Chemical & Engineering News
June 27, 2005


Presidential awards honor chemists for developing cleaner and
economically viable technologies

Stephen K. Ritter

"We have changed innumerable things in the practice of chemistry, but
the most important thing we have changed is our minds," commented
American Chemical Society President William F. Carroll, speaking last
week at a ceremony honoring the winners of the 2005 Presidential Green
Chemistry Challenge Awards. A few moments earlier, Carroll had
recounted a story about how, during a recent discussion in China, one
student's pronouncement that "pollution is inevitable with growth and
progress" had stopped him cold.

"From the perspective of the chemical industry, pollution and progress
are not synonymous," Carroll recalled telling the student. "Pollution
is waste, and waste means cost." Carroll followed up by telling the
student that the job of chemists is not to find a singular solution to
a technical problem, but to challenge themselves to constantly find
better solutions. "That understanding is fundamental to what we call
green chemistry," Carroll said.

Green chemistry is all about more efficient production of industrial
chemicals, pharmaceuticals, and consumer products. That is to say, the
purpose of green chemistry is to find ways to develop ever-better
chemical products and processes that require fewer reagents, less
solvent, and less energy to produce, while being safer, generating
less waste, and increasing profitability.

The concept of green chemistry was formally established at the
Environmental Protection Agency about 15 years ago in response to the
Pollution Prevention Act of 1990. The principles that guide green
chemistry may seem intuitive or be viewed simply as common sense, but
over the years they have become an intangible framework for the
chemical community. Today, these principles are ingrained in the day-
to-day operations of companies and increasingly are being incorporated
into empirical research carried out at universities and national labs.

Last week, EPA presented the 10th Annual Green Chemistry Awards in
conjunction with ACS, the Green Chemistry Institute, and other
partners to reward noteworthy successes in green chemistry. The awards
were given to five companies and an individual during a ceremony held
on June 20 at the National Academy of Sciences in Washington, D.C.

The awards ceremony took place on the eve of the 9th Annual Green
Chemistry & Engineering Conference, which this year was held in
conjunction with the 2nd International Conference on Green &
Sustainable Chemistry. Incentives and barriers to adopting greener
technologies were a primary topic of discussion throughout the week of
plenary sessions, technical symposia, and workshops that featured
talks by the award winners.

EPA solicits Green Chemistry Award nominations in five categories:
alternative synthetic pathways, alternative solvents and reaction
conditions, designing safer chemicals, small business, and academic.
An independent panel, appointed by ACS, judges the nominations and
selects the award winners.

The Pollution Prevention Act "formally recognized what we had
learned--that laws and regulations alone are not enough to solve our
toughest environmental problems," noted Margaret N. Schneider, acting
deputy assistant administrator of EPA's Office of Prevention,
Pesticides & Toxic Substances. "What we needed was the creation of
scientific and technical innovations that eliminate pollution before
it's created, which we see reflected in the Presidential Green
Chemistry Challenge Awards."

The results of the awards program "are pretty impressive," Schnieder
added. Since it began, EPA's tracking of the impact of the winning
technologies shows them to have prevented on average 140 million lb of
hazardous substances from being produced each year, saved more than 55
million gal of process water per year, and prevented 57 million lb of
carbon dioxide emissions per year, she noted. "In total, by our
current conservative estimates, green chemistry technologies are
preventing more than 3 billion lb of hazardous materials or waste per

There was a bit of a surprise for the alternative synthetic pathways
category this year, as the selection committee named two winners.
Merck was recognized for its redesign of the synthesis of aprepitant,
the active ingredient in Emend, a drug used to reduce nausea and
vomiting caused by cancer chemotherapy. Archer Daniels Midland and
Novozymes were recognized for jointly developing an enzymatic method
to produce ADM's NovaLipid line of zero- and reduced-trans-fat oils
used in food processing.

Aprepitant selectively binds and blocks the neurokinin receptor NK1.
This receptor normally binds substance P, a peptide neurotransmitter
associated with a host of central nervous system and digestive

The original Merck synthesis of aprepitant was workable, and it
allowed the company to move toward commercialization. But it wasn't
sustainable from a green perspective, noted R. P. (Skip) Volante,
Merck's vice president of process research. For example, the synthesis
was carried out in six steps and required some hazardous chemicals,
such as sodium cyanide, dimethyltitanocene, and gaseous ammonia. Some
steps needed cryogenic temperatures, and others generated by-products
such as methane and magnesium chloride. As the drug was wending its
way through clinical trials, the process research team decided that an
entirely new synthesis was needed.

"At Merck, we are driven in process research by our mission statement
to design elegant, practical, and efficient syntheses that are
environmentally and economically viable," Volante told C&EN. "For
aprepitant, we were able to use the latest technology and our
fundamental understanding of chemistry to improve the synthesis and
make a greener process work."

Aprepitant has a morpholine core with two substituents attached to
adjacent ring carbons and a third substituent attached to the
morpholine ring nitrogen. "Overall, the molecule contains three chiral
centers in close proximity to one another as part of a -amino acetal
arrangement, making it a challenging synthetic target," Volante noted.

The new synthesis assembles aprepitant in only three steps by merging
four compound fragments of comparable size and complexity (J. Am.
Chem. Soc. 2003, 125, 2129). To begin, enantiopure trifluoromethylated
phenylethanol is coupled to a racemic morpholine precursor. The
desired isomer of the resulting intermediate crystallizes out of
solution, leaving behind an undesired isomer.

But rather than separating and discarding the unwanted isomer, the
chemists control the reaction conditions to achieve a
"crystallization-induced asymmetric transformation," converting the
unwanted isomer completely to the desired isomer, Volante said. In the
additional two steps, a fluorophenyl group is stereoselectively
attached to the morpholine ring and a triazolinone side chain is added
to the ring.

The streamlined route doubles the overall yield to 76% and
significantly reduces operating costs and the environmental impact,
Volante pointed out. Besides eliminating several hazardous reactants,
the synthesis has reduced both the amount of water used and the amount
of reagents and solvents needed by 80%. Relative to the initial
synthetic route, 340,000 L of waste has been eliminated per metric ton
of aprepitant produced, an 85% reduction. Because the new synthesis
was implemented during the first year of aprepitant production, the
benefits will be realized over nearly the entire product lifetime, he

ADM and Novozymes put their talents together to develop NovaLipids, a
new brand of zero- and reduced-trans-fat vegetable oils that are being
used to make margarine, processed baked goods, and other foods.
Equally important to developing NovaLipids were ADM's process scale-up
expertise and Novozymes' Lipozyme immobilized lipase, noted Inmok Lee,
ADM's manager of vegetable oil research. "Our interest was in
developing oils suitable for making low-trans-fat versions that
perform equally or even better than currently used oils," he said.

Trans fats have been identified as culprits contributing to elevated
blood levels of low-density lipoprotein--the so-called bad form of
cholesterol implicated in cardiovascular diseases--while decreasing
the high-density "good" form of cholesterol. Food processors are under
consumer pressure to reduce the amount of trans fat in foods. As an
added incentive, the Food & Drug Administration has issued rules for
mandatory listing of trans fat on nutritional labels beginning next

Food processors traditionally have partially hydrogenated the
unsaturated fatty acid chains in vegetable oils using a nickel
catalyst. Hydrogenation allows control over the melting
characteristics of the oils, which are important to obtain the desired
texture and taste of foods. But the process leads to some
isomerization of the double bonds, converting cis isomers to trans

One way to avoid forming trans fats is to use fully hydrogenated oil
and "interesterify" it with unhydrogenated oil, Lee explained.
Interesterification typically has been a chemical process that uses
sodium methoxide to cleave and randomly exchange the positions of the
three fatty acid chains of the various triglycerides in oils.

Chemical interesterification avoids formation of additional trans
fats, but a downside is that it produces triglycerides with a
saturated fatty acid chain in the 2-position, which is not normally
encountered in vegetable oil. Chemically interesterified oil also must
be washed with water and sometimes acid to eliminate by-product fatty
acid salts (soaps), and the oils from hydrogenation or
interesterification must be bleached with citric acid and clay to
remove off-color contaminants.

Lipases are generally known to hydrolyze the fatty acid ester bonds of
triglycerides to form free fatty acids. But when the moisture content
of the oil is kept low, Lee said, lipases can also catalyze
interesterification. Low stability of the enzymes and high production
costs previously had been barriers to industrial processes using
lipases, however.

Novozymes in time developed a technique for immobilizing a selected
lipase by spraying the enzyme along with a binder onto porous silica
granules, greatly reducing the cost of immobilization. The granules
are insoluble in the oil and are used as a heterogeneous catalyst for
interesterification in fixed-bed reactors. ADM subsequently developed
pretreatment processes to purify oils before interesterification to
increase the useful life of the immobilized enzymes, Lee noted.

A bonus benefit of Lipozyme is that the enzyme is selective and
interchanges the fatty acid groups only between the 1- and 3-positions
of the triglycerides, he added. This leaves the fatty acid chain in
the 2-position untouched, resulting in a "more natural" oil. In
addition, the only postreaction processing needed is a deodorizing

Since July 2002, ADM has produced more than 15 million lb of lipase-
interesterified oils, and the company is currently expanding the
process, Lee said. "Enzymatic interesterification has provided savings
in capital and operating costs for ADM, while NovaLipid products have
provided food companies with a broad range of options for zero- and
reduced-trans-fat products," he noted. "The benefit of enzymatic
interesterification will depend upon how successful this process will
be at supplanting partial hydrogenation."

One of the most important issues for paints and coatings manufacturers
in recent years has been to develop new products--and new technologies
to apply them--that reduce volatile organic compound (VOC) emissions
to meet more stringent environmental, health, and safety regulations.
The impact these changes are having on the industry is reflected in
the new products developed by winners of Green Chemistry Awards in two

In the alternative solvents and reaction conditions category, BASF was
honored for its acrylate-based UV-cure paint primer for small
automotive repairs. The primer was designed to replace infrared- or
heat-cured diisocyanate-based primers in order to significantly reduce
VOC emissions that are concerns for auto body repair shops, as well as
to reduce repair time and costs.

Traditional primers used in automobile repairs are two-component
systems consisting of a hydroxyl-containing polyacrylate solution and
an aliphatic polyisocyanate, according to Bradley M. Richards, BASF's
manager for coatings R&D. The components are mixed before application,
and they polymerize (cure) when heated to give a high-performance
acrylic urethane film to match the original finish applied by the
automaker, he explained. The curing process typically takes 30 minutes
or longer in a natural-gas-heated oven. Low-VOC waterborne coatings
are also used in repairs, but they require long drying times as well.

BASF's new primer is a one-component urethane acrylate oligomer that,
when exposed to a handheld UV lamp, cross-links to form an acrylic
urethane film in just two to three minutes, Richards noted. The primer
also can be cured in direct sunlight with a two- to five-minute cure

"One of the benefits of the oligomer is that it has a lower viscosity
and a narrower molecular-weight range, so the VOCs are lower,"
Richards told C&EN. The UV primer contains one-third to one-half the
amount of VOCs per gallon as conventional primers, he added. Also,
it's more durable, and application equipment requires less frequent
cleaning than with conventional primers.

The company is currently offering the primer in its R-M product line
as Flash Fill VP126 and in its Glasurit product line as 151-70. The
primer is part of BASF's plan for a complete ecoefficient auto
refinishing coating system, including the foundation layer, primer,
color base coat, and final clear coat. BASF expects its UV-cured
primer to eventually be used in many of the 50,000 body shops in North

In addition to its Green Chemistry Award in the alternative synthetic
pathways category, ADM also garnered the award in the category of
designing safer chemicals for its nonvolatile Archer RC (reactive
coalescent) propylene glycol monoester, an additive for latex
architectural paints.

Coalescents are chemical agents that help latex particles in paints
flow together to form a continuous film for a smooth finish. A primary
coalescent used in the industry is 2,2,4-trimethyl-1,3-pentanediol
monoisobutyrate (TMB), but it's volatile and escapes from the paint as
it dries. An estimated 120 million lb of volatile coalescing agents
are lost to the atmosphere in the U.S. each year, according to ADM.

"There's a need to lower VOCs in latex paints from a regulatory
standpoint, so that is the first application ADM has focused on for
Archer RC because it will have the biggest impact," noted Paul D.
Bloom, ADM's manager of new industrial chemicals. "But there are many
other possible uses for Archer RC as a nonvolatile carrier." Some
examples include inks, caulks, and alkyd paints.

Archer RC is made by chemical interesterification of the fatty acid
chains of triglycerides in corn oil, followed by removal of the
glycerol, Bloom explained. The glycerol coproduct is a useful material
for other applications, he added.

Archer RC and TMB have similar structures, except that Archer RC has a
long fatty acid hydrocarbon tail, approximately 60% of which is
linoleic acid, that significantly increases the molecular weight and
reduces the volatility, Bloom said. Double bonds in the fatty acid
chain are the "reactive" part of the coalescent, allowing the compound
to oxidize and cross-link into the paint film, further reducing the
chance that the compound will evaporate. Besides reducing VOC
emissions, paints using Archer RC have less odor, increased scrub
resistance, and better gloss than paints containing TMB, according to
independent lab tests.

Metabolix, Cambridge, Mass., was selected as the award winner in the
small business category for developing a fermentation process to
produce polyhydroxyalkanoate (PHA) "natural plastics" from renewable
feedstocks such as plant sugars or oils. These readily biodegradable
polyester polymers and copolymers combine the film-barrier properties
of polyesters with the mechanical performance properties of petroleum-
based polyethylene and polypropylene. Metabolix is set to start making
PHAs on a large scale. It will join Cargill and DuPont--former Green
Chemistry Award-winning producers of NatureWorks and Sorona,
respectively--as producers of biobased polymers.

"This award recognizes Metabolix' success in transforming PHA natural
plastics technology from a biological curiosity to a commercial
reality," noted Oliver P. Peoples, one of the company's founders and
its chief scientific officer.

Some bacteria naturally synthesize PHAs for energy storage, much the
way animals produce fat. In the late 1980s, Peoples and Anthony J.
Sinskey, working together at Massachusetts Institute of Technology,
took advantage of this biopolymerization process and used metabolic
engineering techniques they developed to incorporate a series of genes
from various PHA-producing bacteria into a strain of Escherichia coli.
The genes in turn express enzymes that can convert sugar or oil into
polymers via a multistep process within the bacterial cells. Metabolix
was formed in 1992 to commercialize the technology.

The properties of PHAs range from rigid to elastic, depending on the
length of side chains or type of copolymer, and they are suitable for
processing into films, fibers, and molded goods using conventional
polymer-processing equipment, according to James J. Barber, Metabolix'
president and chief executive officer. The plastics have a long shelf
life, he said, yet they quickly biodegrade in soil or water to produce
CO2 and water (in aerobic environments) or CO2 and CH4 (in anaerobic

The company has developed the technology with private funding and with
competitive grants from the Department of Commerce's Advanced
Technology Program and from the Department of Energy. Last fall,
Metabolix announced a joint venture with ADM to commercialize PHAs and
to construct a 50,000-ton-per-year plant based on corn sugar in the

The key markets for PHA plastics include food packaging; disposable
and single-use items, such as dinnerware and coated-paper hot-beverage
cups; and agricultural and soil-stabilizing applications requiring

Separately, in a program sponsored by the Department of Agriculture,
Metabolix is developing genetically engineered plants, such as
switchgrass, a native prairie grass, that can directly produce PHAs in
plant cells. The PHAs could be processed as polymers or depolymerized
to form hydroxy acids for use as chemical feedstocks, and the residual
plant material could be burned for energy or converted to liquid
fuels. Metabolix recently formed a collaboration with BP to further
develop the plant-based technology.

"The successful development of crop-based PHA natural plastics, in
addition to our fermentation-based products, will provide the world
with a range of agriculturally derived polymer products as
alternatives to petrochemical plastics," Barber said.

Robin D. Rogers, Distinguished University Research Professor at the
University of Alabama, Tuscaloosa, received the academic award in the
area of alternative synthetic pathways for developing ionic liquids as
recyclable solvents. The award specifically recognizes Rogers' work
using ionic liquids to dissolve and process cellulose into advanced
functional materials for use in textiles, sensors, and plastics.

Cellulose is an abundant and inexpensive renewable material that could
replace synthetic polymers in select applications, Rogers said.
Although cellulose has been widely studied, its use has been limited
because it's insoluble in water and most common organic solvents.
Using ionic liquids to dissolve and reconstitute cellulose could
reduce volatile emissions common in cellulose processing, decrease
energy requirements, and expand the potential applications for
cellulose, he noted.

"If we can directly utilize the biocomplexity Mother Nature has
provided with cellulose to form new materials, we could eliminate many
unnecessary synthetic steps," Rogers told C&EN.

Ionic liquids typically consist of nitrogen-containing organic cations
and inorganic anions, such as imidazolium salts, that are stable,
nonvolatile liquids at room temperature. They are beginning to be used
as industrial solvents for polymer processing, extraction and
separation processes, and organic synthesis.

Rogers' group found that cellulose readily dissolves in ionic liquids
with gentle heating. So far, the group has demonstrated that cellulose
from wood pulp, field cotton, and other sources rapidly dissolves in
1-butyl-3-methylimidazolium chloride.

Other polymers, nanoparticles, metal-complexing agents, dyes, or
biomolecules such as enzymes can be added as solutions to make
functional materials, Rogers pointed out. "The ionic liquid is simply
the enabler," he said.

Cellulose can be precipitated from ionic liquids by adding water,
ethanol, or acetone, and the ionic liquid can be recovered for reuse.
The regenerated cellulose can be formed into different architectures,
ranging from beads to fibers to films.

Rogers, who is director of Alabama's Center for Green Manufacturing,
is working with several colleagues at Alabama and elsewhere to license
the patents on the cellulose processing and to start a company, called
525Solutions, to develop specific new products. The company is being
launched under the guidance of the Alabama Institute for Manufacturing
Excellence and will be led by Richard P. Swatloski, a recent Ph.D.
graduate from Rogers' group who has worked on the cellulose project.

Copyright 2005 American Chemical Society