2-Mercaptopyridine is an organosulfur compound with the formula HSC5H4N. This yellow crystalline solid is a derivative of pyridine. The compound and its derivatives serve primarily as acylating agents. A few of 2-mercaptopyridine's other uses include serving as a protecting group for amines and imides as well as forming a selective reducing agent. 2-Mercaptopyridine oxidizes to [[2,2′-dipyridyl disulfide]].[1]
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| Preferred IUPAC name
Pyridine-2-thiol | |||
| Other names
2-Thiopyridine
2-Thiopyridone Pyrid-2-thione 2-Pyridyl mercaptan 2-Pyridinethiol 2-Pyridinethione | |||
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| 105787 | |||
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| Properties | |||
| C5H5NS | |||
| Molar mass | 111.16 g·mol−1 | ||
| Appearance | yellow crystalline powder | ||
| Melting point | 128 to 130 °C (262 to 266 °F; 401 to 403 K) | ||
| 50 g/L | |||
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| GHS labelling: | |||
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| Warning | |||
| H315, H319, H335 | |||
| P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, P501 | |||
| Safety data sheet (SDS) | MSDS | ||
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Preparation
edit2-Mercaptopyridine was originally synthesized in 1931 by heating 2-chloropyridine with calcium hydrogen sulfide.[2]
- ClC5H4N + Ca(SH)2 → HSC5H4N + Ca(SH)Cl
A more convenient route to 2-mercaptopyridine is the reaction of 2-chloropyridine and thiourea in ethanol and aqueous ammonia.[3]
2-Mercaptopyridine derivatives can also be generated from precursors lacking preformed pyridine rings. It arises for example in the condensation of α,β-unsaturated ketones, malononitrile, and 4-methylbenzenethiol under microwave irradiation. The reaction is conducted with a base catalyst.[4]
Structure and properties
editSimilar in nature to 2-hydroxypyridine, 2-mercaptopyridine converts to the thione (or more accurately thioamide) tautomer. The preferred form is dependent on temperature, concentration, and solvent. The thione is favored at lower temperatures, lower concentrations, and in less polar solvents.[5][6] 2-Mercaptopyridine is favored in dilute solutions and in solvents capable of hydrogen bonding. These solvents will compete with other 2-mercaptopyridines to prevent self association.[6]
The association constant for this reaction between mutual 2-mercaptopyridines is described below. The ratio is of monosulfide to disulfide in chloroform.[6]
- Kassociation = (2.7±0.5)x103
Reactions
edit2-Mercaptopyridine oxidizes to 2,2'-dipyridyl disulfide. As amines are good catalysts for the oxidation of thiols to disulfides, this process is autocatalytic.
2-Mercaptopyridine can also be prepared by hydride reduction of 2,2'-dipyridyl disulfide.
- C5H4NSSC5H4N + 2H → 2HSC5H4N
Main reactions
edit2-Mercaptopyridine and the disulfide are chelating ligands. 2-mercaptopyridine forms the indium(III) complex In(PyS)3 complexes in supercritical carbon dioxide.[7] 2-Mercaptopyridine may also be used to coat porous media in order to purify plasmid DNA of impurities such as RNA and proteins at relatively quick timescales to similar methods.[8] 2-Mercaptopyridine is also used acylate phenols, amines, and carboxylic acids.[1]
Another application lies in metal-free catalysis: 2-mercaptopyridine can be used as a catalyst for isodesmic C-H borylation of heteroarenes. The particular pattern of Lewis base and Brønsted acid allows to cleave boron-carbons bonds and then form a new boron-carbon bond by lewis pair mediated C-H activation.[9]
References
edit- ^ a b Adams, Edward J.; Skrydstrup, Troels; Lindsay, Karl B.; Skrydstrup, Troels; Lindsay, Karl B. (2007). "2-Pyridinethiol". Encyclopedia of Reagents for Organic Synthesis. doi:10.1002/047084289X.rp286.pub3. ISBN 978-0471936237.
- ^ Räth, C.; Binz, A.; Räth, C. (1931). "Mercaptane und Sulfosäuren des Pyridins. XII. Mitteilung über Derivate des Pyridins". Justus Liebig's Annalen der Chemie. 487: 105–119. doi:10.1002/jlac.19314870107.
- ^ Jones, R. A.; Katritzky, A. R. (1958). "721. Tautomeric pyridines. Part I. Pyrid-2- and -4-thione". Journal of the Chemical Society (Resumed): 3610. doi:10.1039/JR9580003610.
- ^ Wang, Xing-Han; Cao, Xu-Dong; Tu, Shu-Jiang; Zhang, Xiao-Hong; Hao, Wen-Juan; Yan, Shu; Wu, Shan-Shan; Han, Zheng-Guo; Shi, Feng (2009). "An efficient and direct synthesis of 2-thiopyridinesviamicrowave-assisted three-component reaction". Journal of Heterocyclic Chemistry. 46 (5): 886. doi:10.1002/jhet.161.
- ^ Moran, Damian; Sukcharoenphon, Kengkaj; Puchta, Ralph; Schaefer, Henry F.; Schleyer, Paul v. R.; Hoff, Carl D. (2002). "2-Pyridinethiol/2-Pyridinethione Tautomeric Equilibrium. A Comparative Experimental and Computational Study". The Journal of Organic Chemistry. 67 (25): 9061–9. doi:10.1021/jo0263768. PMID 12467429.
- ^ a b c Beak, Peter; Covington, Johnny B.; Smith, Stanley G.; White, J. Matthew; Zeigler, John M. (1980). "Displacement of protomeric equilibriums by self-association: hydroxypyridine-pyridone and mercaptopyridine-thiopyridone isomer pairs". The Journal of Organic Chemistry. 45 (8): 1354. doi:10.1021/jo01296a002.
- ^ Chou, Wei-Lung; Yang, Kai-Chiang (2008). "Effect of various chelating agents on supercritical carbon dioxide extraction of indium(III) ions from acidic aqueous solution". Journal of Hazardous Materials. 154 (1–3): 498–505. doi:10.1016/j.jhazmat.2007.10.052. PMID 18054158.
- ^ Li, Yuan; Dong, Xiao-Yan; Sun, Yan (2007). "Biporous polymeric microspheres coupled with mercaptopyridine for rapid chromatographic purification of plasmid DNA". Journal of Applied Polymer Science. 104 (4): 2205. doi:10.1002/app.24417.
- ^ Rochette, Étienne; Desrosiers, Vincent; Soltani, Yashar; Fontaine, Frédéric-Georges (2019-08-07). "Isodesmic C–H Borylation: Perspectives and Proof of Concept of Transfer Borylation Catalysis". Journal of the American Chemical Society. 141 (31): 12305–12311. doi:10.1021/jacs.9b04305. ISSN 0002-7863. PMID 31283206. S2CID 195844973.