Hydrolysis and alkylating reactivity of aromatic nitrogen mustards

Abstract

Rate constants for the hydrolysis of a series of aromatic nitrogen mustards Ar–X–C₆H₄-N(CH₂CH₂Cl)₂(X = O, CH₂, CONH, S, CO and SO₂) in buffered aqueous acetone mixtures have been obtained using an HPLC technique which allows evaluation of the rate constants for hydrolytic displacement of both chlorines in consecutive reactions. Hydrolysis has a general-base-catalysed component and is accompanied by external chloride ion return. An aziridinium ion intermediate is implicated in at least one pathway. The mustards also alkylate the nucleophiles thiourea and 4-(4-nitrobenzyl)pyridine (NBP) and again the aziridinium ion intermediate is involved since the kinetic behaviour rules out a direct S_N2 pathway.