4-chloro-2-(trifluoromethyl)benzonitrile

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add 4-chloro-2-trifluoromethyl-benzonitrile to formic acid (96%) (15 mL) and water (3 mL). Add nickel-aluminum alloy (1260 mg). Heat at 100° C. overnight. Dilute with ethyl acetate and filter through Celite®. Extract the filtrate with 1 N sodium hydroxide and saturated aqueous sodium chloride, dry (sodium sulfate), filter, and concentrate to give 4-chloro-2-trifluoromethylbenzaldehyde (555 mg, 87%): 1H NMR (400 MHz, MeOH-d4) δ 10.29 (m, 1H), 8.10 (d, 1H, J=8.4 Hz), 7.91 (d, 1H, J=1.6 Hz), 7.85 (dd, 1H, J=8.4, 1.6 Hz). filter through Celite® Extract the filtrate with 1 N sodium hydroxide and saturated aqueous sodium chloride dry (sodium sulfate) filter concentrate

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add 4-chloro-2-trifluoromethyl-benzonitrile to formic acid (96%) (15 mL) and water (3 mL). Add nickel-aluminum alloy (1260 mg). Heat at 100° C. overnight. Dilute with ethyl acetate and filter through Celite®. Extract the filtrate with 1 N sodium hydroxide and saturated aqueous sodium chloride, dry (sodium sulfate), filter, and concentrate to give 4-chloro-2-trifluoromethylbenzaldehyde (555 mg, 87%): 1H NMR (400 MHz, MeOH-d4) δ 10.29 (m, 1H), 8.10 (d, 1H, J=8.4 Hz), 7.91 (d, 1H, J=1.6 Hz), 7.85 (dd, 1H, J=8.4, 1.6 Hz). filter through Celite® Extract the filtrate with 1 N sodium hydroxide and saturated aqueous sodium chloride dry (sodium sulfate) filter concentrate

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add 4-chloro-1-iodo-2-trifluromethylbenzene (1500 mg, 4.89 mmol), zinc cyanide (345 mg, 2.94 mmol), and tetrakis(triphenylphosphine)palladium(0) (564 mg, 0.488 mmol) to anhydrous N,N-dimethylformamide (40 mL). Heat to 80° C. overnight. Cool to room temperature, dilute with toluene, wash with 2 N ammonium hydroxide (3×), saturated aqueous sodium chloride, dry, filter, concentrate to give a residue. Chromatograph the residue on silica gel eluting with hexanes/dichloromethane, to give 4-chloro-2-trifluoromethylbenzonitrile (630 mg, 63%): 1H NMR (400 MHz, CDCl3) δ 7.81-7.78 (m, 2H), 7.67 (dd, 1H, J=8.4, 2.4 Hz). Cool to room temperature wash with 2 N ammonium hydroxide (3×), saturated aqueous sodium chloride dry filter concentrate to give a residue

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add 4-chloro-1-iodo-2-trifluromethylbenzene (1500 mg, 4.89 mmol), zinc cyanide (345 mg, 2.94 mmol), and tetrakis(triphenylphosphine)palladium(0) (564 mg, 0.488 mmol) to anhydrous N,N-dimethylformamide (40 mL). Heat to 80° C. overnight. Cool to room temperature, dilute with toluene, wash with 2 N ammonium hydroxide (3×), saturated aqueous sodium chloride, dry, filter, concentrate to give a residue. Chromatograph the residue on silica gel eluting with hexanes/dichloromethane, to give 4-chloro-2-trifluoromethylbenzonitrile (630 mg, 63%): 1H NMR (400 MHz, CDCl3) δ 7.81-7.78 (m, 2H), 7.67 (dd, 1H, J=8.4, 2.4 Hz). Cool to room temperature wash with 2 N ammonium hydroxide (3×), saturated aqueous sodium chloride dry filter concentrate to give a residue

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add 4-chloro-2-trifluoromethyl-benzonitrile to formic acid (96%) (15 mL) and water (3 mL). Add nickel-aluminum alloy (1260 mg). Heat at 100° C. overnight. Dilute with ethyl acetate and filter through Celite®. Extract the filtrate with 1 N sodium hydroxide and saturated aqueous sodium chloride, dry (sodium sulfate), filter, and concentrate to give 4-chloro-2-trifluoromethylbenzaldehyde (555 mg, 87%): 1H NMR (400 MHz, MeOH-d4) δ 10.29 (m, 1H), 8.10 (d, 1H, J=8.4 Hz), 7.91 (d, 1H, J=1.6 Hz), 7.85 (dd, 1H, J=8.4, 1.6 Hz). filter through Celite® Extract the filtrate with 1 N sodium hydroxide and saturated aqueous sodium chloride dry (sodium sulfate) filter concentrate

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add 4-chloro-1-iodo-2-trifluromethylbenzene (1500 mg, 4.89 mmol), zinc cyanide (345 mg, 2.94 mmol), and tetrakis(triphenylphosphine)palladium(0) (564 mg, 0.488 mmol) to anhydrous N,N-dimethylformamide (40 mL). Heat to 80° C. overnight. Cool to room temperature, dilute with toluene, wash with 2 N ammonium hydroxide (3×), saturated aqueous sodium chloride, dry, filter, concentrate to give a residue. Chromatograph the residue on silica gel eluting with hexanes/dichloromethane, to give 4-chloro-2-trifluoromethylbenzonitrile (630 mg, 63%): 1H NMR (400 MHz, CDCl3) δ 7.81-7.78 (m, 2H), 7.67 (dd, 1H, J=8.4, 2.4 Hz). Cool to room temperature wash with 2 N ammonium hydroxide (3×), saturated aqueous sodium chloride dry filter concentrate to give a residue

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4.47 g of the product obtained in Stage 1 above, 11.2 ml of triglyme, 2.78 g of 5,5-dimethyl hydantoin and 1.34 g of cuprous oxide are introduced then the suspension is agitated and taken to 215° C. for 4 hours. Then it is returned to ambient temperature, followed by filtering, washing with 4.5 ml of triglyme and agitating without exceeding 25° C., 4.5 ml of 22°Be concentrated ammonium hydroxide, 26 ml of water and 4.5 ml of toluene. Agitation is carried out for 15 minutes at 20° C. then the reaction medium is cooled down to -10° C., agitation is carried out for 1 hour, followed by separating, washing with 2.2 ml of toluene then 4.5 ml of water and drying. In this way 1.98 g of expected product (brown crystals) is obtained. M.p.=210° C. is returned to ambient temperature by filtering washing with 4.5 ml of triglyme agitating without exceeding 25° C. Agitation is carried out for 15 minutes at 20° C. agitation is carried out for 1 hour by separating washing with 2.2 ml of toluene 4.5 ml of water and drying

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 100 g of 2-trifluoromethyl-4-chloro iodobenzene, 200 ml of dimethylformamide and 58.7 g of copper cyanide are introduced at 20° C., the reaction medium is heated for 3 hours at 140° C., left to cool down to 20° C., then poured into 600 ml of ice-cooled demineralized water. After filtering, rinsing with 3×200 ml of isopropyl ether, the aqueous phase is decanted and reextracted with 3×200 ml of isopropyl ether. The organic phases are combined and washed with 200 ml of demineralized water and dried. In this way 66.64 g of expected product is obtained. left to cool down to 20° C. After filtering rinsing with 3×200 ml of isopropyl ether the aqueous phase is decanted washed with 200 ml of demineralized water dried

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add 4-chloro-2-trifluoromethyl-benzonitrile to formic acid (96%) (15 mL) and water (3 mL). Add nickel-aluminum alloy (1260 mg). Heat at 100° C. overnight. Dilute with ethyl acetate and filter through Celite®. Extract the filtrate with 1 N sodium hydroxide and saturated aqueous sodium chloride, dry (sodium sulfate), filter, and concentrate to give 4-chloro-2-trifluoromethylbenzaldehyde (555 mg, 87%): 1H NMR (400 MHz, MeOH-d4) δ 10.29 (m, 1H), 8.10 (d, 1H, J=8.4 Hz), 7.91 (d, 1H, J=1.6 Hz), 7.85 (dd, 1H, J=8.4, 1.6 Hz). filter through Celite® Extract the filtrate with 1 N sodium hydroxide and saturated aqueous sodium chloride dry (sodium sulfate) filter concentrate

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add 4-chloro-1-iodo-2-trifluromethylbenzene (1500 mg, 4.89 mmol), zinc cyanide (345 mg, 2.94 mmol), and tetrakis(triphenylphosphine)palladium(0) (564 mg, 0.488 mmol) to anhydrous N,N-dimethylformamide (40 mL). Heat to 80° C. overnight. Cool to room temperature, dilute with toluene, wash with 2 N ammonium hydroxide (3×), saturated aqueous sodium chloride, dry, filter, concentrate to give a residue. Chromatograph the residue on silica gel eluting with hexanes/dichloromethane, to give 4-chloro-2-trifluoromethylbenzonitrile (630 mg, 63%): 1H NMR (400 MHz, CDCl3) δ 7.81-7.78 (m, 2H), 7.67 (dd, 1H, J=8.4, 2.4 Hz). Cool to room temperature wash with 2 N ammonium hydroxide (3×), saturated aqueous sodium chloride dry filter concentrate to give a residue