The alternative strategy is to form the mercaptan before introducing the N-oxide moiety. 2-Mercaptopyridine was originally synthesized in 1931 by heating 2-chloropyridine with calcium hydrosulfide,[6] an approach similar that first used to prepare pyrithione.[8] The analogous thiourea approach via a uronium salt was reported in 1958 and provides a more convenient route to 2-mercaptopyridine.[7] Oxidation to the N-oxide can then be undertaken.
The disulfide dipyrithione, 2,2'-dithiobis(pyridine-N-oxide)
Dipyrithione is used as a fungicide and bactericide,[8] and has been reported to possess novel cytotoxic activity by inducing apoptosis.[21] However, as apoptosis only occurs in higher organisms, this mechanism isn't relevant to the antifungal and bacteric idal properties of pyrithione.
Properties
Tautomerisation of the sodium salt of pyrithione (thione form on the left, thiolate form on the right)
Pyrithione exists as a pair of prototropes, a form of tautomerism whereby the rapid interconversion of constitutional isomers involves the shift of a single proton, in this case between the sulfur and oxygen atoms (shown in the infobox above).[3][22][23]
Salts of the conjugate base of pyrithione can also be considered to exhibit tautomerism by notionally associating the sodium ion with whichever heteroatom bears the negative charge of the anion (as opposed to the formal charges associated with the N-oxide); however, considering the anion alone, this could also be described as an example of resonance.
Pyrithione can be used as a source of hydroxyl radical in organic synthesis[24] as it photochemically decomposes to HO• and (pyridin-2-yl)sulfanyl radical.[25]
Applications
Structures of 1:2 complexes of zinc and the conjugate base of pyrithione Top: Structural formula of the monomer Bottom: Ball-and-stick model of the dimer
The conjugate base of pyrithione (pyrithionate ion) is an anion containing two donor atoms, a sulfur atom and an oxygen atom each bearing a negative formal charge; the nitrogen atom remains formally positively charged. The thiolate anion can be formed by reaction with sodium carbonate, and zinc pyrithione is formed when zinc chloride is added.[10] The anion can act as either a monodentate or bidentateligand and forms a 1:2 complex with a zinc(II) metal centre. Zinc pyrithione has been used since the 1930s though its preparation was not disclosed until a 1955 British patent[13] in which pyrithione was reacted directly with hydrated zinc sulfate in ethanol.[9] In its monomeric form, zinc pyrithione has two of the anions chelated to a zinc centre with a tetrahedral geometry. In the solid state, it forms a dimer in which each zinc centre adopts a trigonal bipyramidal geometry with two of the anions acting as bridging ligands coordinated through the oxygen atoms in the axial positions.[26] In solution, the dimers dissociate via scission of zinc-oxygen bonds to each bridging ligand. Further dissociation of the monomer into its constituents can occur and is undesirable as the complex is more potent in medical applications; for this reason, zinc carbonate can be added to formulations as it inhibits the monomer dissociation.[27]
1 2 USgranted 2809971,Bernstein, Jack&Losee, Kathryn A.,"Heavy-metal derivatives of 1-hydroxy-2-pyridinethiones and method of preparing same",published 1957-10-15, assigned to Olin MathiesonArchived 2016-12-24 at the Wayback Machine
1 2 USgranted 4396766,Farmer, David A.&Katz, Lawrence E.,"Process for producing sodium and zinc pyrithione",published 1983-08-02, assigned to Olin Corporation
1 2 Chernoff, Karen; Lin, Richie; Cohen, Steven R. (2014). "Seborrheic Dermatitis". In Rudikoff, Donald; Cohen, Steven R.; Scheinfeld, Noah (eds.). Atopic Dermatitis and Eczematous Disorders. CRC Press. pp.275–288. ISBN9781840766530. Archived from the original on 2024-02-24. Retrieved 2024-02-24.
↑ Shaw, Elliott; Bernstein, Jack; Losee, Kathryn; Lott, W. A. (1950). "Analogs of Aspergillic Acid. IV. Substituted 2-Bromopyridine-N-oxides and Their Conversion to Cyclic Thiohydroxamic Acids". J. Am. Chem. Soc.72 (10): 4362–4364. Bibcode:1950JAChS..72.4362S. doi:10.1021/ja01166a008.
1 2 Cheng, Hefeng; She, Ji (1990). "14. Improved preparation of 2-mercaptopyridine-N-oxide". Zhongguo Yiyao Gongye Zazhi. 21 (2): 55–56.
↑ Block, Eric; Dane, A. John; Cody, Robert B. (2011). "Crushing Garlic and Slicing Onions: Detection of Sulfenic Acids and Other Reactive Organosulfur Intermediates from Garlic and Other Alliums using Direct Analysis in Real-Time Mass Spectrometry (DART-MS)". Phosphorus Sulfur. 186 (5): 1085–1093. doi:10.1080/10426507.2010.507728. S2CID98520689.
↑ Smith, Michael B. (2013). March's Advanced Organic Chemistry (7thed.). Wiley. p.246. ISBN978-0-470-46259-1.
↑ DeMatteo, Matthew P.; Poole, James S.; Shi, Xiaofeng; Sachdeva, Rakesh; Hatcher, Patrick G.; Hadad, Christopher M.; Platz, Matthew S. (2005). "On the Electrophilicity of Hydroxyl Radical: A Laser Flash Photolysis and Computational Study". Journal of the American Chemical Society. 127 (19): 7094–7109. Bibcode:2005JAChS.127.7094D. doi:10.1021/ja043692q. ISSN0002-7863. PMID15884952.
↑ Barnett, B. L.; Kretschmar, H. C.; Hartman, F. A. (1977). "Structural characterization of bis(N-oxopyridine-2-thionato)zinc(II)". Inorg. Chem.16 (8): 1834–1838. doi:10.1021/ic50174a002.
↑ Bacon, Robert A.; Mizoguchi, Haruko; Schwartz, James R. (2014). "Assessing therapeutic effectiveness of scalp treatments for dandruff and seborrheic dermatitis, part 1: A reliable and relevant method based on the adherent scalp flaking score (ASFS)". J. Dermatolog. Treat.25 (3): 232–236. doi:10.3109/09546634.2012.687089. PMID22515728. S2CID30707098.
↑ USpatent 4039312,Joseph, Marcel&Patru, Gaston,"Bacteriostatic, fungistatic and algicidal compositions, particularly for submarine paints",published 1977-08-02, assigned to Joseph, Marceland Patru, Gaston
This page is based on this Wikipedia article Text is available under the CC BY-SA 4.0 license; additional terms may apply. Images, videos and audio are available under their respective licenses.