Hydrolysis and alkylating reactivity of aromatic nitrogen mustards

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 SN2 pathway.