Sultones ring strain

Sultenes, Sultines, and Sultones.—Further reports have appeared on the formation of sultones from SO3 and dienes and from the cycloaddition of c-amino-methylene-ketones and sulphene. Unusual sultone formations occurred during the reaction of a ketose derivative with mesyl chloride and during the rearrangements of bicyclic ketones that were induced by sulphuric acid, respectively. The kinetics of reactions of sultones (181) with nucleophiles and the enthalpy changes accompanying their alkaline hydrolysis," which allow an estimation of differences in ring strain between the five- and six-membered sultones, have been studied. 

The electrophiles or electrophilic intermediates that are or are postulated to be responsible for the carcinogenic action of chemicals include (i) positively charged carbonium, nitrenium, oxonium and episulfonium ions, (ii) free radicals, (iii) polarized double bonds, (iv) aldehydes, (v) strained rings such as epoxide, aziridine, lactones and sultones, and (vi) quinone/ quinoid/quinoneimine structures. Based on their reactivity (Table I), electrophiles may be graded from "soft" to "hard" similar to the concept of "soft" and "hard" acids and bases (18). In general, soft electrophiles react preferentially with soft nucleophiles whereas hard electrophiles react preferentially with hard nucleophiles. Thus, since the nucleophilic sites in the purine and pyrimidine bases in DNA are moderately hard nucleophiles, moderately hard electrophiles tend to have the greatest likelihood of covalent binding to DNA. Soft electrophiles often deplete the cellular pool of noncritical soft nucleophiles (such as GSH) before they can react with DNA. 

The presence of a sterically strained ring (e.g., epoxide, aziridine, lactones and sultones) in any type of structure. The likelihood of carcinogenicity may increase if the compound contains two or more of these reactive ring structures. 

It seems likely, therefore, that although the major cause of enthalpy strain observed in the alkaline hydrolysis of sultones arises from angle strain, other factors such as 1,3-lone-pair-lone-pair interactions and possibly conjugative effects also contribute to destabilisation of the five-membered ring. 

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