Mustard carbonate analogues: influence of the leaving group

The substitution of a chlorine atom with a carbonate moiety in mustard compounds has led to a new class of molecules, namely mustard carbonates that retain the reactivity of the well-know toxic iprites, but are safe for the operator and the environment [1]. Herein we report the influence of the leaving group on the neighboring effect of sulfur half mustard carbonates (HMCs) usually less reactive than nitrogen ones [2]. Several new 2-(methylthio)ethyl alkyl carbonates have been synthesized and their reactivity has been investigated in both autoclave and neat conditions. The results reactions between the HMCs and phenol performed in autoclave (180 °C, no base, in acetonitrile media) showed that the efficiency of the anchimeric effect is directly dependent on the steric hindrance of the HMC leaving group. The least steric hindered 2-(methylthio)ethyl methyl carbonate gave the methyl (2-phenoxyethyl)sulfane in higher yield, whereas the most steric hindered 2-(methylthio)ethyl t-butyl carbonate did not reacted at all. The influence of the leaving group on the anchimeric effect has been also investigated in neat conditions at 150 °C in the presence of catalytic amount of K2CO3. In this case, due to the absence of the solvent and the presence of the base the reaction is more complicated by transesterification reactions and formation of unwanted products. Interestingly 2-(methylthio)ethyl ethyl carbonate showed to be the most efficient carbonate among the ones studied. This resulted might be ascribed to its ability to free the cyclic intermediate from its molecular cage as intimate ion pair more readily than the other HMCs. Finally, several nucleophiles have been then tested in neat reaction conditions using 2-(methylthio)ethyl ethyl carbonate and a catalytic amount of base. In all cases studied it was observed an almost quantitative anchimeric aided alkylation over SN2 reaction, i.e., formation of ethyl aryl ethers. The best results achieved have led to an enhanced product selectivity, more accessible reaction conditions and a better insight on the reaction mechanism of mustard carbonates.