Synthesis Reference(s)
Journal of Medicinal Chemistry, 39, p. 3375, 1996
DOI: 10.1021/jm9600959
Synthesis
The reaction was carried out with 4-aminobenzoic acid (5 g, 5.78 mmol) and o-phenylenediamine (3.9 g, 3.68 mmol) in polyphosphoric acid (12.5 g) with stirring at 200 °C for 5 hours. Upon completion of the reaction, the mixture was cooled to room temperature and slowly poured into crushed ice. Subsequently, the precipitate was stirred in cold water. The pH was adjusted with ammonium hydroxide solution to 7. The solid product was collected by filtration and washed several times with methanol. Finally, the target compound 4-(1H-benzimidazol-2-yl)aniline (5) was purified as a white solid by silica gel column chromatography using ethyl acetate: hexane (4:1) as eluent. Yield: 82%; Melting point: 207-209 °C; 1H NMR (400 MHz, DMSO-d6): δ= 7.96 (d, 2H, J = 8.72 Hz, ArH), 7.55-7.51 (m, 2H, ArH), 7.16-7.14 (m, 2H, ArH), 6.75 (d, 2H, J = 8.24 Hz, ArH) , 4.45 (bs, 2H, NH2); 13C NMR (100 MHz, DMSO-d6): δ= 152.2,148.4,127.5,120.9,118.6,113.8 (ArC); MS (ESI), m/z: 210.2 (M++1).
References
[1] Chemical and Pharmaceutical Bulletin, 2007, vol. 55, # 1, p. 115 - 117
[2] Chinese Chemical Letters, 2011, vol. 22, # 3, p. 296 - 299
[3] European Journal of Medicinal Chemistry, 2017, vol. 126, p. 24 - 35
[4] European Journal of Medicinal Chemistry, 2016, vol. 117, p. 59 - 69
[5] Journal of the Chilean Chemical Society, 2012, vol. 57, # 2, p. 1122 - 1125,4
