A versatile method for the synthesis of benzimidazoles from o-nitroanilines and aldehydes in one step via a reductive cyclization

Synthesis

Volumn , Issue 1, 2005, Pages 47-56

  Yang, Donglai ^a,b   Fokas, Demosthenes ^a   Li, Jingzhou ^a   Yu, Libing ^a   Baldino, Carmen M ^a  

^a ARQULE INC   (United States)

^b SSCI Incorporated   (United States)

Author keywords

Benzimidazoles; Imidazopyridines; Imidazoquinolines; Reductive cyclization; Sodium dithionite

Indexed keywords

ALDEHYDES; BENZENE; HEATING; SODIUM COMPOUNDS; SOLUTIONS; SOLVENTS;

BENZIMIDAZOLES; HETEROCYLIC RING SYSTEMS; REGIOSELECTIVE SYNTHESIS;

SYNTHESIS (CHEMICAL);

1 (2 PHENYLETHYL) 2 PYRIDIN 2 YL 5 (TRIFLUOROMETHYL) 1H BENZIMIDAZOLE; 1 (3 CHLOROPHENYL) 2 (3 METHYLPHENYL) 5 (TRIFLUOROMETHYL) 1H BENZIMIDAZOLE; 2 (4 FLUOROPHENYL) 7 METHYL 1H IMIDAZO[4,5 B]PYRIDINE; 2 (4 METHOXYPHENYL) 1 (6 METHOXYPYRIDIN 3 YL) 1H BENZIMIDAZOLE; 2 (4 METHOXYPHENYL) 1H BENZIMIDAZOL 5 AMINE; 2 (4 METHOXYPHENYL) 1H BENZIMIDAZOL 5 OL; 2 (4 METHOXYPHENYL) 1H BENZIMIDAZOL 7 OL; 2 (4 METHOXYPHENYL) 1H IMIDAZO[4,5 F]QUINOLINE; 2 CYCLOPROPYL 1 (2 PHENYLETHYL) 5 (TRIFLUOROMETHYL) 1H BENZIMIDAZOLE; 2 NITROANILINE DERIVATIVE; 4 (1 ETHYL 1H BENZIMIDAZOL 2 YL) N,N DIMETHYLANILINE; 4 [2 (4 METHOXYPHENYL) 1H BENZIMIDAZOL 1 YL] N,N DIMETHYLANILINE; 5 CHLORO 2 (2 METHOXYPHENYL) 1H BENZIMIDAZOLE; [2 (2 CHLOROPHENYL) 1H BENZIMIDAZOL 5 YL](PHENYL)METHANONE; ALDEHYDE DERIVATIVE; ANILINE DERIVATIVE; BENZIMIDAZOLE DERIVATIVE; HETEROCYCLIC AMINE; IMIDAZOPYRIDINE DERIVATIVE; IMIDAZOQUINOLINE DERIVATIVE; SODIUM DITHIONITE; UNCLASSIFIED DRUG;

AQUEOUS SOLUTION; ARTICLE; CHEMICAL ANALYSIS; CYCLIZATION; HEATING; REACTION ANALYSIS; REDUCTION; STEREOCHEMISTRY; STRUCTURE ANALYSIS;

EID: 12344311063     PISSN: 00397881     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-2004-834926     Document Type: Article

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46. We observed that the presence of the aldehyde had a dramatic effect on the reduction of the starting o-nitroaniline as shown in Scheme 3. Imine formation could facilitate the aryl nitro group reduction because of electronic effects. Indeed, the fact that the corresponding benzimidazole (rather than the arylene diamine) is captured in high yield as the end product could indicate that the thermodynamically formed benzimidazole might be the one driving the nitro reduction. (Chemical Equation Presented)
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