Thionyl chloride imidazole

Bifonazole (109) is claimed to be remarkably non-toxic and is marketed as a topical antifungal agent overseas. It can be conveniently synthesized in the by now familiar way by reduction of p-phenylbenzophenone (108) with borohydride, conversion to the chloride with thionyl chloride, and then imidazole displacement to bifonazole (109) [39]. 

Tetrahydroimidazo[5,l-c][l,2,4]triazine 474 was prepared (79KGS1540) by treating imidazole derivatives 472 or 473 with hydrazine. Compound 473 was obtained by reaction of the respective imidazole with 1,2-dibromoethane or by the reaction of the alcohol derivative 471 with phosphorus tribromide. On the other hand, chlorination of471 with thionyl chloride gave 472 (Scheme 100). 

Solladie and coworkers avoided the use of a sulfinyl chloride when they prepared (— )-menthyl 1-naphthalenesulfinate in an overall yield of 45% by the reaction of thionyl diimidazole, obtained from imidazole and thionyl chloride, with 0.7 equivalent of ( — )-menthol followed by 1 equivalent of 1-naphthylmagnesium bromide (equation 4). 

Butoconazole Bntoconazole, l-[4-(4-chlorophenyl)-2-[(2,6-dichlorophenyl)thio]butyl]-IH-imidazole (35.2.12), is synthesized from 4-chlorobenzylmagnesium bromide, which is reacted with epichloridrine to make 4-(4 -chlorophenyl)-l-chlorobutan-2-ol (35.2.10), which is reacted with imidazole in the presence of sodium to make 4-(4 -chlorophenyl)-l-(lH-imidazolyl)butanol-2 (35.2.11). The hydroxyl group in the last is replaced with a chlorine atom npon reaction with thionyl chloride, which is then by the reaction with 2,6-dichlorothiophenol bntoconazole [27,28], is obtained. 

SO(Im)2, generated from thionyl chloride and imidazole, is quite effective in the formation of cyclic sulfites from 1,2-diols. For example, furo[2,3,- -l,3,2-dioxathiole 53 was produced by reacting SO(Im)2 with diol 88. In a similar reaction, compounds 89a and 89b yielded 55a and 55b, respectively (Equations 12 and 13) <20040L3913, 2005JME4276>. 

The topical antifungal bifonazole (60-2) dispenses with virtually all but the imidazole ring the intermediate (60-1) is obtained by sequential reduction of 4-phenyl-benzophenone and then reaction of the alcohol with thionyl chloride. Displacement of chlorine by imidazole gives (60-2) [65]. 

The utility of some of these products for side-chain modification has also been demonstrated. For example, 4-chloro-3-formylpyridine undergoes the Hantzsch reaction to give a 4-(3-chloropyridine)-l,4-dihydropyridine derivative (88%). (4-Chloro-3-pyridyl)diphenylmethanol affords aza-analogues (65-70%) of the antimycotic agent chlortrimazol by reaction with thionyl chloride and imidazole derivatives (88JHC81). 

Boronic esters of (R,R)-l,2-dicyclohexyl-l,2-ethanediol or pinanediol react with thionyl chloride and excess imidazole in acetonitrile on a borosilicate glass surface to form the corresponding cyclic sulfites of diols <20010M2920>. Similarly, cyclic sulfites and sulfates have been prepared from silicates of diols <1997TL4841>. 

Mesoionic 1,2,3,5-thiatriazoles 24 that are fused to an imidazole ring were successfully prepared from 1,2-diaminoimidazoles 23 and thionyl chloride (Scheme 3) <1981JOC4065>. The bcnzimidazo[l,2-t ]thiatriazole was prepared in an analogous manner. 

Thionyl chloride (0.829 g) was added over 1 min to a stirred suspension of 1-(triphenylmethyl)-lH-imidazole-4-methanol (1.3 g) in a mixture of dichloromethane (50 ml) and DMF (1.0 ml) at 23°C. The solution so obtained was stirred for 15 min. and extracted with 8% sodium bicarbonate solution (80 ml). The organic phase was washed with water (50 ml), dried and evaporated to give an oil which solidified. The solid was slurried in hexane and filtered to give the title compound (1.28 g), m.p. 139-141°C. 

Sodium hydrogen carbonate Thionyl chloride Copper iodide Diazomethane Imidazole Trifluoroacetic acid Sodium methoxide 7-Bromo-3a,8b-cis-3a,8b-dihydro-3H-5-cyclopenta[b] benzofurancarboxylic acid... 

N-Acylsaccharins (13) possess a certain potential as acylating agents. They will acylate amines, but will react with water or alcohols only when acid or base is present.167 The method was used to acylate a-amino-penicillanic acid.170 Micheel162-165 has based a peptide (38) synthesis on the acyl transfer from 31 [Z = carbobenzoxy, obtained through reaction with DCC or with pseudosaccharin chloride (6) or with thionyl chloride and imidazole] to amino acids. Pseudosaccharin anhydride 323, lee js thg product of a condensation between 6 and 1, mostly from hydrolysis of 6. Formation of 32 tends to occur in nonprotic solvents with base catalysis, even when practical precautions are taken to exclude moisture. Water and protic solvents seem to shield the anion 19 and prevent attack on 6. 

The reagent is prepared by the reaction of thionyl chloride in tetrahydrofurane with 4 equivalents of imidazole the solution, filtered from imidazole hydrochloride. 

This method of imidazolylzinc chloride synthesis has also found application in the synthesis of a sulfonyl chloride to be used in the preparation of some potential factor Xa inhibitors [17]. Thus, following imidazole metalation and quenching with ZnCl2, a chemoselective coupling reaction occurred to provide 16. Treatment with sulfur dioxide provided the sulfinic acid, which upon treatment with thionyl chloride, provided the requisite sulfonyl chloride 17. 

When imidazole-4,5-dicarboxylic acid is heated with acetic anhydride, the bis-azolide (146) which is formed readily hydrolyzes in water to give the monocarboxylic acid. This is a novel method of removing one carboxyl group <82JHC253>, which has been modified to broaden its applicability to the synthesis of mono- and diesters and -amides. Replacement of the acetic anhydride by thionyl chloride forms the related azolide (147) which forms the unstable carboxylic analogue which reacts with nucleophiles such as alcohols and amines (Scheme 81) <84SC251,85JHC413>. 

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