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.     

Cyclization of 3-Ethoxycarbonylmethyl-, 3-Cyanomethyl-, and 3-Acetylmethyl-1-amino-2-methylbenzimidazolium Salts Effected by Acetic Anhydride in the Presence of a Base

3-Ethoxycarbonylmethyl- and 3-cyanomethyl-1-amino-2-methylbenzimidazolium chlorides cyclized at treatment with acetic anhydride in the presence of potassium carbonate to afford a mixture of derivatives of pyrazolo[1,5-a]benzimidazole and 4-aminopyrrolo[1,2-a]benzimidazole. Therewith in the first case prevails the process of pyrazole ring fusion, and in the latter pyrrole ring is fused. 3-Aroyl(thenoyl)methyl-1-amino-2-methylbenzimidazolium bromides under the same conditions are converted into 1-aroyl(thenoyl)-2-methyl- and 2-4-acetamido-3-acetylpyrrolo[1,2-a]benzimidazoles.     

Ring contraction of thia(seleno)diazine rings into pyrazoles in the reaction of 3-aryl-10-methyl-2H-1,3,4-thia(seleno)diazino[3, 2-a]benzimidazolium salts with bases

Reaction of 3-aryl-10-methyl-2H-1,3,4-thiadiazino[3,2-a]benzimidazolium salts with triethylamine led to ring contraction of the thiadiazine ring to a pyrazole ring with the formation of a mixture of derivatives of 3-mercaptopyrazolobenzimidazole and di(pyrazolo[1,5-a]benzimidazolyl-3) disulfide. The disulfides were formed exclusively when these salts react with ethanolic alkali. The reaction with potassium carbonate in acetic anhydridegave3-acetylthiopyrazolo[1,5- a]benzimidazoles. 2-Aryl-4- alkylpyrazolo[1, 5- a]benzimidazoles were formed by heating thiadiazino[3,2-a]benzimidazolium salts in formamide and by treating selenodiazino[3,2-a]benzimidazolium salts with potassium carbonate in acetic anhydride.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1698–1705, 1992.     

Research on imidazo[1,2-a]benzimidazole derivatives. 25. Reaction of 2,9-disubstituted imidazo[1,2-a]benzimidazoles with acrylic acids and their derivatives

The substitutive addition of acrylic acids and their esters, amides, and nitriles to 2,9-disubstituted imidazo[1,2-a]benzimidazoles, which leads to 3-(imidazo[1,2-a]benzimidazol-3-yl)propionic acids and their derivatives, was studied. The rate of addition depends on the structure of the unsaturated compound, the nature of the substituent in the 2 position, the magnitude of the charge on the carbon atom in the 3 position of the heteroring, and the reaction conditions. The addition proceeds most smoothly in polyphosphoric acid (PPA). In the case of acrylonitrile imidazo[1,2-a]benzimidazol-3-ylpropionic acid amides were isolated in PPA. In the reaction of - or -substituted acrylic acids with 2-phenylimidazo[1,2-a]benzimidazoles in PPA, in addition to the corresponding imidazo[1,2-a]benzimidazol-3-ylpropionic acids, products of their intramolecular cyclodehydration at the ortho position of the phenyl substituent are formed.See [1] for Communication 24.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1496–1502, November, 1987.     

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.     

Studies of imidazo[1,2-a]benzimidazole derivatives. 21. Synthesis of haloketones in the imidazo[1,2-a] benzimidazole series

Methods for the synthesis of imidazo[1,2-a]benzimidazole haloketone derivatives have been investigated. It has been found that -bromoketone derivatives of this heterocycle can be prepared either by bromination of 3-acylimidazo[1,2-a]benz-imidazoles with bromine in glacial acetic acid or by acylation of 3-unsubstituted imidazo[1,2-a]benzimidazoles with haloanhydride derivatives of -bromoalkanoic acids. Treatment of imidazo[1,2-a]benzimidazoles with 3-chloropropionyl chloride results in the formation of imidazo[1,2-a]benzimidazolyl-3-propionyl chloride and bis(imidazo[1,2-a]benzimidazolyl)propan-3-one derivatives as side products. Reaction of 2-phenylimidazo[1,2-a]benzimidazoles with 3-bromopropionic acid in polyphosphoric acid gives benzocyclohepten[5,6:4,5]imidazo[1,2-a]benzimidazole derivatives.For Communication 20, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 339–345, March, 1986.     

Synthese von imidazo[1,5-a]- und pyrazino[1,2-a]benzimidazolen

1,2-Dihydro-3H-imidazo[1,5-a]benzimidazoles (6), 1-oxo-1,2-dihydro-3H-imidazo[ 1,5-a] benzimidazoles (8), 3H-imidazo[1,5-a]benzimidazoles (7), 3-oxo-1,2,3,4-tetrahydro-pyrazino[1,2-a] benzimidazoles (12), and 3,4-dioxo-1,2,3,4-tetrahydro-pyrazino[1,2-a]benzinudazoles (13) were synthesized from 2-α-aminobenzyl (benzhydryl)-benzimidazoles (2).     

Research in the field of imidazo[1,2-a]benzimidazole derivatives: XXVII. 1-acylmethyl-2-(ω-hydroxyalkylamino)-benzimidazoles and their transformation into derivatives of tricyclic systems

1-Acylmethyl-2-(ω-hydroxyalkylamino)benzimidazoles were synthesized and their behavior under various conditions was investigated: at the thermolysis without solvent, at heating in DMF or in 2-aminoethanol, hydrohalic acids, and acetic anhydride, in the presence of chlorinating agents (SOCl₂, POCl₃). Depending on the reaction conditions derivatives were obtained of 1H-imidazo[1,2-a]-benzimidazole, 9H-2,3-dihydroimidazo[1,2-a]benzimidazole, and 10H-2,3,4,10-tetrahydropyrimido[1,2-a]-benzimidazole that were suitable synthons for the synthesis of functionally substituted derivatives of these tricyclic systems.     

Acylation of pyrrolo[1,2-a]pyrazines

The acylation of pyrrolo[1,2-a]pyrazines with acetic anhydride and the acid chlorides of various carboxylic acids has been studied. It has been shown that pyrrole[1,2-a]pyrazines are selectively acylated at the α-position of the pyrrole ring when it is free. Products of the condensation of 1-methylsubstituted pyrrolo[1,2-a]pyrazines have been obtained for the first time in the process of acetylation. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, 263–272, February, 2008.     

Base-catalyzed cyclization reactions of 2-[2-(2,4-dimethyl-3-oxopentyl)]benzimidazoles with acetic anhydride and its homologs

2-[2-(2,4-Dimethyl-3-oxopentyl)]benz, imidazoles ( 2-10 ) were obtained by allowing o-phenyl-enediamines to react with 2,2,4,4-tetramethyl-1,3-cyclobutanedione ( 1 ). When refluxed with acetic anhydride (or sterically unhindered homologs) they cyclize in the presence of base to yield the pyrido[1,2-α]benzimidazoles ( 16-21 and 24, 25 ). The 2-[2-(2,4-dimethyl-3-oxo-pentyl) ]imidazolines ( 12 and 14 ) were obtained by reaction of 1,2-diaminoethane and 1,2-diaminopropane, respectively, with 1 . When allowed to react with acetic anhydride/base, they gave only N-acylated products.     

Cyclisierungsbreaktionen von 2-aminobenzimidazolen zu s-triazino[1,2-a]benzimidazolen

2 - Aminobenzimidazolyl - 1 - phenylimidate 1; 1 - cyan - 2 - aminobenzimidazole 5 and 2 - aminobenzimidazolyl - 1 - amidines 8 were synthesized. 1 and 8 give with aromatic aldehydes or acids 1,2 - dihydro - 3 - aryl - 4 - phenoxy(or amino) - s - triazino[1,2-a]- or 2 - aryl - 4 - phenoxy(or amino) - s - triazino[1,2-a] - benzimidazoles 3, 3a, 4, 4a. 5 gives with isocyanates or azomethines tetrahydro - s - triazino[1,2-a] - benzimidazoles 6 and 7. The mass- and IR-spectres of the synthesized compounds are discussed.     

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.     

Synthesis of substituted diazines,diazoles, and condensed thia- and oxadiazoles

The corresponding 2-arylhydrazono-3-oxoimidazo[1,2-a]pyridines, 3-arylhydrazono-2-oxoimidazo [1,2-a]benzothiazoles, 2-oxoimidazolidino[3,2-a]benzimidazoles, 2-oxoimidazo[1,2-a]benzoxazoles, and 2-arylhydrazono-3-oxothiazolo[2,3-a]benzimidazoles were obtained by the condensation of arylazochloroacetyl chlorides with 2-aminopyridine, 2-aminobenzothiazole, 2-aminobenzoxazole, 2-aminobenzimidazole, and 2-mercaptobenzimidazole. 5-Arylhydrazono-1,2-diphenylimidazole-4-ones and 5-arylhydrazono-3,4-diaryl-1,2,4-oxidiazine-6-ones were synthesized by the reaction of arylazochloroacetyl chlorides with N-phenylbenzamidine and N-phenylamidoxime.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 930–936, July, 1971.     

1,2,3,9a-Tetrahydro-9H-imidazo[1,2-a]indoles

When derivatives of 1,2,3,9a-tetrahydro-9H-imidazo[1,2-a]indol-2-one or 1-carbamoylmethyl-2-methylene-2,3-dihydroindole are reacted with lithium aluminum hydride, derivatives of 1,2,3,9a-tetrahydro-9H-imidazo[1,2-a]indole are formed. Under the same conditions 1-(N-phenylcarbamoylmethyl)-2-methylene-2,3-dihydroindole is not cyclized to an imidazo[1,2-a]indole. WHen treated with proton acids imidazo[1,2-a]indoles are converted to 3H-indolium salts. Opening of the imidazolidine ring is also found when imidazo[1,2-a]indole is acylated with benzoyl chloride.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 227–230, February, 1987.     

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.     

Research on imidazo[1,2-a]benzimidazole derivatives. 22. Synthesis of 2,3-dihydroimidazo[1,2-a]benzimidazoles starting from 2-imino-3-(2-hydroxyethyl)benzimidazolines

A -elimination reaction with the formation of 2-imino-3-vinylbenzimidazolines occurs simultaneously with intramolecular alkylation and the formation of an imidazoline ring in the action of alcoholic alkali on 2-imino-3-(2-chloroethyl) benzimidazolines. The thermolysis of 3-chlorethyl-substituted imines without a solvent or in an inert solvent leads exclusively to 2,3-dihydroimidazo[1,2-a] benzimidazoles. An attempt to obtain the latter directly from 2-imino-3-(2-hydroxyethyl) benzimidazolines by the action of a mixture of thionyl chloride and acetic anhydride on them also leads to ambiguous results.See [1] for communication 21.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 918–925, July, 1986.     

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.     

Alkylation of 1,2,3,9a-tetrahydro-9H-imidazo[1,2-a]indol-2-ones

Reaction of 1,2,3,9a-tetrahydro-9H-imidazo[1,2-a]indol-2-ones with dimethyl sulfate and haloalkanes in DMF or DMSO in the presence of potassium hydroxide gives the 1-substituted 1,2,3,9a-tetrahydro-9H-imidazo[1,2-a]indol-2-ones (N-substituted products) and 9,9a-dihydro-3H-imidazo[1,2-a]indoles (O-substituted products). The latter, on treatment with acids and bases, are converted into 1-alkoxycarbonylmethyl-2,3-dihydro-1H-indoles. 1-Ethoxycarbonyl-methyl-2,3-dihydro-1H-indoles on treatment with lithium aluminohydride undergoes cyclization to 2,3,9,9a-tetrahydrooxazolo[3,2-a]indole.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 49–53, January, 1988.     

3-α-Halocarbonyl derivatives of pyrazolo[1,5-a] benzimidazole and their reactions

3-(-haloacyl)-2,4-dialkylpyrazolo[1,5-a]benzimidazoles can be obtained either by brominating 3-acetylpyrazolo[1,5-a]benzimidazoles with bromine in acetic acid, or by acylating the 3-unsubstituted pyrazolobenzimidazoles with haloacetic halides. Halogenation of 3-acetylpyrazolo[1,5-a]benzimidazoles with bromine in acetic acid in the presence of sodium acetate, and bromination with N-bromosuccinimide or 1-chlorobenzotriazole, result in deacylation to give 3,6(7)-dibromo- and 3-chloropyrazolo[1,5-a]benzimidazoles. The mono- and trihaloketones obtained have been used to prepare the corresponding aminoketones, the 3-carboxylic acid, and its derivatives.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 43–48, January, 1988.     

Heteroaromatic annulation of 2-methyl/2-cyanomethylbenzimidazole dianions with alpha-oxoketene dithioacetals: a highly regioselective synthetic protocol for 1,2- and 2,3-substituted/annulated pyrido[1,2-a]benzimidazoles

A highly efficient and regioselective annulation protocol for a series of linearly 2,3- and angularly 1,2-substituted and annulated pyrido[1,2-a]benzimidazoles involving [3 + 3] cyclocondensation of the dianions generated from 2-methyl (2A) and 2-cyanomethyl (3A) benzimidazoles with a variety of alpha-oxoketene dithioacetals has been reported. Thus the dianion 2A derived from 2-methylbenzimidazole has been shown to undergo regioselective 1,2-addition with various alpha-oxoketene dithioacetals derived from acyclic (4a-d) and cyclic ketones (13a,b, 20, 29 and 32) to afford various carbinol acetals which on intramolecular cyclocondensation in the presence of phosphoric acid furnish the corresponding 1-methylthio-2,3-substituted (5a-c) and 2,3-fused linear polycyclic (14a,b,21, 30, and 33) pyrido[1,2-a]benzimidazoles in high yields. Similarly the dianion 3A from 2-cyanomethylbenzimidazole undergoes one-pot conjugate addition-elimination and cyclocondensation with these alpha-oxoketene dithioacetals to give 4-cyano-3-(methylthio)-1(or 1,2-)-substituted (6a-d) and the corresponding angularly 1,2-fused (16a,b, 23, 31, and 34) polycylic analogues of pyrido[1,2-a]benzimidazoles in excellent yields.