2-(2-Bromophenyl)-2-methylpropanenitrile

A/ Preparation of 2-(2'-bromophenyl)-2-methylpropionitrile: Reaction of haloarenes and 2-methylpropionitrile in the presence of various bases in THF. The reaction tubes of Mettler Toledo MiniBlock.(TM). were independently charged with the haloarenes (0.01 mol) identified below and a solution of 2-methylpropionitrile in THF (8.5 mL, 0.01 mol) which was prepared from the nitrile (14 g) and THF (160 mL). An equimolar amount of the base (0.01 mol) was independently added to each tube dropwise at ambient temperature. The reaction mixtures were heated to 65° C. over 1 hour, cooled to ambient temperature and quenched with 5percent HCl (6 mL). The organic phases were separated and the solvents were evaporated. The crude product mixtures were examined using gas chromatography (GC)/mass spectroscopy (MS) and proton nuclear magnetic resonance (A/ Preparation of 2-(2'-bromophenyl)-2-methylpropionitrile: Reaction of haloarenes and 2-methylpropionitrile in the presence of various bases in THF. The reaction tubes of Mettler Toledo MiniBlock.(TM). were independently charged with the haloarenes (0.01 mol) identified below and a solution of 2-methylpropionitrile in THF (8.5 mL, 0.01 mol) which was prepared from the nitrile (14 g) and THF (160 mL). An equimolar amount of the base (0.01 mol) was independently added to each tube dropwise at ambient temperature. The reaction mixtures were heated to 65° C. over 1 hour, cooled to ambient temperature and quenched with 5percent HCl (6 mL). The organic phases were separated and the solvents were evaporated. The crude product mixtures were examined using gas chromatography (GC)/mass spectroscopy (MS) and proton nuclear magnetic resonance (General procedure: To a screw-capped vial (25 mL) were added NaOH (400 mg, 10 mmol), tert-butanol (tBuOH, 10 mL) and 3a (1.12 g, 5 mmol). The vial was sealed with cap and allowed to stir at 100 °C. The reaction was monitored by TLC every hour until the complete consumption of 3a. After total conversion of 3a, the reaction was diluted with CH2Cl2, filtered through a thin Celite pad to remove salt, and concentrated in vacuo. The residue was isolated through a short flash column chromatography by using ethyl acetate as eluent to give the pure compound 1a in 92percent isolated yield; White solid, mp: 73'74 °C; IR (KBr): 3472, 2977, 2932, 1669, 1605, 1468, 1427, 1390, 1360, 1022, 756 cm-1; 1H NMR (600 MHz, CDCl3): delta 7.60 (dd, J1 = 7.8 Hz, J2 = 1.2 Hz, 1H), 7.49 (dd, J1 = 7.8 Hz, J2 = 1.2 Hz, 1H), 7.34 (td, J1 = 7.8 Hz, J2 = 1.2 Hz, 1H), 7.14 (td, J1 = 7.8 Hz, J2 = 1.8 Hz, 1H), 5.72 (br, 1H), 5.23 (br, 1H), 1.65 (s, 6H); 13C NMR (150 MHz, CDCl3): delta 179.0, 143.0, 134.8, 128.6, 127.7, 127.6, 124.1, 48.3, 26.4; HRMS: C10H12BrNO calculated 241.0102, found 241.0098; Registry Number: [173026-22-7]. Compounds 1b'1q were obtained according to this procedure. The synthetic methods for all the nitrile compounds 3 were prepared according to our previous report.2(b) 2-(2-Bromophenyl)-2-methylpropanamide (A34)A mixture of A/ Preparation of (a) 2-(2-Bromophenyl)-2-methylpropanenitrlle (A33)A suspension of t-BuOK (0.898 g, 8.00 mmol) in anhydrous THF (3 mL) and anhydrous NMP (3 mL) was cooled to 0 00 under a N2 atmosphere. To this suspension, 2-(2-bromophenyl)acetonitrile (0.392 g, 2.00 mmol) was added and the mixture was allowed to stir at 0 00 for 10 minutes. lodomethane (0.50 mL, 8.0 mmol)was added carefully over a period of 5 minutes and the resulting mixture was stirred for an additional 1 hour between 0 00 and 10 00. Excess t-BuOK was quenched by the addition of sat. aq. NaHCO3 and the aqueous phase was extracted with EtOAc (3 x 40 mL). The combined organics were washed with brine, dried (MgSO4) and the solvent removed in vacuo to give a yellow residue. Purification by columnchromatography (Biotage Isolera, 24 g Si02 cartridge, 0-15percent EtOAc in petroleum benzine 40-60 00) gave the title compound A33 as a colourless oil (0.377 g, 84percent). LCMS-D: rt 3.48 mm; m/z 197/1 99 [M-CN].To a solution of 2-(2- bromophenyl)-2-methylpropanenitrile (4.0 g, 17.8 mmol), in dry THF (40 mL) was added borane-dimethyl sulfide (5.08 mL, 53.5 mmol) at 0 °C and the reaction mixture was slowly brought to rt, stirred for 1 h and then, heated to reflux for 18 h. The solvent was removed and quenched with MeOH, and heated to reflux for 18 h. The reaction was concentrated and the residue was dissolved in EtOAc, washed with H2O, brine, dried (Na2SO4), flltered and concentrated to give 4.0 g of 103 A as a white solid. MS (ESI) m/z: 230.2 (M+H)+.

Molecular Weight:224.10
XLogP3:3.2
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:222.99966
Monoisotopic Mass:222.99966
Topological Polar Surface Area:23.8
Heavy Atom Count:12
Complexity:201
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes