External activation of epoxides by polarising groups borne by the nucleophile

Abstract

There is much current interest in the chemistry of epoxides which are activated as electrophiles, but almost without exception, systems studied thus far involve internal activation by hydroxy-groups. Herein a new mode of external activation is pointed out, whereby increased susceptibility to nucleophilic attack occurs by interaction of the epoxide with polarising groups such as OH and SH borne by primary amine nucleophiles. Rate data for the reactions of a number of 2-substituted ethylamines with methyloxiran in tetrahydrofuran, ethanol, and water show that while a 2-mercapto-group may increase rates 10–25 fold, a 2-hydroxy-group only appears to be effective in aprotic solvents. Determined values of ΔH‡ and ΔS‡ are discussed, and interpreted as providing evidence for the operation of an intramolecular concerted-like activation process. In drawing a biological analogy, particularly with regard to the physiological action of toxic epoxides, these results draw attention to the possible need to consider alternative modes of in vitro action.