Thioamide

A thioamide is a functional group in organic chemistry in which the carbonyl oxygen of an amide is replaced by sulfur, giving the structure R-C(=S)-NR'R''. This motif is present in simple thioamides such as thiourea (H2N-C(=S)-NH2) and in numerous thioamide derivatives of carboxamides. The C=S bond is longer and less polarized than the C=O bond, which leads to different acidity, basicity, and hydrogen-bonding properties compared with ordinary amides.

Preparation and typical transformations: Thioamides are typically prepared by thionation of amides using reagents such as Lawesson's reagent or phosphorus pentasulfide (P4S10). Other approaches include conversion of nitriles or esters with sulfur-transfer reagents. Thioamides can be oxidized to sulfinyl or sulfonyl derivatives, and N-substituted thioamides serve as versatile intermediates in organic synthesis and in peptide chemistry.

Applications: Thioamides function as amide isosteres in medicinal chemistry to modulate proteolysis resistance and metabolic stability. They appear as pharmacologically active drugs such as methimazole and propylthiouracil, which are thioamide-containing antithyroid agents that inhibit thyroid peroxidase. In peptide chemistry, thioamide substitutions are used as spectroscopic probes and to tune hydrogen-bonding patterns and protease resistance. They also act as ligands in coordination chemistry and in materials science.

Safety and occurrence: Many thioamides are irritants or can be toxic in certain contexts; appropriate handling is required. They range from simple substrates like thiourea to more complex heterocyclic thioamides found in pharmaceuticals and advanced materials.