Benzimidazoles acids

Benzimidazole-2-carboxylic acid decarboxylation, 5, 435 Benzimidazole-3-carboxylic acid, 1-hydroxy-ethyl ester synthesis, 6, 407 Benzimidazoles acidity, 5, 50, 385, 386 acylation, 5, 71, 391, 402, 417 2V-alkyl-... 

H- Benzimidazole, 2,2-pentamethylene-reduction, 5, 423 Benzimidazole-2-carbaldehyde oximes, 5, 436 Benzimidazolecarbaldehydes oxidation, 5, 437 Benzimidazole-2-carbamates 5-substituted as anthelmintics, I, 202 Benzimidazole-l-carboxylic acid, 2-amino-methyl ester reactions, 5, 453 Benzimidazole-2-carboxylic acid decarboxylation, 5, 435 Benzimidazole-3-carboxylic acid, 1-hydroxy-ethyl ester synthesis, 6, 407 Benzimidazoles acidity, 5, 50, 385, 386 acylation, 5, 71, 391, 402, 417 N-alkyl-... 

Place 27 g. of o-phenylenediamine (Section IV,92) in a 250 ml. round-bottomed flask and add 17 -5 g. (16 ml.) of 90 per cent, formic acid (1). Heat the mixture on a water bath at 100° for 2 hours. Cool, add 10 per cent sodium hydroxide solution slowly, with constant rotation of the flask, until the mixture is just alkaline to litmus. Filter off the crude benzimidazole at the pump, wash with ice-cold water, drain well and wash again with 25 ml. of cold water. Dissolve the crude product in 400 ml. of boiling water, add 2 g. of decolourising carbon, and digest for 16 minutes. Filter rapidly at the pump through a pre heated Buchner funnel and flask. Cool the filtrate to about 10°, filter off the benzimidazole, wash with 25 ml. of cold water, and dry at 100°. The yield of pure benzimidazole, m.p. 171-172°, is 26 g. 

Phenylbenzimidazole is nitrated first at the 5-position with mixed acid, and subsequent reaction produces 5-nitro-2-(4-nitrophenyl)-and 5-nitro-2-(3-nitrophenyl)-benzimidazole. 2-Phenyl-, 2-(4-nitro-phenyl)- and 5-nitro-2-phenyl-benzimidazole are nitrated as their conjugate acids. ... 

Several biologically and pharmacologically active compounds have been prepared from the condensation of the acid chloride of 1-naphthoxyacetic acid with carbazole, iadole, or pyrrole ia 2A[ NaOH solution ia ethanol (63). Also, naphthyloxy derivatives of imidazole, benzimidazole, and benzotriazoles have been synthesized and screened for their antimicrobial, analgesic, and antiinflammatory activities. 2-Naphthyloxy derivatives are comparatively more active than 1-naphthyloxy derivatives (64). 

The dianhydride of 1,4,5,8-naphthalene tetracarboxyhc acid [81-30-1] has been of research interest for the preparation of high temperature polymers, ie, polyimides. The condensation of the dianhydride with o-phenylenediamines gives vat dyes and pigments of the benzimidazole type. 

The TT-electron distribution in benzimidazole favors substitution at the 4-position in the conjugate acid, at the 4- and 5-positions in the neutral molecule, and at the 2-position in the conjugate base. These results do not explain the apparently exclusive substitution at the 5-position in nitration. There is thus no general agreement between the rr-electron distribution and the chemical reactivity. 

Imidazoles and benzimidazoles (155) react with acid chloride and alkali to give compounds of type (157), but these are reactions of the cation (156). 1,2,4-Triazoles and tetrazoles similarly undergo ring opening. 

Substituted imidazoles can be acylated at the 2-position by acid chlorides in the presence of triethylamine. This reaction proceeds by proton loss on the (V-acylated intermediate (241). An analogous reaction with phenyl isocyanate gives (242), probably via a similar mechanism. Benzimidazoles react similarly, but pyrazoles do not (80AHC(27)24l) cf. Section 4.02.1.4.6). 

Chichibabin reaction, 5, 409-410 sulfonation, 5, 429 synthesis, 5, 160, 161, 457-498, 496 tautomerism, 5, 365 toxicity, 1, 139 UV spectra, 5, 356, 357 2H-Benzimidazoles 3,3-dioxides synthesis, 6, 407 2V,7ST-dioxides reactions, 5, 456 Benzimidazoles, aryl-oxidation, 5, 433 Benzimidazoles, nitro-mass spectra, 5, 359 reduction, 5, 441 Benzimidazole-2-sulfonic acids reactions... 

If one amino group in o-phenylenediamine is converted to an amide group by formic acid, the intermediate benzimidazole is formed. This reaction, conducted with a wide range of reactants, produces resins (polybenzimidazoles) used as high-temperature adhesives for laminates in the aerospace industry. Heat insulation is made by including tiny bubbles of silica and all... 

Dmitrofluorobenzene also serves as an arylation agent for a wide vanety of biologically useful amines including aromatic amines [5b], ammo acids [57], and ammocarbohydrates [55,59] Weak nucleophilic amines such as benzimidazole [60] and fluoroamines [61] can also be arylated (equation 30)... 

Alkylation of the cyclization product 115 and the following hydrolysis gave 9-alkyl substituted 6-oxo-6,9-dihydroimidazo[4,5-/i]quinoline-7-carboxylic acid derivatives 119, compounds useful as antibacterials (no data) [80JAP(K)1], 4(7)-Aminobenzimidazole can react with 1,3-diketones as a bidentate nucleophile, but with 2,4-pentanedione in glacial acetic acid it gives a Combes product, l//-6,8-dimethylimidazo[4,5-/i]quinoline 120, accompanied by 4(7)-acetamido-benzimidazole (91T7459). 

Benzimidazole is also aromatic (65AX573, 97T13111), less acidic and more basic in the gas phase than imidazole (83AGE323), although in solution the basicity trend is reverted. This is ascribed to the polarization effects of the annulation. 

Benzimidazoles are generally synthesized from ortho-diamino-benzenes and carboxylic acid derivatives. The antihistaminic agent, clemizole (60), for example, can be prepared by first reacting ortho-diaminobenzene (57) with chloroacetic acid to form 2-chloro-methylbenzimidazole (58). Displacement of the halogen with pyro-... 

The finding that the anthelmintic thiazoloimidazole levamisole showed immunoregulatory activity spurred further investigation of this heterocyclic system. Synthesis of a highly modified analogue starts by displacement of bromine in keto ester 149 by sulfur in substituted benzimidazole 148. Cyclization of the product (150), leads initially to the carbinol 151. Removal of the ester group by saponification in base followed by acid-catalyzed dehydration of the carbinol affords the immune regulator tilomisole (152) [28]. 

Chemical Name (5-benzoyl-1 H-benzimidazol-2-yl)carbamic acid methyl ester Common Name Methyl-5-benzoyl-2-benzimidazole carbamate... 

Acidic hydrolysis of benzodiazepine 4 gives 2-(cyanomethyl)benzimidazole hydrochloride 8.288... 

Ring opening also occurs when the hydrochloride 4 HCI is treated with hydroxylamine hydrochloride and triethylamine the product 17 is converted into the benzimidazole 18 by hydrochloric acid.295... 

Polyphosphoric acid is preferred except in the case of the formamido compounds 1, R3 = H. The synthesis fails with diphenylamine derivatives lacking a substituent on nitrogen, benzimidazoles being produced (see Houben-Weyl, Vol. E8c, p 231 flf). 

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