Thioamide.html



General structure of a thioamide.

Thioamide (rarely, thionamide) is a functional group with the general structure R-CS-NR'R, where R, R', and R are organic groups. They are analogous to amides but they exhibit greater multiple bond character along the C-N bond, resulting in a larger rotational barrier.¹ One of the best known thioamides is thioacetamide, which is used as a source of the sulfide ion and is a building block in heterocyclic chemistry.

Preparation and structure

Thioamides are typically prepared by treating amides with phosphorus sulfides such as phosphorus pentasulfide and, in more specialized applications, Lawesson's reagent.²³ An alternative route entails the reaction of nitriles with hydrogen sulfide. The Willgerodt-Kindler reaction reaction also affords benzylthioamides.⁴

Thioamides in biochemistry and medicine

Thioamides are also a class of drugs which are used to control thyrotoxicosis.

Thioamides have been incorporated into peptides as isosters for the amide bond. Peptide modifications are analogoues of the native peptide, which can reveal the structure-activity-relationship (SAR). Analogoues of peptides can also be used as drugs with an improved oral bioavailability. Thioamides inhibit the enzyme thyroid peroxidase in the thyroid, reducing the synthesis of triiodothyronine (T3) and thyroxine (T4); block uptake of iodotyrosines from the colloid. They also block iodine release from peripheral hormone. Maximum effects occur only after a month since hormone depletion is caused by reduced synthesis, which is a slow process.

An adverse effect of thioamides is that they penetrate the placental barrier, thus caution is advised when used during pregnancy. 10% of patients report skin eruptions (such as macules and papules), Urticaria, Dermatitis, Fever, and Arthralgia.^{citation needed} 0.03% of all patients develop agranulocytosis, a dangerous side-effect.

Members of the thioamide group include Methimazole, Carbimazole converted in vivo to methimazole, and Propylthiouracil

References

1. ^ Kenneth B. Wiberg, Paul R. Rablen (1995). "Why Does Thioformamide Have a Larger Rotational Barrier Than Formamide?". J. Am. Chem. Soc. 117 (8): 2201-2209. 
2. ^ R. Gompper, W. Elser (1973). "2-Methylmercapto-N-Methyl-Δ2-Pyrroline". Org. Synth.; Coll. Vol. 5: 780. 
3. ^ George Schwarz (1955). "2,4-Dimethylthiazole" Organic Syntheses". Org. Synth.; Coll. Vol. 3: 332. 
4. ^ Andreas Rolfs and Jürgen Liebscher (1998). "3-Morpholino-2-Phenylthioacrylic Acid Morpholide and 5-(4-Bromobenzoyl-2-(4-Morpholino)-3-Phenylthiophene". Org. Synth.; Coll. Vol. 9: 99.