Hydrolysis of Thioethers and Related Reactions

The chemistry of organic sulfur compounds does not always parallel that of their corresponding oxygen analogues, and metal-directed chemistry has proved to be of considerable utility in promoting copy-cat reactions. For example, ethers are readily cleaved upon treatment with strong mineral acids, whereas thioethers are unreactive under these conditions (Fig. 4-37). 

However, the reaction requires only a general acid catalyst rather than the specific acid catalyst H+, and the corresponding reactions of the soft thioether may be better mediated by softer Lewis acids such as Cu+, Ag+, Hg2+, Pd2+, Pt2+ or Au3+. In many cases the aqua-ted metal ion is the most convenient Lewis acid, but in the case of some metals, particularly the second and third row transition metal ions, the aqua ions are not isolable and other complexes (particularly those with chloride ligands) are equally effective. The role of these softer metal ions as Lewis acids is two-fold. Firstly, the sulfur is co-ordinated to the metal, which increases the polarisation of the C-S bond and enhances the electrophilic character of the carbon, and, secondly, the thiol (or thiolate) leaving group is stabilised by co-ordination (Fig. 4-39). 

In the same manner, the hydrolysis of thioesters and thioamides is dramatically (and synthetically usefully) accelerated in the presence of mercury(n) compounds. Notice that a variety of reactions is occurring sequentially in the examples presented in Fig. 4-40. 

The use of soft metal ions to direct the course of reactions of sulfur compounds has been utilised in the preparation of nitriles from thioamides. The first step involves the alkylation of the thioamide to give the iminothioester, which is then converted to the nitrile on treatment with mercury(n) salts (Fig. 4-41). 

Note that these reactions are reversible, and indeed one of the best methods for the preparation of thioether complexes is by alkylation of a co-ordinated thiolate. In general, the dealkylation reactions require forcing conditions, but in some cases they proceed in an 

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