Cytotoxic compounds. Part XIV. Reactions of the bismethanesulphonates of 3-arylthiopropane-1,2-diols and of 2-arylthiopropane-1,3-diols with nucleophiles

Abstract

The products formed in the title reactions have been examined by ¹H n.m.r. spectroscopy. The aryl group was p-methoxy-, p-methylthio-, p-chloro-, or 2,4-dinitro-phenyl, and the ease of cyclisation to an episulphonium ion, as judged by the formation of rearranged products, decreases in that order. Solvolysis in acetic acid gives mainly the 1,2-diacetate in all cases, the result of thermodynamic control (except with the 2,4-dinitro-compounds, where kinetic control obtains). With potassium acetate in acetic anhydride, mixtures of isomeric diacetates are formed in which the proportion of 1,3-compound decreases with increasing electron-withdrawing character of the aryl group, and a similar trend occurs with tetramethylammonium acetate in acetone, though elimination then competes to an increasing extent, becoming the exclusive mode of reaction of the 2,4-dinitro-compounds. With sodium methoxide, elimination is dominant and sometimes is accompanied by allylic rearrangement. All the elimination reactions occur without the intervention of an episulphonium ion. Solvolysis in methanol proceeds under kinetic control and gives mixtures of the 1,2- and 1,3-dimethyl ethers. Sodium phenyl sulphide effects substitution at least very largely by direct S_N2 attack, and this occurs also in the reactions of the two 2,4-dinitro-compounds with lithium bromide, but the other bismethanesulphonates give mixtures of dibromides, formed under thermodynamic control. With sodium azide, substitution occurs both directly and through intermediate episulphonium ions.

The ¹H n.m.r. spectra of twenty allyl and vinyl sulphides are reported.