Thione form (carbothioic O-acid)
Thiol form (carbothioic S-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).[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.

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:[3]

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.[4]

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.[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:

R−X + CH3COS− → R−SC(O)CH3 + X−
R−SC(O)CH3 + H2O → R−SH + CH3CO2H

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]

See also

References

  1. ^ Cremlyn, R.J. (1996). An introduction to organosulfur chemistry. Chichester: Wiley. ISBN 0-471-95512-4.
  2. ^ Matthys J. Janssen (1969). "Thiolo, Thiono and Dithio Acids and Esters". In Saul Patai (ed.). Carboxylic Acids and Esters. PATAI'S Chemistry of Functional Groups. pp. 705–764. doi:10.1002/9780470771099.ch15. ISBN 978-0-470-77109-9.
  3. ^ Noble, Jr., Paul; Tarbell, D. S. (1952). "Thiobenzoic Acid". Organic Syntheses. 32: 101. doi:10.15227/orgsyn.032.0101.
  4. ^ Hildebrand, U.; Ockels, W.; Lex, J.; Budzikiewicz, H. (1983). "Zur Struktur Eines 1:1-Adduktes von Pyridin-2,6-Dicarbothiosäure und Pyridin". Phosphorus and Sulfur and the Related Elements. 16 (3): 361–364. doi:10.1080/03086648308080490.
  5. ^ M. R. Crampton (1974). "Acidity and hydrogen-bonding". In Saul Patai (ed.). The Chemistry of the Thiol Group. Chichester: John Wiley & Sons Ltd. p. 402.
  6. ^ a b "21.1.2.6.1: Variation 1: From thiocarboxylic acids". Science of Synthesis: Houben–Weyl Methods of Molecular Transformations. Vol. 21: Three Carbon-Heteroatom Bonds: Amides and Derivatives, Peptides, Lactams. Georg Thieme Verlag. 2005. pp. 52–54. ISBN 978-3-13-171951-5.
  7. ^ a b Xie, Sheng; Zhang, Yang; Ramström, Olof; Yan, Mingdi (2016). "Base-catalyzed synthesis of aryl amides from aryl azides and aldehydes". Chem. Sci. 7 (1): 713–718. doi:10.1039/C5SC03510D. PMC 5952891. PMID 29896355.
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