2-(4-methylphenyl)acetonitrile

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

Procedure: 5 ml of a 50% strength sodium hydroxide solution are added to a solution of 0.36 g (1 mmol) of the compound of Example 1, of 0.13 g (1 mmol) of 4-methylbenzyl cyanide and of 0.05 g of polyethylene glycol 400 in 15 ml of toluene. The mixture is left at ambient temperature for 2 hours. The organic phase is separated off, washed with water, dried and evaporated. The product is purified by chromatography on a silica column (CH2Cl2 eluent) The organic phase is separated off washed with water dried evaporated The product is purified by chromatography on a silica column (CH2Cl2 eluent)

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

Procedure: 4-Methylbenzyl cyanide (10 g) in ether was added dropwise under nitrogen to lithium aluminium hydride (2.9 g) in ether. The solution was refluxed for 1 h at the end of addition. The reaction mixture was cooled, water (3 ml), 2N.NaOH (3 ml), and further water (9 ml) were added, the reaction mixture filtered, the residue washed with chloroform and the combined solvents dried (MgSO4). Evaporation gave 2-(4-methylphenyl)ethanamine (11.59 g). The solution was refluxed for 1 h at the end of addition The reaction mixture was cooled the reaction mixture filtered the residue washed with chloroform the combined solvents dried (MgSO4) Evaporation

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

Procedure: 4-Methylbenzyl cyanide (10 g) in ether was added dropwise under nitrogen to lithium aluminium hydride (2.9 g) in ether. The solution was refluxed for 1 h at the end of addition. The reaction mixture was cooled, water (3 ml), 2N.NaOH (3 ml), and further water (9 ml) were added, the reaction mixture filtered, the residue washed with chloroform and the combined solvents dried (MgSO4). Evaporation gave 2-(4-methylphenyl)ethanamine (11.59 g). The solution was refluxed for 1 h at the end of addition The reaction mixture was cooled the reaction mixture filtered the residue washed with chloroform the combined solvents dried (MgSO4) Evaporation

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

Procedure: Following the procedures outlined in Examples 1 and 3, p-methylphenylacetonitrile and diethyl oxalate are reacted in alcoholic sodium ethoxide to obtain ethyl 3-cyano-3-(p-methylphenyl)-pyruvate, m.p. 86°-88° C. The latter is reacted with p-methylphenylacetonitrile to give 2,5-di-(p-methylphenyl)-3,4-dioxoadiponitrile, m.p. 270°-272° C.

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

Procedure: Following the procedures outlined in Examples 1 and 3, p-methylphenylacetonitrile and diethyl oxalate are reacted in alcoholic sodium ethoxide to obtain ethyl 3-cyano-3-(p-methylphenyl)-pyruvate, m.p. 86°-88° C. The latter is reacted with p-methylphenylacetonitrile to give 2,5-di-(p-methylphenyl)-3,4-dioxoadiponitrile, m.p. 270°-272° C.

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

Procedure: To 150 ml of 6 N hydrochloric acid was added 17.7 g of 2-amino-4-chloro-5-sulfamylaniline followed by the addition of 15.7 g of 4-methylbenzyl cyanide; the mixture was then refluxed for 9 hours. The precipitate was collected by filtration and added to 300 ml of concentration ammonium hydroxide. After stirring for ten minutes at ambient temperature, the solid was collected and then added to 300 ml of water and stirred at 40° C. for ten minutes. The crude product was collected and dissolved in 1 liter of methanol which was brought to a boil; after stirring for five minutes, charcoal was added, and stirring continued for ten more minutes. The mixture was then filtered through two sheets of filter paper and then through Celite. Concentration in vacuo provided a solid which upon recrystallization from acetonitrile provided 3.0 g of pink crystals, m.p. 214°-217°. the mixture was then refluxed for 9 hours The precipitate was collected by filtration added to 300 ml of concentration ammonium hydroxide the solid was collected added to 300 ml of water stirred at 40° C. for ten minutes The crude product was collected dissolved in 1 liter of methanol which after stirring for five minutes charcoal was added stirring The mixture was then filtered through two sheets of filter paper Concentration in vacuo provided a solid which upon recrystallization from acetonitrile

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

Procedure: 10.8 g (201 mmol) of ammonium chloride are suspended in 200 ml of dry toluene and the suspension is cooled to 0° C. 100 ml of a 2M solution of trimethylaluminium in hexane are added dropwise and the mixture is stirred at room temperature until the evolution of gas is complete. After addition of 13.2 g (100 mmol) of 4-methylbenzyl cyanide, the reaction mixture is stirred overnight at 80° C. (bath). The cooled reaction mixture is treated with ice-cooling with 35 ml of methanol and then stirred at room temperature for a further 1 h. The solid is then first filtered off with suction, and the filter cake is washed several times with methanol. The filtrate is concentrated, the residue is resuspended in dichloromethane/methanol 10/1 and the insoluble solid is separated off. The filtrate is then again evacuated from the solvent in vacuo. the reaction mixture is stirred overnight at 80° C. (bath) The cooled reaction mixture is treated with ice- stirred at room temperature for a further 1 h The solid is then first filtered off with suction the filter cake is washed several times with methanol The filtrate is concentrated the insoluble solid is separated off The filtrate is then again evacuated from the solvent in vacuo

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

Procedure: Sodium ethoxide (2 eq) is dissolved in ethanol (200 mL) and 4-methylphenylacetonitrile (10.0) and ethyl ethoxyacetate (1.5 eq) are slowly added. The reaction mixture is stirred for 1 hour under reflux. Upon completion of the reaction, ethanol is removed under reduced pressure and water (100 mL) and ethyl acetate are added. The organic layer is removed and the aqueous layer is acidified by adding acetic acid (10 mL) and extracted 3 times with ethyl acetate. The extracted organic layer is collected, washed with water and dehydrated with MgSO4. After concentration under reduced pressure, the produced solid is recrystallized with Hx:EA=20:1 to obtain the target compound (70-95%). under reflux is removed under reduced pressure and water (100 mL) and ethyl acetate are added The organic layer is removed by adding acetic acid (10 mL) extracted 3 times with ethyl acetate The extracted organic layer is collected washed with water After concentration under reduced pressure the produced solid is recrystallized with Hx

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

Procedure: Sodium ethoxide (2 eq) is dissolved in ethanol (200 mL) and 4-methylphenylacetonitrile (10.0) and ethyl ethoxyacetate (1.5 eq) are slowly added. The reaction mixture is stirred for 1 hour under reflux. Upon completion of the reaction, ethanol is removed under reduced pressure and water (100 mL) and ethyl acetate are added. The organic layer is removed and the aqueous layer is acidified by adding acetic acid (10 mL) and extracted 3 times with ethyl acetate. The extracted organic layer is collected, washed with water and dehydrated with MgSO4. After concentration under reduced pressure, the produced solid is recrystallized with Hx:EA=20:1 to obtain the target compound (70-95%). under reflux is removed under reduced pressure and water (100 mL) and ethyl acetate are added The organic layer is removed by adding acetic acid (10 mL) extracted 3 times with ethyl acetate The extracted organic layer is collected washed with water After concentration under reduced pressure the produced solid is recrystallized with Hx

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

Procedure: Sodium ethoxide (2 eq) is dissolved in ethanol (200 mL) and 4-methylphenylacetonitrile (10.0) and ethyl ethoxyacetate (1.5 eq) are slowly added. The reaction mixture is stirred for 1 hour under reflux. Upon completion of the reaction, ethanol is removed under reduced pressure and water (100 mL) and ethyl acetate are added. The organic layer is removed and the aqueous layer is acidified by adding acetic acid (10 mL) and extracted 3 times with ethyl acetate. The extracted organic layer is collected, washed with water and dehydrated with MgSO4. After concentration under reduced pressure, the produced solid is recrystallized with Hx:EA=20:1 to obtain the target compound (70-95%). under reflux is removed under reduced pressure and water (100 mL) and ethyl acetate are added The organic layer is removed by adding acetic acid (10 mL) extracted 3 times with ethyl acetate The extracted organic layer is collected washed with water After concentration under reduced pressure the produced solid is recrystallized with Hx

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 40 g of KOH are dissolved in 200 ml of methanol and heated up to 55° C. To the solution are added 25 g (0.19 mol) of 4-methylphenylacetonitrile, followed by 18 ml (0.17 mol) of nitrobenzene. The reaction mixture is stirred at 55° C. for 2.5 hrs. After cooling, 400 ml of water are added with stirring. The resulting solution is acidified by addition of 110 ml of acetic acid in 100 ml of water, leading to a yellow precipitate. The mixture is then filtered, and the solid is washed with a mixture of methanol and water, and methanol. After the solid is dried in air, 29.6 g (74%) of (4-Hydroxyimino-cyclohexa-2,5-dienylidene)-(4-methylphenyl)-acetonitrile are obtained in the form of a yellow powder having a melting point of 148-151° C. (dec.). After cooling with stirring The mixture is then filtered the solid is washed with a mixture of methanol and water, and methanol After the solid is dried in air, 29.6 g (74%) of (4-Hydroxyimino-cyclohexa-2,5-dienylidene)-(4-methylphenyl)-acetonitrile are obtained in the form of a yellow powder

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

Procedure: 9.79 g (50.93 mmol) of 3-nitrophthalimide are dissolved in 450 ml of DMF, and 10.56 g (76.39 mmol) of potassium carbonate are added. The suspension is treated with ultrasound for 10 min. 10.7 g (50.93 mmol) of 2-[4-(bromomethyl)phenyl]acetonitrile (obtained by reaction of 2-(4-methylphenyl)acetonitrile with N-bromosuccinimide (NBS) and azobisisobutyronitrile (AIBN) in carbon tetrachloride, cf. E. Laurent, B. Marquet, R. Tardivel; Tetrahedron; 47; 24; 1991; pp. 3969-3980) are then added, and the reaction mixture is stirred at room temperature for 20 h. The suspension is then poured into a mixture of 300 ml of 2 N hydrochloric acid and 3 l of water. The crystals formed are filtered off with suction, washed with water and dried under reduced pressure. This gives 12 g (73% of theory) of the desired compound. Rf (SiO2, CH2Cl2/EtOH=100/1)=0.55, MS=322.2 (M+H+). The suspension is treated with ultrasound for 10 min