Benzothiazole

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Benzothiazole
Benzothiazole numbering.png
Space filling model of benzothiazole Benzothiazole-space-filling.png
Space filling model of benzothiazole
Ball-and-stick model of benzothiazole Benzothiazole-ball-and-stick.png
Ball-and-stick model of benzothiazole
Names
Preferred IUPAC name
1,3-Benzothiazole
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.002.179 OOjs UI icon edit-ltr-progressive.svg
PubChem CID
UNII
  • InChI=1S/C7H5NS/c1-2-4-7-6(3-1)8-5-9-7/h1-5H Yes check.svgY
    Key: IOJUPLGTWVMSFF-UHFFFAOYSA-N Yes check.svgY
  • InChI=1/C7H5NS/c1-2-4-7-6(3-1)8-5-9-7/h1-5H
    Key: IOJUPLGTWVMSFF-UHFFFAOYAC
  • n1c2ccccc2sc1
Properties
C7H5NS
Molar mass 135.1863 g/mol
Appearancecolorless liquid
Density 1.238 g/mL
Melting point 2 °C (36 °F; 275 K)
Boiling point 227 to 228 °C (441 to 442 °F; 500 to 501 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Benzothiazole, or more specifically 1,3-benzothiazole, is an aromatic heterocyclic compound with the chemical formula C
7H
5NS. It is colorless, slightly viscous liquid. Although the parent compound, benzothiazole is not widely used, many of its derivatives are found in commercial products or in nature. Firefly luciferin can be considered a derivative of benzothiazole. [1] It has a sulfurous odor and meaty flavor. [2]

Contents

The three structural isomers of benzothizaole are 1,3-benzothiazole, 1,2-benzothiazole and 2,1-benzothiazole.

Structure and reactivity

Benzothiazoles consist of a 5-membered 1,3-thiazole ring fused to a benzene ring. The nine atoms of the bicycle and the attached substituents are coplanar. The heterocyclic core of the molecule is readily substituted at the methyne (CH) centre in the thiazole ring. Thiazole is electron-withdrawing.

Synthesis and biosynthesis

Benzothiazoles are typically prepared by treatment of 2-mercaptoaniline. [3] For example, acid chlorides are effective: [4]

C6H4(NH2)SH + RC(O)Cl → C6H4(N)SCR + HCl + H2O

Many other precursors have been used, commonly aldehydes in the presence of oxidants. In some cases, benzothiazoles are prepared directly from anilines, a process that entails ortho functionalization. [5]

Naturally occurring benzothiazoles are proposed to arise by condensation of cysteine with quinones. [1]

Uses

Dyes

The dye thioflavin is a benzothiazole derivative. [6]

Food additives

Benzothiazole occurs naturally in some foods but is also used as a food additive. [1] It has a sulfurous odor and meaty flavor. [7] The European Food Safety Authority assessment had "no safety concern at estimated levels of intake as a flavouring substance". [8]

Rubber additive

Accelerators for the sulfur vulcanization of rubber are based on 2-mercaptobenzothiazoles. [9]

Pharmacology

Ziprasidone is used to treat schizophrenia and bipolar disorder. Ziprasidone.svg
Ziprasidone is used to treat schizophrenia and bipolar disorder.

Benzothiazoles have been widely investigated for their bioactivity. [10] [11] The benzothiazole moiety is, for example, seen in certain dopamine-acting drugs, e.g. riluzole and pramipexole. Moreover, benzothiazole derivatives act as monoamine oxidase inhibitors or dopamine antagonists:

See also

Safety and environmental considerations

Benzothiazoles are widely used in the vulcanization of rubber, so their possible role in the environment has attracted attention. Evidence suggests that they biodegrade readily. [17]

References

  1. 1 2 3 Le Bozec, Lucille; Moody, Christopher J. (2009). "Naturally Occurring Nitrogen–Sulfur Compounds. The Benzothiazole Alkaloids". Australian Journal of Chemistry. 62 (7): 639. doi:10.1071/CH09126.
  2. ↑ "Benzothiazole". The Good Scents Company. Retrieved 2020-10-06.
  3. ↑ Gill, Rupinder K.; Rawal, Ravindra K.; Bariwal, Jitender (2015). "Recent Advances in the Chemistry and Biology of Benzothiazoles". Archiv der Pharmazie. 348 (3): 155–178. doi:10.1002/ardp.201400340. PMID   25682746.
  4. ↑ T. E. Gilchrist "Heterocyclic Chemistry" 3rd Edition, Longman, 1992.
  5. ↑ Würfel, Hendryk; Jakobi, Dörthe (2018). "Syntheses of Substituted 2-Cyano-benzothiazoles". Organic Syntheses. 95: 177–191. doi:10.15227/orgsyn.095.0177.
  6. ↑ Gill, Rupinder K.; Rawal, Ravindra K.; Bariwal, Jitender (2015). "Recent Advances in the Chemistry and Biology of Benzothiazoles". Archiv der Pharmazie. 348 (3): 155–178. doi: 10.1002/ardp.201400340 . PMID   25682746. S2CID   10421792.
  7. ↑ "Benzothiazole". The Good Scents Company. Retrieved 2020-10-06.
  8. ↑ "Flavouring Group Evaluation 76, (FGE.76) - Consideration of sulphur-containing heterocyclic compounds evaluated by JECFA (59th meeting) structurally related to thiazoles, thiophene, thiazoline and thienyl derivatives from chemical group 29, miscellaneous". EFSA Journal. 6 (11): 875. 2008. doi: 10.2903/j.efsa.2008.875 .
  9. ↑ Engels, Hans-Wilhelm; Weidenhaupt, Herrmann-Josef; Pieroth, Manfred; Hofmann, Werner; Menting, Karl-Hans; Mergenhagen, Thomas; Schmoll, Ralf; Uhrlandt, Stefan (2004), "Rubber, 4. Chemicals and Additives", Ullmann's Encyclopedia of Industrial Chemistry, doi:10.1002/14356007.a23_365.pub2, ISBN   3-527-30673-0
  10. ↑ Rouf, Abdul; Tanyeli, Cihangir (2015). "Bioactive thiazole and benzothiazole derivatives". European Journal of Medicinal Chemistry. 97: 911–927. doi:10.1016/j.ejmech.2014.10.058. PMID   25455640.
  11. ↑ Keri, Rangappa S.; Patil, Mahadeo R.; Patil, Siddappa A.; Budagumpi, Srinivasa (2015). "A comprehensive review in current developments of benzothiazole-based molecules in medicinal chemistry". European Journal of Medicinal Chemistry. 89: 207–251. doi:10.1016/j.ejmech.2014.10.059. PMID   25462241.
  12. ↑ le Roux, Anandie; Petzer, Anél; Cloete, Stephanus J.; Petzer, Jacobus P. (2025-03-01). "An investigation of the monoamine oxidase inhibition properties of benzothiazole derivatives". Results in Chemistry. 14: 102142. doi: 10.1016/j.rechem.2025.102142 . ISSN   2211-7156.
  13. ↑ Acar Çevik, Ulviye; Osmaniye, Derya; Sağlik, Begüm N.; Levent, Serkan; K. Çavuşoğlu, Betül; Karaduman, Abdullah B.; D. Özkay, Ümide; Özkay, Yusuf; Kaplancikli, Zafer A.; Turan, Gülhan (2020). "Synthesis of new benzothiazole derivatives bearing thiadiazole as monoamine oxidase inhibitors". Journal of Heterocyclic Chemistry. 57 (5): 2225–2233. doi:10.1002/jhet.3942. ISSN   1943-5193.
  14. ↑ Turan, Gülhan; Osmaniye, Derya; Sağlik, Begüm Nurpelin; Çevik, Ulviye Acar; Levent, Serkan; Çavuşoğlu, Betül Kaya; Özkay, Ümide Demir; Özkay, Yusuf; Kaplancikli, Zafer Asım (2020-06-02). "Synthesis and monoamine oxidase A/B inhibitory evaluation of new benzothiazole-thiazolylhydrazine derivatives". Phosphorus, Sulfur, and Silicon and the Related Elements. 195 (6): 491–497. doi:10.1080/10426507.2020.1722667. ISSN   1042-6507.
  15. ↑ Boateng, Comfort A.; Nilson, Ashley N.; Placide, Rebekah; Pham, Mimi L.; Jakobs, Franziska M.; Boldizsar, Noelia; McIntosh, Scot; Stallings, Leia S.; Korankyi, Ivana V.; Kelshikar, Shreya; Shah, Nisha; Panasis, Diandra; Muccilli, Abigail; Ladik, Maria; Maslonka, Brianna (2023-09-14). "Pharmacology and Therapeutic Potential of Benzothiazole Analogues for Cocaine Use Disorder". Journal of Medicinal Chemistry. 66 (17): 12141–12162. doi:10.1021/acs.jmedchem.3c00734. ISSN   0022-2623. PMC   10510399 . PMID   37646374.
  16. ↑ Sampson, Dinithia; Zhu, Xue Y.; Eyunni, Suresh V. K.; Etukala, Jagan R.; Ofori, Edward; Bricker, Barbara; Lamango, Nazarius S.; Setola, Vincent; Roth, Bryan L.; Ablordeppey, Seth Y. (2014-06-15). "Identification of a new selective dopamine D4 receptor ligand". Bioorganic & Medicinal Chemistry. 22 (12): 3105–3114. doi:10.1016/j.bmc.2014.04.026. ISSN   0968-0896. PMC   4096627 . PMID   24800940.
  17. ↑ Clarke, Bradley O.; Smith, Stephen R. (2011). "Review of 'emerging' organic contaminants in biosolids and assessment of international research priorities for the agricultural use of biosolids". Environment International. 37 (1): 226–247. Bibcode:2011EnInt..37..226C. doi:10.1016/j.envint.2010.06.004. PMID   20797791.
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