Thiocarboxylic acid

In organic chemistry, thiocarboxylic acids or carbothioic acids are organosulfur compounds related to carboxylic acids by replacement of one of the oxygen atoms with a sulfur atom. Two tautomers are possible: a thione form (RC(S)OH) and a thiol form (RC(O)SH). These are sometimes also referred to as "carbothioic O-acid" and "carbothioic S-acid" respectively. Of these the thiol form is most common (e.g. thioacetic acid).

A naturally occurring thiocarboxylic acid is pyridine-2,6-dicarbothioic acid, a siderophore.

Synthesis
Thiocarboxylic acids are typically prepared by salt metathesis from the acid chloride, as in the following conversion of benzoyl chloride to thiobenzoic acid using potassium hydrosulfide according to the following idealized equation:
 * C6H5C(O)Cl + KSH -> C6H5C(O)SH + KCl

2,6-Pyridinedicarbothioic acid is synthesized by treating the diacid dichloride with a solution of H2S in pyridine:
 * NC5H3(COCl)2 + 2 H2S  +  2 C5H5N  → [C5H5NH+][HNC5H3(COS)2-] + [C5H5NH]Cl

This reaction produces the orange pyridinium salt of pyridinium-2,6-dicarbothioate. Treatment of this salt with sulfuric acid gives colorless the bis(thiocarboxylic acid, which can then be extracted with dichloromethane.

Reactions
At neutral pH, thiocarboxylic acids are fully ionized. Thiocarboxylic acids are about 100 times more acidic than the analogous carboxylic acids. For PhC(O)SH pKa = 2.48 vs 4.20 for PhC(O)OH. For thioacetic acid the pKa is near 3.4 vs 4.72 for acetic acid.

The conjugate base of thioacetic acid, thioacetate is reagents for installing thiol groups via the displacement of alkyl halides to give the thioester, which in turn are susceptible to hydrolysis:
 * R\sX + CH3COS-  ->  R\sSC(O)CH3  +  X-
 * R\sSC(O)CH3 + H2O  ->  R\sSH  +  CH3CO2H

Thiocarboxylic acids react with various nitrogen functional groups, such as organic azide, nitro, and isocyanate compounds, to give amides under mild conditions. This method avoids needing a highly nucleophilic aniline or other amine to initiate an amide-forming acyl substitution, but requires synthesis and handling of the unstable thiocarboxylic acid. Unlike the Schmidt reaction or other nucleophilic-attack pathways, the reaction with an aryl or alkyl azide begins with a [3+2] cycloaddition; the resulting heterocycle expels N2 and the sulfur atom to give the monosubstituted amide.