A mild and efficient synthesis of N-aryl glycines by the rearrangement of 2-chloro-N-aryl acetamides

TL;DR

A new method was developed to efficiently synthesize N-aryl glycines using a one-pot process with high yields.

Contribution

The paper introduces a mild and efficient one-pot synthesis of N-aryl glycines using intermolecular cyclization and ring opening.

Findings

The synthesis of N-aryl glycines was achieved in high yields using CuCl2·2H2O and KOH.

Both electron-donating and electron-withdrawing substituents on aromatic rings were well tolerated.

The reaction proceeds via an intermediate 1,4-diarylpiperazine-2,5-dione.

Abstract

A mild and efficient one-pot procedure was developed for the synthesis of substituted N-aryl glycines from 2-chloro-N-aryl acetamides by intermolecular cyclization in the presence of CuCl2·2H2O and KOH under reflux condition in acetonitrile medium. The reaction mechanism substantiates the formation of the intermediate 1,4-diarylpiperazine-2,5-dione, which on cleaving with ethanolic KOH afforded the desired products in high yields and in short durations. Both electron-donating and electron-withdrawing substituents on the aromatic rings were well tolerated.

An intermolecular cyclization of 2-chloro-N-aryl acetamides followed by ring opening of the intermediate 1,4-diarylpiperazine-2,5-diones afforded N-aryl glycines in an efficient, one-pot sequential addition process.

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