Pyridine-2-thioacetamide

Sachs and his colleagues had begun work that would show that H+/K+-ATPase, as the proton pump, moves acid across the membranes of gastric parietal cells (Blum et al, 1971). Scientists at the Swedish firm had focused on imidazoles and specifically, benzimidazoles, apparently in part because cimetidine (like histamine) is an imidazole. By adding a benzimidazole moiety to pyridine-2-thioacetamide, a known antisecretory agent, a new class of substituted benzimidazoles, which would later yield omeprazole was created (Fellenius, 1981). These congeners were sufficiently novel so that patent approval, a necessary component of the project, was likely if the compounds proved useful. 

Aromatic thioamides can be prepared as described in the literature by different ways, either by S -> O exchange between the corresponding benzamides and phosphorus pentasulfide in pyridine solution in the presence of triethylamine (65, 646) as strong base, or by action of H2S on the appropriate nitrile with pyridine and triethylamine solvents using the method of Fairfull et al. (34, 374, 503). In this reaction, thioacetamide in acidic medium can also be used as a H2S generator with dimethylform-amide as the solvent (485). 

This type of method has been used to prepare l,2,4-thiadiazolo[2,3- ]pyridine derivatives. The oxidative hetero-cyclization is exemplified by the formation of compound 86 from thioacetamide 85 using nitrosobenzene (Equation 24) <2004S2975>. 

Oxygen can be transferred from the arene oxides to nitrogen-, sulfur-, or phosphorus-containing substrates like pyridine, thiourea, N-methyl-benzothiazol-2-thione, thioacetamide, thiosemicarbazide, thiols, thio ethers, triphenylphosphine,21,160,161 etc. Parent hydrocarbons are formed as products.162 Thus the dimethoxycarbonyl oxide 269 on heating with pyridine produces 9,10-dimethoxycarbonylphenanthrene (270). The reaction of 1 or its... 

The reaction between acetyl- and benzoyl- thioacetamides and oijl-unsaturatcd aldehydes in refluxing pyridine yields a dienic thioamide through a Claisen-like condensation. Spontaneous electrocyclization affords the ZH-thiopyran (Scheme 111). Substituted piperidine-2-thione derivatives result when the reaction is carried out in ethanol using triethylamine as the base <2003T4183>. 

Cyano(thioacetamide) (285) and 2-cyano-2-(tosyloxyimino)acetamide (286, R = CONH2) gave 3-amino-6-cyano-5-thioxo-4,5-dihydro-2-pyrazinecarbox-amide (287) (pyridine—Et20, 20°C, 12 h 85%) 1401 the same thioamide (285) and a-(tosyloxyimino)malononitrile (286, R = CN) likewise gave 3-amino-5-thioxo-4,5-dihydro-2,6-pyrazinedicarbonitrile (287, R = CN) (90%).1401... 

Analogs with an acetyl, thioacetamide, or cyano group in the 3 position of the pyridine ring have all been shown 219) to exhibit the same stereochemistry for hydrogen transfer as NAD+. It was concluded 219) that interactions between enzyme and coenzyme were solely responsible for the A-side stereo specificity of NAD in LADH which agrees with the X-ray results (Section II,C,3,a). 

The selectivity of the formation of dimer [3,3]metacyclophanes lb and 8 versus trimer 18-membered macrocycles 2b and 9 which were perceived as crown ether analogues, was discussed by Vogtle in 1983 [6]. Both 1,3-bis(bromomethyl)benzene and 2,6-bis(bromomethyl)pyridine building blocks were used, with thioacetamide as the source of sulfur. Increasing the size of the counterion of the carbonate base raises the amount of trimers. Apparently, no higher oligomers were formed (Scheme 16.2). 

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