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| Names | |||
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| Preferred IUPAC name 1,3-Thiazole | |||
| Other names Thiazole | |||
| Identifiers | |||
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3D model (JSmol) | |||
| ChEBI | |||
| ChEMBL | |||
| ChemSpider |
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| ECHA InfoCard | 100.005.475 | ||
| UNII | |||
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| Properties | |||
| C3H3NS | |||
| Molar mass | 85.12 g·mol−1 | ||
| Boiling point | 116 to 118 °C (241 to 244 °F; 389 to 391 K) | ||
| Acidity (pKa) | 2.5 (of conjugate acid)[1] | ||
| −50.55·10−6 cm3/mol | |||
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |||
Thiazole (/ˈθaɪ.əzoʊl/), or1,3-thiazole, is a 5-memberedheterocyclic 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 apyridine-like odor and the molecular formula C3H3NS.[2] The thiazole ring is notable as a component of thevitaminthiamine (B1).
Thiazoles are members of theazoles, heterocycles that includeimidazoles andoxazoles. Thiazole can also be considered afunctional group when part of a larger molecule.
Being planar thiazoles are characterized by significant pi-electrondelocalization and have some degree ofaromaticity, more so than the correspondingoxazoles. This aromaticity is evidenced by the1H NMR chemical shift of the ring protons, which absorb between 7.27 and 8.77 ppm, indicating a strongdiamagnetic ring current. The calculated pi-electron density marks C5 as the primary site for electrophilic substitution, and C2-H as susceptible to deprotonation.
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 inepothilone. Other important thiazole derivatives arebenzothiazoles, for example, the firefly chemicalluciferin. Whereas thiazoles are well represented inbiomolecules, oxazoles are not. It is found in naturally occurring peptides, and utilised in the development of peptidomimetics (i.e. molecules that mimic the function and structure of peptides).[3]
Commercial significant thiazoles include mainly dyes andfungicides. Thifluzamide, Tricyclazole, andThiabendazole are marketed for control of various agricultural pests. Another widely used thiazole derivative is the non-steroidal anti-inflammatory drugMeloxicam. The followinganthroquinone dyes contain benzothiazole subunits: Algol Yellow 8 (CAS# [6451-12-3]), Algol Yellow GC (CAS# [129-09-9]), Indanthren Rubine B (CAS# [6371-49-9]), Indanthren Blue CLG (CAS# [6371-50-2], and Indanthren Blue CLB (CAS#[6492-78-0]). These thiazole dye are used for dyeingcotton.
Various laboratory methods exist for theorganic synthesis of thiazoles. Prominent is the Hantzsch thiazole synthesis, which is a reaction betweenhaloketones andthioamides. For example, 2,4-dimethylthiazole is synthesized fromthioacetamide andchloroacetone.[4] In theCook-Heilbron synthesis, thiazoles arise by the condensation of α-aminonitrile withcarbon disulfide. Thiazoles can be accessed by acylation of 2-aminothiolates, often available by theHerz reaction.
Thiazoles are generally formed via reactions ofcysteine, which provides the N-C-C-S backbone of the ring. Thiamine does not fit this pattern however. Several biosynthesis routes lead to the thiazole ring as required for the formation of thiamine.[5] Sulfur of the thiazole is derived from cysteine. In anaerobic bacteria, the CN group is derived from dehydroglycine.
With a pKa of 2.5 for the conjugate acid, thiazoles are far less basic thanimidazole (pKa =7).[6]
Deprotonation with strong bases occurs at C2-H. The negative charge on this position is stabilized as anylide.Hauser bases andorganolithium compounds react at this site, replacing the proton. 2-Lithiothiazoles are also generated by metal-halogen exchange from 2-bromothiazole.[7]
Electrophilic aromatic substitution at C5 but requireactivating groups such as amethyl group, as illustrated inbromination:
Oxidation at nitrogen gives the aromatic thiazoleN-oxide; many oxidizing agents exist, such asmCPBA; a novel one ishypofluorous acid prepared fromfluorine and water inacetonitrile; some of the oxidation takes place at sulfur, leading to non-aromaticsulfoxide/sulfone:[8] ThiazoleN-oxides are useful in Palladium-catalysed C-H arylations, where theN-oxide is able to shift the reactivity to reliably favor the 2-position, and allows for these reactions to be carried out under much more mild conditions.[9]
Alkylation of thiazoles at nitrogen forms athiazolium cation. Thiazolium salts are catalysts in theStetter reaction and theBenzoin condensation. Deprotonation ofN-alkyl thiazolium salts give thefree carbenes[11] andtransition metal carbene complexes.
Alagebrium is a thiazolium-based drug.
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