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.     

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

The protonation of a number of pyrrolo[1,2-a]imidazole derivatives in trifluoroacetic acid was studied by PMR spectroscopy. The 5,7-unsubstituted compounds form a mixture of two forms of cations, the structures of which correspond to the addition of a proton to the C₅ and C₇ atoms of the two-ring system with predominance (60–90%) of the 5-C cation. The introduction of a CH₃ group into the 5 position changes the direction of protonation to favor predominant (95%) formation of the 7-C cation. The 7-methyl derivatives of pyrroloimidazole are protonated exclusively at the C₅ atom. It is demonstrated that the basicity of the pyrroloimidazoles considerably surpasses the basicity of indolicine derivatives. The comparative proton-acceptor capacity of these systems is compared with the energy indexes and the reactivity indexes calculated by the simple MO LCAO method.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 492–497, April, 1972.     

Synthesis of pyrrolo[1,2-a]pyrimidine derivatives

8-Cyanopyrrolo[1,2-a]pyrimidines, the cyano group of which is eliminated when they are heated with phosphoric acid, were obtained by reaction of 2-amino-3-cyanopyrroles with acetylacetone.Compounds Ia, c-g were described earlier in [3], while Ib, h are described in the present work.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1677–1681, December, 1976.     

Protonation of pyrrolo [1,2-α] Pyrimidine derivatives

The protonation of pyrrolo [1,2-] pyrimidine and 6, 7, 8, 9-tetrahydropyrimido [1, 2-] indole derivatives in CF₃COOH (at –15 to +25° C) and in CF₃COOH/H₂SO₄ (at 25°) was studied by PMR spectroscopy. The investigated compounds form monocations, the structure of which corresponds to the addition of a proton to the carbon atom of th pyrrole fragment in the position to the bridge nitrogen atom.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 686–692, May, 1976.     

Synthesis of unsymmetrically tetrasubstituted pyrroles and studies of AIEE in pyrrolo[1,2-a]pyrimidine derivatives

Pyrroles are among the most important heterocycles in pharmaceuticals and agrochemicals. Construction of pyrrole scaffolds with different substituents and a free NH group, however, is challenging. Herein, a metal-free method for the synthesis of unsymmetrically tetrasubstituted NH-pyrroles using a consecutive chemoselective double cyanation is reported. The desired pyrroles were obtained with yields up to 99% and good functional group tolerance. Mechanistic studies identified a reaction mechanism that features a subtle sequence of first cyano-addition and migration, followed by cyano-addition and aromatization to afford the pyrrole skeleton. Pyrrolo[1,2-a]pyrimidines are synthesized as the synthetic applications of NH-pyrroles, and these pyrrolo[1,2-a]pyrimidines exhibit unpredicted time-dependent aggregation-induced emission enhancement (AIEE) properties.

A novel method for the challenging synthesis of unsymmetrically tetrasubstituted NH-pyrroles from chalcone derivatives is reported. The pyrrolo[1,2-a]pyrimidine derivatives that were synthesized from NH-pyrroles exhibit AIE and AIEE property.     

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.     

Pyrrolothienopyrazines: Synthèse de la pyrrolo[1,2-a]thieno[3,2-e]pyrazine et de la pyrrolo[1,2-a]thieno[2,3-e]pyrazine

The synthesis of pyrrolo[1,2-α]thieno[3,2-e]pyrazine and pyrrolo[1,2-α]-thieno[2,3-e]pyrazine is described. These syntheses could be achieved by intramolecular cyclization of 2- (and 3-) (1-pyrrolyl)-3- (and -2)-thienyl-amines obtained by hydrolysis of carbamates or by cleavage of the corresponding ureas. An original way giving better results was also studied via a Curtius rearrangement by reaction between the azide and aldehyde groupings. The synthesis of 2- (and -3)-2-formyl-1-pyrrolyl)-2- (and -3)-thenoylazide is described.     

Synthesis of pyrido[2,3-e]pyrrolo[1,2-a]pyrazine derivatives via tandem iminium cyclization and smiles rearrangement

The tandem iminium cyclization and Smiles rearrangement of pyridinyloxyacetaldehyde 1 and a primary amine generated a novel pyrido[2,3-e]pyrrolo[1,2-a]pyrazine scaffold. TFA was discovered to be an efficient catalyst in the reactions with aromatic amines, whereas TiCl4 was found to be superior in the case of aliphatic amines. This methodology proved to be efficient in the preparation of a library of diversified pyrido[2,3-e]pyrrolo[1,2-a]pyrazine derivatives.     

A facile synthesis of pyrrolo[1,2-a]pyrimidines and pyrrolo[1,2-a]imidazoles

The one-step synthesis of 8-t-butoxycarbonyl-6,7-dimethyl-2-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrimidine from acetyl methyl carbinol, 3-aminopropionic acid, and t-butyl cyanoacetate is reported. Utilizing a similar technology under basic conditions, 7-substituted 5,6-dimethyl-2-oxo-2,3-dihydro-(1H)-pyrrolo[1,2-a]imidazole is synthesized from acetyl methyl carbinol, ethyl glycinate, and the appropriate acetonitrile.     

Cyclization of 1-benzyl-1,2-dihydro-2-(substituted methylene)quinolines to pyrrolo[1,2-a]quinoline derivatives

1-Alkyl-2-alkylthioquinolinium salts were prepared from 1-alkyl-2(1H)-quinolones via 1-alkyl-2(1H)-thioquinolones in two steps. Under mild conditions, the reaction of 1-alkyl-2-alkylthioquinolinium iodides with active methylene compounds in the presence of sodium hydride afforded 1-alkyl-1,2-dihydro-2-(substituted methylene)quinolines in good yields. The cyclization of 1-benzylquinolines using acetic anhydride produced the corresponding pyrrolo[1,2-a]quinoline derivatives.     

Synthesis and anti-inflammatory activity of imidazo [1,2-a] pyrimidine derivatives

A series of imidazo[1,2-a]pyrimidine derivatives substituted adjacently with two aryls at positions 2 and 3 were designed and synthesized in order to improve their anti-inflammatory activities. Biological tests suggested that these compounds have antiinflammatory activities with COX-2 selectivity to some extent.     

Synthesis and properties of pyrrolo[1,2-a]pyrazines (review)

The synthesis and properties of pyrrolo[1,2-a]pyrazines are reviewed.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1299–1311, October, 1991.     

A new method for the synthesis of pyrrolo[1,2-a]pyrazines and pyrrolo[1,2-a] quinoxalines

A new method is proposed for the synthesis of pyrrolo[1,2-a]pyrazines and pyrrolo[1,2-a]-quinoxalines. By the alkylation of sodium derivatives of 2-acylpyrroles with -bromo carbonyl compounds or their acetals and subsequent treatment of the reaction products with ammonium acetate in acetic acid, a number of derivatives of pyrrolo[1,2-a]pyrazine, including the first member of the class, pyrrolo[1,2-a]pyrazine itself, have been obtained. Similarly, from 2-benzoylpyrrole and the dimethyl ketal of -bromocyclohexanone was obtained 4-phenyltetrahydropyrrolo[1,2-a]quinoxaline, which readily dehydrogenates in the presence of Raney nickel to form 4-phenylpyrrolo[1,2-a]quinoxaline.Translated from Khimiya Geterotsiklicheskikh Soedinenii, Vol. 6, No. 8, pp.1048–1050, August, 1970.     

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.     

A new approach to the synthesis of pyrrolo[1,2-a]indole derivatives

Reactions of 2-(3,3-diamino-2-cyanoprop-2-enylidene)indolin-3-ones with amide acetals afforded derivatives of 3-aminomethyleneamino-2-cyano-9-oxo-9H-pyrrolo[1,2-a]indole and 3-amino-2-cyano-9-oxo-9H-pyrrolo[1,2-a]indole. The rate and pathway of the reaction depend on the reagents and solvents. The formation schemes for the compounds obtained were proposed. Their structures were proven by IR and ¹H NMR spectroscopy and mass spectrometry and confirmed by independent syntheses. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2186–2192, December, 2006.