4-(1H-BENZOIMIDAZOL-2-YL)-PHENYLAMINE

A mixture of 4-aminobenzoic acid (5 g, 5.78 mmol) and o-phenylenediamine (3.9 g, 3.68 mmol) were stirred in polyphosphoric acid (12.5 gm) at 200 °C for 5 h. The reaction mixturewas cooled and poured into crushed ice. The precipitate was thenstirred in cold water. Ammonium hydroxide solution was added until the pH 7 was achieved. The resulting solid was filtered andwashed several times with methanol and column chromatographedon silica gel in ethyl acetate: hexane (4:1) to afford thedesired product 4-(1H-benzimidazol-2-yl)-phenylamine (5) aswhite solid; yield: 82percent; mp: 207-209 °C; A mixture of 4-aminobenzoic acid (5 g, 5.78 mmol) and o-phenylenediamine (3.9 g, 3.68 mmol) were stirred in a syrupy polyphosphoric acid (12.5 gm) at 200 °C for 5 h. General procedure: Eaton’s reagent (10 vol; wt/vol)) was added drop wise to a wellpulverised mixture of the corresponding 1, 2-phenylenediamine(2a–e)/1, 2-diaminopyridine (2f) (1 equiv) and 4-amino benzoicacid (1 equiv) at 0 C. The reaction mixture was then heated at130 C for 5–6 h (monitored by TLC and LCMS for completion).The reaction mixture was cooled and neutralised with 10percent sodiumhydroxide solution to pH of 6–7, the precipitate formed was filteredand washed repeatedly with water and dried. The solidobtained was recrystallized from ethanol to afford the desiredproduct in good yield as described below.Amixture of o-phenylenediamine 1 (1.08 g, 0.01 mol) and paminobenzoicacid 2 (1.37 g, 0.01 mol) were stirred in asyrupy o-phosphoric acid (15 ml) at 200 °C for 2 h. Thereaction mixture was cooled and poured on crushed ice. Thebulky white precipitate obtained was stirred in cold water(150 ml) and sodium hydroxide solution (5 M) was addeduntil the pH 7. The resulting solid obtained 3 was filteredand recrystallized from methanol. Yield = 70percent, m.p.246–248 °C. IR (KBr) cm−1: 3357 (NH), 2985 (Ar–CH), 1675 (C=N), 1586 (C=C). 1H-NMR (CDCl3, 500 MHz) δppm: 7.09–8.24 (m, 8H, Ar–CH), 5.78 (s, 1H, NH ofbenzimidazole), 4.30 (s, 2H, NH2). 13C-NMR (CDCl3, 500 MHz) δ ppm: 155.2 (C-2), 148.5 (C′-1), 139.6 (C-8 and C-9), 130.3 (C′-3 and C′-5), 124.7 (C-5 and C-6), 122.2 (C′-4), 119.5 (C′-2 and C′-6), 118.1 (C-4 and C-7). EI-MS m/z: 209(M+). Anal. calcd for C13H11N3: C, 74.62; H, 5.30; N, 20.08. Found: C, 74.86; H, 5.28; N, 20.01.4-Aminobenzoic acid (5.00 g, 36.46 mmol), o-phenylenediamine (3.94 g, 36.46 mmol) andPPA (50.0 g, 10 eq.) were added to a 50 mL reaction vessel with a drying tube and heated at220 °C, with stirring for 5 h. The reaction progress was monitored by TLC using a 6:94mixture of MeOH:DCM. The resulting mixture was washed with 200 mL hot water into a10percent NaHCO3 solution (200 mL) and basified yielding a brown solid. This solid was washedwith water (3 x 400 mL) and crystallized from methanol and water to yield light brown needlecrystals of 1 (4.68 g, 61percent yield).ATR-FTIR max /cm-1 3360, 3441 (NH2); m.p. 240 - 241 °C (lit. 240 - 241 °C) [1]; Rf(MeOH/DCM 6:94) 0.49; δH (DMSO-d6, 400 MHz) 5.54 (s, 2H, NH2), 6.68 (d, J = 8.6 Hz, 2H), 7.11 (m, 2H), 7.49 (m, 2H), 7.86 (d, J = 8.6 Hz, 2H); δC (DMSO-d6, 100.6 MHz) 113.5, 113.5, 114.2 (Cquat), 117.3 (Cquat), 121.2, 127.7, 150.5 (Cquat), 152.6 (Cquat); HRMS-ES+Calculated: 210.1031 [M+H]+ for C13H12N3, Observed: 210.1031; C18 HPLC, flow rate: 1mL/min, H2O / acetonitrile (40:60), 99.1percent.4-(1H-Benzo[d]imidazol-2-yl)aniline was synthesized from o-phenylenediamine and p-aminobenzoic acid in the presence of an acid as a dehydrating agent. A mixture of o-phenylenediamine (30 mmol) and p-aminobenzoic acid (45 mmol) was refluxed in o-phosphoric acid (30 mL) at 180-200 °C for 4 h on an oil bath. After that, the reaction mixture was cooled to 50-60 °C and poured onto crushed ice. The reaction mixture was then neutralized with a sodium hydroxide solution (10percent, 70 mL) and the precipitate was collected by filtration. The raw product was washed with an excess 10percent sodium hydroxide solution and water and then dried. The product was further puried by crystallization from ethanol. Mp: 248.1-249.8 °C (lit. mp: 248 °C ; yield = 55percent; IR (KBr) ν1, 2-phenlendiamine (6.5 g, 60 mmol), 4-aminobenzoic acid (7.0 g, 51 mmol) and polyphosphoric acid (25 g) were placed into a flask and were stirred at 220 C for 4 hrs. After the mixture was cooled to ambient temperature, to the dark lump was added aq. K2CO3 (10 percent, 400 mL). The lump was neutralized with aq. NaHCO3 to pH ca. 7, and the formed solid was collected by filtration. The solid was washed with hot water (50-70 C) till the water was colorless. recrystallization in ethyl acetate (800 ml, Charcoal 3g) gave a white solid (4.2 g, 33 percent) as pure product. MS m/z = 210 (M+1)o-Phenylenediamine (8.8 mmol, 1.0 g) and p-aminobenzoicacid (8.2 mmol, 1.1 g) were mixed with 12 mL oforthophosphoric acid in an Erlenmeyer flask and irradiatedin a microwave oven for 15 minutes at 170W with intermediateshaking. The reaction mixture was diluted with colddistilled water and was rendered alkaline with ammoniumhydroxide solution. The crude product separated was filteredunder vacuum and recrystallized from ethanol-water. (0.4 g, 33percent) mp 250°C. IR: 3500-3400 (N-H str., br), 3048, 3001(Ar-H str.), 1606 (C=N 1441 (C=C str.), 1273 (C-N str.), 834(N-H wagging), 745 (Ar-H bending); 1H-NMR (CDCl3): 7.9 (dap, 2H, J=9.0, ArH), 7.55 (m, 2H, ArH), 7.15 (m, 2H, ArH), 6.7 (dap, 2H, J=9.08, ArH), 4.7 (br s, 1H, NH), 3.9(br s, 2H, NH2).

Molecular Weight:209.25
XLogP3:2.6
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:209.095297364
Monoisotopic Mass:209.095297364
Topological Polar Surface Area:54.7
Heavy Atom Count:16
Complexity:235
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes