Cytotoxic compounds. Part XV. Reactions of the methanesulphonates of 1-arylthiopropan-2-ols and of 2-(2,4-dinitrophenylthio)propan-1-ol 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, or phenyl, and the formation of an episulphonium intermediate is favoured by electron-donation from the aromatic ring. Solvolysis in acetic acid gives mainly the secondary acetates, the products (except those from the 2,4-dinitro-compounds) being thermodynamically controlled. With potassium acetate in acetic anhydride, approximately equal proportions of primary and secondary acetates are formed, except from the secondary 2,4-dinitro-compound, which gives 50% of 1-(2,4-dinitrophenylthio)propene. With tetramethylammonium acetate and with sodium methoxide, both 2,4-dinitro-compounds give vinyl sulphides, the other methanesulphonates yielding only mixtures of acetates or methyl ethers; the elimination reactions do not involve an intermediate episulphonium ion. Solvolysis in methanol gives mainly or entirely the secondary methyl ether, under kinetic control from the 2,4-dinitro-compounds but under varying degrees of thermodynamic control from the other methanesulphonates. An episulphonium intermediate is involved in the reactions of all the methanesulphonates with lithium bromide and with sodium azide, and in the reaction of the p-methoxy-compound with sodium phenyl sulphide, mixtures of bromides, azides, or sulphides being obtained; but the p-methylthio- and the p-chloro-compounds react with sodium phenyl sulphide by direct substitution, to give single products.