The methylation of pharmaceuticals has been shown to prevent the toxic buildup of drugs by preventing CYP enzyme inhibition. Thus, direct methods for the methylation of heteroaromatic systems are in high demand in the pharmaceutical industry. Here we report the methylation of several heterocycles using Fenton Chemistry. The reaction utilizes substituted ferrocene compounds as catalysts with hydrogen peroxide and DMSO to generate a methyl radical. This one step reaction proceeds at ambient temperatures and has already been used to successfully methylate the billion-dollar drug Chantix. The prominence of heterocycles in nature and society also makes this reaction extremely valuable in other fields like agrochemistry, food chemistry, and materials chemistry. This study reports our efforts to optimize the reaction using caffeine as a model substrate.

Methylation of heterocycles using Fenton chemistry

245th National Meeting (2013)

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