Van Leusen reaction

[1] When aldehydes are employed, the Van Leusen reaction is particularly useful to form oxazoles and imidazoles.

The reaction mechanism consists of the initial deprotonation of TosMIC, which is facile thanks to the electron-withdrawing effect of both sulfone and isocyanide groups.

If the substrate is an aldehyde, then elimination of the excellent tosyl leaving group can occur readily.

If an aldimine is used, formed from the condensation of an aldehyde with an amine, then imidazoles can be generated through the same process.

This is then solvolysed by an acidic alcohol solution to give the nitrile product.