The Greening of Science

Hannah Hoag

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.)

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 Ph.D. 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.

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.

Hannah Hoag is a freelance writer living in Montreal, Canada.