Preparation and Reactions of Sulfides

Treatment of a thiol with a base, such as NaH, gives the corresponding thiolate ion (RS ), which undergoes reaction with a primary or secondary alkyl halide to give a sulfide. The reaction occurs by an Sn2 mechanism, analogous to the Williamson synthesis of ethers (Section 13.9). 

Perhaps surprisingly in light of their close structural similarity, sulfides and ethers differ substantially in their chemistry. Because the valence electrons on sulfur are farther from the nucleus and are less tightly held than those on oxygen (3p electrons versus 2p electrons), sulfur compounds are more nucleophilic than their oxygen analogs. Unlike dialkyl ethers, dialkyl sulfides 

The most common example of this process in living organisms is the reaction of the amino acid methionine with adenosine triphosphate (ATP Section 6.8) to give S-adenosylmethionine. The reaction is somewhat unusual in that the biological leaving group in this Sn2 process is the triphosphate ion rather than the more frequently seen diphosphate ion (Section 12.10). 

Another difference between sulfides and ethers is that sulfides are easily oxidized. Treatment of a sulfide with hydrogen peroxide, H2O2, at room temperature yields the corresponding sulfoxide (R2SO), and further oxidation of the sulfoxide with a peroxyacid yields a sulfone (R2S02]- 

Dimethyl sulfoxide (DMSO) is a particularly well-known sulfoxide that is often used as a polar aprotic solvent. It must be handled with care, however. 

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