a category of their own (Benign
Products).
C-5
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A voting procedure was used to develop priority rankings for the topics in
each of these four categories. For topics in the Benign Reaction Design category,
workgroup members also discussed the timeframe for the proposed research, who
should conduct the research, and whether federal funding is needed in each area.
The group felt that all of the recommendations regarding Education and
Implementation had significant potential for short-term returns. The two items in
the Benign Products category were designated as medium-term undertakings.
At the conclusion of their deliberations, the group selected T. Collins of
Carnegie Mellon University to present their findings to the workshop as a whole.
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MINUTES OF THE
WORKGROUP ON BENIGN BIOSYNTHESIS
The Workgroup on Benign Biosynthesis was co-facilitated by J. Frost of
Michigan State University and P. Elankovan of the Michigan Biotechnology
Institute. R. Brenner of the U.S. EPA served as Chart Writer for the workgroup,
while C. Potter served as EPA Writer. Other members of the workgroup were:
T. Leib
General Electric Research and
Development
J. Schultz
University of Pittsburgh
M. Seibert
National Renewable Energy Laboratory
V. Vilker
National Institute of Standards and
Technology
L. Webster
U.S. EPA
S. Barnett
University of Rhode Island
D. Bishop
U.S. EPA
M. Bradford
AE Staley Manufacturing
Company
D. Cameron
University of Wisconsin at
Madison
R. Dobbs
U.S. EPA
D. Kompala
University of Colorado at Boulder
To begin the workgroup meeting, each member of the group introduced
him- or herself and offered a brief description the area of his or her primary
interest. Following a brainstorming session during which individual group
members expressed their general views regarding areas of needed research, the
group agreed to focus on research needs in four major areas:
• Feedstocks
• Pathway Engineering
C-7
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• Reaction Engineering
• Processing
As the group discussed each of these areas, there was a great deal of
attention to semantics; in general, group members wanted to identify as many
options as possible without giving the impression that their list of topics was an
exhaustive one. In addition, the group thought it important to provide specific
examples for each general research need they had identified.
Under the general category of Feedstocks, the group developed the
following recommendations:
• Research is needed on the use of renewable feedstocks for the
production of chemicals. Feedstocks that might be explored in this
regard include carbon dioxide and methane, lignin, carbohydrates,
mixed organic wastes, industrial and municipal sludge, and lipids.
• Research is needed on customizing feedstocks to produce chemicals. In
this context, customization includes genetic as well as chemical/physical
manipulation of feedstock-producing lifeforms.
• Research is needed to explore the use of non-carbon-based feedstocks
in biosynthesis. Non-carbon-based feedstocks might include nitrogen-
based compounds (fertilizer, nitrogen-containing chemicals), minerals
(ceramics, metals), non-metals (sulfur- and phosphorus-containing
chemicals), and water (hydrogen and oxygen).
Under the general category of Pathway Engineering, the group developed
the following recommendations:
Research is needed in the genetic modification of lifeforms to produce
chemicals. Attributes that might be candidates for such modification
include selectivity, yield, tolerance, productivity, titer, and robustness.
C-8
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Research is needed to expand and utilize biocatalyst diversity. Among
the different types of biocatalysts that could be investigated are
organisms, enzymes, catalytic antibodies, genes, and ribozymes.
Research is needed to develop tools for pathway engineering.
Examples of needed tools include pathway modeling programs,
databases (gene pool, sequence, thermodynamics), and tools that allow
an integration of thermodynamic, kinetic, stoichiometric, and molecular
biological information.
Under the general category of Reaction Engineering, the group developed
the following recommendations:
Research is needed in stabilization of enzymes. In this context, factors
that contribute to enzyme stability are temperature, solvents, pH,
pressure, and electrolytes.
Research is needed in electron transfer methods. Examples of such
methods include cofactor regeneration, photochemistry, and
electrochemistry.
Research is needed in improving the productivity and selectivity of
biocatalytic conversions. Approaches that might prove to be of benefit
in this regard include phase-transfer catalysis, non-aqueous media,
supercritical fluids, biocatalyst immobilization, post-translational
biocatalyst modification, and substrate/product transport.
Under the general category of Processing, the group developed the
following recommendations:
Databases need to be established. Examples include databases dealing
with the physical/chemical properties of aqueous and aqueous/ organic
systems and databases dealing with process alternatives.
Research is needed on methods of improved separation and purification
of chemicals from biosynthetic processes. Problems that need to be
addressed in this area include dilute solutions, aqueous solutions, trace
contaminants, multi-phase systems, and waste (salts, solvents,
adsorbants).
C-9
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• Research is needed on reactor design and modelling. Examples of
needed work in this area include process synthesis/integration, process
design and modelling, integration of biocatalytic and abiotic catalytic
methodologies, databases for process alternatives, and sensors/controls.
When the group completed its recommendations in each of these four
areas, there was not time for discussion of the relative priority, timerrame,
research sponsor, or need for federal funding for individual research initiatives.
The group agreed to complete this portion of its work by fax polling after the
workshop was over. The group selected D. Cameron of the University of
Wisconsin at Madison to present their findings to the workshop as a whole.
C-10
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MINUTES OF THE
WORKGROUP ON BENIGN ENGINEERING APPROACHES
The Workgroup on Benign Engineering Approaches was facilitated by A.
Ford of Lamar University. Ford had to leave the meeting for approximately an
hour, during which time C. Sciance of the DuPont Experimental Station served as
facilitator. J. Hermann of EPA served as Chart Writer for the workgroup, while
T. Harten served as EPA Writer. Other members of the workgroup were:
M. Anand
Air Products & Chemicals, Inc.
P. Biswas
University of Cincinnati
G. Brown
Union Carbide
T. Evans
The Dow Chemical Company
R. Fisher
Cargill, Inc.
T. Foust
U.S. Department of Energy
G. Howell
U.S. EPA
J. Hunt
National Science Foundation
K. Kar
U.S. EPA
P. Kokitkar
Michigan State University
A. Lee
Naional Institute of Standards
and Technology
R. Mather
Hoechst Celanese Corporation
H. McGee
Virginia Commonwealth
University
C. Nassaralla
Michigan Technological
University
E. Nauman
Rensselaer Polytechnic Institute
W. Schmeal
Electric Power Research Institute
K. Schultz
Sandia National Laboratories
J. Watson
Oak Ridge National Laboratory
R. Wellek
National Science Foundation
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To begin the session, Ford suggested that the group go once around the
table, allowing each workgroup member to propose a research topic. Because of
the large size of the group, it was agreed that going once around the table would
be all that time allowed. Following discussion of each issue as it was raised, the
group agreed to the following distillation of the topics that had been discussed:
• Enzymatic catalysts (including the use of catalysts to obtain higher
product concentrations, issues related to catalyst attrition, the use of
catalysts in separation processes, and the development of non-toxic
catalysts)
• Freezing processes and melt crystallizations, particularly as they relate
to organic separations
• Separation processes that avoid phase changes
• Reaction design to minimize the need for separations
• Microwave- or radiation-enhanced reactions
• Confinement techniques
• Control of abnormal processes
• Redesign of valves and fittings
• Remote sensors (especially as related to reducing the cost of
monitoring critical emissions and to increasing the use of area-wide
monitoring strategies)
• Unit operations (including physical separations, better modeling of unit
operations, and methods for separating materials of value from wastes)
• Methods of water removal (especially as they relate to the dilute
systems characteristic of biotechnologic processes)
• Membrane technology (including the development of new polymers)
• Hybrid unit operations
C-12
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• Application of pinch technology to environmental aspects of process
development and evaluation
• Gas phase/aerosol processing
• Disposal of bioprocess wastes (including both genetic and non-genetic
techniques)
• Fluidized bed combustors
• Better understanding of emissions
• High-temperature combustion chemistry
• Adding value to solid wastes (i.e., fruitful use versus disposal)
• Non-chemical sources for electron exchange
• Supercritical fluids as solvents
• Renewable feedstocks (including methane coupling)
• Partial oxidation of wastes to syngas
• New technology approaches that start from the ground up
Just before the lunch break, workgroup members were asked to vote for
those topics they considered of highest priority. Each workgroup member was
given a total of five votes to spread among the nominated research topics as he or
she saw fit.
After the lunch break, one person suggested that, in addition to the
technology issues the group had identified, it might be good to try to capture the
part of the morning discussion that had had to do with what he described as
"front-end" issues cutting across all of the various technology areas. As examples
of such issues, he listed the following:
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• Defining exactly what is meant by benign technology
• Developing life cycle tools that could be used in making and defending
process decisions
• Expanding efforts in benign synthesis to involve additional players, such
as small companies, companies with related processes, and suppliers
• Promoting effective cooperative efforts
• Promoting the concept of benign chemistry as part of the professional
education of chemists and chemical engineers
Other group members agreed that these issues were important and should be part
of the workgroup's recommendations.
Following the voting on individual research topics, some members of the
workgroup expressed concern about the extent to which overlaps among the
topics might obfuscate the results of the voting process. To organize the topics
in a more manageable form, the workgroup developed seven general categories,
as follows:
• Unit Operations
• Sensors
• Containment
• Catalysis
• Process Synthesis
• Combustion
• By-Products
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To develop proactive statements about the research recommended in each
of these general areas, the workgroup broke into smaller teams, one addressing
each of these seven areas and one to formulate the group's recommendations
regarding front-end issues. One member from each team was selected to present
that team's findings to the workshop as a whole.
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MINUTES OF THE
WORKGROUP ON COMPUTER-BASED METHODS
The Workgroup on Computer-Based Methods was facilitated by
C. Brunner of the U.S. EPA. D. Timberlake of EPA served as Chart Writer for
the workgroup, while J. Spooner served as EPA Writer. Other members of the
workgroup were:
P. Radecki
H. Bostian Michigan Technological University
U.S. EPA
G. Rosasco
S. Ford National Institute of Standards
U.S. EPA and Technology
D. Meyer
The C.W. Nofsinger Company
To set a framework for the group's discussion, Bostian described several
past efforts related to process simulation that had been jointly sponsored by EPA
and other federal agencies. Workgroup participants were given copies of the
report of a December, 1992, Workshop on Environmental Considerations in
Process Design and Simulation, as well as the minutes of meetings of a Process
Simulation Workgroup that had grown out of that workshop. To the extent
possible, it would be good to avoid duplicating these earlier efforts.
Brunner presented a brief outline of the procedure that would be followed
by the workgroup. He indicated that he would go around the table twice,
soliciting ideas from workgroup members, after which the floor would be opened
for additional discussion or recommendations. Regarding the issue of whether to
focus on broader or more specific recommendations for research, the group
decided that it would probably be best to keep their recommendations relatively
broad.
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During the first round of suggestions, the following issues were raised for
consideration:
• Maintenance of software and databases
• Integration of energy and mass transfer networks
• Process design, especially from the perspective of retrofitting
• Methods for addressing environmental concerns at the design concept
stage
• Artificial intelligence for process simulation
• Methods for overcoming obstacles to information transfer and assuring
that the information engineers need for process design is available to
them
• Guidelines for making process design decisions
During the second round, the following issues were raised:
• Methods for performing environmental impact evaluation
• Development of dynamic process simulators to deal with start-ups,
shutdowns, upsets, etc.
• Regulatory forecasting
• Small-customer modules
Brunner noted that a number of issues had been suggested on the cards
submitted by workshop participants serving on other workgroups. Among these,
he listed the following:
• Reaction path synthesis
• Surrogate selection
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• Total cost assessment
• The tendency for new development to focus on user interface features
rather than more robust modelling
• Improved optimization
• The observation that simulators tend to be good accounting devices but
not good predictors, and that the better reactor models are proprietary
systems not included in commercially available simulators
• Methods to address the formidable chemical engineering problems that
often occur during process scale-up
• Methods of predicting the formation of trace contaminants
• Expert guidance/heuristics for pollution prevention design
• Catalyst design
• Aqueous systems/electrolytes
Following the morning break, workgroup members offered additional
topics for research:
• Uncertainty analysis guidance similar to expert guidance in flowsheet
building
• Stochastic modeling
• Data acquisition/predictions in a laboratory setting
• Data retrieval from proprietary sources (e.g., vendors, operating
companies)
• Chemical structure-based data prediction
• Incorporation of life cycle assessment (which may be a long-term need)
• Toxicity data retrieval and prediction
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Integration of product-based methods (e.g., solvent substitution,
materials selection)
Application of industrial ecology analysis
To facilitate consideration of this broad range of topics, the workgroup
attempted to devise categories that would subsume multiple research topics.
Although there was some difficulty in coming up with names for these categories,
the group eventually settled on the following six categories:
• Integrating Activities
• Decision-Making Tools
• Expanded Process Simulation
• Decision Support
• Reaction Engineering
• Data and Characterization
Regarding the timeframe within which a significant impact of the
recommended research could be expected, the group agreed that all of the items
they had discussed were ones that had the potential to produce such an impact in
the short-term (i.e., within 5 years). There was a reluctance among some group
members to place a specific timeframe on each item, since there was some fear
that items identified as longer-term needs might be put off.
The group also had some difficulty in assigning the various tasks to
industry, government, and/or academia. In general, however, they felt that
industry and academia should be involved in all of these efforts, while government
should only be involved in some. Government participation was considered
especially important for topics like regulatory forecasting, which involve issues
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where the government clearly plays an important if not determinative role.
Bostian made a plea that the group not suggest that government funding is
needed for all of its recommendations, and Brunner suggested that government
funding be requested only where it is definitely needed.
Following the lunch break, a voting procedure was used to rank the topics
in each category in terms of their relative priority. In this procedure, each
workgroup member was allotted 10 votes per category, no more than 6 of which
could be allocated to a single research topic. One workgroup member abstained
from the voting due to a lack of adequate background in computer-based
methods.
When the voting was complete, P. Radecki was selected to present the
workgroup's recommendations to the workshop as a whole.
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*L'.S. GOVERNMENT PRINTING OFFICE: 1 9 94-5 5 0-00 1 ' 00 1 7 3
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