Green Chemistry Principle #3

Less Hazardous Chemical Syntheses

Wherever practicable, synthetic methods should be designed to use and generate substances that possess little or no toxicity to human health and the environment.

Contributed by David J. C. Constable, Ph.D., Director, ACS Green Chemistry Institute®

When you think about it, this is a two-part principle divided by the first two words, “wherever practicable.” Saying those two words implies that it may not be practical or possible to avoid using substances that are toxic, and this is, if you will, the get out of jail card most chemists use to try to avoid applying this principle to their work. Let’s face it; chemists use toxic substances all the time because reactive chemicals afford reactions that are kinetically and thermodynamically favorable. And unless—and until—replacement chemicals along with new synthetic protocols are developed, inherently toxic materials will continue to be used. But it’s easier to say that it isn’t practicable and dispense with any thought about the chemical choices that are made.

It’s not that adhering to this principle is particularly difficult to do; it’s more that chemists are disinterested in doing it. For the synthetic organic chemist, effecting a successful chemical transformation in a new way or with a new molecule or in a new order is what matters. I have heard such arguments, as “all the other stuff in the flask is just there to make the transformation possible so it really doesn’t matter,” or “you have to be realistic and focus on the science.” Saying these things implies that the only science that matters is activating a carbon atom to functionalize it, or adding a ligand to a catalyst, etc., etc. This principle is asking chemists to broaden their definition of what constitutes good science.

What many have shown over and over again is that toxicity and the attendant hazard and risk associated with a chemical reaction is directly related to all the other “stuff” in a flask. In fact, the chemistry or chemical transformation in a synthesis generally impacts the overall toxicity profile (and most other measures of sustainability and green) of a product or process the least, except in those cases where we deliberately are producing a molecule that is toxic or biologically active by design. That is certainly the case for many molecules that are synthesized as in the pharmaceutical or agriculture chemical business—the molecules are toxic and/or have other effects on living organisms by design.

The chemicals and materials used in effecting chemical transformations matter and chemists need to pay more attention to the choices they make about what goes into the flask. It’s easy to discount all the other “stuff” and focus all our energy on the synthetic pathway that delivers the desired product. But when we ignore all the other “stuff,” we pay a high price and it’s a price we need to stop paying.

Occasionally, chemists do produce molecules that have toxic or other hazardous effects, and the next principle will have something to say about designing safer molecules.