Reactions of 2-carbonyl- and 2-hydroxy(or methoxy)alkyl-substituted benzimidazoles with arenes in the superacid CF3SO3H. NMR and DFT studies of dicationic electrophilic species

Reactions of 2-carbonyl- and 2-hydroxy(or methoxy)alkylbenzimidazoles with arenes in the Brønsted superacid TfOH resulted in the formation of the corresponding Friedel–Crafts reaction products, 2-diarylmethyl and 2-arylmethyl-substituted benzimidazoles, in yields up to 90%. The reaction intermediates, protonated species derived from starting benzimidazoles in TfOH, were thoroughly studied by means of NMR and DFT calculations and plausible reaction mechanisms are discussed.

Potassium carbonate (5 mmol) was added to a stirring solution of benzimidazole-2-methanol (1 mmol) in DMF (2 mL). The reaction mixture was stirred at room temperature for 24 h prior to being diluted with methylene chloride (8 mL) and sodium chloride (8 mL). The organic layer was separated, and the aqueous layer was extracted with methylene chloride (8 mL × 2). The combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo to provide a crude product, which was subjected to column purification using DCM/MeOH 100:5 (v/v) as eluent to yield the title compounds.

S5
General procedure for the reaction of benzimidazoles 1,2 with arenes in TfOH and H2SO4. Synthesis of compounds 9-11 (Table 3 and Scheme 2). Benzimidazole 1 or 2 (1 mmol) was added to the mixture of TfOH (1 mL) or H2SO4 (2 mL) and arene (2-18 mmol). Reaction mixture was stirred at room temperature for the time as indicated in Table 3 or Scheme 2. The mixture was poured into ice water (30 mL). After extraction with CH2Cl2 (3 × 30 mL), the combined extracts were consequently washed with water (50 mL), saturated aqueous solution of Na2CO3 (30 mL), water (50 mL), dried with anhydrous Na2SO4 and evaporated in vacuo to give crude products, which was subjected to chromatographic separation on silica gel using petroleum ether/diethyl ether as an eluent.
General procedure for the reaction of benzimidazole 1 with benzene under the action of strong Lewis acids AlCl3 or AlBr3. Synthesis of compound 9a (Table 3). Benzimidazole 1 (1 mmol) was added to the mixture of AlCl3 or AlBr3 (5.0 mmol) in benzene (3 mL). The reaction mixture was stirred at room temperature for the time as indicated in Table 1. The mixture was quenched with ice water (50 mL), extracted and worked-up as described above.
General procedures for the reaction of benzimidazoles 3-8 with arenes in TfOH in high pressure tube. Synthesis of compounds 12-14 (Tables 4, 5, Scheme 3). Solution of benzimidazole (0.1 mmol) in TfOH (1 mL) and arene (0.1 mL) was magnetically stirred at 140 °C in glass high pressure tube for 2.5 h, then poured into water (50 mL). After extraction with CH2Cl2 (3 × 30 mL), the combined extracts were consequently washed with water (50 mL), saturated aqueous solution of Na2CO3 (30 mL), water (50 mL), dried with anhydrous Na2SO4 and evaporated in vacuo to give crude products, which were subjected to chromatographic separation on silica gel using petroleum ether/diethyl ether as an eluent.

Summary of Natural Population Analysis:
Natural

Summary of Natural Population Analysis:
Natural

Summary of Natural Population Analysis:
Natural

Summary of Natural Population Analysis:
Natural

Summary of Natural Population Analysis:
Natural