Benzimidazole-2-thiol

Methoxyphenylene diamine 12 was treated with potassium ethylxanthate to afford benzimidazole-thiol 13. The coupling of thiol 13 and chloromethyl-pyridine 11 was then... 

Keywords Viehe salt, benzimidazole thiol, waste-free, solid-solid reaction... 

The first compound of this class with inhibitory activity on the enzyme and on acid secretion was the 2-(pyridylmethyl)sulfinylbenzimidazole, timopra-zole, and the fust pump inhibitor used clinically was omeprazole, 2-[[3,5-dimethyl-4-methoxypyridin-2-yl] methylsulfinyl]-5-methoxy- lH-benzimidazole. Omeprazole is an acid-activated prodrug. Omeprazole and the other PPIs are accumulated in the acidic space of the parietal cell due to the pKa of the pyridine nitrogen and these are converted due to protonation of the benzimidazole nitrogen first to a thiol-reactive cationic sulfenic acid and then dehydrated to form the sulfenamide (Fig. 1). These thiophilic cations then bind to luminally... 

The halogen in 5-bromofuran-2-carboxaldehyde is readily displaced by aromatic thiols, and the aromatic residue can be provided by pyridazine, benzeneselenazole, benzimidazole, benzoxazole, etc. as well as benzene.181... 

In much the same vein, nitration of 2,3-dimethylpyridine Al-oxide (49-1) affords the nitro derivative (49-2). The newly introduced nitro group is then displaced by the aUcoxide from 3-methoxypropanol to afford the corresponding ether (49-3). Proceeding much as above, the methyl group at the position adj acent to the nitrogen is converted to its chloride (49-5). Condensation with benzimidazol-2-thiol then affords rabeprazole (49-6) [52]. 

In effect, antifoggants enhance the difference between the rate of formation of the desired image density and that of fog density. Many heterocyclic compounds have been claimed to restrain fog. These include suitably substituted benzotriazoles, benzimidazoles, indazoles, oxazoles, thiazoles, triazoles and tetrazoles. Heterocyclic compounds bearing a thiol substituent invariably show some antifoggant activity. Thus phenylmercaptotetrazole (16) which contains both a thiol group and a tetrazole ring is very effective (59MI11400). 

Specified impurities A, B, C, D, E, F, G. Other detectable impurities H, I. A. 5-Methoxy-lH-benzimidazole-2-thiol... 

Chloromethyl-4,5-dimethoxy-3-methylpyridinium chloride (about 1.5 g) are added to a solution of 5-difluoromethoxy-lH-benzimidazole-2-thiol in 10 ml of ethanol and 10 ml of 1 N sodium hydroxide solution. The yellow reaction mixture is stirred at 20°C for 1 hour, a further 10 ml of water are added,... 

Fig. 3.9 The acid-catalyzed rearrangement of the substituted benzimidazole pantoprazole (prodrug) to the cyclic sulfenamide (active principle) and its reaction with thiols.

The reaction cascade induced by treatment with acids. Formation of 5H-pyriodo [l, 2 4,5] [1,2,4] thiadiazino benzimidazole-13-ium salts and their reactions with thiols./. Org. Chem.,... 

Sturm E, Kruger U, Senn-Bilfinger J, Figala V, Klemm K, Kohl B, et al. (H+-K+)-ATPase inhibiting 2-[(2-pyridyl-methyl)sulfmyl]benzimidazoles. 1. Their reaction with thiols under acidic conditions. Disulfide containing 2-pyridinio-benzimidazolides as mimics for the... 

C.E. Song and coworkers [64,65] found that treatment of AT-[2-(lff-benzimidazol-2-ylthio)phenyl]thioureas 126 (Scheme 43) with DCC in acetonitrile at reflux results in cyclization with elimination of hydrogen sulphide to afford 127. It is noteworthy that the respective Iff-[ 1,2,4]-triazole-3-thiol... 

Sulfinic acids and sulfoxides are not particularly common, being readily oxidized to the sulfonic acids and sulfones, respectively. Sulfonic acids have high melting points and probably exist as zwitterions. They are amphoteric, but mainly display the characteristics of weak acids. The sulfonic acid group activates an adjacent halogen to nucleophilic displacement, and may itself be displaced, e.g. reaction of alkylamines with benzimidazole-2-sulfonic acid. Imidazolesulfonic acids resist esterification and acid chloride formation, and are only hydrolyzed by concentrated hydrochloric acid at 170 °C the 2-isomers are more resistant than the 4- or 5-isomers. Aqueous alkali converts the free acids into hydroxy derivatives. Sulfonyl chlorides are accessible via the thiols (Section 4.07.3.6.1) which react with ammonia to form sulfonamides, or are reduced by tin(II) chloride to thiols (77JHC889). 

Imidazole- and benzimidazole-2-thiols usually exist largely as the thione tautomers. The thiol (thione) group is susceptible to alkylation (especially in alkaline media), and can be oxidized to sulfide, disulfide and sulfonic acid. This oxidation can often be carried out quite selectively by careful choice of oxidizing agent. The sulfur function can be removed with nitric acid, iron(III) chloride, hydrogen peroxide or, most commonly, Raney nickel. Alkyl- and arylthio groups can be oxidized to sulfoxide or sulfone. 

In the uncondensed imidazoles the standard method reacts an a-aminocarbonyl compound with a thiocyanate (see Section 4.1 and Table 4.1.1). If a 2-alkylthioimidazole is required directly, one can combine an N-alkyT or A -arylcarbonimidodithioate in refluxing acetic acid with the aminocarbonyl substrate (see Section 4.1 and Scheme 4.1.3). Alternatively, reaction between thiourea and a two-carbon synthon (ot-hydroxy-, a-halogeno-, a-dicarbonyl) leads to imidazoline-2-thiones (see Section 4.3). In sulfuric acid, 3-butynylthiourea cyclizes to 4,5-dimethylimidazolin-2-thione (see Section 2.2.1). 1-Substituted 2-methylthioimidazoles can be made, albeit in rather poor yields, from appropriately substituted 2-azabutadienes (see Section 3.2 and Scheme 3.2.3), and 2-arylthioimidazoles are available in moderate yields from benzyl isocyanides and arylsulfenyl chlorides (see Section 4.2 and Scheme 4.2.12). Ring transformations of 5-amino-2-alkylaminothiazoles and 2-acylamino-5-aminothiazoles may have occasional applications (see Section 6.1.2.7). The ease with which a thiol group or imidazole or benzimidazole can be alkylated, in comparison with the annular nitrogens, usually makes it more convenient to prepare alkylthioimidazoles from the thiols (or thiones). 

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