2-Mercaptopyridine

Preparation

2-Mercaptopyridine was originally synthesized in 1931 by heating 2-chloropyridine with calcium hydrogen sulfide. :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.

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.

Structure and properties

Similar 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 thiol is favored at lower temperatures, lower concentrations, and in less polar solvents. 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.

The association constant for this reaction between mutual 2-mercaptopyridines is described below. The ratio is of monosulfide to disulfide in chloroform. :Kassociation = (2.7±0.5)x103

Reactions

2-Mercaptopyridine oxidizes to 2,2'-dipyridyl disulfide. As amines are good catalysts for the oxidation of thiols to disulfides, this process is autocatalytic. :[[File:2-mercaptopyridine self association.png|600px|class=skin-invert-image]]

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 precursors to the chelating ligand . This anion forms the indium(III) complex In(PyS)3 complex. 2-Mercaptopyridine has also been investigated as a reagent to purify plasmid DNA of impurities such as RNA and proteins at relatively quick timescales to similar methods. 2-Mercaptopyridine is also used acylate phenols, amines, and carboxylic acids.

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.

References

References

1. (2007). "Encyclopedia of Reagents for Organic Synthesis".
2. (1931). "Mercaptane und Sulfosäuren des Pyridins. XII. Mitteilung über Derivate des Pyridins". Justus Liebig's Annalen der Chemie.
3. (1958). "721. Tautomeric pyridines. Part I. Pyrid-2- and -4-thione". Journal of the Chemical Society (Resumed).
4. (2009). "An efficient and direct synthesis of 2-thiopyridinesviamicrowave-assisted three-component reaction". Journal of Heterocyclic Chemistry.
5. (2002). "2-Pyridinethiol/2-Pyridinethione Tautomeric Equilibrium. A Comparative Experimental and Computational Study". The Journal of Organic Chemistry.
6. (1980). "Displacement of protomeric equilibriums by self-association: hydroxypyridine-pyridone and mercaptopyridine-thiopyridone isomer pairs". The Journal of Organic Chemistry.
7. (2004). "Quinoline-2(1 ''H'' )-thione, a structure with ''Z'' ′ = 8". Acta Crystallographica Section C Crystal Structure Communications.
8. (2008). "Effect of various chelating agents on supercritical carbon dioxide extraction of indium(III) ions from acidic aqueous solution". Journal of Hazardous Materials.
9. (2007). "Biporous polymeric microspheres coupled with mercaptopyridine for rapid chromatographic purification of plasmid DNA". Journal of Applied Polymer Science.
10. Rochette, Étienne. (2019-08-07). "Isodesmic C–H Borylation: Perspectives and Proof of Concept of Transfer Borylation Catalysis". Journal of the American Chemical Society.