Full structural formula
Skeletal formula with numbers
Ball-and-stick model
Space-filling model
Preferred IUPAC name
Other names
3D model (JSmol)
ECHA InfoCard 100.005.475 Edit this at Wikidata
  • InChI=1S/C3H3NS/c1-2-5-3-4-1/h1-3H checkY
  • InChI=1/C3H3NS/c1-2-5-3-4-1/h1-3H
  • n1ccsc1
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 their standard state (at 25 °C [77 °F], 100 kPa).
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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.[2] The thiazole ring is notable as a component of the vitamin thiamine (B1).

Molecular and electronic structure[]

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 (between 7.27 and 8.77 ppm), 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.

Thiazole electron densities and numbering scheme

Occurrence of thiazoles and thiazolium salts[]

Bleomycin is a thiazole-containing anti-cancer drug.

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 (i.e. molecules that mimic the function and structure of peptides).[3]

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 drug Meloxicam. The following anthroquinone 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 dyeing cotton.

Organic synthesis[]

Various laboratory methods exist for the organic synthesis of thiazoles. Prominent is the Hantzsch thiazole synthesis is a reaction between haloketones and thioamides. For example, 2,4-dimethylthiazole is synthesized from thioacetamide and chloroacetone.[4][5] Another example [6] is given below:

Hantsch Thiazole Synthesis


Thiazoles are generally formed via reactions of cysteine, 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.[7] 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 than imidazole (pKa =7).[8]

Deprotonation at C2: the negative charge on this position is stabilized as an ylide; Hauser bases and organolithium compounds react at this site, replacing the proton

Thiazole deprotonation

2-(trimethylsiliyl)thiazole [9] (with a trimethylsilyl group in the 2-position) is a stable substitute and reacts with a range of electrophiles such as aldehydes, acyl halides, and ketenes
Thiazole bromination
Thiazole Nucleophilic Aromatic Substitution
Thiazole oxidation
Thiazole cycloaddition

Thiazolium salts[]

Alkylation of thiazoles at nitrogen forms a thiazolium cation. Thiazolium salts are catalysts in the Stetter reaction and the Benzoin condensation. Deprotonation of N-alkyl thiazolium salts give the free carbenes[11] and transition metal carbene complexes.

Structure of thiazoles (left) and thiazolium salts (right)

Alagebrium is a thiazolium-based drug.


  1. ^ Zoltewicz, J. A.; Deady, L. W. (1978). Quaternization of Heteroaromatic Compounds. Quantitative Aspects. Advances in Heterocyclic Chemistry. Vol. 22. pp. 71–121. doi:10.1016/S0065-2725(08)60103-8. ISBN 9780120206223.
  2. ^ Eicher, T.; Hauptmann, S. (2003). The Chemistry of Heterocycles: Structure, Reactions, Syntheses, and Applications. ISBN 978-3-527-30720-3.
  3. ^ Mak, Jeffrey Y. W.; Xu, Weijun; Fairlie, David P. (2015-01-01). Peptidomimetics I (PDF). Topics in Heterocyclic Chemistry. Vol. 48. Springer Berlin Heidelberg. pp. 235–266. doi:10.1007/7081_2015_176. ISBN 978-3-319-49117-2.
  4. ^ J. R. Byers; J. B. Dickey (1939). "2-Amino-4-methylthiazole". Organic Syntheses. 19: 10. doi:10.15227/orgsyn.019.0010.
  5. ^ George Schwarz (1945). "2,4-Dimethylthiazole". Organic Syntheses. 25: 35. doi:10.15227/orgsyn.025.0035.
  6. ^ a b Alajarín, M.; Cabrera, J.; Pastor, A.; Sánchez-Andrada, P.; Bautista, D. (2006). "On the [2+2] Cycloaddition of 2-Aminothiazoles and Dimethyl Acetylenedicarboxylate. Experimental and Computational Evidence of a Thermal Disrotatory Ring Opening of Fused Cyclobutenes". J. Org. Chem. 71 (14): 5328–5339. doi:10.1021/jo060664c. PMID 16808523.
  7. ^ Kriek, M.; Martins, F.; Leonardi, R.; Fairhurst, S. A.; Lowe, D. J.; Roach, P. L. (2007). "Thiazole Synthase from Escherichia coli: An Investigation of the Substrates and Purified Proteins Required for Activity in vitro" (PDF). J. Biol. Chem. 282 (24): 17413–17423. doi:10.1074/jbc.M700782200. PMID 17403671.
  8. ^ Thomas L. Gilchrist "Heterocyclic Chemistry" 3rd ed. Addison Wesley: Essex, England, 1997. 414 pp. ISBN 0-582-27843-0.
  9. ^ a b Dondoni, A.; Merino, P. (1995). "Diastereoselective Homologation of D-(R)-Glyceraldehyde Acetonide using 2-(Trimethylsilyl)thiazole". Organic Syntheses. 72: 21.{{cite journal}}: CS1 maint: multiple names: authors list (link); Collective Volume, vol. 9, p. 952
  10. ^ Amir, E.; Rozen, S. (2006). "Easy Access to the Family of Thiazole N-oxides using HOF·CH3CN". Chemical Communications. 2006 (21): 2262–2264. doi:10.1039/b602594c. PMID 16718323.
  11. ^ Arduengo, A. J.; Goerlich, J. R.; Marshall, W. J. (1997). "A Stable Thiazol-2-ylidene and Its Dimer". Liebigs Annalen. 1997 (2): 365–374. doi:10.1002/jlac.199719970213.