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'):

1. Thiol addition to give hemithioacetal:

   ${\displaystyle {\ce {RSH + R'CH(O) -> R'CH(SR)OH}}}$

2. Thiol addition with loss of water to give dithioacetal:

   ${\displaystyle {\ce {RSH + R'CH(OH)SR -> R'CH(SR)2 + H2O}}}$

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:

${\displaystyle {\ce {R'CHS2C2H4 + R2NLi -> R'CLiS2C2H4 + R2NH}}}$

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.