2-Amino-5-bromobenzonitrile

white to light yellow crystal powder

A solution of 2-aminobenzonitrile (11.8g, 0.1 mol) in AcOH (120 ml) was treated with ammonium bromide (10.3 g, 0.105 mol) and hydrogen peroxide (10.2 ml, 35 percent in water, 0.105 mol). This mixture was stirred at room temperature for ca. 24 hours until LCMS analysis showed the reaction was complete. The mixture was concentrated to remove the AcOH, prior to stirring the residue with 30 percent aqueous NaOH solution until basic. The resulting solid was removed by filtration and washed with water before drying. This solid was then dissolved in an excess of DCM. The solution was concentrated until precipitation started and then allowed to stand until crystallisation was complete. The resulting solid was removed by filtration and washed with a little DCM. This gave the desired compound as an off white crystalline solid (19.2 g, 97 percent).To a stirred solution of 2-aminobenzonitrile (25 g, 210 mmol) in dichloromethane (500 mL) was added NBS (41.4 g, 230 mmol) portion wise and the mixture was stirred at 0 °C for 2 h. The reaction mixture was gradually warmed to room temperature and was quenched with sodium bicarbonate solution (200 mL). The organic layer was separated, washed with brine, dried over sodium sulfate andconcentrated under reduced pressure to afford 2-amino-S -bromobenzonitrile (38 g, 92percent yield) as a pale brown solid: ‘H NMR (400 MHz, DMSO-d6) 7, 61 (d, J 2.5 Hz, 1H), 7.43 (dd, J= 9, 2.5 Hz, 1H), 6.75 (d, J= 9Hz, 1H), 6.28 (bs, 2H).1L in the reactor into a 2-aminobenzonitrile 35.1 g (297 mmol), N-bromosuccinimide 55.56 g (312 mmol) and 350 mL of dimethylformamide was stirred for 4 hours. Insert the distilled water, to remove the resulting solids by filtration and the reaction solution by column chromatography to give the intermediate 1-a 54.2 g (yield 92.6percent).1L reactor while nitrogen to 2-amino-benzonitrile 35.1 g (297 mmol), 350 mL of dimethylformamide is stirred. Then put the N-bromo-succinimide 55.56 g (312 mmol) slowly to the reactor. After raising to room temperature, the mixture was stirred for 4 hours. When the reaction is completed, distilled water was added dropwise thereto at room temperature, brown crystals were filtered saenggimyeon The crystals were separated by column chromatography to obtain the compound 54.2 g (yield: 92.6percent) represented by [Intermediate 5-a].In a 1-L reactor, 2-aminobenzonitrile (35.1 g, 297 mmol), N-bromosuccinimide (55.56 g (312 mmol), and dimethylformamide (350 mL) were placed and stirred together for 4 hours. Distilled water was added before filtration of the reaction mixture. Purification by column chromatography afforded Intermediate 1-i (54.2 g): yield 92.6percentGeneral procedure: To a magnetic solution of aromatic compound (1 mmol)in acetonitrile (5 mL), OXBTEATB (0.233 g, 0.5 mmol) wasadded and stirred at room temperature for the appropriatetime (Table 1). The reaction was monitored by TLC (eluent:n-hexane/ethyl acetate: 5/1). The reaction mixture was transferredinto a separatory funnel after filtration of OXBTEABand was extracted with water (15 mL) and dichloromethane(20 mL). The organic layer was dried over anhydrousNa2SO4, and the solvent was concentrated in a rotary evaporator.The crude product was purified by passing it over acolumn of silica gel using a mixture of n-hexane and ethylacetate as the eluent. In order to regenerate the reagent, whitesolid was treated with liquid bromine. All the product structureswere confirmed by comparison of melting point or 1HNMR spectra with ones reported in the literature [29a-29e].Step 1 : 2-Amino-5-bromobenzonitrile (P36a)To a solution of 2-aminobenzonitrile (14.9 g, 100 mmol) was added a solution of NBS (17.8 g, 100 mmol) in DMF at rt. The mixture was stirred overnight at rt, then water (30 mL) was added and the mixture was extracted with EtStep 1: 2-Amino-5-bromobenzonitrile (P4a)To a solution of 2-aminobenzonitrile (14.9 g, 100 mmol) was added a solution of NBS (17.8 g, 100 mmol) in DMF at ii. The mixture was stirred overnight at rt, then water (30 mL) was addedand the mixture was extracted with Et20 (3 x 250 mL). The organic layer was washed with brine, dried over Na2SO4, concentrated and purified by CC to give compound P4a (19 g, 83percent).Step 1 : 2-Amino-5-bromobenzonitrile (P4a) To a solution of 2-aminobenzonitrile (14.9 g, 100 mmol) was added a solution of NBS (17.8 g, 100 mmol) in DMF at rt. The mixture was stirred overnight at rt, then water (30 mL) was added and the mixture was extracted with EtN-bromosuccinimide (17.8 g, 0.10 mol) was added in portions at room temperature to a stirred solution of anthranilonitrile (Aldrich, 11.8 g, 0.10 mol) in DMF (100 mL).After a mild exothermic reaction occurred, the red solution was stirred under nitrogen overnight. The reaction mixture was diluted with water (-100 mL) and CH2C12 (200 mL). The phases were separated. The organic phase was washed with [H20] (3X) and brine, dried [(NA2S04)] and concentrated in vacuo to give 21 g of red residue which was dissolved in ether (25 mL), and hexane was added to knock out 13.6 (70 percent yield, lst crop) g of red solid product: [MP] [95-97 C.] IR (diffuse reflectance) 3357, 2219, 1633, 1560, 1486, 1305, 1257, 1180, 1157, 889, 866, 830, 666, 656, 641 [CRRI 1.] Anal. Calcd for [C7HSBRN2] : C, 42.67 ; H, 2.56 ; N, 14.22 ; Br, 40.55. Found: C, 42.75 ; H, 2.54 ; N, 14.25 ; Br, 40.34.N-Bromosuccinimide (12.5g, 0.07mol) was added in portions to a solution of anthranilonitrile (7.5g, 0.06mol) in DCM at O

Molecular Weight:197.03
XLogP3:2.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:195.96361
Monoisotopic Mass:195.96361
Topological Polar Surface Area:49.8
Heavy Atom Count:10
Complexity:160
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes