Using pyridine-2-thiones

A number of zinc compounds with organic constituents (e.g., zinc salts of organic acids) have therapeutic uses. These include antidandruff zinc pyridinethione, antifungal zinc undecylenate used to treat athlete s foot, zinc stearate and palmitate (zinc soap), and antibacterial zinc bacitracin. Zinc naphthenate is used as a low-toxicity wood preservative, and zinc phenolsulfonate has insecticidal properties and was once used as an intestinal antiseptic. The inhalation of zinc soaps by infants has been known to cause acute fatal pneumonitis characterized by lung lesions similar to, but more serious than, those caused by talc. Zinc pyridine thione (zinc 2-pyridinethiol-l-oxide) has been shown to cause retinal detachment and blindness in dogs this is an apparently species-specific effect because laboratory tests at the same and even much higher dosages in monkeys and rodents do not show the same effect. 

UV/Vis spectra of simple pyridines have also been used as the basis for the assignment of electronic transitions of more complex structures. This is demonstrated through the comparison of the spectra of the pyridine thiones 25 and thiazole thiones such as 26 <2005EJ0869>. 

Chloropyridine serves as a raw material in the production of pyridine-thiones these are manufactured by the reaction of chloropyridine with H2O2 or other peroxides, followed by a nucleophilic reaction of the N-oxide with sodium hydrogen sulfide to produce the thiol. The zinc salt is used as an active ingredient (anti-dandruff agent) in hair shampoos. 

Besides being useful precursors to pyrroles pyridine-2-ones -4-ones, -4-thiones. and -4-imines 4-alkylidene-dihydropyridines thiophenes 1,2,4-triazoles thiapyrane-2-thiones, isoquinoline-3-ones isoben-zothiophenes and 4-mercaptoimidazolium hydroxide inner salts, mesoionic thiazoles are potentially useful in the construction of molecules with herbicidic (39). central nerve stimulating, and antiinflammatory properties (40,41). Application in dye synthesis has likewise been reported (42). 

Treatment of resin-bound iminophosphorane 190 with an excess of solid CO2 and CS2 in a sealed glass tube, and with aryl isocyanates afforded 1-oxo-, 1-thioxo- 191, and l-arylimino-l//-pyrido[l,2-r ]pyrimidine-3-carboxylates 192, respectively (Scheme 13) <2001JME1011 >. Reaction of iminophosphorane 193, derived from 2-(2-azidophenyl)-pyridine using excess PPI13, with CS2 yielded 6//-pyrido[l,2-rlquinazoline-6-thione 194 (Equation 40). 

Reduction of the pyridyl disulfide end after SPDP modification releases the pyridine-2-thione leaving group and generates a terminal—SH group. This procedure allows sulfhydryl-reactive derivatives such as maleimide-activated enzymes (Chapter 26, Section 2.3) to be conjugated with DNA probes for use in hybridization assays (Malcolm and Nicolas, 1984). 

Spectroscopically invisible carbenes can be monitored by the ylide method .92 Here, the carbene reacts with a nucleophile Y to form a strongly absorbing and long-lived ylide, competitively with all other routes of decay. Although pyridine (Py) stands out as the most popular probe, nitriles and thiones have also been used. In the presence of an additional quencher, the observed pseudo-first-order rate constant for ylide formation is given by Eq. 2.92,93 A plot of obs vs. [Q] at constant [Y ] will provide kq. With Q = HX, complications can arise from protonation of Y and/or the derived ylides. The available data indicate that alcohols are compatible with the pyridine-ylide probe technique. 

Stmctures of a wide number of hcxahydro-oxazolo[3,2- pyndincs have been determined using X-ray analysis. In most cases, the objective was stmctural confirmation and results usually were unexceptional. It should just be mentioned here that the crystal structure of trans-(3R,2aS)-(—)-3-phenyl-2,3,5,6,7,8-hexahydro-oxazolo[3,2-tf]pyridine-5-thione revealed a significant participation of the tautomeric thio-enolic form as reflected by the short N-C(=S) bond length of 1.328 A <2003AXEo519>. 

An intriguing use of a quaternary ammonium salt in a two-phase reaction is to be found with the regeneration of 1 -benzyl-1,4-dihydronicotinamide by sodium dithionite in a biomimetic reduction of thiones to thiols [12], The use of sodium dithionite in the presence of sodium carbonate for the 1,4-reduction of the pyri-dinium salts to 1,4-dihydropyridines is well established but, as both the dithionite and the pyridinium salts are soluble in water and the dihydropyridine and the thione are insoluble in the aqueous phase and totally soluble in the organic phase, it is difficult to identify the role of the quaternary ammonium salt in the reduction cycle. It is clear, however, that in the presence of benzyltriethylammonium chloride, the pyridine system is involved in as many as ten reduction cycles during the complete conversion of the thione into the thiol. In the absence of the catalyst, the thione is recovered quantitatively from the reaction mixture. As yet, the procedure does not appear to have any synthetic utility. 

Analogous substitution reactions take place with alkane- and arene-thiolate anions <73JCS(P1)16S9), and pyridine-2- and -4-thiones are usually prepared by use of sodium or potassium hydrogen sulfide or thiourea (74JCS(P1)2300). 

Brassilexin 48 and sinalexin 49 are among the most potent phytoalexins produced by economically important cruciferous plants. The most efficient preparation of brassilexin 48, sinalexin 49, and analogues 52 reported uses a Vilsmeier formylation-amination of readily available indoline-2-thiones 50 followed by an aqueous ammonia work-up procedure with subsequent oxidation of the 3-(amino)methyleneindoline-2-thione intermediates 51 using iodine in pyridine (Scheme 10) <20010L1213, 2005JOC1828>. The reaction yields are dictated by the efficiency of the... 

Some general observations for 4-nitroimidazo[4,5- ]pyridin-2-ones, imidazo[4,5- ]pyridine-2-thiones, imidazo[4,5-f]pyridine-2-thiones, imidazo[4,5- ]quinolin-2-ones, isothiazolo[5,4- ]pyridine-2-thiones, and 3/f-l,2-dithiolo[4,3-f]pyridine-3-thiones are reported in <1996CHEC-II(7)283>. The majority of compounds in this review have been isolated using standard chromatographic techniques. 

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