Cytotoxic compounds. Part 21. Chloro-, methoxy-, and methoxy-carbonyl-derivatives of (bis-2-chloroethylamino)-phenols and -anilines

Abstract

New or improved syntheses are described of some NN-bis-2-chloroethylanilines carrying both a free phenolic group and a methoxycarbonyl ring substituent.

A study has been made of the hydroxyethylation, with ethylene oxide, of a variety of chloro-, methoxy-, and methoxycarbonyl-nitroanilines, and of methoxy- and methoxycarbonyl-N-acylphenylenediamines. Bishydroxy-ethylation was inhibited by an o-methoxycarbonyl group and by an o- or p-nitro-group, but otherwise the NN-bis-2-hydroxyethyl derivatives were obtained and subsequently converted into the NN-bis-2-chloroethyl compounds. Reduction of the nitro-group, or hydrolysis of the acylamino-group, in these dichlorides led to NN-bis-2-chloroethylanilines carrying both a free amino-group and also a methoxycarbonyl-, methoxy-, or chloro-group as ring substituents.

The ring-substituted (bis-2-chloroethylamino)-phenols or -anilines are precursors of mustard urethanes having potential importance as anti-tumour agents.