Preparation of novel acyl pyrazoles and triazoles by means of oxidative functionalization reactions

Abstract

Novel acyl pyrazoles and acyl triazoles have been prepared by means of the oxidative amidation of aldehydes in the presence of the requisite azole. Yields range from modest to good in both cases, and some limitations of the substrate scope have been discovered. Acyl pyrazoles were prepared by treatment of a mixture of aldehyde and pyrazole with an oxoammonium salt bearing the nitrate anion. In the case of acyl triazoles, the oxidative functionalization was performed using sodium persulfate as a terminal oxidant in the presence of a catalytic quantity of a nitroxide.

Recent advancements in the use of Bobbitt's salt and 4-acetamidoTEMPO

“…Further advances through oxidation with the nitrate Bobbitt's salt (82), which facilitates oxidative amination with pyrazole and similar heterocycles without any additional additives and in high yield. 72,73…”

“…39 The substrate scope of this reaction is fairly large and works best when electron-donating substituents are present on the aryl ring and the corresponding alcohol partner Scheme 22 Oxidation of aldehydes and ketones both stoichiometrically with 1 and catalytically using 2 to access N-acyl pyrazoles. [70][71][72][73] Scheme 23 Oxidative cleavage of ethers by 1. 39,41,74,75 is highly hindered (e.g., 106a-c).…”