Use of free radical inhibitors or antioxidants to increase the overall yield of organic synthesis steps.

kilomentor | 25 March, 2011 13:30

The use of radical inhibitors or antioxidants to improve yields does not appear to have many precedents in organic synthesis. A key word search provided only two references both related to the stabilization of m-chloroperbenzoic acid to thermal degradation during the epoxidation of resistant olefins. Y. Kishi, M. Aratani, H. Tanino, T. Fukuyama and T. Goto, J.C.S. Chem. Comm. 1972 64 and D.M. Tal, Steroids (1989), 54(1), 113-22. Synthetic chemists apparently assume that free radical reactions do not occur unless free radical initiators are present in the reaction mixture or unless the reaction mixture is irradiated. It might seem they think it can’t happen unless they are intending it to happen. Obviously this is not true! Free radical reactions can take place not just during the contemplated reaction phase but during the work-up of the reaction when we might think that all the reacting is stopped. Actual the opportunity is greater in the work-up phase this phase usually takes more time, particularly when the process is being scaled up. Are free-radical reactions inhibited by particular pH ranges of the solvent medium? No they are not. The most frequent type of free radical reaction is oxidation and only the relative amounts of different species that can be oxidized are affected by pH not particularly the oxidation rates. Oxidation often produces coloured products when it can introduce new unsaturation into molecules. The presence of unexpected colour in a reaction is suggestive of an unanticipated oxidation. I recall that in the preparation of some aniline compounds the procedure teaches the addition of hydrogen sulfide to the aqueous phase during isolation to prevent colour development from exposure to air during work up and crystallization. The usual response to coloured product is to use charcoal in the recrystallization rather than trying to prevent coloured by-products in the first place. The knock against the prophylactic (preventative) use of free radical inhibitors is that they are just one more substance to have to clean up during the work up, isolation and purification. Perhaps these radical inhibitors could be immobilized on an insoluble polymer so they could be filtered off after use. Has this been done to anyone’s knowledge?

Comments

Re: Use of free radical inhibitors or antioxidants to increase the overall yield of organic synthesis steps.

Nick K | 15/04/2011, 09:27

In the case of free-radical oxidation during workup perhaps the best tactic would be to use deoxygenated solvents. That way nothing extraneous is added.

reply

plumbing | 12/10/2011, 06:06

An antioxidant is a molecule capable of inhibiting the oxidation of other molecules.

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kilomentor