SCIENCE & TECHNOLOGY
GREEN CHEMISTRY GETS GREENER Catalysis, agriculture are part of myriad efforts to expand environmentally benign practices STEPHEN K. RITTER, C&EN WASHINGTON
I
N JUST OVER IO YEARS, GREEN CHEM-
istry has grown from a grassroots idea initiated by a few chemists to a concept that has permeated all of chemistry. Evidence of this rapid growth was clear by the number of talks last month at the American Chemical Society's national meeting in Orlando, Fla., that focused on developing environmentally benign laboratory and industrial practices. Most of the green chemistry presentations were made in symposia organized by the Division of Industrial & Engineering Chemistry (I&EC). Topics included green catalysis, separations using supercritical C 0 2 , agricultural green chemistry, and green chemistry in the pharmaceutical industry (C&EN, April 22, page 30). The Society Committee on Education also sponsored a general session that provided an introduction to green chemistry. In the catalysis arena, meeting sessions covered homogeneous catalysis; heterogeneous catalysis; biocatalysis; and alternative catalysis involving photolysis, sonication, and ultrasound. Chemistry professor Chao-Jun Li of Tulane University discussed his group's efforts to apply the principles of green chemistry to make chemistry not only environmentally benign but also more efficient. The greenest course of action is to minimize the number of reactions, Li stipulated. His group has become expert in demonstrating this reaction-elimination principle through C - H bond activation of organic substrates using an array of metalmediated and -catalyzed syntheses. Typically these syntheses are carried out in open air under aqueous conditions or with no solvent. In many of the reactions, protection of hydroxyl, carboxylic acid, and amine groups isn't necessary, Li noted.
In total, these modifications offer potentially large savings in time, energy, and organic reagents in addition to reducing or eliminating by-products, he explained. Li's efforts in this area earned him a 2001 Presidential Green Chemistry Challenge Award. ONE OF SEVERAL example reactions described during talks by Li and by postdoc Chunmei Wei was the direct addition of a terminal alkyne (phenylacetylene) to various imines [Chem. Commun., 2002,268}. The imines are first generated in situ from an aldehyde and aniline, followed by addition of phenylacetylene and a RuCl3-CuBr cocatalyst. The proposed mechanism involves simultaneous C - H activation of the alkyne by ruthenium and the imine by copper. The ruthenium intermediate is thought to undergo a Grignard-type addition to the activated imine to give the acetylenic amine product and regenerate the cocatalyst. The reactions can be carried out in water or under solventless conditions, Li noted, with yields generally above 85%. Li and Wei first tried RuCl 3 and CuBr separately as the catalyst but obtained low yields. They later determined that the combination of the two metal salts gives optimal results. During their investigations they further discovered that the alkyneimine additions can be carried out enantioselectively using copper bis(oxazolinyOpyridine complexes \J. Am. Chem. Soc, 124,5638(2002)}. T h e reactions in water lead to yields of chiral amines generally above 65% with enantiomeric excesses of 7 8 - 9 1 % . In toluene, the conversions are generally above 80% with enantiomeric excesses of 82-96%, Li said, although using the or-
ganic solvent is less desirable. 'These addition reactions have many possible applications in the synthesis of pharmaceuticals, fine chemicals, and agricultural chemicals," Li stated. As the number of chemists practicing greener chemistry continues to grow, so do the opportunities to form collaborations drawing on the strengths of different research groups. One such example is a new collaborative effort between Li's group at Tulane and the groups of Rajender S. Varma ofthe Clean Processes Branch of EPAs National Risk Management Research Laboratory, Cincinnati, and Luc Moens of the National Renewable Energy Laboratory, Golden, Colo. One area of focus for this collaboration is the development of new catalyst systems in ionic liquids. Graduate student Charlene C. K. Keh in Li's group discussed some of the initial results: a Prins-type cyclization of homoallylic alcohols with aldehydes in an ionic liquid for the direct preparation of a series of tetrahydropyranols. The reaction includes l-butyl-3-methylimidazolium hexafluorophosphate as the ionic liquid and cerium triflate as a catalyst. A small amount ofbenzoic acid is added to assist the Lewis acid catalysis, Keh noted, which optimizes yields at about 80%. The ionic liquids, supplied by the Varma and Moens groups, can be used up to three times without any loss in reaction yield, she said. Varma's group has been exploring the use of ionic liquids as both a solvent and a cocatalyst. One example is the palladiumcatalyzed oxidation of styrene to acetophenone (Wacker reaction) under solventless conditions using H 2 0 2 as the oxidant [Green Chem., 4,170 (2002)}. The addition of a small amount of an ionic liquid, such as l-butyl-3-methylimidazolium tetrafluoroborate, significantly enhances the reaction yield with high selectivity for acetophenone over benzaldehyde. Postdoc Vasudevan V. Namboodiri in Varma's group described a microwave-assisted solventless synthesis of ionic liquids in high purity that should aid the collaborative research. Ionic liquids are generally prepared by refluxing an alky! halide and an imidazole in an organic solvent for several hours, Namboodiri said. In the new method, the ionic liquid can
"One of the important areas under the umbrella of green chemistry is going to be how researchers, government agencies, and industry work together to develop sustainable agriculture." 38
C & E N / MAY 2 0 , 2002
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that is nearly two orders of magnitude greater than in pure supercritical C0 2 . The reaction pressure needed is only 60 to 90 bar compared with 200 bar or greater normally needed to solubilize the catalyst. The catalyst can be conveniently recovered by increasing the C 0 2 pressure until the catalyst precipitates, he added.
"THE COMBINATION OF significant solvent replacement [up to 80%] with C0 2 , RCH + C6H5NH2 + HC = C - C 6 H 5 much higher turnover rates, moderate reHoO,40°C +* action pressures, and facile catalyst separation makes these processes both enviHNC6H5 ronmentally and economically appealing," Cu catal st Busch concluded. C6H5CH + C6H5NH2 + HC = C - C 6 H 5 y » ) = C6H5 35 °C c.H One of the promising developments in green catalysis has been the preparation Toluene: 83% yield, 93% ee H2O:77%yield,80%ee Ac = acetyl, ee = enantiomeric excess of tetraamido macrocyclic ligand (TAML) iron(III) activators by Carnegie Mellon be prepared simply by heating the reao limiting because of low reaction rates, in- University chemistry professor TerrenceJ. tants together in a conventional microwave adequate catalyst solubilities, and high Collins. In 1999, Collins received a Presidential Green Chemistry Challenge Award oven without solvent in aprocess that takes process pressures. only a few minutes [Chem. Commun., 2001, A mixture of organic solvent with C0 2 , for demonstrating that TAML activators 643}. The method provides an opportu- a system termed a C02-expanded solvent, significantly increase the oxidizing ability nity to generate ionic liquids in situ and is away to complement supercritical C 0 2 of hydrogen peroxide and that the carry out a subsequent reaction all in one as a reaction medium, Busch explained. In TAML/H 2 0 2 system can be used in a vapot, Namboodiri said. one example, the Kansas researchers use riety of commercial applications. Chemistry professor Daryle H. Busch acetonitrile with C 0 2 in a 1:1 volume ratio In two talks in Orlando, Collins deof the University of Kansas discussed his to oxidize 2,6-di-ter£-butylphenol to the scribed his group's ongoing efforts to group's work with Kansas chemical engi- corresponding 1,4-benzoquinone \J. Am. study the properties of TAML activators neering professor Bala SubramanianVs Chem. Soc, 124,2513 (2002)]. The reaction and elaborated on several applications group on "C02-expanded" solvents for cat- provides better than 80% selectivity using being developed. Areas under investigaalytic oxidations. Supercritical C 0 2 has 0 2 as the oxidant and a cobalt(II) catalyst. tion include replacement of chlorine or long been considered a green solvent, Carbon dioxide increases the solubility chlorine dioxide in wood pulp processBusch noted, and it has been shown to be of 0 2 nearly two orders of magnitude com- ing, paper and textile mill effluent deuseful in a number of oxidation reactions. pared with neat acetonitrile, Busch said, colorization, laundry applications, deBut as many green chemistry researchers while the acetonitrile aids in catalyst solu- contamination of chemical and biological are finding, pure supercritical C 0 2 can be bility and allows a catalyst turnover rate warfare agents, and oxidation of sulfur 0
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contaminants in petroleum refining. "TAML activators are water soluble, and different examples allow access to a broad p H range {1 to 13}," Collins noted. "The activators are relatively easy to synthesize, and they function well in nanomolar to low-micromolar concentrations." The activators can be readily modified to achieve a desired selectivity, he added, and for most applications minimal capital costs will be needed for their implementation. Initial lab tests indicate that the TAML activators have low toxicity, but complete toxicology studies to check environmental persistence and bioaccumulation are still needed, Collins said. COLLINS REPORTED that his group has most recently used TAML activators for the rapid total destruction of chlorophenols [Science, 296, 270 and 326 (2002)}. Chlorophenols, which are recognized by EPA as persistent environmental pollutants, are commonly used in pesticides, wood preservatives, and personal care products. They are also a by-product of wood pulp bleaching. Bacteria and fungi can be used to break down chlorophenols, Collins noted, but that process takes days. In addition, when peroxidase enzymes are used by microorganisms to digest chlorophenols, toxic chlorinated organics such as dioxins and dibenzofurans are formed. Several chemical methods to degrade chlorophenols are already known, Collins added. For example, he pointed to "seminal work" by chemist Bernard Meunier of the National Center for Scientific Research, in Toulouse, France, on the use of H 2 0 2 with an iron phthalocyanine cata-
lyst. However, Meunier's system requires a larger amount of catalyst and a cosolvent, Collins said, and the chlorophenol destruction is much less complete. Less than 10 |xM of a TAML iron activator can promote 0.5 M H 2 0 2 to degrade millimolar aqueous solutions of pentachlorophenol or 2,4,6-trichlorophenol to nonhazardous products, Collins said. The process, which takes about 10 minutes under ambient conditions, converts nearly 99% of the chlorophenols to a mixture of CO, C 0 2 , and HC1 along with biodegradable chlorinated and nonchlorinated Q to C 4 organic acids. After further treatment, most of the remaining small chlorinated organics are degraded and no measurable amounts of dioxins are observed. 'TAML activators have been developed around a different design concept compared to what nature uses in producing enzymes," Collins told C&EN. "Nature designs around the big idea that any desired reaction can be sped up in the presence of myriad simultaneously occurring reactions. In contrast, we have followed the central design concept that reactions we do not want to occur in an oxidation process can be slowed down without suppressing the rate of the targeted reactions. After 20 years of catalyst design work, we are learning that this approach has considerable merit for solving problems in green oxidation chemistry" The theme of several sessions in I&EC's program was developing greener technologies to help lessen the environmental impact of the production and use of chemicals for agriculture and agriculture-based technologies. The sessions were part of the
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B L A C K W A T E R The Tarawera River in New Zealand, flowing into the Pacific Ocean, is discolored by residual lignin discharged in treated wastewater from a paper m i l l . In a field t r i a l , Collins and coworkers are using a TAML activator to promote H 2 0 2 to further degrade the lignin, resulting in a 50% reduction of color in the wastewater.
HTTP://PUBS.ACS.ORG/CEN
first effort at an ACS meeting "to bring green chemistry and agricultural practices on the same page," according to co-organizer William M. Nelson, a researcher at the Illinois Waste Management & Research Center, Champaign. "One of the important areas under the umbrella ofgreen chemistry is going to be how researchers, government agencies, and industry work together to develop sustainable agriculture to provide food and renewable resources for a growing population," noted Nelson, whose research includes microbial degradation of hydrocarbons in waste streams. Although there have been some great technology ideas derived from environmentally benign chemistry over the years, he added, often these ideas fall flat economically when it comes to industry's bottom line. But persistent work and continued innovations are now helping to diffuse these greener technologies into industry, Nelson said. A BROAD RANGE of these agricultural technologies were discussed in presentations that focused on the use of environmentally friendlier natural and synthetic compounds for pest control, production of chemicals from biomass, light harvesting in plants by chlorophylls, and bioremediation of chemicals in soils by plants. Green chemistry is perfect for the agriculture industry to explore real-world environmental problems and help find solutions, added David E. Barnekow, a senior scientist at Dow AgroSciences, Indianapolis. "Modern agriculture is focused on the design of chemicals formulated to be applied at lower rates as well as to be less environmentally persistent, less toxic, and more selective," he said. One example Barnekow outlined is Dow AgroSciences' nitrapyrin-based nitrogen stabilizers that make more efficient use of fertilizers by reducing leaching or decomposition in the field. Another example he noted is Dow AgroSciences' Sentricon termite-control system. Sentricon uses outdoor bait stations that contain hexaflumuron, a halogenated benzamide, which inhibits the synthesis of chitin during the termites' exoskeleton molting process. In 1994, hexaflumuron became the first pesticide registered under EPA's reduced-risk pesticide initiative, and the Sentricon system earned Dow AgroSciences a 2000 Presidential Green Chemistry Challenge Award. In a subsequent lecture, entomologist James E. Dripps from Dow AgroSciences elaborated on the development of spinosad, HTTP://PUBS.ACS.ORG/CEN
a natural-product pesticide. Spinosad's ac- appear to disrupt insect nicotinic and tive ingredients, spinosyn A and spinosyn e-aminobutyric acid receptor function. In field tests, Dow AgroSciences' spinD, are produced by the soil bacterium Sacosyn-based products have been shown to caropolyspora spinosa. There are 22 natural spinosyns that vary in activity against insect not leach, to not be environmentally perand mite pests, Dripps noted. Although a sistent, and to have low mammalian toximode of action is not clear, the spinosyns city The pesticide acts on caterpillar pests
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SCIENCE & TECHNOLOGY that attack cotton, fruits, vegetables, and other plants but does not harm beneficial insects, such as ladybugs. These advantages earned these products EPA's reduced-risk pesticide designation, and spinosad earned Dow AgroSciences a 1999 Presidential Green Chemistry Challenge Award. Quantitative structure-activity relationship analysis of the spinosyns has now led to the synthesis of several hundred semisynthetic spinosoids, Dripps added. Several of these compounds are more active than spinosad but are less stable in sunlight. The company is now exploring how to improve their stability The U.S. Department of Agriculture, through its Agricultural Research Service (ARS), has quite a few research initiatives under way to address environmentally friendlier pest management, as several symposium speakers in Orlando related. For example, ARS's Natural Products Utilization Research Unit, University, Miss., is focusing on identifying natural products to replace synthetic pesticides, according to research leader Stephen O. Duke. One of the projects that Duke discussed was work by microbiologist Kevin K. Schrader tofindan alternative to synthet-
ic algicides for controlling blue-green algae in catfish aquaculture ponds. Schrader presented his work during a session on aquaculture in the Division ofAgricultural & Food Chemistry Some blue-green algae, such as Oscillatoria perornata, produce 2-methylisoborneol, a terpene that accumulates in catfish to give them an undesirable musty flavor. Copper-based products and Diuron, a urea-based weed killer, are currently used to control algae, Duke noted. However, these products have a low degree of selectivity toward blue-green algae, are environmentally persistent, and can be perceived negatively by consumers because of the use of synthetic chemicals. Schrader and coworkers used a bioassay to screen natural compounds for activity against 0. perornata. The researchers discovered that 9,10-anthraquinone, found in some plants, was much more selective and significandy outperforms the currendy used algicides in lab tests. In catfish ponds, however, efficacy testing found that anthraquinone is not very effective in killing the algae. The researchers then tested a number of other natural quinones and discovered
EDUCATION
Energy Department Initiative Targets Biobased Products Industry
T
he growing interest in developing fuels, chemical feedstocks, and other products from renewable biomass means that there is an increased demand for trained scientists in the biobased products industry. To address this demand, the Department of Energy has created an education initiative that encourages universities and companies to work together to develop curricula that emphasize the needed multidisciplinary training. The initiative is supported by the Bush Administration's National Energy Policy. A symposium at the ACS national meeting in Orlando, organized by the Industrial & Engineering Chemistry Division's newly formed Industrial Bio-Based Technology Subdivision, provided an opportunity for the eight universities participating in the DOE initiative to report on their progress. The session included talks by faculty representing departments as varied as chemistry, chemical engineering, biological systems engineering, and agricultural economics. The universities have received grants averaging $100,000
U2
C & E N / MAY 2 0 , 2002
per year for three years to cover the administrative costs of designing and implementing the curricula and for some graduate student stipends. Most of the universities are focusing on strengthening their existing graduate programs, which may include offering an area of specialization in biobased products or, eventually, new degree programs. Some of the steps being taken include having students take courses in different departments, offering interdisciplinary team-taught courses, providing a greater emphasis on multidisciplinary research, and establishing better links to industry through internships, mentors, and seminar speakers. Some of the universities are planning to develop continuing education courses as welt. The participating universities are the University of Nebraska, Lincoln; the University of Missouri, Columbia; Oklahoma State University; Iowa State University; Kansas State University; Michigan State University; Colorado School of Mines; and the University of Georgia.
a proprietary compound, developed in conjunction with N. P. Dhammika Nanayakkara of the National Center for Natural Products Research at the University of Mississippi, that is very effective against O. perornata. The new algicide is currently being patented. MOVING FROM agricultural chemistry to chemistry from agriculture, professor Kris Arvid Berglund of the department of chemical engineering and materials science at Michigan State University discussed the direct production of chemical feedstocks from biomass. (Berglund will soon join the faculty of Lulea University of Technology, in Sweden.) Biomass provides an opportunity to bypass petroleum but still use the concept ofgenerating family trees of compounds by starting from a few simple platform molecules such as methane, ethanol, and lactic acid, Berglund said. In Orlando, Berglund primarily discussed the use of succinic acid as a feedstock that can be used to prepare valueadded chemicals and polymers. The patented technology to generate succinic acid involves a two-step fermentation of sugars derived from plants—such as corn, sugar beets, or wood—by a strain of Escherichia colt. The process, which has been validated on a 150,000-L scale, generates a succinate ion that is isolated as ammonium succinate. Succinic acid can be precipitated from solution by the addition of ammonium bisulfate. Succinate salts, succinate esters, and succinic acid can be converted to a host ofuseful industrial and consumer products, Berglund said. Succinate salts are becoming popular as noncorrosive, low-toxicity runway deicing chemicals used in conjunction with glycols, he noted. Diethyl succinate is being used as a low-volatile, low-toxicity replacement for chlorinated solvents for cleaning metal parts. Succinic acid is used in food and beverages as an acidulant, similar to citric acid, and can be used as a monomer for polyesters, he added. Berglund and coworkers' research has been completed over a number ofyears with funding and technology development from the Department of Energy Being able to learn from nature while doing agricultural chemistry and to utilize natural resources such as enzymes and technologies such as photosynthesis, Nelson said, "amply illustrates why agricultural applications of green chemistry are a central component both to the practice of green chemistry and to the future development of agriculture." • HTTP://PUBS.ACS.ORG/CEN
