Selective N1-Acylation of Indazoles with Acid Anhydrides Using an Electrochemical Approach

Abstract

An electrochemical synthesis method for the selective N1-acylation of indazoles has been developed. This “anion pool” approach electrochemically reduces indazole molecules generating indazole anions and H2. Acid anhydrides are then introduced to the solution resulting in selective acylation of the N1-position of the indazoles. This procedure can also be applied to the acylation of benzimidazoles and indoles. The reaction can also be performed using a 9 V battery without loss of reaction efficiency.

The preparation and applications of amides using electrosynthesis

“…43 This same group have also had success with producing acylated indazoles 49 using this method as shown in Scheme 28. 44 The mechanism for this reaction is the same as in Scheme 27 with the exception that esters were not produced in this work.…”

“…43 Scheme 28 Electrochemical acylation of indazoles using the anion pool method. 44 Scheme 29 Cathodic reduction of diimines. 46 Scheme 30 Electrochemical cleavage of carboxylic acid hydrazides.…”

Electrochemical Functionalization of Imidazopyridine and Indazole: An Overview

“…Vannucci et al [45] . in 2019 reported an electrochemical methodology for selective N ‐1 acylation of 1 H ‐indazoles ( 36 ).…”

Direct Catalytic Functionalization of Indazole Derivatives

“…The in situ anionic indazole was prepared first with the help of anion pool approach and then it was treated with acid anhydride which resulted in N-1 acylated indazole (46 b) (Scheme 46). [110] The reaction was done in a two compartment electrochemical H-cell in which electrodes used were made by inexpensive reticulated vitreous carbon (RVC). The cathodic chamber contained 1H-indazole and 0.5 M tetrabutylammonium hexafluorophosphate (NBu 4 PF 6 ) in acetonitrile and the anodic chamber was composed of 0.05 M ferrocene and 0.1 M NBu 4 PF 6 in acetonitrile.…”