Oxydation of heterocycle, an advance for efficient synthesis of active molecules

Heterocycles play an important role in therapeutic chemistry. Currently, more than 85% of all biologically active molecules contain at least one heterocycle. The FDA (Food and Drug Administration) database reveals that 14% of active ingredients containing a nitrogen heterocycle are pyridines, mainly mono- or di-substituted. Therefore, the study of mono-, di-, and tri-substituted pyridine’s reactivity is important in the development of new biologically active molecules. In this study, we focused on a particular family of pyridines: 2-pyridinecarboxaldehydes. The latter are often obtained by oxidation of the corresponding 2-methylpyridines. However, these reactions usually require the use of dangerous reagents such as oxygen, or expensive catalysts.

Oxidation reactions are very common in organic chemistry, but aldehydes can be susceptible to overoxidation to carboxylic acids. It is therefore essential to develop and optimise oxidation conditions to limit this undesirable subproduct. In our laboratory, we have developed a method for oxidation of various 2-methylpyridines to their 2-pyridinecarboxaldehyde analogues, whereas limiting overoxidation. This method led to better yields than those described in the literature, while simplify the operating mode.