2-Mercaptopyridine

2-Mercaptopyridine
Other names 2-thiopyridine; 2-thiopyridone; pyrid-2-thione; 2-pyridyl mercaptan; 2-pyridinethiol; 2-pyridinethione
Identifiers
CAS number	2637-34-5 Y
ChemSpider	2005897 Y
DrugBank	DB03329
ChEBI	CHEBI:45223 Y
ChEMBL	CHEMBL1235541 N
Jmol-3D images	Image 1
SMILES S=C1/C=C\C=C/N1
InChI InChI=1S/C5H5NS/c7-5-3-1-2-4-6-5/h1-4H,(H,6,7) Y Key: WHMDPDGBKYUEMW-UHFFFAOYSA-N Y InChI=1/C5H5NS/c7-5-3-1-2-4-6-5/h1-4H,(H,6,7) Key: WHMDPDGBKYUEMW-UHFFFAOYAE
Properties
Molecular formula	C5H5NS
Molar mass	111.16 g mol−1
Appearance	yellow crystalline powder
Melting point	128-130°C (400-403 K)
Solubility in water	50 g/L
Hazards
MSDS	MSDS
N (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

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]

Preparation

2-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

Similar in nature to 2-hydroxypyridine, 2-mercaptopyridine converts to the thione 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 oxidizes to 2,2’-dipyridyl disulfide. 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]

K_association = (2.7±0.5)x10³

2-Mercaptopyridine can also be prepared by hydride reduction of 2,2’-dipyridyl disulfide.

C₅H₄NSSC₅H₄N + 2H → 2HSC₅H₄N

Main reactions

2-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]

References

1. ^ ^{a b} Adams, Edward J.; Skrydstrup, Troels; Lindsay, Karl B.; Skrydstrup, Troels; Lindsay, Karl B. (2007). 2-Pyridinethiol. doi:10.1002/047084289X.rp286.pub3. 
2. ^ 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. doi:10.1002/jlac.19314870107. 
3. ^ 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. 
4. ^ Wang, Xing-Han; Cao, Xu-Dong; Tu, Shu-Jiang; Zhang, Xiao-Hong; Hao, Wen-Juan; Yan, Shu; Wu, Shan-Shan; Han, Zheng-Guo et al. (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. 
5. ^ 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. doi:10.1021/jo0263768. PMID 12467429. 
6. ^ ^{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. 
7. ^ 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. doi:10.1016/j.jhazmat.2007.10.052. PMID 18054158. 
8. ^ 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.