Pyrrolo benzimidazol

Schulz, W. G. Nieman, R. A. Skibo, E. B. Evidence for DNA phosphate backbone alkylation and cleavage by pyrrolo[l,2-a] benzimidazoles, small molecules capable of causing sequence specific phosphodiester bond hydrolysis. Proc. Natl. Acad. Sci. USA 1995, 92, 11854-11858. 

Pyrrolo[l,2-a]benzimidazoles [181] (R = H, Me, Ph R = Me, CH2Ph), unsubstituted at the 1- and 3-positions, protonate in trifluoroacetic acid exclusively on C-1 (Alekseeva et al., 1972b). A methyl substituent in the 1-position leads to mixtures of C-1 and C-3 protonated forms, the relative amounts depending on the presence and nature of substituents at C-3. Without a C-3 substituent, the extent of protonation at the position is 81%, but decreases to 18% in the 3-methyl- and 3-phenyl derivatives the basicity of the derivatives increases simultaneously. 

Alekseeva et al. (1972b) have carried out a comparison of calculated values of localization energies and free valency indices of pyrrolo[ 1,2-a] imidazole, pyrrolo[l,2-a] benzimidazole and indolizine. In all these molecules the a-position of the pyrrole ring is calculated to be more reactive than the / -position. The free valence indices increase in the order indolizine < pyrrolobenzimidazole < pyrroloimidazole, which is also the order of increasing basicity. 

Das symmetrische 2,5-Bis-[2-pyridyl-amino]-l,4-dichlor-benzol setzt sich bei der Photolyse un-ter zweifacher Cyclisierung zu 13H-(Pyrido[l, 2-a]-(pyrrolo[2,3-h pyrido) [3,2-f]-benzimidazol ) (37%) um. Nebenprodukte sind.die monocyclisierten 8-(2-Pyridyl-amino)-[Pg.247]

Pyrrolo[2,l-6]thiazoles,28,29,270-273 pyrrolo[l,2-a]imidazoles,38,274-277 pyrrolo[ l,2-a]benzimidazoles,38, 278-288 pyrrolol l,2-6]-s-triazoles,289 and pyrrolo[2,l-c]-s-triazoles290 have been prepared by this route. 

The situation is more complex for 364 if R — methyl or benzyl, for then a series of compounds is formed. These have been described as as azepinobenzimidazoles,210 but are probably cyclobuta[4,5]pyrrolo-[l,2-a]benzimidazoles (cf. 369 and compounds from DM AD and 2-methylquinoline). Minor products from these reactions may have structure 365, and similar compounds have been obtained from 2-benzimidazolylacetonitrile and ethyl 2-benzimidazolylacetate.208... 

Reaction of 3-substituted 1-alkylbenzimidazolium ylids (424) (derived from the salts 423) with EP gave228 pyrrolo[l,2-a]benzimidazoles (425). 

Chemical Name 2H-Benzimidazol-2-one, l,3-dihydro-l-[l-[(4-methyl-4H,6H-pyrrolo[l,2-a][4,l]benzoxazepin-4-yl)methyl]-4-piperidinyl]-, maleate (1 1)... 

To a solution of 7.5 g thereof, in 300 ml of tetrahydrofuran is added 5 g of l,l -carbonyldiimidazole and the resultant mixture stirred at room temperature for 1 hour. To this mixture is added 5 g of l,3-dihydro-l-(4-piperidyl)-2H-benzimidazol-2-one, and the reaction is heated at reflux temperature for 48 hours. After cooling to room temperature, the reaction mixture is poured into 150 ml of ice-water and extracted into 150 ml of methylene chloride. The organic extracts are washed successively with 150 ml of sodium carbonate solution, 150 ml of water and 150 ml of dilute hydrochloric acid, then dried over magnesium sulfate, filtered, and the solvent is evaporated under reduced pressure to yield l,3-dihydro-l- l-[(4-methyl-4H,6H-pyrrolo[l,2-a][4,l]benzoxazepin-4-yl)carbonyl]-4-piperidinyl -2H-benzimidazol-2-one, m.p. 208°-210°C. 

Dihydro-2-methyMH-pyrrolo[l,2-a]benzimidazole (Table 1, Column C, Entry 4)... 

Tr-Density calculations for l//,5//-pyrrolo[2,3-/Iindole (8.164) and 3//,6//-pyrrolo 3,2-c]indole (8.165) indicate 3,7- and 1,8-substitution, respectively, as found in acylation and diazonium coupling (83CHE871). MO calculations indicate that the 1- and 3-positions are the most reactive ones in 4//-pyrrolo[ 1,2-u]benzimidazole (8.166) (74CHE230). The same result is more easily deduced and understood as follows. Although the lone pair on N-4 can be delocalized to the 1-, 3-, 5-, or 7-positions, the important factor is delocalization of the lone pair from N-9 to the 1- and 3-positions (e.g., as in 8.167). Although the 6tt pyrrole ring of the ground... 

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