3-(2-chlorophenyl)propanenitrile

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

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

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

Procedure: A stirred solution of 2-chlorohydrocinnamonitrile (Aldrich Chemical Co., 1.66 g, 10 mmol) in dichloromethane (100 ml) was cooled to −78° C. and treated dropwise with diisobutylaluminum hydride (1.42 g, 10 mmol). The reaction was stirred 1 hr at rt, cooled to −78° C. and treated with a solution of 1-(1-naphthyl)ethylamine (1.71 g, 10 mmol) in dichloromethane (25 ml). The reaction was transferred to an ice bath and stirred 2 hr. After this time the reaction was poured directly into a stirred solution of ethanolic sodium borohydride (50 ml of 0.2 M, 10 mmol). The mixture was stirred 30 min at rt and the excess sodium borohydride quenched by the addition of 10% HCl. The solution was then made basic by the addition of 10 N NaOH and transferred to a separatory funnel washing with diethyl ether (300 ml). The aqueous phase was removed and the remaining organic layer washed with 1 N NaOH (3×100 ml). The organic layer was dried over anhydrous magnesium sulfate, and concentrated to an oil. Chromatography of this material through silica gel using a gradient of chloroform to 10% methanol-chloroform afforded 2.34 g (72% yield) of (R)-N-[3-(2-chlorophenyl)propyl]-1-(1-naphthyl)ethylamine, 12Z, as a clear oil; m/z (rel. int.) 323 (M+, 2), 308 (63), 288 (7), 196 (5), 184 (5), 155 (100), 125 (24), 115 (8), 103 (4), 91 (3), 77 (7). cooled to −78° C. The reaction was transferred to an ice bath stirred 2 hr The mixture was stirred 30 min at rt the excess sodium borohydride quenched by the addition of 10% HCl The solution was then made basic by the addition of 10 N NaOH transferred to a separatory funnel washing with diethyl ether (300 ml) The aqueous phase was removed the remaining organic layer washed with 1 N NaOH (3×100 ml) The organic layer was dried over anhydrous magnesium sulfate concentrated to an oil

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

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

Procedure: The imine V was prepared in a manner similar to that of imine III in Example I using 3-(2-chlorophenyl)propylamine and 3'-methoxyacetophenone. 3-(2-chlorophenyl)propylamine was obtained by the reduction (BH3 --SMe2 complex) of 2-chlorohydrocinnamonitrile (Aldrich Chemical Co., Milwaukee, Wis., U.S.A.). This process afforded 1-methyl-1-(3-methoxy)phenyl-5-(2-chloro)phenyl-2-aza-1-pentene (imine V), a single component, as analyzed by GC/EI-MS: m/z (rel. int.) 301 (M+, 1), 266 (22), 162 (100), 125 (26), 91 (13), 77 (9).

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

Procedure: The imine V was prepared in a manner similar to that of imine III in Example I using 3-(2-chlorophenyl)propylamine and 3'-methoxyacetophenone. 3-(2-chlorophenyl)propylamine was obtained by the reduction (BH3 --SMe2 complex) of 2-chlorohydrocinnamonitrile (Aldrich Chemical Co., Milwaukee, Wis., U.S.A.). This process afforded 1-methyl-1-(3-methoxy)phenyl-5-(2-chloro)phenyl-2-aza-1-pentene (imine V), a single component, as analyzed by GC/EI-MS: m/z (rel. int.) 301 (M+, 1), 266 (22), 162 (100), 125 (26), 91 (13), 77 (9).

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

Procedure: A 3-liter, three-necked flask equipped with a dry ice condenser, mechanical stirrer and Claisen adapter fitted with an ammonia gas inlet and nitrogen inlet is rinsed with acetone, dried in an oven at 125° C., and heated with an air gun while flushing with nitrogen. The apparatus is cooled in a dry ice-acetone bath and the condenser is filled with a dry ice-acetone mixture. Ammonia gas flow is initiated and 600 ml is condensed out. The ammonia inlet tube is replaced by a stopper, and 0.4 g of powdered iron (III) nitrate is added. Sodium metal, 51.52 g (2.24 moles) is added in small portions over 1 hour. After all the sodium is added, the dry ice bath is removed and cooling is left to the dry ice condenser. Complete conversion of the sodium/ammonia solution to sodamide is indicated by a color change from deep blue to gray. Next, 92.82 g (0.56 mole) of 3-(o-chlorophenyl)propionitrile is added over a period of 10 minutes. The last traces of the nitrile are washed into the flask with small amounts of anhydrous ethyl ether. The dark green reaction mixture is stirred vigorously for 3 hours and then is treated with 134.4 g (1.68 moles) of solid ammonium nitrate. The ammonia is allowed to evaporate overnight at room temperature. Water (420 ml) is cautiously added to the residue. The organic layer is taken up in two 224-ml portions of chloroform, and the solutions are combined and washed twice with 140 ml of aqueous 5 percent hydrochloric acid and once with 140 ml of water. The chloroform solution is dried over anhydrous magnesium sulfate, filtered, and evaporated on a rotary evaporator. The residual liquid is distilled under reduced pressure through an insulated 12-inch Vigreux column. The product is collected at 59° C.-69° C./0.2 mm Hg. The infrared, 'H and 13C nuclear magnetic resonance are run to identify the product. The yield is 50 percent. A 3-liter, three-necked flask equipped with a dry ice condenser, mechanical stirrer Claisen adapter fitted with an ammonia gas inlet and nitrogen inlet is rinsed with acetone dried in an oven at 125° C. heated with an air gun while flushing with nitrogen The apparatus is cooled in a dry ice-acetone bath the condenser is filled with a dry ice-acetone mixture condensed out is added the dry ice bath is removed cooling is left to the dry ice condenser The last traces of the nitrile are washed into the flask with small amounts of anhydrous ethyl ether to evaporate overnight at room temperature Water (420 ml) is cautiously added to the residue washed twice with 140 ml of aqueous 5 percent hydrochloric acid and once with 140 ml of water The chloroform solution is dried over anhydrous magnesium sulfate filtered evaporated on a rotary evaporator The residual liquid is distilled under reduced pressure through an insulated 12-inch Vigreux column The product is collected at 59° C.-69° C./0.2 mm Hg

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

Procedure: A stirred solution of 2-chlorohydrocinnamonitrile (Aldrich Chemical Co., 1.66 g, 10 mmol) in dichloromethane (100 ml) was cooled to −78° C. and treated dropwise with diisobutylaluminum hydride (1.42 g, 10 mmol). The reaction was stirred 1 hr at rt, cooled to −78° C. and treated with a solution of 1-(1-naphthyl)ethylamine (1.71 g, 10 mmol) in dichloromethane (25 ml). The reaction was transferred to an ice bath and stirred 2 hr. After this time the reaction was poured directly into a stirred solution of ethanolic sodium borohydride (50 ml of 0.2 M, 10 mmol). The mixture was stirred 30 min at rt and the excess sodium borohydride quenched by the addition of 10% HCl. The solution was then made basic by the addition of 10 N NaOH and transferred to a separatory funnel washing with diethyl ether (300 ml). The aqueous phase was removed and the remaining organic layer washed with 1 N NaOH (3×100 ml). The organic layer was dried over anhydrous magnesium sulfate, and concentrated to an oil. Chromatography of this material through silica gel using a gradient of chloroform to 10% methanol-chloroform afforded 2.34 g (72% yield) of (R)-N-[3-(2-chlorophenyl)propyl]-1-(1-naphthyl)ethylamine, 12Z, as a clear oil; m/z (rel. int.) 323 (M+, 2), 308 (63), 288 (7), 196 (5), 184 (5), 155 (100), 125 (24), 115 (8), 103 (4), 91 (3), 77 (7). cooled to −78° C. The reaction was transferred to an ice bath stirred 2 hr The mixture was stirred 30 min at rt the excess sodium borohydride quenched by the addition of 10% HCl The solution was then made basic by the addition of 10 N NaOH transferred to a separatory funnel washing with diethyl ether (300 ml) The aqueous phase was removed the remaining organic layer washed with 1 N NaOH (3×100 ml) The organic layer was dried over anhydrous magnesium sulfate concentrated to an oil

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

Procedure: A stirred solution of 2-chlorohydrocinnamonitrile (Aldrich Chemical Co., 1.66 g, 10 mmol) in dichloromethane (100 ml) was cooled to −78° C. and treated dropwise with diisobutylaluminum hydride (1.42 g, 10 mmol). The reaction was stirred 1 hr at rt, cooled to −78° C. and treated with a solution of 1-(1-naphthyl)ethylamine (1.71 g, 10 mmol) in dichloromethane (25 ml). The reaction was transferred to an ice bath and stirred 2 hr. After this time the reaction was poured directly into a stirred solution of ethanolic sodium borohydride (50 ml of 0.2 M, 10 mmol). The mixture was stirred 30 min at rt and the excess sodium borohydride quenched by the addition of 10% HCl. The solution was then made basic by the addition of 10 N NaOH and transferred to a separatory funnel washing with diethyl ether (300 ml). The aqueous phase was removed and the remaining organic layer washed with 1 N NaOH (3×100 ml). The organic layer was dried over anhydrous magnesium sulfate, and concentrated to an oil. Chromatography of this material through silica gel using a gradient of chloroform to 10% methanol-chloroform afforded 2.34 g (72% yield) of (R)-N-[3-(2-chlorophenyl)propyl]-1-(1-naphthyl)ethylamine, 12Z, as a clear oil; m/z (rel. int.) 323 (M+, 2), 308 (63), 288 (7), 196 (5), 184 (5), 155 (100), 125 (24), 115 (8), 103 (4), 91 (3), 77 (7). cooled to −78° C. The reaction was transferred to an ice bath stirred 2 hr The mixture was stirred 30 min at rt the excess sodium borohydride quenched by the addition of 10% HCl The solution was then made basic by the addition of 10 N NaOH transferred to a separatory funnel washing with diethyl ether (300 ml) The aqueous phase was removed the remaining organic layer washed with 1 N NaOH (3×100 ml) The organic layer was dried over anhydrous magnesium sulfate concentrated to an oil

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

Procedure: The imine V was prepared in a manner similar to that of imine III in Example I using 3-(2-chlorophenyl)propylamine and 3'-methoxyacetophenone. 3-(2-chlorophenyl)propylamine was obtained by the reduction (BH3 --SMe2 complex) of 2-chlorohydrocinnamonitrile (Aldrich Chemical Co., Milwaukee, Wis., U.S.A.). This process afforded 1-methyl-1-(3-methoxy)phenyl-5-(2-chloro)phenyl-2-aza-1-pentene (imine V), a single component, as analyzed by GC/EI-MS: m/z (rel. int.) 301 (M+, 1), 266 (22), 162 (100), 125 (26), 91 (13), 77 (9).

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

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

Procedure: A 3-liter, three-necked flask equipped with a dry ice condenser, mechanical stirrer and Claisen adapter fitted with an ammonia gas inlet and nitrogen inlet is rinsed with acetone, dried in an oven at 125° C., and heated with an air gun while flushing with nitrogen. The apparatus is cooled in a dry ice-acetone bath and the condenser is filled with a dry ice-acetone mixture. Ammonia gas flow is initiated and 600 ml is condensed out. The ammonia inlet tube is replaced by a stopper, and 0.4 g of powdered iron (III) nitrate is added. Sodium metal, 51.52 g (2.24 moles) is added in small portions over 1 hour. After all the sodium is added, the dry ice bath is removed and cooling is left to the dry ice condenser. Complete conversion of the sodium/ammonium solution to sodamide is indicated by a color change from deep blue to gray. Next, 92.82 g (0.56 mole) of 3-(o-chlorophenyl)propionitrile is added over a period of 10 minutes. The last traces of the nitrile are washed into the flask with small amounts of anhydrous ethyl ether. The dark green reaction mixture is stirred vigorously for 3 hours and then is treated with 134.4 g (1.68 moles) of solid ammonium nitrate. The ammonia is allowed to evaporate overnight at room temperature. Water (420 ml) is cautiously added to the residue. The organic layer is taken up in two 224-ml portions of chloroform, and the solutions are combined and washed twice with 140 ml of aqueous 5 percent hydrochloric acid and once with 140 ml of water. The chloroform solution is dried over anhydrous magnesium sulfate, filtered, and evaporated on a rotary evaporator. The residual liquid is distilled under reduced pressure through an insulated 12-inch Vigreux column. The product is collected at 59° C.-69° C./0.2 mm Hg. The infrared, 'H and 13C nuclear magnetic resonance are run to identify the product. The yield is 50 percent. A 3-liter, three-necked flask equipped with a dry ice condenser, mechanical stirrer Claisen adapter fitted with an ammonia gas inlet and nitrogen inlet is rinsed with acetone dried in an oven at 125° C. heated with an air gun while flushing with nitrogen The apparatus is cooled in a dry ice-acetone bath the condenser is filled with a dry ice-acetone mixture condensed out is added the dry ice bath is removed cooling is left to the dry ice condenser The last traces of the nitrile are washed into the flask with small amounts of anhydrous ethyl ether to evaporate overnight at room temperature Water (420 ml) is cautiously added to the residue washed twice with 140 ml of aqueous 5 percent hydrochloric acid and once with 140 ml of water The chloroform solution is dried over anhydrous magnesium sulfate filtered evaporated on a rotary evaporator The residual liquid is distilled under reduced pressure through an insulated 12-inch Vigreux column The product is collected at 59° C.-69° C./0.2 mm Hg