Water as a natural reaction medium

It’s not that hard to change this. In fact, if “change” is based solely on science, then we are already there, in harmony with biology, which is water-based. And the payoff is substantial, replete with bonuses reflecting much more than minimizing pollution and ensuring that planetary resources are available to future generations. Put another way, going green is a win-win on all levels.

The secret to doing organic chemistry in water is no secret at all; rather, it has been hidden in plain sight, perhaps for billions of years. Nature itself provides the answer: Life could not exist without the synthesis of complex, water-insoluble biomolecules such as polypeptides or vitamins under aqueous conditions. The power of “chemistry in water” is actually something we experience at first hand every day. On a large scale, “chemistry in water” can also be observed when oil companies clean up marine spills. It’s obvious: The know-how is already there, at least conceptually. So why has organic synthesis been so slow to adapt?

The challenge lies in finding the appropriate “reaction vessels” for water-insoluble biomolecules. Throughout evolution, nature’s reaction “flasks” for water-insoluble biomolecules have been, and still are, a variety of membranes, vesicles, and micellar arrays, in water. Could it be that simple?

Yes and no. The good news is that, in principle, organic synthesis should be possible in these reactors; the reactants would be accommodated, as well as the catalysts that speed up these reactions. Making all sorts of products would then be feasible because, unlike enzymes, these particular biomolecules are “brain-dead”; they have no biases and no recognition of what’s coming in to react and what products are being formed.

The bad news is that a nanoreactor must be identified that is suitable for organic synthesis; it must be capable of accommodating many different types of chemistry, such as that routinely used by the fine chemical industry (especially pharmaceutical and agrochemical companies). This has been the “valley of death” that has remained unfilled for centuries: It is the difference between recognizing the need and creating the technologies that make organic synthesis “in water” possible. Let’s understand that it’s the nanoreactors that are “in water”; the actual chemistry involving water-insoluble reactants and catalysts takes place within the inner cores, which serve as the “solvent” for various reactions.

Nature, with its membranes, vesicles and micelles, has likely relied on these concepts over the millennia for its chemistry in water involving insoluble educts. Molecules of interest within the fine chemicals industry tend to be rather complex, so the tools needed to make them in water need to be equally sophisticated. Therefore, new surfactants to be used in an aqueous medium, present in very limited amounts, must not only be “benign by design” but must also allow many reactions to be run efficiently. Did someone just ask, “What about palladium chemistry?”