Synthesis 2022; 54(11): 2595-2603
DOI: 10.1055/a-1742-3723
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Microwave-Assisted Aminoalkylation of Phenols via Mustard Carbonate Analogues

Monica Viviano
a   Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132 - 84084 Fisciano, Salerno, Italy
,
Giacomo Trapasso
b   Department of Environmental Sciences Informatics and Statistics, Ca’ Foscari University of Venice, Campus Scientifico, Via Torino 155, 30172 Venezia Mestre, Italy
,
Mattia Annatelli
b   Department of Environmental Sciences Informatics and Statistics, Ca’ Foscari University of Venice, Campus Scientifico, Via Torino 155, 30172 Venezia Mestre, Italy
,
Ciro Milite
a   Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132 - 84084 Fisciano, Salerno, Italy
,
a   Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132 - 84084 Fisciano, Salerno, Italy
,
Fabio Aricò
b   Department of Environmental Sciences Informatics and Statistics, Ca’ Foscari University of Venice, Campus Scientifico, Via Torino 155, 30172 Venezia Mestre, Italy
› Author Affiliations
We thank Istituto Nazionale della Previdenza Sociale (INPS) for funding the Ph.D. fellowship of Giacomo Trapasso. Prof. S. Castellano acknowledges Regione Campania (Italy) for funding (Grant B61G18000470007).


Abstract

A microwave-assisted chlorine-free direct phenol substitution is presented, which is indicated as a key green chemistry research area for pharmaceuticals manufacturers. The reaction of β-aminocarbonates (mustard carbonates) with several substituted phenols in the presence of a polar solvent (acetonitrile or butanol) led to the related aminoalkylated products via the anchimeric assistance of the nitrogen incorporated in the organic carbonate backbone. The aminoalkylation required short reaction time (7 min) and the related products were isolated in high yields (>90%) via quick liquid-liquid extraction or column chromatography depending on the solvent employed. Furthermore, microwave irradiation also promoted the one-pot aminoalkylation of phenol in excellent yield. In this approach a β-aminoalcohol was reacted with phenol in the presence of diethyl carbonate, used for the in situ formation β-aminocarbonate, key intermediate in the consequent anchimerically driven alkylation. The resulting product, namely N,N-dimethyl-2-phenoxyethanamine, was isolated as pure in almost quantitative yield.

Supporting Information



Publication History

Received: 05 November 2021

Accepted after revision: 17 January 2022

Publication Date:
17 January 2022 (online)

© 2022. Thieme. All rights reserved

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