(2S,5R)-5-methyl-2-propan-2-ylcyclohexan-1-one

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

Procedure: In a 2 l three-necked flask there are introduced 308 g of 1-menthone (2 mol), 276 g of glycerol (3 mol) and 5 g of potassium hydrogen sulphate in toluene. This mixture is refluxed in a water separator. After 7 hours, 42 g of water have separated. The mixture is neutralised and distilled. 42 g of water have separated distilled

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

Procedure: In a 2 l three-necked flask there are introduced 308 g of 1-menthone (2 mol), 276 g of glycerol (3 mol) and 5 g of potassium hydrogen sulphate in toluene. This mixture is refluxed in a water separator. After 7 hours, 42 g of water have separated. The mixture is neutralised and distilled. 42 g of water have separated distilled

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

Procedure: A mixture of 19.6 g of the pyrrolidine-enamine of p-menthone, 10 ml of methylvinyl ketone and 150 ml of anhydrous benzene is refluxed under nitrogen for 20 hours. The mixture is then cooled and treated with 6 g of sodium acetate in 12 ml of water as well as with 12 ml of acetic acid. The mixture is again refluxed for 4 hours. Then, the product is extracted with benzene and the solvent evaporated. The residue is fractionated in vacuo and there is obtained 1-methyl-4-isopropyl-2-(3'-oxobutyl)-cyclohexan-3-one with a boiling point of 88°-90°C. is refluxed under nitrogen for 20 hours The mixture is then cooled The mixture is again refluxed for 4 hours Then, the product is extracted with benzene the solvent evaporated

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

Procedure: A mixture of 19.6 g of the pyrrolidine-enamine of p-menthone, 10 ml of methylvinyl ketone and 150 ml of anhydrous benzene is refluxed under nitrogen for 20 hours. The mixture is then cooled and treated with 6 g of sodium acetate in 12 ml of water as well as with 12 ml of acetic acid. The mixture is again refluxed for 4 hours. Then, the product is extracted with benzene and the solvent evaporated. The residue is fractionated in vacuo and there is obtained 1-methyl-4-isopropyl-2-(3'-oxobutyl)-cyclohexan-3-one with a boiling point of 88°-90°C. is refluxed under nitrogen for 20 hours The mixture is then cooled The mixture is again refluxed for 4 hours Then, the product is extracted with benzene the solvent evaporated

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

Procedure: A pure sample of tertbutyl 3(R)-benzoylamino-2(S)-hydroxy-3-phenylthiopropionate was obtained via the same reaction sequence, but using the boron reagent di{[(1S,2S,5R)-2-isopropyl-5-methylcyclohex-1-yl]-methyl}boron bromide, derived from (-)menthone. Compound tertbutyl 3(R)-benzoylamino-2(S)-hydroxy-3-phenylthiopropionate was treated with excess (S)-(-)-α-methoxy-α-(trifluoromethyl) phenylacetic acid in dichloromethane in the presence of 1,3-dicyclohexylcarbodiimide (DCC) and catalytic 4-dimethylaminopyridine (DMAP). The Mosher derivative tertbutyl 3(R)-benzoylamino-2(S)-O-[(S)-α-methoxy-α-trifluoromethyl)phenyl]acetyl-3-phenylthiopropionate was obtained:

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

Procedure: A pure sample of tertbutyl 3(R)-benzoylamino-2(S)-hydroxy-3-phenylthiopropionate was obtained via the same reaction sequence, but using the boron reagent di{[(1S,2S,5R)-2-isopropyl-5-methylcyclohex-1-yl]-methyl}boron bromide, derived from (-)menthone. Compound tertbutyl 3(R)-benzoylamino-2(S)-hydroxy-3-phenylthiopropionate was treated with excess (S)-(-)-α-methoxy-α-(trifluoromethyl) phenylacetic acid in dichloromethane in the presence of 1,3-dicyclohexylcarbodiimide (DCC) and catalytic 4-dimethylaminopyridine (DMAP). The Mosher derivative tertbutyl 3(R)-benzoylamino-2(S)-O-[(S)-α-methoxy-α-trifluoromethyl)phenyl]acetyl-3-phenylthiopropionate was obtained:

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

Procedure: 156 ml of a commercially obtainable 8M ethanolic methylamine solution are added to 62.8 g glycine.imethyl ester hydrochloride (500 mmol) in 160 ml ethanols. at room temperature and the mixture is stirred overnight with exclusion of moisture. 40.5 g triethylamine (400 mmol) and 61.6 g (-)-menthone (400 mmol) are then added to the suspension and the mixture is boiled under reflux for 18 h under an inert gas (argon) using a Soxhlet attachment which is filled with 100 g molecular sieve 3A (capacity: 14%). Thereafter, the solvent is removed and the residue is taken up in a two-phase system of water/diethyl ether. After the organic phase has been separated off, extraction is carried out twice more with diethyl ether and the extract is dried over sodium sulphate. After the yellow solution has been evaporated, the residue can be recrystallized from cyclohexane/diethyl ether =8:2. During distillation of the mother liquor in vacuo, the content of the desired compound can be increased by cyclizing the chain tautomer. Unreacted menthone passes over as the first fraction (70° .C/1 mbar), followed by a mixture of the desired product and chain tautomer (140-150° C., 1 mbar). After cyclohexane has been added to the product fraction, further product can be obtained as a crystalline solid with a melting point of 125° C. The yield is 65%. under reflux for 18 h under an inert gas (argon) Thereafter, the solvent is removed After the organic phase has been separated off extraction the extract is dried over sodium sulphate After the yellow solution has been evaporated the residue can be recrystallized from cyclohexane/diethyl ether =8:2 During distillation of the mother liquor in vacuo the content of the desired compound can be increased passes over as the first fraction (70° .C/1 mbar) followed by a mixture of the desired product and chain tautomer (140-150° C., 1 mbar) After cyclohexane has been added to the product fraction, further product can be obtained as a crystalline solid with a melting point of 125° C

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

Procedure: 156 ml of a commercially obtainable 8M ethanolic methylamine solution are added to 62.8 g glycine.imethyl ester hydrochloride (500 mmol) in 160 ml ethanols. at room temperature and the mixture is stirred overnight with exclusion of moisture. 40.5 g triethylamine (400 mmol) and 61.6 g (-)-menthone (400 mmol) are then added to the suspension and the mixture is boiled under reflux for 18 h under an inert gas (argon) using a Soxhlet attachment which is filled with 100 g molecular sieve 3A (capacity: 14%). Thereafter, the solvent is removed and the residue is taken up in a two-phase system of water/diethyl ether. After the organic phase has been separated off, extraction is carried out twice more with diethyl ether and the extract is dried over sodium sulphate. After the yellow solution has been evaporated, the residue can be recrystallized from cyclohexane/diethyl ether =8:2. During distillation of the mother liquor in vacuo, the content of the desired compound can be increased by cyclizing the chain tautomer. Unreacted menthone passes over as the first fraction (70° .C/1 mbar), followed by a mixture of the desired product and chain tautomer (140-150° C., 1 mbar). After cyclohexane has been added to the product fraction, further product can be obtained as a crystalline solid with a melting point of 125° C. The yield is 65%. under reflux for 18 h under an inert gas (argon) Thereafter, the solvent is removed After the organic phase has been separated off extraction the extract is dried over sodium sulphate After the yellow solution has been evaporated the residue can be recrystallized from cyclohexane/diethyl ether =8:2 During distillation of the mother liquor in vacuo the content of the desired compound can be increased passes over as the first fraction (70° .C/1 mbar) followed by a mixture of the desired product and chain tautomer (140-150° C., 1 mbar) After cyclohexane has been added to the product fraction, further product can be obtained as a crystalline solid with a melting point of 125° C

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

Procedure: A compound having general Formula 3, exemplified by 6-Isopropyl-3-methyl-2-{4-[(4-propoxy-benzylidene)-amino]-benzylidene}-cyclohexanone (Compound 3; FIG. 1) can be prepared as follows. A solution of menthone (154 mg, 1.0 mmol) and 4-aminobenzaldehyde (121 mg, 1.0 mmol) in dimethylsulfoxide is treated with potassium hydroxide (56 mg, 1.0 mmol). The reaction is stirred until no futher reaction occurs. The reaction mixture is poured into ethyl acetate and water. The organic phase is collected, dried and concentrated to give 2-(4-Amino-benzylidene)-6-isopropyl-3-methyl-cyclohexanone. The 2-(4-Amino-benzylidene)-6-isopropyl-3-methyl-cyclohexanone is dissolved in dichloromethane and treated with 4-propoxybenzaldehyde (164 mg, 1.0 mmol) and anhydrous Na2SO4. The reaction mixture is stirred until no further reaction occurs. The reaction mixture is filtered and concentrated to give the title compound. can be prepared The organic phase is collected dried concentrated

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

Procedure: A compound having general Formula 3, exemplified by 6-Isopropyl-3-methyl-2-{4-[(4-propoxy-benzylidene)-amino]-benzylidene}-cyclohexanone (Compound 3; FIG. 1) can be prepared as follows. A solution of menthone (154 mg, 1.0 mmol) and 4-aminobenzaldehyde (121 mg, 1.0 mmol) in dimethylsulfoxide is treated with potassium hydroxide (56 mg, 1.0 mmol). The reaction is stirred until no further reaction occurs. The reaction mixture is poured into ethyl acetate and water. The organic phase is collected, dried and concentrated to give 2-(4-Amino-benzylidene)-6-isopropyl-3-methyl-cyclohexanone. The 2-(4-Amino-benzylidene)-6-isopropyl-3-methyl-cyclohexanone is dissolved in dichloromethane and treated with 4-propoxybenzaldehyde (164 mg, 1.0 mmol) and anhydrous Na2SO4. The reaction mixture is stirred until no further reaction occurs. The reaction mixture is filtered and concentrated to give the title compound. can be prepared The organic phase is collected dried concentrated

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

Procedure: In a 2 l three-necked flask there are introduced 308 g of 1-menthone (2 mol), 276 g of glycerol (3 mol) and 5 g of potassium hydrogen sulphate in toluene. This mixture is refluxed in a water separator. After 7 hours, 42 g of water have separated. The mixture is neutralised and distilled. 42 g of water have separated distilled

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

Procedure: A compound having general Formula 3, exemplified by 6-Isopropyl-3-methyl-2-{4-[(4-propoxy-benzylidene)-amino]-benzylidene}-cyclohexanone (Compound 3; FIG. 1) can be prepared as follows. A solution of menthone (154 mg, 1.0 mmol) and 4-aminobenzaldehyde (121 mg, 1.0 mmol) in dimethylsulfoxide is treated with potassium hydroxide (56 mg, 1.0 mmol). The reaction is stirred until no futher reaction occurs. The reaction mixture is poured into ethyl acetate and water. The organic phase is collected, dried and concentrated to give 2-(4-Amino-benzylidene)-6-isopropyl-3-methyl-cyclohexanone. The 2-(4-Amino-benzylidene)-6-isopropyl-3-methyl-cyclohexanone is dissolved in dichloromethane and treated with 4-propoxybenzaldehyde (164 mg, 1.0 mmol) and anhydrous Na2SO4. The reaction mixture is stirred until no further reaction occurs. The reaction mixture is filtered and concentrated to give the title compound. can be prepared The organic phase is collected dried concentrated