Thiazole, or 1,3-thiazole, is a heterocyclic compound that contains both sulfur and nitrogen; the term 'thiazole' also refers to a large family of derivatives. Thiazole itself is a pale yellow liquid with a pyridine-like odor and the molecular formula C3H3NS. The thiazole ring is notable as a component of the vitaminthiamine.
Thiazoles are members of the azoles, heterocycles that include imidazoles and oxazoles. Thiazole can also be considered a functional group. Oxazoles are related compounds, with sulfur replaced by oxygen. Thiazoles are structurally similar to imidazoles, with the thiazole sulfur replaced by nitrogen. Thiazole rings are planar and aromatic. Thiazoles are characterized by larger pi-electron delocalization than the corresponding oxazoles and have therefore greater aromaticity. This aromaticity is evidenced by the chemical shift of the ring protons in proton NMR spectroscopy, clearly indicating a strong diamagnetic ring current. The calculated pi-electron density marks C5 as the primary site for electrophilic substitution, and C2 as the site for nucleophilic substitution.
Occurrence of thiazoles and thiazolium salts
Thiazoles are found in a variety of specialized products, often fused with benzene derivatives, the so-called benzothiazoles. In addition to vitamin B1, the thiazole ring is found in epothilone. Other important thiazole derivatives are benzothiazoles, for example, the firefly chemical luciferin. Whereas thiazoles are well represented in biomolecules, oxazoles are not. It is found in naturally occurring peptides, and utilised in the development of peptidomimetics. Commercial significant thiazoles include mainly dyes and fungicides. Thifluzamide, Tricyclazole, and Thiabendazole are marketed for control of various agricultural pests. Another widely used thiazole derivative is the non-steroidal anti-inflammatory drugMeloxicam. The following anthroquinone dyes contain benzothiazole subunits: Algol Yellow 8, Algol Yellow GC, Indanthren Rubine B, Indanthren Blue CLG. These thiazole dye are used for dyeing cotton.
Organic synthesis
Various laboratory methods exist for the organic synthesis of thiazoles.
Certain thiazoles can be accessed through application of the Herz reaction.
Biosynthesis
Several biosynthesis routes lead to the thiazole ring as required for the formation of thiamine. Sulfur of the thiazole is derived from cysteine. In anaerobic bacteria, the CN group is derived from dehydroglycine.
Reactions
The reactivity of a thiazole can be summarized as follows:
Organic oxidation at nitrogen gives the aromatic thiazole N-oxide; many oxidizing agents exist, such as mCPBA; a novel one is hypofluorous acid prepared from fluorine and water in acetonitrile; some of the oxidation takes place at sulfur, leading to non-aromatic sulfoxide/sulfone:
Thiazoles can react in cycloadditions, but in general at high temperatures due to favorable aromatic stabilization of the reactant; Diels-Alder reactions with alkynes are followed by extrusion of sulfur, and the endproduct is a pyridine; in one study, a very mild reaction of a 2-thiazole with dimethyl acetylenedicarboxylate to a pyridine was found to proceed through a zwitterionic intermediate in a formal cycloaddition to a cyclobutene, then to a 1,3-thiazepine in a 4-electron electrocyclic ring openening and then to a 7-thia-2-azanorcaradiene in a 6-electron electrocyclic ring, closing before extruding the sulfur atom.
