Research on imidazo[1,2-a]benzimidazole derivatives XIII. Synthesis and properties of alcohols of the imidazo[1,2-a]benzimidazole series

Various hydroxy derivatives of imidazo[1,2-a]benzimidazole were synthesized from its 3-bromo, 3-formyl, and 3-acetyl derivatives. The properties and pharmacological activity of the products were studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 126–134, January, 1976.     

Mass spectra of pyrrolo [1,2-a]benzimidazole and imidazo[1,2-a]benzimidazole derivatives

The closeness of the electronic structures of the ions formed in the first act of disintegration of the ions is responsible for the monotypic character of the subsequent fragmentation of pyrrolo[1,2-a]benzimidazole and imidazo[1,2-a]benzimidazole derivatives. The mass-spectrometric disintegration of the investigated systems has something in common with the fragmentation of thiazolo[3,2-a]benzimidazole derivatives.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, 1124–1127, August, 1975.     

Imidazo[1,2-a]benzimidazole derivatives

3-Amino derivatives of 9-alkyl(benzyl)-2-arylimidazo[1,2-a]benzimidazoles, obtained by the reduction of the appropriate 3-nitro(nitroso) derivatives, are extremely unstable, and the imidazole ring opens readily resulting in conversion to 2-(-carboxybenzylamino)benzimidazoles. The reaction apparently proceeds through the intermediate formation of 2-(-cyanobenzylamino)benzimidazole, which is a tautomeric form of the 3-amino compound and can react as such to form 3-acylamino derivatives and anils. If there is a methyl group in the 3-position of the ring, the amine is quite stable and can be isolated in free form.See [1] for communication IV.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 673–677, May, 1971.     

Reaction of pyrido[1,2-a]benzimidazole and tetrahydropyrido[1,2-a]benzimidazole with acetylenedicarboxylic ester

Previously unknown polynuclear condensed systems with bridgehead nitrogen atoms have been obtained by treating acetylenedicarboxylic ester with pyrido[1,2-a]-benzimidazole and tetrahydropyrido[1,2-a]benzimidazole.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 239–241, February, 1986.     

One-pot synthesis of imidazo[1,2-b]pyrazole,imidazo[1,2-b]-1,2,4-triazole,imidazo[1,2-a]pyridine,imidazo[1,2-a]pyrimidine,imidazo[1,2-a]benzimidazole,and 1,2,4-triazolo[4,3-a]benzimidazole derivatives

Hydrazonoyl bromides 1a-c react with 5-amino-3-phenyl-1H-pyrazole, 5-amino-1H-1,2,4-triazole, 2-aminopyridine, and 2-aminobenzimidazole to afford the corresponding imidazol[1,2-b]pyrazoles 10, imidazo[1,2-b]-1,2,4-triazoles 11, imidazo[1,2-a]pyridines 16, imidazo[1,2-a]pyrimidines 17, and imidazo[1,2-a]benzimidazoles 20, respectively. Compounds 1a-c reacted also with 2-methylthiobenzimidazole to give 1,2,4-triazolo[4,3-a]benzimidazole derivatives 21. © 1997 John Wiley & Sons, Inc.     

New pyrazino[1,2-a]benzimidazole derivatives

1-Ethoxycarbonyl-3-phenyl- and 3-phenylpyrazino[1,2-a]benzimidazoles were synthesized by reaction of 2-ethoxalyl- and 2-diethoxymethyl-N-phenacylbenzimidazoles, obtained from the corresponding sodium derivatives of benzimidazole and phenacyl bromide, with ammonium acetate.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1266–1267, September, 1976.     

Research on imidazo[1,2-a]benzimidazole derivatives XI. Synthesis of 2-arylamino derivatives of 9-methylimidazo[1,2-a]benzimidazole

2-Arylamino derivatives of 9-methylimidazo[1,2-a]benzimidazole were obtained by cyclization of the products of the reaction of 2-amino-1-methylbenzimidazole with chloroacetic acid anilides. The former undergo diazo coupling and acetylation in the 3 position of the system, and the amino groups of secondary amines are also acetylated.See [1] for communication X.Translated from Khimiya Geterotsiklicheskikh, No. 10, pp. 1394–1398, October, 1975.     

Research on imidazo[1,2-a]benzimidazole derivatives

Depending on the nature of the substituent in the 2 position of the heteroring, imidazo[1,2-a] benzimidazole derivatives undergo either mononitration in the 3 position or form dinitro derivatives. In the latter case, one nitro group enters the phenyl group in the 2 position, and the other enters the benzimidazole fragment of the molecule.     

Research on imidazo[1,2-a]benzimidazole derivatives

The debenzylation of N-benzylimidazo[1,2-a]benzimidazoles with sodium in liquid ammonia was studied. The debenzylation of the 2-phenyl-substituted derivative is accompanied by hydrogenation of the outer imidazole ring to give 2-phenyl-2,3-dihydro-1H-imidazo[1,2-a]benzimidazole, the alkylation of which in alkaline media and neutral media, respectively, gives the 1-methyl derivative and the 9-methyl derivative. The 1-methyl derivative was subjected to quaternization and bromination; the latter proceeds in the condensed benzene ring. Debenzylation of the 2-methyl derivative of imidazo[1,2-a]benzimidazole is not accompanied by hydrogenation but gives 2-methyl-1(9)H-imidazo[1,2-a]benzimidazole.See [1] for communication VI.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 791–796, June, 1973.     

Research on imidazo[1,2-a]benzimidazole derivatives

The action of excess nitrous acid on 9-methyl-2-phenylimidazo[1,2-a]benzimidazole results in opening of the outer imidazole ring and the formation of unstable 1-methyl-2-nitrosimino-3-oximinophenacylbenzimidazoline. The products of cleavage of this compound in alkali, acid, and alcohol solutions were studied.See [1] for Communication 18.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 68–70, January, 1980.     

Research on imidazo[1,2-a] benzimidazole derivatives

2-Acyl-substituted 3-methyl(phenyl)-9-methylimidazo[1,2-a]benzimidazoles were synthesized by three methods: by the reaction of -halo ketones with 3-benzoyl-2-imino-1-methylbenzimi-dazoline, by reaction of acetic anhydride or acetyl bromide with 1-methyl-2-phenacylaminobenzimidazole, and by acylation of 3-substituted imidazo[1,2-a]benzimidazoles. Some of the properties of the resulting 2-acyl-substituted compounds were studied.See [1] for communication XIV.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 111–115, January, 1977.     

Investigation of imidazo[1,2-a]benzimidazole derivatives

Esters of 1-alkyl- and 1-aralkyl-2-iminobenzimidazoline-3-acetic acids are converted to esters of 2,9-dimethylimidazo[1,2,-a]benzimidazole-3-carboxylic acid on heating with acetic anhydride. The brief action of acetic anhydride on the free iminobenzimidazolineacetic acids gives 2-oxo-2,3-dihydroimidazo[1,2-a]benzimidazoles, which are converted to 2,9-substituted 3-acetylimidazo[1,2-a]benzimidazoles on prolonged heating with acetic anhydride.See [1] for communication V.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 111–114, January, 1973.     

Research on imidazo[1,2-a] benzimidazole derivatives

,-Unsaturated ketones of the imidazo[1,2-a]benztmidazole series were synthesized from 3-formyl- and 3-acetyl-substituted imidazo[1,2-a]benzimidazoles by crotonic condensation in the presence of alkaline catalysts. The ,-unsaturated ketones can also be obtained by direct acylation of 3-unsubstituted imidazo[1,2-a]benzimidazoles with the chlorides of unsaturated acids. The properties and pharmacological activity of the ketones obtained were studied.See [1] for communication XIII.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1660–1665, December, 1976.     

Protonation of pyrrolo[1,2-a]benzimidazole derivatives

The protonation of a number of pyrrolo[1,2-a]benzimidazole derivatives in trifluoroacetic acid was studied by PMR spectroscopy. 1,3-Unsubstituted compounds are protonated exclusively at the C₁ atom. Under similar conditions, pyrrolobenzimidazoles that have a methyl group in the 1 position form a mixture of two protonated forms, which correspond to the addition of a proton to C₁ and C₃, respectively. The relative percentage of the C₃-protonated form decreases successively (from 81 to 18%) on passing from the 3-unsubstituted compound to the corresponding 3-phenyl and 3-methyl derivatives. The basicity constants of the pyrrolobenzimidazoles decrease symbatically with an increase in the relative percentage of this form. The relative proton-acceptor capacity of indolicine, pyrrolo[1,2-a]-imidazole, and pyrrolo[1,2-a]benzimidazole were examined on the basis of the protonation data and the reactivity indexes, calculated by the simple Hückel MO method.Translated from Khimiya Geterotsiklicheskih Soedinenii, No. 8, pp. 1132–1137, August, 1972.     

1,2-Diphenylimidazo[1,2-a]benzimidazole in electrophilic substitution reactions

Vilsmeier formylation of 1,2-diphenylimidazo[1,2-a]benzimidazole leads to the 3-formyl derivative, while heating with acetic anhydride in sulfuric acid gives the 3-acetyl derivative. The nitration of this benzimidazole with potassium nitrate in sulfuric acid gives a mixture of mono-, di-, and trinitro derivatives. Bromination in chloroform leads to a mixture containing the mono- and dibromo derivatives. The structures of the compounds obtained were confirmed by their IR, PMR, and mass spectra.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1251–1254, September, 1981.     

Studies on derivatives of imidazo[1,2-a]benzimidazole

It has been found that 9-methyl-2-phenyl- and 2,9-dimethylimidazo[1,2-a]benzimidazoles undergo direct formylation at position 3. The formyl derivatives obtained take part in a series of condensations characteristic for aldehydes, but they do not undergo the Cannizzaro disproportionation.For Communication I, see [1].Translated from Geterotsiklicheskikh Soedinenii, Vol. 6, No. 6, pp. 838–841, June, 1970.     

Research on imidazo[1,2-a]benzimidazole derivatives XII. 3-Acyl-substituted imidazo[1,2-a]benzimidazoles

Stable 3-acetyl derivatives of imidazo[1,2-a]benzimidazole were synthesized by the action of acetic anhydride on 2,9-disubstituted imidazo[1,2-a]benzimidazole. The former were also obtained by cyclization of 1-alkyl (aralkyl) -3-acylmethyl-2-iminobenzimidazoline hydrobromides in acetic anhydride in the presence of anhydrous sodium acetate. 3-Benzoyl-substituted imidazo[1,2-a]benzimidazoles, which are unstable in acidic media, were synthesized by the action of benzoyl chloride in the presence of pyridine or excess starting imidazo [1,2-a] benzimidazole.See [1] for communication XI.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 121– 125, January, 1976.     

Research on imidazo[1,2-a]benzimidazole derivatives.

3-Alkoxycarbonyl-2-arylimidazo[1,2-a]benzimidazoles were synthesized by alkaline cleavage of 3-trichloromethyl ketones of the imidazo[1,2-a]benzimidazole series, which are formed by acylation of this three-ring system with trichloroacetyl chloride. The same compounds were also obtained by esterification of the corresponding 3-carboxylic acid. The haloform reaction with 3-acetyl-2-phenylimidazo[1,2-a]benzimidazole proceeds anomalously and leads to bis(9-methy1-2-phenylimidazo[1,2-a]benzimidazo1-3-yl)-2-buten-1,4-dione, the structure of which was confirmed by independent synthesis.See [1] for communication XV.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 522–525, April, 1978.