2 Substituted Benzimidazole

Reason for the exclusive formation of 2-substituted benzimidazole is uncertain but it is very interesting because most of the acid mediate transformation to benzimidazole gave 1,2-disubstituted derivatives. One possible reasons for exclusive formation of 2-substituted chiral benzimidazole or 2-(2-alkoxy phenyl) substituted benzimidazole could be the formation of H-bond between NH and 2 or β -alkoxy oxygen (Figure 3.2) may prevent further reaction with second molecules of aldehyde since excess aldehyde have no influence on the course of the reaction. Crystal structure of compound 3.3.4j (entry 10, Table 3.3) clearly indicated the presence of strong hydrogen bond between benzimidazole NH and side chain oxygen atom. Herein disfavouring to bis-imine formation leading to 1, 2-disubstituted benzimidazole due to steric congestion could not be avoided. Formation of …show more content…
1) formation with aromatic aldehydes possessing electron with-drawing group might be disrupted by the powerful PIL-II catalyst and the second amino group of monoimine (B, eq. 2) is allowed for ring closing to construct dihydrobenzimidazole-PIL-II intermediate (D). Subsequent releases of PIL-II.H leading to synthesis of 2-substituted benzimidazoles (4). We performed another experiment using 2-chlorobenzaldehyde and OPD in the presence of 5 mol% of PIL-II under N2 atmosphere, we were pleased to observe that only 2-(2-chlorophenyl) benzimidazole (4a) was formed after 1 h at room temperature in 72% yield. A possible mechanism to explain the exclusive formation of the 2-disubstituted benzimidazoles from the reaction between OPD and 2-alkoxy aldehyde is depicted in eq. 3. Presumably, -NH2 group of OPD attack PIL-II activated aldehyde forming imine (E), which is arrested immediately after its formation via hydrogen bonding and immediately undergoes ring closing to dihydrobenzimidazole F followed by aromatization to afford 2-substituted benzimidazoles