Thioacetal

In organosulfur chemistry, thioacetals are the sulfur (thio-) analogues of acetals (R−CH(−OR)₂). There are two classes: the less-common monothioacetals, with the formula R−CH(−OR')−SR", and the dithioacetals, with the formula R−CH(−SR')₂ (symmetric dithioacetals) or R−CH(−SR')−SR" (asymmetric dithioacetals).^[1]

The symmetric dithioacetals are relatively common. They are prepared by condensation of thiols (−SH) or dithiols (two −SH groups) with aldehydes (−CH=O). These reactions proceed via the intermediacy of hemithioacetals (R−CH(−OH)−SR'):

Thiol addition to give hemithioacetal:

RSH + R'CH(O) → R'CH(SR)OH

Thiol addition with loss of water to give dithioacetal:

RSH + R'CH(OH)SR → R'CH(SR)₂ + H₂O

Such reactions typically employ either a Lewis acid or Brønsted acid as catalyst.

Dithioacetals generated from aldehydes and either 1,2-ethanedithiol or 1,3-propanedithiol are especially common among this class of molecules for use in organic synthesis.^[2]

The carbonyl carbon of an aldehyde is electrophilic and therefore susceptible to attack by nucleophiles, whereas the analogous central carbon of a dithioacetal is not electrophilic. As a result, dithioacetals can serve as protective groups for aldehydes.

Far from being unreactive, and in a reaction unlike that of aldehydes, that carbon can be deprotonated to render it nucleophilic:

R'CHS₂C₂H₄ + R₂NLi → R'CLiS₂C₂H₄ + R₂NH

The inversion of polarity between R'(H)C^δ+=O^δ− and R'CLi(SR)₂ is referred to as umpolung. The reaction is commonly performed using the 1,3-dithiane. The lithiated intermediate can be used for various nucleophilic bond-forming reactions, and then the dithioketal hydrolyzed back to its carbonyl form. This overall process, the Corey–Seebach reaction, gives the synthetic equivalent of an acyl anion.

References

^ IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version: (2006–) "thioacetals". doi:10.1351/goldbook.T06348
^ P. Stütz and P. A. Stadler (1977). "3-Alkylated and 3-Acylated Indoles from a Common Precursor: 3-Benzylindole and 3-Benzoylindole". Organic Syntheses. 56: 8. doi:10.15227/orgsyn.056.0008.

[1] IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version: (2006–) "thioacetals". doi:10.1351/goldbook.T06348

[2] P. Stütz and P. A. Stadler (1977). "3-Alkylated and 3-Acylated Indoles from a Common Precursor: 3-Benzylindole and 3-Benzoylindole". Organic Syntheses. 56: 8. doi:10.15227/orgsyn.056.0008.

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See also

References