3-Chloro-5-(hydroxymethyl)benzonitrile

General procedure: Toa stirring solution of 4-chloro-3-formylbenzonitrile (5.00 g , 30.2 mmol) inethanol (50 mL), NaBH4 (571 mg, 15.1 mmol) was added batch-wise over 1 minuteunder stirring at room temperature. After 1 hr, the reaction mixture wasconcentrated in vacuo to afford an off-white solid, treated with 2M HC1 (200mL) and DCM (260 mL), effervescence and dissolution occurred. The layers wereseparated, the organic layer was dried over Na2SC>4, the mixturefiltered and concentrated in vacuo to afford the title compound (4.86 g, 96percent)as an off-white solid; H NMR (500 MHz, DMSO) delta 4.58 (d, 2H), 5.63(t, 1H), 7.65 (d, 1H), 7.78 (dd, 1H), 7.85 - 7.94 (m, 1H).Step 4: 3-Chloro-5-cyanobenzyl carbonochloridate S-Chloro-S-hydroxymethyl-benzonitrile: 3-Chloro-5-methyl-benzonitrile (4.19g, 27.64mmoi) in carbon tetrachloride (60ml) was refluxed with N-bromosuccinimide (4.92g, 27 64mmoi) and benzoyl peroxide (669mg, 2.7deltammol) for 5hr. After cooling to room temperature, the mixture was filtered and evaporated in vacuo The residue was purified by silica gel column chromatography (eiuent, ether hexane (from 1 20 to 1 4)) to give 6 84g of S-Bromomethyi-delta-chloro-benzonitrile as a mixture containing starting material. This mixture was stirred with sodium acetate (4.53g, 55.28mmoi) in DMF (50ml) for overnight at room temperature The mixture was diluted with ether, washed with water three times, dried with MgSO4, filtered, and evaporated in vacuo to give Acetic acid 3-chloro-delta-cyano-benzyl ester. The residue was stirred with ammonium hydroxide (10mi) in methanol (40ml). The mixture was then evaporated in vacuo and the residue was purified by silica gel column chromatography (eluent, ethyl acetate: hexane (1 :2)) to afford 1.43g (30percent for 3 steps) of S-Chloro-S-hydroxymethyl-benzonitrile as a white solid, m.p. 110-1 1 1 0C; 1H-NMR(200MHz, CDCI3) delta 2.06(1 H, t, J=5.6Hz), 4.74(2H1 d, J=5.6Hz), 7.55(2H, s), 7.61(1 H1 s); m/z (El) 167(M+).S-Chloro-S-formyl-benzonitrile: To a stirred solution of 3-Chloro-5-hydroxymethyI- benzonitrile (1.43g, 8.53mmol) in dichloromethane (50ml), were added pyridinium chlorochromate (2.76g, 12.8mmol) and celite (2.76g). After stirring for 2hr. at room temperature, the mixture was diluted with ether and filtered through a plug of silica gel. The plug was washed with ether. The combined filtrate was evaporated in vacuo and the residue was purified by silica gel column chromatography (eluent, ethyl acetate: hexane (1 :4)) to afford 1.28g (90percent) of a white solid, m.p. 132-133 0C; 1H- NMR(200MHz, CDCI3) delta 7.89(1H, s), 8.05(1H, s), 8.09(1 H, s), 10.02(1H1 s); m/z (El) 165(M+).(Step 3) Triphenylphosphine (0.94 g) was suspended in acetonitrile (20 ml), bromine (0.19 ml) was added, and the mixture was stirred for 30 min. A solution (10 ml) of Toa solution of (Step 2) To a mixed solution of 3-chloro-5-cyanobenzoate (1.13 g) obtained in Step 1 in tetrahydrofuran:ethanol=10:1 (33 ml) was added lithium tetrahydroborate (0.19 g) at 0°C. After stirring at 60°C for 2 hr, the reaction solution was quenched with ice and extracted with ethyl acetate. The extract was washed with 1N hydrochloric acid and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was treated by silica gel chromatography (ethyl acetate:hexane=1:1) to give

Molecular Weight:167.59
XLogP3:1.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:167.0137915
Monoisotopic Mass:167.0137915
Topological Polar Surface Area:44
Heavy Atom Count:11
Complexity:174
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes