Distillations magazine

Unexpected Stories from Science’s Past
July 1, 2008 Environment

The Greening of Chemistry

Innovations have reduced industry’s impact on human health and the environment while also saving companies money.


A philosophy only recently introduced to the chemicals industry, green chemistry promotes the careful design of chemicals manufacturing processes to reduce the use of toxic components and minimize waste and energy use. The sustainable and more benign practices that follow green chemistry’s principles have found support in industry and government and are being researched more and more by universities and government agencies around the world.

When ibuprofen, the popular pain reliever that remedies headaches, stiff muscles, and fevers, was first manufactured in the 1960s, it generated more waste than drug. Chemists were making ibuprofen by adding an excess of aluminum trichloride to isobutyl-benzene and pushing through a six-step reaction with solvents and separation agents. Although the method certainly turned out the drug, it was highly inefficient and produced unwanted by-products at each step of the way: an annual production of 30 million pounds of ibuprofen generated 45 million pounds of waste, mostly tossed for scrap.

But in the early 1990s ibuprofen got a makeover. Using catalysts rather than excess reagents to drive the reactions, chemists halved the number of stages in the ibuprofen manufacturing process and eliminated carbon tetrachloride, a toxic solvent, from the process. In the new process, atom economy—the percentage of raw materials and reagents used in the synthesis that ends up in the final product—hovered between 80% and 99%. Those materials and reagents that didn’t end up in the final product, such as acetic acid, could be reclaimed or recycled. The revamped reaction was not only good for business (in that it reduced clean-up costs and minimized the consumption of raw materials), it was good for the environment.

More recently a new type of chemistry—green chemistry—is taking hold of academia, industry, and government.

One doesn’t have to look too far into the past to find examples of chemicals and chemical processes that have had a negative impact on human health and the environment. But more recently a new type of chemistry—green chemistry—is taking hold of academia, industry, and government. Green chemistry rethinks the design of chemical processes and offers environmental benefits by reducing waste, eliminating expensive chemical treatments, and reducing the use of energy and resources. According to the American Chemical Society (ACS) this chemical revolution unleashes scientists’ creativity and inventiveness while increasing the performance and value of chemicals and materials.

Industrial Origins, Nobel Ends

Green chemistry has become fashionable only in the last two decades, but its origins can be traced to 1950s industry. In 1956 chemists in DuPont’s petrochemical department in Wilmington, Delaware, found that passing propene over a molybdenum-on-aluminum catalyst produced a mixture of propene, ethene, and 1-butene. Other chemists were uncovering similar results when they combined olefins (alkenes) with other molybdenum catalysts. The products were the result of breaking and rebuilding the double bonds in the alkenes. The carbon of the double bond of one alkene swapped places with one carbon of the double bond of the other alkene. But chemists lacked a mechanism to explain what was taking place.

A number of theories were proposed over the next 15 years, but it wasn’t until 1971 that Yves Chauvin of the Institut Français du Pétrole along with student Jean-Louis Hérisson identified the process: a metal carbene was kicking off the reaction. Chauvin called it a molecular dance, in which one partner was cast off for another. Twenty years later, Richard Schrock of the Massachusetts Institute of Technology uncovered which metals could be used as catalysts. One group of molybdenum catalysts was particularly effective at rearranging the compounds’ double bonds. But these were highly reactive and sensitive to both oxygen and moisture. They were far from perfect. In 1992, Robert Grubbs, of the California Institute of Technology, discovered a ruthenium catalyst that was stable in air and more selective than Schrock’s catalysts.

Together these chemists’ contributions explained and developed the olefin metathesis reaction, creating a new tool to shorten the route to a desired molecule and reduce the number of unwanted and often hazardous by-products. Its discovery opened up new opportunities in the industrial production of pharmaceuticals, plastics, and other materials.

Their work also earned Chauvin, Schrock, and Grubbs the Nobel Prize in Chemistry in 2005. Per Ahlberg, a member of the Royal Swedish Academy of Sciences and of the Nobel Committee for Chemistry, proclaimed during his presentation speech, “Metathesis also saves energy and material and is kind to the environment. It takes us a step toward a ‘greener’ future.” The occasion marked the first time that the Royal Swedish Academy of Sciences recognized green chemistry—the design of chemicals and processes that reduce or eliminate the use and production of substances hazardous to humans and the environment—but the field had been steadily gaining ground for more than a decade.

Incentivizing Green Practices

Legislation has controlled the use, treatment, and disposal of chemicals since the 1960s. This traditional “command and control” regulatory approach cost businesses billions of dollars yet still allowed the release of several billion pounds of chemical waste into the environment every year. That was set to change in 1990, when the U.S. Congress passed the Pollution Prevention Act, which sought to reduce pollution at its source.

A year earlier, Paul Anastas was a young synthetic organic chemist at Brandeis University. He had just earned a PhD in chemistry and had a promising career in cancer research ahead of him, but he yearned for something more. Instead of designing molecules to fight cancer and working as an industrial consultant, he wanted to develop a framework that prevented the occurrence of cancer in the first place. That meant preventing hazardous wastes from being released into the environment by redesigning chemical processes and products at the molecular level so that they were “benign by design.” In 1989 Anastas accepted a position at the Office of Pollution Prevention and Toxic Substances at the U.S. Environmental Protection Agency (EPA); by 1991 he had coined the term green chemistry.

Today about a dozen American universities and colleges offer classes in green chemistry.

Even with the Pollution Prevention Act in place, there was little financial motivation for industry—or academia—to look for alternative chemical processes. The EPA and the National Science Foundation (NSF) launched a slew of grant programs in hopes of eliciting some solutions. In 1991 the EPA launched a green chemistry program. One part of the program, “Alternative Synthetic Pathways for Pollution Prevention,” offered grants to design and synthesize chemicals that would curb the production of pollutants. In 1992 the NSF teamed up with the nonprofit Council for Chemical Research to develop the “Environmentally Benign Chemical Synthesis and Processing” research program. It dispersed $950,000 among projects that sought to develop more selective catalysts and new or cleaner reactions that would replace those requiring toxic feedstocks or solvents, and others that would eliminate aerosol particles.

It was around this time that Anastas crossed paths with a chemist at the Polaroid Corporation named John Warner. Warner had developed a process called noncovalent derivatization to stabilize the molecules in multilayered instant film and keep the film from deteriorating while it sat on store shelves. The chemistry was simple and less toxic; it satisfied the principles of green chemistry that the EPA was trying to promote. The pair became advocates for the future of green chemistry, speaking on the topic whenever they could.

When Terry Collins, now the director of the Institute for Green Oxidation Chemistry at Carnegie Mellon University, first heard about Anastas’s green chemistry, he realized his research interests aligned with the EPA’s initiatives. (Since the 1980s, Collins had been looking for catalysts that could activate hydrogen peroxide as an alternative to chlorine bleaches, thereby reducing or possibly even eliminating chlorinated by-products from wastewater.) He realized that his students were learning the technical properties of chemicals but not learning about their hazards. How could the next generation of chemists be expected to have their future research guided by the principles of green chemistry if they knew nothing about it? In 1992 Collins launched the first university-level class in green chemistry. Today about a dozen American universities and colleges offer classes in green chemistry.

Although there was growing institutional and industrial support for green chemistry, Anastas felt there was little recognition for those who had embraced it and not enough research funding to encourage others to do so. While still at the EPA Anastas pushed for the development of an awards program that would honor companies and individuals who had designed chemicals and processes that avoided waste and pollution.

The Presidential Green Chemistry Challenge Awards were announced in 1995, growing out of the Clinton administration’s “Reinventing Environmental Regulations Initiative.” For the first awards in 1991 the judges selected five projects that exemplified scientific innovation, industrial applicability, and health and environmental safety. Among them was a novel marine antifouling agent developed by Rohm and Haas: SEA-NINE 211 controlled the growth of plants and animals on the hulls of ships without the toxicity and persistence associated with conventional anti-fouling agents. The compound, 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one, degraded rapidly in seawater and sediment and would not bioaccumulate in marine organisms. (The company won the award again in 1998 for developing a less-toxic pesticide for controlling caterpillar pests in crops and in turf such as that kept on golf courses.)

Year after year green chemistry has continued to influence new projects and initiatives. Anastas assembled a group of green innovators from industry, academia, and the national laboratories to cofound the Green Chemistry Institute (GCI) in 1997. The nonprofit organization aimed to inspire research, organize meetings, and build industrial partnerships. (It became part of the ACS in 2001.)

Anastas assembled a group of green innovators from industry, academia, and the national laboratories to cofound the Green Chemistry Institute in 1997.

In 1998 Anastas and Warner paired up to publish Green Chemistry: Theory and Practice, a basic introduction to green chemistry that outlined the 12 principles of green chemistry (see Table) and articulated the need for safer solvents, renewable feedstocks, and catalytic reagents, and highlighted the importance of designing chemicals for degradation. In 2001, under Warner’s leadership, the University of Massachusetts–Boston (UMB) began accepting students into the first green chemistry PhD program.

Warner’s enthusiasm spread to the pharmaceutical industry. In the late 1990s, Buzz Cue, a former vice president of pharmaceutical sciences at Pfizer’s research labs in Groton, Connecticut, was a member of the science advisory board at UMB. He saw a role for green chemistry in the pharmaceutical industry, particularly at the level of manufacturing. In 2005 Cue, Anastas (who had since moved on to head the Green Chemistry Institute at the ACS), and a handful of global pharmaceutical companies, including Pfizer, formed the GCI pharmaceutical roundtable. The group identified 10 reactions that needed greener alternatives and set out to fund up to 2 projects in academic research laboratories annually. The roundtable has funded 3 labs to date.

An Unwasted Effort

Perhaps one of the most important applications of green chemistry is in the design and manufacturing of pharmaceutical products. On a waste-to-product ratio, the pharmaceutical industry is one of the least environmentally acceptable, generating 25 to 100 pounds of waste for every pound of active pharmaceutical ingredient manufactured. As much as 80% of that waste is solvent. Although solvents play a critical role in drug manufacturing by providing a reaction medium and transferring heat, the largest volumes are used to separate unwanted compounds from the final product.

On a waste-to-product ratio, the pharmaceutical industry is one of the least environmentally acceptable, generating 25 to 100 pounds of waste for every pound of active pharmaceutical ingredient manufactured.

Why not design the reaction to reduce waste in the first place? In 2002 Pfizer won the Presidential Green Challenge award for improving the manufacturing process for sertraline, the active ingredient in the antidepressant Zoloft. By using a more selective palladium catalyst, the new manufacturing process cut a three-step reaction sequence down to a single reaction, with the bonus of eliminating unwanted by-products. It swapped the relatively benign ethanol for four solvents—methylene chloride, tetrahydrafuran, toluene, and hexane—and eliminated 310,000 pounds of titanium tetrachloride, 220,000 pounds of 50% sodium hydroxide, 330,000 pounds of 35% hydrochloric acid waste, and 970,000 pounds of solid titanium dioxide waste annually. The new process generated less waste by incorporating a greater proportion of the raw materials into the product and reduced costs associated with the storage, treatment, and disposal of the waste. Cue called it a “double-economic benefit.” Green chemistry continues to influence the pharmaceutical industry, but it remains challenging to get small- and medium-sized companies and the generics industry to learn and apply its principles.

Other industries are also taking notice. Specialty materials companies like Rohm and Haas continue to replace toxic ingredients with greener alternatives in everything from insulation batts to wood preservation. Medical technologies, wood manufacturing, consumer products, printing, paints, and pest control have all been made less hazardous through green chemistry.

Even so, funding to study green chemistry and to develop benign chemistry has always been, and remains, sparse. Some iterations of proposed legislation failed to pass in the Senate in 2004 and 2005. However, despite the many challenges that remain, the 2007 approval by the House of Representatives of a bill that would allocate nearly $200 million over three years for green chemistry research and development is certainly good news.

The history of green chemistry, though brief, shows how the optimism of a few enthusiasts can be a spark of inspiration in academia and industry. Legislation hasn’t solved the problem of toxic chemicals, but it has caused industry to realize that there are economic benefits to designing smarter reactions.

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