thioacetal

{{short description|Organosulfur compounds of the form –CH(O–)S– or –CH(S–)2}}

Image:Thioacetal.png

Image:Dithioacetal.png

In organosulfur chemistry, thioacetals are the sulfur (thio-) analogues of acetals ({{chem2|R\sCH(\sOR)2}}). There are two classes: the less-common monothioacetals, with the formula {{chem2|R\sCH(\sOR')\sSR"}}, and the dithioacetals, with the formula {{chem2|R\sCH(\sSR')2}} (symmetric dithioacetals) or {{chem2|R\sCH(\sSR')\sSR"}} (asymmetric dithioacetals).{{GoldBookRef |title=thioacetals |file=T06348 }}

The symmetric dithioacetals are relatively common. They are prepared by condensation of thiols ({{chem2|\sSH}}) or dithiols (two {{chem2|\sSH}} groups) with aldehydes ({{chem2|\sCH\dO}}). These reactions proceed via the intermediacy of hemithioacetals ({{chem2|R\sCH(\sOH)\sSR'}}):

:Thiol addition to give hemithioacetal:

::{{chem2 | RSH + R'CH(O) -> R'CH(SR)OH }}

:Thiol addition with loss of water to give dithioacetal:

::{{chem2 | 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.{{cite journal | doi = 10.15227/orgsyn.056.0008 | author = P. Stütz and P. A. Stadler | title = 3-Alkylated and 3-Acylated Indoles from a Common Precursor: 3-Benzylindole and 3-Benzoylindole | journal = Organic Syntheses | date = 1977 | volume = 56 | page = 8 }}

:File:Dithioacetal_Synthesis_V.1.svg

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:

:{{chem2 | R'CHS2C2H4 + R2NLi -> R'CLiS2C2H4 + R2NH }}

The inversion of polarity between {{chem2|R'(H)C^{δ+}\dO^{δ−} }} and {{chem2|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.