Thioether

A thioether (similar to sulfide) is a functional group in organic chemistry that has the structure R¹-S-R² as shown on right. Like many other sulfur-containing compounds, volatile thioethers characteristically have foul odors.^[1]

A thioether is similar to an ether except that it contains a sulfur atom in place of the oxygen. Because oxygen and sulfur belong to the chalcogens group in the periodic table, the chemical properties of ethers and thioethers share some commonalities. This functional group is important in biology, most notably in the amino acid methionine and the cofactor biotin.

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Preparation

• Thioethers are typically prepared by the alkylation of thiols:

R-Br + HS-R' → R-S-R' + HBr

Such reactions are accelerated in the presence of base, which converts the thiol into the more nucleophilic thiolate.

• An alternative method of synthesis includes the addition of a thiol to an alkene, typically catalysed by free radicals:

R-CH=CH₂ + HS-R' → R-CH₂-CH₂-S-R'

• Thioethers can also be prepared via the Pummerer rearrangement.

Reactions

• While ethers are generally stable, thioethers (R-S-R) are easily oxidized to the sulfoxides (R-S(=O)-R), which can themselves be further oxidized to sulfones (R-S(=O)₂-R). For example, dimethyl sulfide can be oxidized as follows:

S(CH₃)₂ + O → OS(CH₃)₂

OS(CH₃)₂ + O → O₂S(CH₃)₂

Typical oxidants include peroxides.

• The sulfur-sulfur bond in disulfides is susceptible to cleavage by nucleophiles, and reaction with a carbon nucleophile produces a thioether:

R₃C^- + R¹S-SR² → R₃CSR¹ + R²S^-

• Trialkysulfonium salts react with nucleophiles with a dialkyl sulfide as a leaving group:

Nu^- + R₃S⁺ → Nu-R + R-S-R

This reaction is exploited in biological systems as a means of transferring an alkyl group. For example, S-adenosylmethionine acts as a methylating agent in biological S_N2 reactions.

• Ethers can be alkylated at oxygen only with difficulty to give highly reactive trialkyloxonium salts. In contrast, thioethers are readily alkylated to give stable sulfonium salts, such as trimethylsulfonium:

S(CH₃)₂ + CH₃I → [S(CH₃)₃]⁺I^-

Thiophenes

The heterocyclic compound thiophene is formally a thioether. Because of the aromatic character of this heterocycle, the nonbonding electrons on sulfur, normally responsible for the nucleophilicity so characteristic of thioethers, are delocalized into the π-system. Consequently thiophene exhibits few properties expected for a thioether - thiophene is non-nucleophilic at sulfur and, in fact, is sweet-smelling. Upon hydrogenation, thiophene gives tetrahydrothiophene, C₄H₈S, which indeed does behave as a typical thioether.

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