2-phenylpropanenitrile

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: Charge to an autoclave hydrogenation apparatus under nitrogen water-wet 5% palladium on carbon (453 g), ethanol (6.36 L), 2-phenylpropionitrile (636 g, 4.85 moles) and finally concentrated (12M) hydrochloric acid (613 g, 5.6 mole). Stir the mixture rapidly and pressurize to 75 to 78 psi with hydrogen. Heat the mixture 50° C. to 64° C. for 3 hours. Depressurize and filter the reaction mixture to afford two lots of filtrate. Concentrate filtrates under reduced pressure to approximately 400 mL each. Add methyl tert-butyl ether (MTBE) (2.2 L each) to each lot. Stir the precipitate overnight. Filter and wash solids with fresh MTBE (100 mL) and dry overnight. Combine the lots to afford 2-phenyl-1-propylamine HCl (634.4 g, 76.2%) as a white powder. Charge to an autoclave hydrogenation apparatus under nitrogen water-wet 5% palladium on carbon (453 g) Heat the mixture 50° C. to 64° C. for 3 hours Depressurize and filter the reaction mixture to afford two lots of filtrate Stir the precipitate overnight Filter wash solids with fresh MTBE (100 mL) dry overnight

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-phenylpropionitrile (5 g, 38 mmol) in 50 mL of DMSO was added 42 mL of 1 M THF solution of sodium bis(trimethylsilyl)amide (NaHMDS). After 15 minutes, the reaction was cooled to 0° C. and 4.6 mL of ethyl iodide was added. The reaction was then stirred for 30 minutes. As TLC showed the reaction was complete, the reaction mixture was poured into water and extracted with diethyl ether. The organics were combined, washed four times with water, washed with brine, dried over magnesium sulfate, and concentrated in vacuo to give 6.1 g of 2-methyl-2-phenylbutyronitrile as an oil. extracted with diethyl ether washed four times with water washed with brine dried over magnesium sulfate concentrated in vacuo

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

Procedure: To a solution of 2-phenylpropionitrile (4.04 g, 30.79 mmol) in 40 mL of DMSO was added 34 mL (34 mmol) of a 1 M solution of sodium bis(trimethylsilyl)amide (NaHMDS) in THF over a 5 minute period. After 10 minutes, allyl bromide (6 mL, 69.33 mmol) was added dropwise (exothermic). The mixture was cooled with an ice-water bath. The mixture stirred for 20 minutes, becoming a solid mass. An additional 20 mL of DMSO was added. After 10 minutes, the mixture was diluted with 200 mL of ammonium chloride and extracted with three 100 mL portions of ethyl acetate. The combined organic layers were washed with six 75 mL portions of brine, dried over magnesium sulfate, filtered, and concentrated in vacuo to afford 5.25 g (99.5% yield) of 2-methyl-2-phenylpent-4-enenitrile as yellow oil which was used without further purification. The mixture was cooled with an ice-water bath After 10 minutes extracted with three 100 mL portions of ethyl acetate The combined organic layers were washed with six 75 mL portions of brine dried over magnesium sulfate filtered concentrated in vacuo

Conditions: temp:57.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To an autoclave hydrogenation apparatus under nitrogen was charged water-wet 5% palladium on carbon (453 g), ethanol (6.36 L), 2-phenylpropionitrile (636 g, 4.85 moles) and finally concentrated (12 M) hydrochloric acid (613 g, 5.6 mole). The mixture was stirred rapidly and pressurized to 75-78 psi with hydrogen. The mixture was then heated to 50-64° C. for 3 hours. 1H NMR analysis of an aliquot showed less than 5% starting material. The reaction mixture was depressurized and filtered to afford two lots of filtrate that were concentrated under reduced pressure to ˜400 mL each. To each lot was added methyl tert-butyl ether (MTBE) (2.2 L each) and the precipitated solids were allowed to stir overnight. Each lot was filtered and the collected solids were each washed with fresh MTBE (100 mL) and dried overnight. The lots were combined to afford 2-phenyl-1-propylamine HCl (634.4 g, 76.2%) as a white powder. filtered to afford two lots of filtrate that were concentrated under reduced pressure to ˜400 mL each To each lot was added methyl tert-butyl ether (MTBE) (2.2 L each) to stir overnight Each lot was filtered each washed with fresh MTBE (100 mL) dried overnight

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

Procedure: By a method similar to Example 11, a reaction was carried out using 2,4,5,6-tetrafluoroisophthalonitrile, instead of 3,4,5,6-tetrafluorophthalonitrile. After 5 hours, the reaction solution was analyzed by gas chromatography, whereupon the conversion of 2,4,5,6-tetrafluoroisophthalonitrile was found to be 36% and the yield of 2,3,4,6-tetrafluorobenzonitrile (based on 2,4,5,6-tetrafluoroisophthalonitrile) was 20%. At the same time, 1.1 mmol of α-methylbenzylcyanide was produced. This corresponded to 0.35 times molar amount relative to the production of 2,3,4,6-tetrafluorobenzonitrile.

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

Procedure: 100 g of ethylbenzene and 3.0 g of 5% palladium/activated carbon were added to a 1000 cc stainless steel autoclave. The gas phase was sufficiently replaced with hydrogen gas, then hydrogen gas was used to apply a pressure of 0.3 MPa and make the temperature 100° C. and catalytic pretreatment was carried out for 1 hour. The gas phase was again sufficiently replaced with nitrogen, then 3.0 g of the reaction material, that is, 2,3,5,6-tetrafluoroterephthalonitrile was added. The nitrogen atmosphere was maintained, the autoclave sealed as it was at atmospheric pressure, and the temperature held at 175° C. After 3 hours, the reaction solution was analyzed by gas chromatography, whereupon the conversion of 2,3,5,6-tetrafluoroterephthalonitrile was found to be 100% and the yield of 2,3,5,6-tetrafluorobenzonitrile (based on 2,3,5,6-tetrafluoroterephthalonitrile) was 95%. At the same time, 13.4 mmol of α-methylbenzylcyanide was produced. This corresponded to 0.95 times molar amount relative to the production of 2,3,5,6-tetrafluorobenzonitrile. the temperature 100° C. and catalytic pretreatment The nitrogen atmosphere was maintained the autoclave sealed as it held at 175° C After 3 hours

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

Procedure: A mixture of 1.5 g (+) Diop (2,3-O-Isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane, Aldrich Chemical Co.), 300 mg NiI2, 300 mg zinc dust, 2 ml commercial stabilized styrene, and 2 ml acetonitrile was stirred at 80° for 5 hr. then 250 μl HCN/CH3CN (11N) was added overnight by syringe pump. After addition of 2 ml styrene, 1 ml CH3CN and ca. 100 mg zinc dust another 400 μl HCN/CH3CN was added during eight hours. After addition of 4 ml styrene and 100 mg zinc addition of HCN/CH3CN at 50 μl/hr was continued overnight. The mixture was then diluted with 50 ml heptane and 25 ml ether. The mixture was filtered and the filtrate was concentrated to an oil which was diluted with an equal volume of toluene. The VPC analysis indicated that the two isomeric products PhCH(CN)CH3 and PhCH2CH2CN had been formed in approximately equal amounts. The PhCH(CN)CH3 was isolated by preparative VPC as described above to give 120 mg [α]D25 +1.1° C5.5% in CD3CN. An e.e. of about 10% is estimated based on the reported [α]D25 value of 10° for the pure isomer. The 1H nmr spectrum was as expected for PhCH(CN)CH3. The major product was apparently styrene polymer which hampered the isolation of the nitrile products. was added during eight hours was continued overnight The mixture was filtered the filtrate was concentrated to an oil which was diluted with an equal volume of toluene had been formed in approximately equal amounts

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

Procedure: This compound is synthesized according to Makosza, et al with some modifications (Makosza, M., et al, Tetrahedron (1974), 30: 3723). A solution of 4-chloronitrobenzene (31.5 g, 0.2 mol) in pyridine (100 mL) is added dropwise to a vigorously stirred suspension of KOH (fine powder 70.0 g) and α-methylbenzylcyanide (26.2 g, 0.2 mol) in pyridine (150 mL), with the reaction temperature being maintained at 10° C. The reaction mixture is stirred for 24 hours at 25° C., and poured onto an excess of HCl-ice mixture. The acidic aqueous mixture is extracted with benzene, the organic phase washed with brine, dried (Na), and the benzene evaporated under vacuum. A crude product 42.5 g (84 wt %) results and is recrystallized from isopropanolpetroleum ether to give Compound 7 as white crystals, This compound is synthesized The acidic aqueous mixture is extracted with benzene the organic phase washed with brine dried (Na) the benzene evaporated under vacuum A crude product 42.5 g (84 wt %) results is recrystallized from isopropanolpetroleum ether

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

Procedure: A mixture of 1.5 g (+) Diop (2,3-0-Isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane, Aldrich Chemical Co.), 300 mg NiI2, 300 mg zinc dust, 2 ml commercial stabilized styrene, and 2 ml acetonitrile was stirred at 80° for 5 hr. then 250 μl HCN/CH3CN (11N) was added overnight by syringe pump. After addition of 2 ml styrene, 1 ml CH3CN and ca. 100 mg zinc dust another 400 μl HCN/CH3CN was added during eight hours. After addition of 4 ml styrene and 100 mg zinc addition of HCN/CH3CN at 50 μl/hr was continued overnight. The mixture was then diluted with 50 ml heptane and 25 ml ether. The mixture was filtered and the filtrate was concentrated to an oil which was diluted with an equal volume of toluene. The VPC analysis indicated that the two isomeric products PhCH(CN)CH3 and PhCH2CH2CN had been formed in approximately equal amounts. The PhCH(CN)CH3 was isolated by preparative VPC as described above to give 120 mg [α]25D +1.1° C5.5% in CD3CN. An e.e. of about 10% is estimated based on the reported [α]25D value of 10° for the pure isomer. The 1H nmr spectrum was as expected for PhCH(CN)CH3. The major product was apparently styrene polymer which hampered the isolation of the nitrile products. was added during eight hours was continued overnight The mixture was filtered the filtrate was concentrated to an oil which was diluted with an equal volume of toluene had been formed in approximately equal amounts

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

Procedure: Phenylpropionitrile (1 g, 7.6 mmol) was reacted with hydroxylamine (50% in water, 0.94 cm3, 15.2 mmol, 2 eq) in EtOH (7.6 cm3) in the same manner as in the preparation of N′-hydroxybenzimidamide (EtOAc used in extraction) to give the product N′-hydroxy-3-phenylpropanimidamide (0.88 g, 70.5%) as a white solid, mp 42-43° C.