Researchers optimized a reaction involving DEAD to reduce chemical waste

The Mitsunobu reaction is key to using alcohols in organic chemistry, but it also generates considerable chemical waste

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Alcohols are heavily used in organic chemistry because they are cheap and widely available. However, they are also quite stable and react slowly. Before their use, alcohols require a pre-activation step, and one of the most common ways to do it is the Mitsunobu reaction

This reaction involves the use of the chemical diethyl azodicarboxylate, which is known as DEAD in the chemistry community for its high toxicity. DEAD is used in a stoichiometric amount (i.e. a one-to-one ratio) with respect to the alcohol in this reaction. This means that if we want to modify 1,000 units of alcohol, we need 1,000 units of DEAD, which will consequently produce 1,000 units of chemical waste. This major drawback prevents the implementation of the Mitsunobu reaction on a larger industrial scale, especially in uses such as the production of drug candidates.

Recently, researchers at the University of Nottingham have managed to design and optimize a new way of carrying out the Mitsunobu reaction through the use of an organocatalyst. Here, an organocatalyst refers to an organic compound which can speed up a chemical reaction, but isn't consumed by the reaction. Specifically, the researchers designed a phosphine oxide compound to optimize the Mitsunobu reaction. 

The way this newly optimized reaction works is the following: the alcohol is bound to the organocatalyst, which leads to the formation of "activated" alcohol. Once the alcohol is activated, it reacts much more quickly with a nucleophile (i.e. a chemical species which donates electrons), leading to the formation of the desired product and returns the organocatalyst to its original state. In this state, the organocatalyst can bind to a new unit of alcohol and repeats the reaction. This cycle keeps on repeating until all the alcohol units undergo activation and are used up.

Replacing DEAD with an organocatalyst not only has the advantages of removing a highly toxic and dangerous chemical compound, but also forms water as the only side-product. This newly optimized reaction was used to produce thiocarlide, a drug used to treat tuberculosis, which highlights the potential of this newly optimized reaction and its promising application on an industrial scale.