2-phenacylcyclohexan-1-one

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

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

Procedure: Following a procedure similar to that of Example 1C but using 64.9 g. of 2-(2-oxocyclohexyl)acetophenone and 37 g. of 4-methoxyaniline in 180 ml. glacial acetic acid there was obtained 80.9 g. of 1-(4-methoxyphenol)-2-phenol-4,5,6,7-tetrahydroindole; m.p. 132°-133°C. (isopropyl alcohol).

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

Procedure: Following a procedure similar to that of Example 1C but using 64.9 g. of 2-(2-oxocyclohexyl)acetophenone and 37 g. of 4-methoxyaniline in 180 ml. glacial acetic acid there was obtained 80.9 g. of 1-(4-methoxyphenol)-2-phenol-4,5,6,7-tetrahydroindole; m.p. 132°-133°C. (isopropyl alcohol).

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

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

Procedure: To a 250-mL round-bottomed flask containing 2.4 mL of 1-cyclohex-1-en-1-ylpyrrolidine was added 20 mL anhydrous NMP followed by NaI (0.645 g), under nitrogen. The flask was fitted with an addition funnel containing 2-bromo-1-phenylethanone (4.12 g) dissolved in 35 mL anhydrous NMP, which was dropped into the enamine solution over 60 min. This solution was stirred at ambient temperature for 10 h, then 90 mL of water was added to the solution and it was stirred for another 11 hours, under nitrogen. The solution was then extracted twice with ethyl acetate and water, the organic layers combined and further washed with water (3×), dried over sodium sulphate, filtered and evaporated to give a yellow oil. The oil was purified by Flash chromatography using a gradient cyclohexane:EtOAc (9:1). The product 2-(2-oxo-2-phenylethyl)cyclohexanone was used directly for the next reaction. (4.1 g, 91% yield, 98% purity by HPLC). MS(ESI+): 217.4; MS(ESI−): 215.6. The flask was fitted with an addition funnel was stirred for another 11 hours, under nitrogen The solution was then extracted twice with ethyl acetate and water further washed with water (3×) dried over sodium sulphate filtered evaporated to give a yellow oil The oil was purified by Flash chromatography The product 2-(2-oxo-2-phenylethyl)cyclohexanone was used directly for the next reaction

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

Procedure: A solution of 60.9 g (0.31 mole) of phenacyl bromide in 150 ml. of toluene is added dropwise with stirring to a refluxing solution of 46.6 g of 1-pyrrolidino-1-cyclohexene in 150 ml. of toluene. The mixture is heated under reflux for 2 hours, diluted with 150 ml. of water, refluxed for 3 hours and cooled. The layers are separated and the aqueous phase is extracted with ether. The organic solution is dried and concentrated to an oil. The oil is distilled to give an orange liquid which solidifies. The resulting solid is recrystallized from an ether petroleum mixture to give 2-phenacylcyclohexanone as tan crystals, m.p. 44°-45° C. The mixture is heated under reflux for 2 hours diluted with 150 ml cooled The layers are separated the aqueous phase is extracted with ether The organic solution is dried concentrated to an oil The oil is distilled to give an orange liquid which The resulting solid is recrystallized from an ether petroleum mixture

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

Procedure: A mixture of 8.1 g. (0.038 mole) of 2-phenacylcyclohexanone, 8.7 g. (0.038 mole) of 5-amino-3-bromosalicylic acid, and 50 ml. of glacial acetic acid was heated under reflux for 1 hour, cooled and filtered. Recrystallization of the collected solid from acetonitrile gave 7.0 g. (46%) of yellow crystals, m.p. 209°-210°. A mixture of 8.1 g under reflux for 1 hour cooled filtered Recrystallization of the collected solid from acetonitrile gave 7.0 g

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

Procedure: A mixture of 10.3 g. (0.048 mole) of 2-phenacylcyclohexanone, 10 g. (0.048 mole) of 3-acetamido-5-aminosalicylic acid, and 70 ml. of glacial acetic acid was heated under reflux under nitrogen for 1 hour, cooled and filtered. Recrystallization of the collected solid from acetic acid gave 10.5 g. (57%) of crystals, m.p. 232°-234°. A mixture of 10.3 g under reflux under nitrogen for 1 hour cooled filtered Recrystallization of the collected solid from acetic acid gave 10.5 g

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

Procedure: A mixture of 11.7 g. (0.054 mole) of 2-phenacylcyclohexanone, 10.5 g. (0.054 mole) of 2-acetamido-5-aminobenzoic acid, and 50 ml. of glacial acetic acid was heated under reflux for 4 hours, cooled, diluted with 15 ml. of methanol and filtered. The collected solid was recrystallized from acetonitrile to provide 9.45 g. (47%) of crystals, m.p. 192° -194°. A mixture of 11.7 g under reflux for 4 hours cooled diluted with 15 ml of methanol and filtered The collected solid was recrystallized from acetonitrile to provide 9.45 g

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

Procedure: a mixture of 10.3 g. (0.047 mole) of 2-phenacylcyclohexanone, 8.8 g. (0.047 mole) of 5-amino-3-chlorosalicylic acid, and 45 ml. of glacial acetic acid was heated under reflux for 1 hour, cooled and filtered. The collected solid was recrystallized from acetonitrile to provide 13.3 g. (77%) of crystals, m.p. 223°-225°. a mixture of 10.3 g under reflux for 1 hour cooled filtered The collected solid was recrystallized from acetonitrile to provide 13.3 g

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

Procedure: A mixture of 6.5 g. (0.029 mole) of 5-amino-4-trifluoromethylsalicylic acid, 6.35 g. (0.029 mole) of 2-phenacylcyclohexanone, and 30 ml. of glacial acetic acid was heated under reflux for 3 hours, cooled and filtered. The filter cake was recrystallized from acetic acid to provide 4.6 g. (39%) of gold crystals, m.p. 188°-190°. A mixture of 6.5 g under reflux for 3 hours cooled filtered The filter cake was recrystallized from acetic acid to provide 4.6 g

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

Procedure: A solution of 49.7 g. (0.23 mole) of 2-phenacylcyclohexanone, 35.2 g. (0.23 mole) of 5-aminosalicylic acid, and 135 ml. of glacial acetic acid was heated under reflux under nitrogen for 31/2 hours. A solid separated and was collected, washed with water, and recrystallized from acetic acid to provide 46.0 g. (60%) of pale yellow crystals, m.p. 209°-211°. under reflux under nitrogen for 31/2 hours A solid separated was collected washed with water recrystallized from acetic acid to provide 46.0 g