Thioether

General structure of a thioether with the blue marked functional group.

A thioether is a functional group in organosulfur chemistry with the connectivity C–S–C as shown on right. Like many other sulfur-containing compounds, volatile thioethers have foul odors.^[1] A thioether is similar to an ether except that it contains a sulfur atom in place of the oxygen. The grouping of oxygen and sulfur in the periodic table suggests that the chemical properties of ethers and thioethers are somewhat similar.

Nomenclature

Thioethers are sometimes called sulfides, especially in the older literature and this term remains in use for the names of specific thioethers. The two organic substituents are indicated by the prefixes. (CH₃)₂S is called dimethylsulfide. Some thioethers are named by modifying the common name for the corresponding ether. For example, C₆H₅SCH₃ is methyl phenyl sulfide, but is more commonly called thioanisole, since its structure is related to that for anisole, C₆H₅OCH₃.

Structure and properties

Thioether is an angular functional group, the C–S–C angle approaching 90°. The C–S bonds are about 180 pm.

Thioethers are characterized by their strong odors, which are similar to thiol odor. This odor limits the applications of volatile thioethers. In terms of their physical properties they resemble ethers but are less volatile, higher melting, and less hydrophilic. These properties follow from the polarizability of the divalent sulfur center, which is greater than that for oxygen in ethers.

Thiophenes

Thiophenes are a special class of thioether-containing heterocyclic compounds. Because of their aromatic character, they are non-nucleophilic. The nonbonding electrons on sulfur are delocalized into the π-system. As a consequence, 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.

Occurrence and applications

Thioethers are important in biology, notably in the amino acid methionine and the cofactor biotin.Petroleum contains many organosulfur compounds, including thioethers. Polyphenylene sulfide is a useful high temperature plastic. Coenzyme M, CH
3SCH
2CH
2SO−
3, is the precursor to methane (i.e. natural gas) via the process of methanogenesis.

Selected thiothers, from left, dimethylsulfide, coenzyme-M, the amino acid methionine, the vitamin biotin, and the engineering plastic polyphenylene sulfide.

Preparation

Thioethers are typically prepared by the alkylation of thiols:

R–Br + HS–R′ → R–S–R′ + HBr

Such reactions are usually conducted in the presence of base, which converts the thiol into the more nucleophilic thiolate. Analogously, the reaction of disulfides with organolithium reagents produces thioethers:

R₃CLi + R¹S–SR² → R₃CSR¹ + R²SLi

Analogous reactions are known starting with Grignard reagents.

Alternatively, thioethers can be synthesized by the addition of a thiol to an alkene:

R–CH=CH₂ + HS–R′ → R–CH₂–CH₂–S–R′

This reaction is often catalysed by free radicals.

Thioethers can also be prepared by many other methods, such as the Pummerer rearrangement. 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.

Reactions

Oxidation

While, in general, ethers are non-oxidizable, thioethers can be easily oxidized to the sulfoxides (R–S(=O)–R), which can themselves be further oxidized to sulfones (R–S(=O)₂–R). Hydrogen peroxide is a typical oxidant. For example, dimethyl sulfide can be oxidized as follows:

S(CH₃)₂ + H₂O₂ → OS(CH₃)₂ + H₂O

OS(CH₃)₂ + H₂O₂ → O₂S(CH₃)₂ + H₂O

Alkylation

Ethers can be alkylated at oxygen only with difficulty, but thioethers are readily alkylated to give stable sulfonium salts, such as trimethylsulfonium iodide:

S(CH₃)₂ + CH₃I → [S(CH₃)₃]⁺I⁻

Binding to transition metals

In analogy to their easy alkylation, thioethers bind to metals to form coordination complexes. They are classified as soft ligands, but their affinity for metals is lower than typical phosphines. Chelating thioethers are known, such as 1,4,7-trithiacyclononane.

Hydrogenolysis

Thioethers undergo hydrogenolysis in the presence of certain metals:

R–S–R′ + 2 H₂ → RH + R′H + H₂S

Raney nickel is useful for stoichiometric reactions in organic synthesis whereas molybdenum-based catalysts are used to "sweeten" petroleum fractions, in the process called hydrodesulfurization.

References

1. Cremlyn, R. J. (1996). An Introduction to Organosulfur Chemistry. Chichester: John Wiley and Sons. ISBN 0-471-95512-4.