Electrochemical anion pool synthesis of amides with concurrent benzyl ester synthesis

Abstract

An atom economic, electrochemical, concurrent synthesis of amides and benzoic esters.

The preparation and applications of amides using electrosynthesis

“…It was found that in order for the ester product to be produced in good yield, a continual current had to be applied after amide formation to reduce any adventitious protons in solution, thereby maintaining the nucleophilic nature of the resulting carboxylates 47 long enough for them to react with benzyl bromide. 43 The yields for products produced using this method were good, for both the amide and the ester products, and the reac-tion proved viable on gram scale, however it should be noted that on this larger scale there was some disparity between the yield of the amide and that of the benzoic ester. It was found that the amide could be synthesised in high yield, but the benzoic ester proved much lower yielding.…”

“…The resulting carboxylate 47 is then exposed to benzyl bromide to give the ester product 48. 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.…”

“…Research published by Dissanayake and co-workers in 2019 showed a highly sustainable and atom-efficient approach to amide synthesis using this method in a divided cell as shown in Scheme 26. 43 The authors made excellent use of inexpensive Reticulated Vitreous Carbon (RVC) electrodes and anhydrides 46 as the acyl source in this work, ensuring that the carboxylates 47 that are formed after initial reaction of the anhydrides were not wasted by reacting them further with benzyl bromide. This led to a highly atom-efficient process that produced two very useful products from every reaction: an amide and an ester 48.…”

“…This issue was rectified by adding a catalytic amount of K 2 CO 3 base to break up benzoate homoconjugated dimers that were likely forming, thereby bringing the yields for both the amide and the ester to above 80%. 43 The mechanism for this reaction is shown in Scheme 27, starting with amine cathodic reduction/deprotonation, which then reacts with the anhydride 46 to give an amide product. The resulting carboxylate 47 is then exposed to benzyl bromide to give the ester product 48.…”

“…45 Interestingly, in the work of Boujlel and Scheme 26 Electrochemical anion pool method for amide and ester synthesis. 43 Scheme 25 N-Heterocyclic carbene prepared by cathodic reduction of an ionic liquid to mediate amide synthesis. 42 Simonet in 1985, the combination of molecular O 2 and cathodic reduction was also used to produce amide products, this time through the cleavage of diimides 50, as in Scheme 29.…”