Thiocarboxylic acid

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Thioic O-acid.svg
Thione form (carbothioic O-acid)
Thioic acid.svg
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).

Contents

Thiocarboxylic acids are rare in nature, however the biosynthetic components for producing them appear widespread in bacteria. [3] Examples include pyridine-2,6-dicarbothioic acid, [4] and thioquinolobactin. [3]

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: [5]

C6H5C(O)Cl + KSH → C6H5C(O)SH + KCl

Covalent sulfides, such as P2S5, generally give poor yields unless catalyzed with triphenylstibine oxide. [6]

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. [7]

Reactions

At neutral pH, thiocarboxylic acids are fully ionized. Thiocarboxylic acids are about 100 times more acidic than the analogous carboxylic acids. Thiobenzoic acid has a pKa of 2.48 compared with 4.20 for benzoic acid, and thioacetic acid has a pKa near 3.4 compared with 4.72 for acetic acid. [8] Alkylation of the corresponding thioate ion gives a thioester. [9]

The conjugate base of thioacetic acid, thioacetate, is a reagent used for installing thiol groups via the displacement of alkyl halides by a two-step process. The halide is displaced to give a thioester intermedate, which is then hydrolyzed:

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. [10] [11] 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. [11] Unlike the Schmidt reaction or other nucleophilic-attack pathways, 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. [10]

Halogens or their equivalents (e.g. sulfuryl chloride) oxidize thiocarboxylic acids to acylsulfenyl halides. The latter are unstable, and decay over the course of several hours to the free halogen and the diacyl disulfide. [12]

See also

Related Research Articles

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<span class="mw-page-title-main">Thioester</span> Organosulfur compounds of the form R–SC(=O)–R’

In organic chemistry, thioesters are organosulfur compounds with the molecular structure R−C(=O)−S−R’. They are analogous to carboxylate esters with the sulfur in the thioester replacing oxygen in the carboxylate ester, as implied by the thio- prefix. They are the product of esterification of a carboxylic acid with a thiol. In biochemistry, the best-known thioesters are derivatives of coenzyme A, e.g., acetyl-CoA. The R and R' represent organyl groups, or H in the case of R.

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In organic chemistry, an acyl halide is a chemical compound derived from an oxoacid by replacing a hydroxyl group with a halide group.

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<span class="mw-page-title-main">2,6-Pyridinedicarbothioic acid</span> Chemical compound

2,6-Pyridinedicarbothioic acid (PDTC) is an organosulfur compound that is produced by some bacteria. It functions as a, a low molecular weight compound that scavenges iron. Siderophores solubilize compounds by forming strong complexes. PDTC is secreted by the soil bacteria Pseudomonas stutzeri and Pseudomonas putida.

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<span class="mw-page-title-main">Sulfenamide</span> Molecules of the form >N–S–

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<span class="mw-page-title-main">Sulfinyl halide</span> Class of chemical compounds

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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. 1 2 Dong, Liao-Bin; Rudolf, Jeffrey D.; Kang, Dingding; Wang, Nan; He, Cyndi Qixin; Deng, Youchao; Huang, Yong; Houk, K. N.; Duan, Yanwen; Shen, Ben (2018). "Biosynthesis of thiocarboxylic acid-containing natural products". Nature Communications. 9: 2362. Bibcode:2018NatCo...9.2362D. doi:10.1038/s41467-018-04747-y. PMID   29915173.
  4. ↑ Budzikiewicz, Herbert (2010). "Microbial Siderophores". In Kinghorn, A. Douglas; Falk, Heinz; Kobayashi, Junichi (eds.). Fortschritte der Chemie organischer Naturstoffe / Progress in the Chemistry of Organic Natural Products, Vol. 92[Progress in the Chemistry of Organic Natural Products]. Vol. 92. pp. 1–75. doi:10.1007/978-3-211-99661-4_1. ISBN   978-3-211-99660-7. PMID   20198464.
  5. ↑ Noble, Jr., Paul; Tarbell, D. S. (1952). "Thiobenzoic Acid". Organic Syntheses. 32: 101. doi:10.15227/orgsyn.032.0101.
  6. ↑ Collier, S. J. (2007). "Product class 8: Thiocarboxylic S-acids, selenocarboxylic Se-acids, tellurocarboxylic Te-acids, and derivatives". In Panek, J. S. (ed.). Category 3, Compounds with Four and Three Carbon Heteroatom Bonds: Three Carbon—Heteroatom Bonds: Esters, and Lactones; Peroxy Acids and R(CO)OX Compounds; R(CO)X, X=S, Se, Te. Science of Synthesis. Stuttgart: Georg Thieme Verlag. p. 1600. doi:10.1055/sos-sd-020-01480. ISBN   978-3-13-144691-6.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ Matthys J. Janssen "Carboxylic Acids and Esters" in PATAI's Chemistry of Functional Groups: Carboxylic Acids and Esters, Saul Patai, Ed. John Wiley, 1969, New York: pp. 705–764. doi : 10.1002/9780470771099.ch15
  10. 1 2 "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.
  11. 1 2 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.
  12. ↑ Ogawa Akiya; Sonoda Noboru (1995). "Acylsulfur, -selenium, or -tellurium functions". In Moody, Christopher J. (ed.). Comprehensive Organic Functional Group Transformations. Vol. 5. Oxford, UK: Pergamon. pp. 244–246. ISBN   0-08-042326-4. LCCN   95-31088.
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