Pyridine, 2- sulfinyl

Chloro-a,/3-unsaturated aldehydes condense with ammonium thiocyanate to give isothiazoles (76EGP122249). 2,3-Diphenylcyclopropenone reacts with iV-sulfinyl-cyclohexylamine in the presence of nickel tetracarbonyl to give the isothiazolin-3-one 1-oxide (197) (79SST(5)345). Cholesteryl acetate reacts with trithiazyl trichloride in pyridine to give the isothiazolo steroid (198) (77JCS(P1)916). 

A concerted elimination-cyclization mechansim, involving a sulfenyl halide in a 1,3-butadiene-1-thio system, is the most probable mechanism for the formation of benzo[6 Jthiophenes from cinnamic acids or 4-aryl-2-butanones by treatment with thionyl chloride. The reactions shown in Scheme 5 have been carefully worked out, and the intermediates isolated (75JOC3037). The unique aspect of this synthesis is the reduction of the sulfinyl chloride (a) by thionyl chloride to form the sulfenyl chloride (b). The intermediate (b) was isolated and converted in pyridine to the 3-chlorobenzo[6]thiophene-2-carbonyl chloride in 36% yield (73TL125). The reaction is probably initiated by a sulfenyl ion attack on the aromatic ring, since it is promoted by electron-releasing groups para to the site of ring closure. For example, when X in (36) was N02, a 23% yield of (37), a mixture of 5-and 7-nitro derivatives, was obtained, but when X in (36) was OMe, a 54% yield of (37) was obtained, contaminated with some 3,4-dichloro-5-methoxybenzo[6]thiophene-2-carboxylic acid. 

Omeprazole Omeprazole contains less than 99% and not more than the equivalent of 101% of 5-methoxy-2-[[(KS)-(4-methoxy-3,5-dimethyl-pyridine-2-yl)methyl]sulfinyl]-lH-benzimidazole, calculated with reference to the dried substance. 

E. 4-Methoxy-2-[[(i S)-(5-methoxy-lid-benzimidazole-2-yl)sulfinyl] methyl]-3,5-dimethyl-pyridine-l-oxide... 

Keto-sulfones, which contain a 2-pyridyl ketone moiety, react with alkylidenemalononitriles to afford 2-amino-5-sulfonyl-4-aryl-6-(pyridin-2-yl)-47/-pyran-3-carbonitriles 86 (Equation 47) <1997JOC6575>. Likewise, (3-keto-sulfoxides featuring a 2-pyridyl ketone moiety react with alkylidenemalononitriles to form 2-amino-5-sulfinyl-4-aryl-6-(pyridin-2-yl)-4//-pyran-3-carbonitriles. Additionally, chiral (3-keto-sulfoxides that contain a 2-pyridyl ketone moiety can add to alkylidenemalononitriles with high stereoselectivity <1997JOC6575>. 

The presence of a coordinating group in the sulfinimine may strongly influence the selectivity of the reaction with Grignard derivatives. In the case of 2-pyridyl ftrt-butylsulfinimines, the diastereoselectivity of the addition is reversed due to the coordination with the pyridine nitrogen. " Attempts have been made to prepare sulfinyl chiral... 

Ife RJ, Dyke CA, Keeling DJ, Meenan E, Meeson ML, Parsons ME, et al. 2-[[(4-Amino-2-pyridyl)methyl]sulfinyl]-benzimidazole H+/K+-ATPase inhibitors. The relationship between pyridine basicity, stability, and activity. /. Med. Chem., 1989, 32(8), 1970-1977. 

The reactions of the other sulfinyl chlorides (n-Pr, z -Pr, p-Tol) with DAG using z -Pr2NEt as base led to the formation of (S)-sulfinate esters as the major isomers with high selectivity (89 to >95%) instead of (/ -)sulfinate esters predominantly obtained when pyridine was used as base (70 to > 95% de, Table 20). 

The obvious question is whether the achiral stereodirecting base effect observed with DAG is a particular case of this alcohol or general behavior of secondary chiral carbinols. In order to answer this question and to get a better insight into the mechanism of the reaction, the reactivity of different chiral carbinols with methane-sulfinyl chloride was tested using the optimal conditions previously determined for DAG (1) in the presence of i-Pr2NEt in toluene at -78 °C, and (2) with pyridine in THF at -78 °C.116... 

Pantoprazole Sodium. The active ingredient in Pro-tonix (pantoprazole sodium) is a substituted benzimidazole, sodium 5-(difluoromethoxy)-2-l (3.4-dimethoxy-2-pyridi-nyl)methyl sulfinyl -l/y-benzimidazole sesquihydratc (1.5 HjO). a compound with a molecular weight of 432.4. The benzimidazoles have weakly ba.sic (pyridine N. pK, 3.%) and acidic (benzimidazole N-H. pK 0.89) properties, which facilitate their formulation as salts of alkaline materials (Fig. 21-17). Pantoprazole sodium. sesquihydratc is a while to off-while crystalline powder and is racemic. Pantoprazole sodium sesquihydratc is freely soluble in water, very. slightly. soluble in phosphate buffer at pH 7.4, and practically insoluble in n-hexane. The stability of Ihe compound in aqueous solution is pH dependent the rate of degradation increases with decreasing pH. At ambient temperature, the degradation half-life is approximately 2.8 hours at pH 5.0 and approximately 220 hours at pH 7.8. 

A sulfinyl or sulfonyl group at the 2- or 4-position of a pyridine ring can be displaced by nucleophiles (i.e. alkoxides, thiolates, and cyanide) to afford the corresponding ipso substitution products. Similarly, 2-halo-6-methylsul-finyl- or 2-halo-6-methylsulfonylpyridines react with nucleophiles to give... 

Unstable tosylates. Tosylates have usually been prepared by reaction of the alcohol with tosyl chloride in pyridine. However, the method is not generally suitable for hindered alcohols or very reactive alcohols. Coates and Chen4 have reported a new method that is suitable for hindered or unstable tosylates. The alcohol is converted into the p-toluenesulfinate ester5 by reaction with p-toluene-sulfinyl chloride6 in ether containing 1 equivalent of pyridine yield 70-85%. The sulfinates are then oxidized to the sulfonates by m-chloroperbenzoic acid in methylene chloride at 0°, yield 75-88%. The tosylates of r-butyl alcohol, 2-bicyclo-... 

A multitude of iV-sulfinyl compounds and sulfur diimides bearing a variety of substituents on the nitrogen atom(s) have been prepared. The iV-sulfinyl compounds are commonly generated by treatment of the parent aniline, amine, sulfonamide, etc., with thionyl chloride and pyridine [Eq. 

The resulting iV-sulfinyl derivatives can often be distilled and/or crystallized but are water sensitive and thus are frequently prepared in situ for subsequent cycloaddition reactions. Symmetrically substituted sulfur diimides can usually be prepared by the reaction of SCI2 or S2CI2 with the parent NH2 compound in the presence of a base such as pyridine or triethylamine [Eq. (4)]. ... 

A 1 4 mixture of methyl o-nitromandelate (116 R1 = OH, R2 = H) and thionyl chloride at room temperature yields not the expected a-chloro compound (116 R1 = Cl, R2 = H), but the 5-chloroanthranil-3-carboxylate (118 R = H).144 Reaction conditions are, however, critical for example, neat thionyl chloride at room temperature produces only the sulfite ester of 116, whereas in pyridine at — 80°C the a-chloro compound (116 R1 = Cl, R2 = H) is obtained. The chloromandelate (116 R1 = OH, R2 = Cl) is inert to boiling thionyl chloride, but on prolonged (12 h) treatment with thionyl chloride in chloroform it yields the dichloroanthranil 118 (R = Cl). A mechanistic rationale (Scheme 16) involving the sulfinyl chloride 117 is proposed. 

Yields of the aniline derivatives are usually almost quantitative for aliphatic amines they lie between 35% and 65% if pyridine is added to bind the hydrogen chloride evolved. Sulfinylation of sulfonamides is considerably slower but gives good yields after several days refluxing. 

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