Inorganic chemistry, thiocarboxylic acidsorcarbothioic 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).[1][2] 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.
Thiocarboxylic acids are typically prepared by salt metathesis from the acid chloride, as in the following conversion of benzoyl chloridetothiobenzoic acid using potassium hydrosulfide according to the following idealized equation:[3]
2,6-Pyridinedicarbothioic acid is synthesized by treating the diacid dichloride with a solution of H2S in pyridine:
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.[4]
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.[5]
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:
Thiocarboxylic acids react with various nitrogen functional groups, such as organic azide, nitro, and isocyanate compounds, to give amides under mild conditions.[6][7] 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.[7] 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.[6]