2-cyclohexylphenol

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: The alkylation of Example 1A is repeated except the reaction is run at 140° C. The product contains 3.2 percent cyclohexene, 23.3 percent phenol, 13.7 cyclohexylphenyl ether, 57.7 percent ortho cyclohexyl phenol, and about 0.7 percent di-adduct. This product is then distilled in a POPE™ 2-inch wiped film still at 170° C., 1.7 psig (0.11 atm.) and 500 rpm (revolutions per minute). The heavies stream (distillation product which is not volatilized off) has about 0.7 percent cyclohexene, 44.3 percent phenol, 15.5 percent cyclohexylphenyl ether, 38 percent ortho cyclohexylphenol and 0.2 percent di-adduct. The heavies stream is reacted under the same conditions as Example 1A, except the reaction temperature is about 235° C. resulting in a product having about 0.05 percent cyclohexene, about 42.7 percent phenol, about 0.05 percent cyclohexylphenyl ether, about 53 percent orthocyclohexyphenol and about 0.4 percent di-adduct. This product from the heavies stream is then reacted under the same conditions as described by Example 1B. Example 1B resulted in essentially the same conversion and selectivity as described in Example 1B. is run at 140° C This product is then distilled in a POPE™ 2-inch still at 170° C. The heavies stream (distillation product which The heavies stream is reacted under the same conditions as Example 1A, except the reaction temperature is about 235° C. resulting in a product This product from the heavies stream is then reacted under the same conditions Example 1B resulted in essentially the same conversion and selectivity

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

Procedure: The alkylation of Example 1A is repeated except the reaction is run at 140° C. The product contains 3.2 percent cyclohexene, 23.3 percent phenol, 13.7 cyclohexylphenyl ether, 57.7 percent ortho cyclohexyl phenol, and about 0.7 percent di-adduct. This product is then distilled in a POPE™ 2-inch wiped film still at 170° C., 1.7 psig (0.11 atm.) and 500 rpm (revolutions per minute). The heavies stream (distillation product which is not volatilized off) has about 0.7 percent cyclohexene, 44.3 percent phenol, 15.5 percent cyclohexylphenyl ether, 38 percent ortho cyclohexylphenol and 0.2 percent di-adduct. The heavies stream is reacted under the same conditions as Example 1A, except the reaction temperature is about 235° C. resulting in a product having about 0.05 percent cyclohexene, about 42.7 percent phenol, about 0.05 percent cyclohexylphenyl ether, about 53 percent orthocyclohexyphenol and about 0.4 percent di-adduct. This product from the heavies stream is then reacted under the same conditions as described by Example 1B. Example 1B resulted in essentially the same conversion and selectivity as described in Example 1B. is run at 140° C This product is then distilled in a POPE™ 2-inch still at 170° C. The heavies stream (distillation product which The heavies stream is reacted under the same conditions as Example 1A, except the reaction temperature is about 235° C. resulting in a product This product from the heavies stream is then reacted under the same conditions Example 1B resulted in essentially the same conversion and selectivity

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

Procedure: 27 g of the catalyst prepared according to Example 1 were additionally impregnated with a solution of 0.81 g of K2SO4 in 10 ml of water and then dried at 120° C. for 20 hours. 30 ml (25.5 g) of the catalyst thus prepared were heated to 400° C. in a stream of hydrogen (10 l/hour), using the reaction tube described in Example 1, and were kept at this temperature for 68 hours. The oven temperature was then reduced to 350° C. and the dehydrogenation reaction was carried out without a carrier gas. 11.7 g/hour of the isomer mixture 2-cyclohexenylcyclohexanone and 2-cyclohexylidenecyclohexanone were thereby used. 3,972 g of reaction product containing 92.3% of o-phenylphenol and 0.5% of cyclohexylphenol were obtained in the course of 358 hours. dried at 120° C. for 20 hours 30 ml (25.5 g) of the catalyst thus prepared was then reduced to 350° C. the dehydrogenation reaction 3,972 g of reaction product

Conditions: temp:30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 15 g (85 mmol) of o-cyclohexylphenol and 16.5 g (93 mmol) of nicotinic acid chloride hydrochloride was mixed with 200 ml of dry pyridine and stirred for 24 hours at 30° C. After cooling precipitated pyridine hydrochloride was sucked off and 300 ml of water added. The precipitated raw product was washed with two 200 ml portions of water, dissolved in alcohol and reduced by means of a rotary evaporator. The remaining viscous oil was dissolved in 500 ml of dry ether and hydrochlorinated with HCl gas. Subsequently, the mixture was filtered, washed with ether and dried. After cooling precipitated pyridine hydrochloride 300 ml of water added The precipitated raw product was washed with two 200 ml portions of water dissolved in alcohol reduced by means of a rotary evaporator The remaining viscous oil was dissolved in 500 ml of dry ether and hydrochlorinated with HCl gas Subsequently, the mixture was filtered washed with ether dried

Conditions: temp:30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 15 g (85 mmol) of o-cyclohexylphenol and 16.5 g (93 mmol) of nicotinic acid chloride hydrochloride was mixed with 200 ml of dry pyridine and stirred for 24 hours at 30° C. After cooling precipitated pyridine hydrochloride was sucked off and 300 ml of water added. The precipitated raw product was washed with two 200 ml portions of water, dissolved in alcohol and reduced by means of a rotary evaporator. The remaining viscous oil was dissolved in 500 ml of dry ether and hydrochlorinated with HCl gas. Subsequently, the mixture was filtered, washed with ether and dried. After cooling precipitated pyridine hydrochloride 300 ml of water added The precipitated raw product was washed with two 200 ml portions of water dissolved in alcohol reduced by means of a rotary evaporator The remaining viscous oil was dissolved in 500 ml of dry ether and hydrochlorinated with HCl gas Subsequently, the mixture was filtered washed with ether dried

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

Procedure: 17.6 g (100 mmol) of cyclohexylphenol and 19 g (106 mmol) of nicotinic acid chloride hydrochloride was mixed with 250 ml of dry pyridine and kept at 40° C. for 4 hours. Subsequently, the mixture was cooled in the ice bath, and water added in portions. After addition of 10 ml of water a clear solution was obtained. Water (50 ml) was admixed until strong turbidity appeared. After stirring the mixture for a longer period of time the product crystallized in the ice bath. The precipitate was sucked off, freed from pyridine by washing with water and dried. A second fraction was obtained from the filtrate by further adding water (60 ml). added in portions was obtained crystallized in the ice bath by washing with water dried A second fraction was obtained from the filtrate

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

Procedure: To a stirring solution of 2-cyclohexylphenol (26.0 g, 146.8 mmol) in glacial acetic acid (100 mL) was added HBr in acetic acid (150 mL of 33% w/w,) and H2O (52 mL), followed by the dropwise addition of DMSO (100 mL) over 10 min. The reaction was then carefully quenched with saturated NaHCO3 and concentrated in vacuo. The residue was brought up in ether (400 mL), washed with water (2×100 mL) and brine (1×100 mL), and dried over anhydrous Na2SO4, filtered and concentration to yield a crude oil that was purified by silica gel column chromatography, using 15-30% EtOAc/hexane gradient to yield 4-bromo-2-cyclohexyl-phenol (35.0 g, 93%) The reaction was then carefully quenched with saturated NaHCO3 concentrated in vacuo washed with water (2×100 mL) and brine (1×100 mL) dried over anhydrous Na2SO4 filtered concentration to yield a crude oil that was purified by silica gel column chromatography

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

Procedure: To a stirring solution of 2-cyclohexylphenol (26.0 g, 146.8 mmol) in glacial acetic acid (100 mL) was added HBr in acetic acid (150 mL of 33% w/w,) and H2O (52 mL), followed by the dropwise addition of DMSO (100 mL) over 10 min. The reaction was then carefully quenched with saturated NaHCO3 and concentrated in vacuo. The residue was brought up in ether (400 mL), washed with water (2×100 mL) and brine (1×100 mL), and dried over anhydrous Na2SO4, filtered and concentration to yield a crude oil that was purified by silica gel column chromatography, using 15-30% EtOAc/hexane gradient to yield 4-bromo-2-cyclohexyl-phenol (35.0 g, 93%) The reaction was then carefully quenched with saturated NaHCO3 concentrated in vacuo washed with water (2×100 mL) and brine (1×100 mL) dried over anhydrous Na2SO4 filtered concentration to yield a crude oil that was purified by silica gel column chromatography

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

Procedure: In an analogous manner to the stepwise sequence outlined in intermediate 19, starting from 4,5-dichloro-2-(tetrahydropyran-2-yl)-2H-pyridazin-3-one (Intermediate 20) and 2-cyclohexylphenol and alkylating with 2-bromo-3-cyclopentyl-propionic acid methyl ester (Intermediate 10) afforded 2-[4-(2-cyclohexylphenoxy)-6-oxo-6H-pyridazin-1-yl]-3-cyclopentylpropionic acid (17.1 g, 72%) as a white solid; LC-MS [M+H+]=411.2; HPLC (0.17% trifluoroacetic acid in acetonitrile/water, 50%-100% acetonitrile, gradient, 1 mL/min, Venusil MP-C18, C18-15 cm×4.6 mm-5 μm), 254 nm, 95.8%, 214 nm, 97.2%. 1H-NMR (CDCl3, 300 MHz) δ 1.04-1.77 (m, 19H), 2.05-2.11 (m, 1H), 2.22-2.31 (m, 1H), 2.59-2.66 (t, 1H), 5.27-5.32 (dd, J=10.2 Hz, 4.8 Hz, 1H), 5.88-5.89 (d, J=2.4 Hz, 1H), 6.98-7.00 (m, 1H), 7.19-7.26 (m, 2H), 7.34-7.37 (m, 1H), 7.84-7.85 (d, J=2.7 Hz, 1H).

Conditions: temp:30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 15 g (85 mmol) of o-cyclohexylphenol and 16.5 g (93 mmol) of nicotinic acid chloride hydrochloride was mixed with 200 ml of dry pyridine and stirred for 24 hours at 30° C. After cooling precipitated pyridine hydrochloride was sucked off and 300 ml of water added. The precipitated raw product was washed with two 200 ml portions of water, dissolved in alcohol and reduced by means of a rotary evaporator. The remaining viscous oil was dissolved in 500 ml of dry ether and hydrochlorinated with HCl gas. Subsequently, the mixture was filtered, washed with ether and dried. After cooling precipitated pyridine hydrochloride 300 ml of water added The precipitated raw product was washed with two 200 ml portions of water dissolved in alcohol reduced by means of a rotary evaporator The remaining viscous oil was dissolved in 500 ml of dry ether and hydrochlorinated with HCl gas Subsequently, the mixture was filtered washed with ether dried