Thioamide

thumb|right|150px|class=skin-invert-image|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.

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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:

:300px|Thionamide Synthesis

Imidoyl chlorides react with hydrogen sulfide to produce thioamides.

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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.

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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.

More easily than the corresponding amides, thioamides oxidize and reduce. 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.

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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.