Symposium report: Transitioning into Green Chemistry

28 May 2009

Microwave heating: A versatile tool for clean organic synthesis and biofuel - Nicholas E. Leadbeater

Nicholas Leadbeater, University of Connecticut, Storrs, US, began the morning session by discussing the applications of microwave chemistry for organic reactions utilizing a large collection of scientific research grade microwaves. Compared to conventinal heating, microwave heating can provide reduced reaction times while, in many cases, obtaining higher yields. The Leadbeater group has demonstrated that microwave chemistry can be used for reactions with equi-molar gaseous reagents, as well as, photochemical reactions via the production of UV light in situ. A number of microwave organic reactions proceed efficiently in green solvents such as water and ethanol. These reactions can be carried out on the millimole to mole scale. Comparisons were made between batch and continuous flow methods. Continuous flow methods are preferred when considering the inability of microwaves to penetrate larger reaction volumes. Moreover, in terms of energy efficiency, continuous flow requires 26 kJ per liter, as opposed to the 94 kJ per liter required for batch synthesis. Leadbeater also addressed advances in using an in situ Raman probe; providing reaction monitoring, and kinetic data.

Catalysis as a key technology and fundamental science for green chemistry - Walter Leitner

To engineer a catalytic reaction, four aspects must be analyzed: the synthetic transformation, the reaction media, the catalyst, and the materials. Walter Leitner, RWTH Aachen University, Germany, demonstrated the use of a nickel catalyst for the dimerization of olefins and hydrovinylation of olefins, employing an optimal ligand. Leitner discussed the advantages of continuous flow synthesis when using supercritical carbon dioxide and ionic liquids. In order to put reaction engineering into perspective, Leitner presented a schematic presentation of a hydrovinylation reaction of an olefin. Using this example to drive home the point, Leitner stressed the need to rework synthesis that employs the use of biomass and carbon dioxide.

Design, performance, and mechanistic chemistry of Fe-TAML activators: Reducing and eliminating hazardous substances - Terrence Collins, Carnegie Mellon University Institute for Green Science

Tereence Collins presented his groups strategy for the optimization of ligands for use as oxidizing complexes. He emphasized the kinetics and pH dependence of Iron (III)- Tetra-Amido-Macrocylic-Ligand (TAML) and other similar derivatives. A chronological timeline was presented on the catalytic process and rate constants using a steady state process. The pH dependence of these ligands were discussed in detail. It was discovered that optimal conditions, for high peroxidase-like activities for Iron (III)-TAML, were between a pH of 6 to 12 and between 25°C to 45°C. However, the peroxidase-like activities were influenced to a greater extent by the pH. A reaction mechanism was proposed to account for this pH dependence of the peroxidaze activity of the TAML catalyst. The versatility of the oxidant stems from the superior design of the ligands and overall structure of TAML. TAML, a general oxidative catalyst, has been shown to be a green alternative for traditional oxidations, which usually employ chlorine, ozone, or hazardous heavy metals.

Green Solvents: The good, the bad, and the ugly - Joan F. Brennecke

Alternative green solvents include water, low volatility solvents, supercritical carbon dioxide, and ionic liquids. Joan Brennecke, University of Nortre Dame, Indiana, US, focused on the use of supercritical carbon dioxide and ionic liquids. Supercritical carbon dioxide is a very favorable green solvent due to its non-toxic nature, abundance, and recyclability. Another advantage includes the tendency of carbon dioxide to increase the solubility of many solids. Supercritical carbon dioxide can be applied to a number of applications such as separations, reactions, and materials synthesis. Since supercritical carbon dioxide has both gaseous and liquid properties above the critical point, these properties can be tuned to favor the necessary reaction conditions. A drawback of using supercritical carbon dioxide is the pressure required to compress the gas. To achieve this pressure, a system requires a large input of energy. Currently, the advantages of this solvent outweigh the high energy cost associated with these proceses. Ionic liquids have recently gained popularity as an alternative solvent due to their nonvolatile properties. These low melting organic salts remain fluid over large temperature ranges and have a high thermal conductivity. Ionic liquids have been used as nonvolatile electrolytes in batteries and solar cells, acid scavengers, gas separations, and liquid separations. Due to a wide range of properties, ionic liquids offer an excellent compliment to supercritical carbon dioxide and are have possible industrial applications.

Green chemistry: Principles, practice, and economics - Mary M. Kirchhoff

The Academic Keynote Speaker, Mary Kirchhoff of the American Chemical Society wrapped up the morning session by discussing a number of green chemistry advances that have been recognized by the United States Environmental Protection Agency's (US EPA) Presidential Green Chemistry Challenge. The US EPA has recognized and rewarded innovations using green chemistry since 1996. Awards are given in the areas of academia, small business, greener synthetic pathways, greener reaction conditions, and designing greener chemicals. Kirchoff highlighted the innovations that received awards for 2008, as well as, previous technologies. Since 1996, the award winning technologies have eliminated 93 million pounds of hazardous chemicals and solvents, and saved 21 billion gallons of water, a testament to not only their technology but also their application. The objective of these awards is to encourage chemists to rethink synthetic strategies and incorporate greener practices into their methodology development. Kirchhoff ended her talk by stating that "chemistry today should focus on sustainable development." This development should meet the needs of the present without compromising the ability of future generations. She encouraged that in order to achieve this goal and further change the traditional chemist's mindset, green chemistry must be incorporated into the standard chemistry curriculum. Future chemists should be trained with green chemistry practices from the onset of their education; better equiping chemists of tomorrow with the necessary skills needed to bring about better chemistry practices.

Successful academic-industry collaboration in green technologies through the federation model - Lisa B. Cleckner

Lisa Cleckner gave an overview of the Syracuse Centers of Excellence (CoE) located in Syracuse, New York, US. One of the objectives of the CoE is to create jobs in New York through collaborations in technology application and development. This center, initiated in 2001, is based on a collaboration between academic researchers and industry partners, which currently consists of more than 150 companies and 12 academic research institutions. One of the main concerns of the Center for Environmental and Energy Systems is indoor environmental quality (IEQ) and environmental quality systems. Some examples of products that have been developed from these collaborations include the Isolation Air System, which provides clean air during hospital surge capacity events, and NuClimate air quality systems for heating, ventilation, and air conditioning (HVAC) systems. Examples of energy research and development, include projects looking at cellulose as a possible route for ethanol production (at the State University of New York College of Environmental Science and Forestry) and energy conservation on dairy farms (at Cornell University). The Syracuse CoE serves as an excellent example of how academic researchers and industrial project developers can benefit mutually from these collaborations. The CoE will continue to promote innovation, knowledge transfer, and skill transfer to further achieve sustainability.

The University of Connecticut Graduate Student Symposium Planning Committee (GSSPC). Front Row: Naimish Sardesai, Justin D. Fair (Chairman), Besnik Bajrami. Back Row: Dr. Tyson A. Miller (Faculty Advisor), Michelle L. Dean, Christine M. Cardillo, Sadagopan Krishnan. Not Pictured: Ashley L. Bartelson

Green chemistry through innovation at Merck: The synthesis of Januvia - Joseph D. Armstrong III

Joseph Armstrong, Merck Research Laboratories, New Jersey, US, provided an overview of green processes developed at Merck, where green chemistry is promoted through innovation. Through the integration of green chemistry principles into their processes, the company developed practical, scalable, efficient, cost effective, and environmentally benign manufacturing routes for drug candidates regardless of complexity. The type II diabetes drug, Januvia, was used to exemplify this approach. Januvia, a drug of medium complexity, was developed with the twelve principles of green chemistry in mind from the initial stages of development. When the first generation of Januvia demonstrated the potential for moderate dose strength and high patient demand, the initial synthesis was refined and made more efficient. By focusing on substrate and catalyst control, the synthesis was optimized to have a 95% ee and 98% yield (from a inital 52% yield). The final process developed to synthesize this drug is atom economical, efficient, and utilizes an unprecedented asymmetric hydrogenation of an unprotected enamine. The e-factor (kg waste per kg product) for this process was improved from 275 to 44 and from 75 to 0 for solid and liquid waste, respectively. Implementing the green by design approach, Merck has been able to successfully develop processes that have minimum waste generation, are atom economical, energy efficient, utilize renewable feedstocks, incorporate safer reactions, and are overall less hazardous production syntheses.

Lessons learned through measuring green chemistry performance of development routes at GlaxoSmithKline - David Constable

This presentation provided an overview of how GlaxoSmithKleine (GSK) approaches green chemistry via an analytical perspective. GSK measures their processes via metrics, such as the e-factor and mass intensity. David Constable, GSK,  contested that "it is more significant to measure the efficiency of a process rather than just the overall yield." The Fast Lifecycle Assessment for Synthetic Chemistry is a tool that was developed and is used by GSK. This tool helps in identifying "hidden" environmental impacts, shows the percent improvement of a process, performs "what if" comparisons, and measures overall progress. The core metrics include yield, reaction mass efficiency (RME), the number of stages and chemical steps, the total number of solvents and solvents per stage, mass intensity and mass productivity (efficiency), and the process life cycle environmental impact. To put this into perspective, to achieve a mass productivity greater than 1%, the reaction mass efficiency must be greater than 25%. This provides a 40% chance of the mass productivity being greater than 1%. These metrics contained in Fast Lifecycle Assessment for Synthetic Chemistry help to inform project teams on the efficiency and improvisation of their processes. Metrics are collected at all stages of development, however careful analysis of these metrics must be implemented for a successful outcome.

Practice of sustainable chemistry at Dow: Historical and future perspectives - Victor A. Atiemo-Obeng

Victor Atiemo-Obeng's presentation focused on the success of Dow Chemical Company and its longtime strides to become more energy efficient and sustainable. Beginning in 1986 with the development of the Waste Reduction Always Pays (WRAP) program, sustainability has been integrated into Dow's corporate strategy. Dow also started a life cycle assessment initiative in 1990, established global EHS goals in 1996 to achieve by 2005, and set global sustainability goals to be achieved by 2015. In 2005, Dow's EHS performance tracking over a ten year period reported an energy intensity of 900 trillion btus saved, emissions reduced by 30,000 tons, solid waste reduced by 1.6 billion pounds, water use reduced by 183 billion pounds, personal safety and health incidents reduced by 84%, and over $5 billion saved with an additional $1 billion in investment. The sustainability goals of 2006 emphasize the importance of sustainability in today's world. Dow has recognized that sustainable chemistry is required to achieve breakthroughs in current and future world challenges. Dow also considers product safety, the local protection of human health, and the environment contributing to the community success, energy efficiency, and conservation as top priorities. Dow, like other companies, evaluates their processes based on various factors, such as feedstock access and supply, chemical synthesis and reaction reagents, catalysts, solvents, chemical analysis, process separations, recycle and reuse measures in processes, formulations, mass and energy balances, mass and heat transfer, thermodynamics, reactor design, unit operations, material selection, process control, costs of capital and operations, life cycle assessment, as well as siteing and geography.

Greening the pharmaceutical industry: Accomplishments and opportunities - Berkeley W. Cue Jr

A pharmaceutical companies' mission is to discover and develop new medicines that will enable patients to live longer, healthier and more productive lives says Berkley Cue Jr, Private Consultant. But the pharmaceutical industry's commitment to improving health is not complete without a commitment to a healthy environment as well. Green chemistry is the utilization of a set of principles that reduces or eliminates the use or generation of hazardous substances in the design, manufacture and application of chemical products. Originally, it was not the pharmaceutical companies' strategy to adopt green chemistry since they had the belief that the design and manufacture of pharmaceuticals was so beneficial to mankind that its waste should be tolerated. Manufacturing divisions and/or EHS regulations drove many improvements that were made. By 2005, the landscape was changing rapidly, as pharmaceutical companies were discussing sustainability and the bottom line in annual reports. Paul Anastas along with Cue formed the ACS Green Chemistry Initiative (GCI). Initially, the members included Eli Lilly, Merck, and Pfizer. Since the formation of the CGI, nine additional companies have joined. The success of the ACS GCI pharmaceutical roundtable is evident by other organizations creating similar initiatives. Looking more closely at the pharmaceutical industry as a whole, Cue points out a number of goals that must be met and areas where improvement can be made. First, chemical syntheses should be designed to prevent waste, leaving little to no waste to be treated or cleaned up. Overall pharmaceutical e-factors have improved, but not all that dramatically over the last 15 years. When green chemistry principles are included in the process design from the beginning, up to 10-fold lower e-factors have been achieved. Chemical products should be designed to be fully effective, yet have little or no toxicity. Among all the sectors of chemical enterprise, no sector studies the toxicity of products, including environmental fate and effects studies, more than the pharmaceutical industry. Raw materials and feedstocks that are renewable should be used rather than those that are depleting. Renewable feedstocks are often made from agricultural products or are the wastes of other processes. Today's drugs are manufactured from chemicals that are derived from fossil fuel byproducts. The pharmaceutical industry has had no significant discussions about new sources of building blocks. To reduce waste, it was recommended to use catalytic reactions wherever possible. Catalysts are used in small amounts and can carry out a single reaction many times over. It is recommended that the use of blocking or protecting groups be avoided, since they require addition reagents, steps and waste. Syntheses should be designed so that the final product contains the maximum proportion of the starting materials possible. The use of solvents separation agents, or auxiliary chemicals should be avoided. To limit the amount of energy consumption required for a reaction, reactions should be run at ambient temperature and under atmospheric pressure whenever possible. One of the most challenging green chemistry principles for the pharmaceutical industry is to overcome assurances that chemical products can be broken down into innocuous substances after secretion and prevent their accumulation in the environment. To achieve these goals and meet these challenges, processes should be analyzed in real time to further prevent pollution. The above recommendations leave numerous prospects for the continuing progress towards a greener pharmaceutical industry.

Poster Session - Transitioning into Green Chemistry

The closing event of the symposium was a poster session and exposition. The kickoff speaker, Dr. Thomas Lane, ACS President-Elect, opened the evening session with a short address to the audience before opening the session to the poster presenters. He discussed the importance of sustainability and green chemistry as an initiative that the entire ACS community should be taking in interest in. A number of posters were presented, focusing on a wide varuety of green chemistry topics. The posters ranged from subjects covering the greening of academic laboratory exercises, environmentally benign fuels, atom economy processes, and reactions performed in green solvents. Sponsors displayed products and company information during the evening session.  The low key atmosphere, together with the refreshments, provided an ideal environment for the sharing of scientific ideas surrounding green chemistry. 

Symposium Sponsors

We are extremely grateful for the sponsorship from the following companies and organizations. Their assistance provided for a world-class event. Office of the President-Elect, ACS (main sponsor of the evening poster session); ACS Corporation Associates (main sponsor of the Academic Session); Pfizer Inc. (main sponsor of the Industrial Session); University of Connecticut Graduate School, Eli Lilly and Company; The Dow Chemical Company; ACS Division of Chemical Education; Honeywell; University of Connecticut Department of Chemistry; CEM Corp.; Allergan; Hampford Research Inc.; Milestone; Biotage; ACS Connecticut Valley Section; University of Connecticut Document Production Center; ACS Division of Environmental Chemistry; ACS Green Chemistry Institute; ACS Division of Organic Chemistry; ACS Division of Fuel Chemistry, ACS Division of Analytical Chemistry, ACS Division of Medicinal Chemistry, ACS Division of Agrochemicals; and the ACS Committee on Environmental Improvement.

Conclusions

The UConn GSSPC, as well as people around the world, has recognized the importance of transitioning chemistry toward the use of greener chemistry practices within both academia and industry. This daylong symposium "Transitioning into Green Chemistry", provided a highly focused venue consisting all on the exclusive topic of green chemistry. Topics ranged from applications of green chemistry, implementing green chemistry, recognizing green chemistry advances, and calling for the further use of green chemistry practices and education. Overall, the point was made that green chemistry is a vital field to both the progress and sustainability of chemistry as a whole. 

Justin D. Fair, Ashley L. Bartelson, Besnik Bajrami, Christine M. Cardillo, Michelle L. Dean, Sadagopan Krishnan, Naimish Sardesai and Tyson A. Miller.
University of Connecticut, Department of Chemistry, 55 North Eagleville Road, Unit 3060, Storrs, CT 06269-3060 USA