Thioamide

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Class of organic compounds

title: "Thioamide" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public tags: ["thioamides", "functional-groups"] description: "Class of organic compounds" topic_path: "general/thioamides" source: "https://en.wikipedia.org/wiki/Thioamide" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Class of organic compounds ::

::figure[src="https://upload.wikimedia.org/wikipedia/commons/a/a4/Thioamide.png" caption="General structure of a thioamide"] ::

A thioamide (rarely, thionamide, but also known as thiourylenes) is a functional group with the general structure , where are any groups (typically organyl groups or hydrogen). Analogous to amides, thioamides exhibit greater multiple bond character along the C-N bond, resulting in a larger rotational barrier.

Synthesis

Thioamides are typically prepared by treating amides with phosphorus pentasulfide, a reaction first described in the 1870s. An alternative to P2S5 is its more soluble analogue Lawesson's reagent. These transformations can be seen in the synthesis of tolrestat. :[[File:Tolrestat synthesis.svg|700px]]

Specialized methods

The Willgerodt-Kindler reaction provides a route to thioamides from aryl-alkyl ketones.

Nitriles react with hydrogen sulfide to afford thioamides. The reaction can be catalyzed by both base and acid: :[[File:Thionamid-Synthese V5.svg|300px|Thionamide Synthesis]]

Imidoyl chlorides react with hydrogen sulfide to produce thioamides. :[[File:Reaktion Imidchloride und Hydrogensulfid.svg|300px]]

Thioacylation is possible, but not with thioic acids, as amines preferentially displace the sulfur. Thionoesters form amidines with primary amines, but thioacylate secondary amines perfectly well. Thioketenes, dithiocarboxylic acids, and their thioesters attack amines of all sorts to give thioamides. The aryl acids react slowly, but much faster with a Hauser base. Trans-thioamidation is also possible, especially from a thiourea. Carbon acids attack isothiocyanates to give thioamides.

Reactions

In the presence of silver and mercury salts, thioamides characteristally hydrolyze to give the amide: : In qualitative inorganic analysis, thioacetamide is in fact used as a source of the sulfide ion.

Thioamides are Brønsted amphoteric, protonating at S and deprotonating at N or the α carbon. Strong nucleophiles may displace either substituent at the electrophilic carbon atom.

Conversely, electrophiles typically attack at N. Alkyl halides and alcohols attack either S or N, but often rearrange to a net S-alkylation.

More easily than the corresponding amides, thioamides oxidize and reduce. Although reduction with Raney nickel is popular, the reaction requires stoichiometric nickel, because the sulfur will poison any hydrogenation catalyst. Oxidation does not proceed past the quasi-sulfine.

Thioamides are precursors to heterocycles. Such approaches often exploit the nucleophilicity of the thione-like sulfur.

Structure

The C(R)(N)(S) core of thioamides is planar. Using thioacetamide as representative: the C-S, C-N, and C-C distances are 1.68, 1.31, and 1.50 Å, respectively. The short C-S and C-N distances indicate multiple bonding. : ↔ Nevertheless, thioamides do not protrope or form zwitterions,

Some thioamides exhibit the phenomenon of atropisomerism, reflecting the partial double bond character of their C-N bonds.

In biochemistry and medicine

thumb|left|130px|[[Ethionamide]] is a thioamide-based [[antibiotic]] used to treat [[tuberculosis]] Thiopurines, mimics of purines, are used to treat a number of autoimmune diseases. Some thioamides are used to control thyrotoxicosis. They inhibit the enzyme thyroid peroxidase in the thyroid, suppressing the synthesis of triiodothyronine (T3) and thyroxine (T4), thereby blocking uptake of iodotyrosines from the colloid. They also block iodine release from peripheral hormone.

Thioamides have been incorporated into peptides as isosteres for the amide bond. Natural examples include the polythioamides: thioviridamide, thioholgamide A, and closthioamide.

Some herbicides are contain thioamide groups.

Related compounds

Thioureas are a subset of thioamides. Some are items of commerce and some are bioactive.

Selenoamides are analogues of thioamides but with Se in place of S. They are uncommon.

References

References

  1. (1995). "Why Does Thioformamide Have a Larger Rotational Barrier Than Formamide?". [[J. Am. Chem. Soc.]].
  2. (1878). "Preparation of Thiamides". Journal of the Chemical Society, Abstracts.
  3. (1973). "2-Methylmercapto-''N''-Methyl-Δ2-Pyrroline".
  4. (1980). "Studies on Organophosphorus Compounds XXXI. Synthesis of Thiolactams and Thioimides". Nouveau Journal de Chimie.
  5. (1997). "3-Morpholino-2-Phenylthioacrylic Acid Morpholide and 5-(4-Bromobenzoyl-2-(4-Morpholino)-3-Phenylthiophene".
  6. (1970). "The Chemistry of Amides". Interscience (Wiley).
  7. (1998). "Conversion of the thiocarbonyl group into the carbonyl group". Tetrahedron.
  8. (1972). "Acyl Halides".
  9. (2003). "Thioamides as Useful Synthons in the Synthesis of Heterocycles". Chemical Reviews.
  10. Schwarz, George. (1945). "2,4-Dimethylthiazole".
  11. Trevor W. Hambley. (2002). "Insights into Bonding and Hydrogen Bond Directionality in Thioacetamide from the Experimental Charge Distribution". J. Chem. Soc., Perkin Trans..
  12. {{March6th
  13. (2024). "Thioamides in medicinal chemistry and as small molecule therapeutic agents". European Journal of Medicinal Chemistry.

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thioamidesfunctional-groups