Synthesis
General procedure for the synthesis of benzimidazole-2-acetic acid from 2-cyanomethylbenzimidazole: A mixture of 1 g of 2-cyanomethylbenzimidazole (3a-b) with 2 ml of 37% aqueous hydrochloric acid in the presence of 1 ml of benzenesulphonic acid was heated and stirred under reflux conditions for 4-5 hours. The reaction process was monitored by thin layer chromatography (TLC). Upon completion of the reaction, the reaction mixture was cooled to room temperature and extracted with ether (3 x 30 ml), followed by removal of solvent by distillation under reduced pressure to afford the target products benzimidazole-2-acetic acid (4a-b).
4.3.1. 1H-benzimidazole-2-acetic acid (4a, C9H8N2O2) was a green solid, hygroscopic, with a yield of 81% and a melting point of 240-242 °C; TLC Rf value of 0.42 [unfolding reagent ratio of toluene: ethyl acetate: formic acid (5:4:1)]; IR spectra (KBr, cm^-1 ): 3624 (O-H telescoping vibration) 3230 (N-H stretching vibration), 1722 (C=O stretching vibration); 1H NMR (300MHz, DMSO-d6) δ (ppm): 3.64 (single peak, 2H, CH2COOH), 7.58 (double peaks, 2H, J=7.5,0.9Hz, H-5,6 on benzimidazole ring), 7.92 (double peaks, 2H, J=7.5 Hz, H-4,7 on the benzimidazole ring), 10.59 (broad peak, 1H, COOH), 12.03 (broad peak, 1H, NH).13C NMR (75 MHz, DMSO-d6) δ (ppm): 164.20, 152.20, 131.95, 128.32, 122.50, 48.40. Calculated values for elemental analysis (%) : C, 61.36; H, 4.58; N, 15.90; measured values (%): C, 61.33; H, 4.56; N, 15.92.
References
[1] Patent: US5792768, 1998, A
[2] Farmaco, 2002, vol. 57, # 5, p. 363 - 367
[3] European Journal of Medicinal Chemistry, 2017, vol. 126, p. 853 - 869
[4] Journal of Medicinal Chemistry, 1993, vol. 36, # 12, p. 1746 - 1753
[5] Patent: WO2017/68089, 2017, A2. Location in patent: Page/Page column 243
