Process for Producing Vitamin a or Its Carboxylic Acid Esters, and Itermediate Compounds Useful for the Process

The following Examples illustrate the present invention more specifically. It should be understood however, that these examples in no way restrict the scope of the present invention.

A 200 ml three-necked flask purged with nitrogen gas was charged with 10.80 g (38.8 mmoles) of beta-cyclogeranyl phenyl sulfone (1) and 100 ml of toluene, and then 24.2 ml (25.6 mmoles) of a diethyl ether solution of ethyl magnesium bromide (1.06 moles/liter) was added dropwise at an inside temperature of 20.degree. to 25.degree. C. After the addition, the mixture was stirred at 40.degree. to 45.degree. C. for 3 hours. The flask was then cooled so that its inside temperature became -40.degree. to -30.degree. C. To the resulting solution was added dropwise a solution of 4.02 g (19.1 mmoles) of 8-acetoxy-2,6-dimethyl-2(E),6(E)-octadien-1-al (2-1) in 10 ml of toluene. After the addition, the mixture was vigorously stirred at the above temperature for 2 hours. A 10% aqueous solution of hydrochloric acid was added to the reaction mixture, and the toluene layer was separated. The toluene layer was washed with water and then with a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate. Toluene was evaporated from the toluene layer, and the residue was chromatographed on a silica gel column using an eluent composed of a 7:3 by volume mixture of hexane and ethyl acetate to give 8.46 g of a colorless transparent oil. By the following analytical data, this product was determined to be a mixture of diastereomers of 1-acetoxy-8-hydroxy-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-p henylsulfonyl-2(E),6(E)-nonadiene (3).

Yield 91%.

NMR .delta. CDCl.sub.3 (CH.sub.3).sub.3 SiOSi(CH.sub.3).sub.3 : 0.61-2.03 (m, 28H); 2.87 (br, 1H); 3.95, 4.20 (d. 1H in total); 4.50 (d, 2H); 4.85, 4.97 (d, 1H in total); 5.25, 5.62 (m, 2H in total); 7.40-8.03 (m, 5H).

IR (film) .nu. (cm.sup.-1 ): 3500 (OH), 1735 (C.dbd.O), 1140 (SO.sub.2).

FD-MASS m/e: 488 (M.sup.+). ##STR19##

A 100 ml flask was charged with 2.67 g (5.5 mmoles) of compound (3) and 9.65 ml (110 mmoles) of methylal, and the mixture was stirred to form a solution. To the solution was added 0.22 g (1.54 mmoles) of phosphorus pentoxide, and the mixture was stirred at room temperature. Two hours and 5 hours later respectively, 0.21 g of phosphorus pentoxide was added, and the reaction was carried out for 24 hours.

A saturated aqueous solution of sodium bicarbonate was put in a separating funnel, and the solution portion of the reaction mixture was added to it. Toluene and a saturated aqueous solution of sodium bicarbonate were added to the residue, and the mixture was stirred whereby the tarry material dissolved. The resulting aqueous layer and organic layer were transferred to the separating funnel. The separated organic layer was washed with a saturated aqueous solution of sodium bicarbonate and dried over anhydrous magnesium sulfate.

The anhydrous magnesium sulfate was removed by filtration, and the solvent was evaporated at 40.degree. C. to give a red oily product. The oily product was chromatographed on a silica gel column using an eluent composed of a mixture of ethyl acetate and n-hexane in a ratio of from 1:6 to 1:4 to give 2.68 g of a yellow oil. By the following analytical data, this product was determined to be 1acetoxy-3,7-dimethyl-8-methoxymethoxy-9-phenylsulfonyl-9(2,6,6-trimethyl- 1-cyclohexen-1-yl)-2(E),6(E)-nonadiene (4). Yield 92%.

NMR .delta. CDCl.sub.3 (CH.sub.3).sub.3 SiOSi(CH.sub.3).sub.3 : 0.69-1.99 (m, 28H); 3.16, 3.35 (s, 3H); 3.96-5.60 (m, 8H); 7.38-8.01 (m, 5H).

IR (film) .nu. (cm.sup.-1): 1730 (C.dbd.O), 1140 (SO.sub.2).

FD-MASS m/e: 532(M.sup.+). ##STR20##

A 100 ml flask was charged with 2.68 g of compound (4) and 11 ml of methanol, and the mixture was stirred to form a solution. Sodium hydroxide (0.33 g) was added, and the mixture was stirred at room temperature for 1.5 hours. The reaction mixture was transferred to a separating funnel, and a large amount of water and toluene were added to extract the mixture with toluene. The toluene extract was washed with a saturated aqueous solution of ammonium chloride and water, and dried over anhydrous magnesium sulfate. The anhydrous magnesium sulfate was removed by filtration, and toluene was evaporated at 40.degree. C. under reduced pressure to give a red oily product. The oily product was chromatographed on a silica gel column using an eluent composed of a mixture of ethyl acetate and n-hexane in a ratio of from 1:1 to 1:4 to give 2.34 g of a yellow oil. By the following analytical data, this product was determined to be 1-hydroxy-3,7-dimethyl-8-methoxymethoxy-9-phenylsulfonyl-9-(2,6,6-trimethy l-1-cyclohexenl-yl)-2(E),6(E)-nonadiene (5).

NMR .delta. CDCl.sub.3 (CH.sub.3).sub.3 SiOSi(CH.sub.3).sub.3 : 0.68-2.04 (m, 26H); 3.15, 3.35 (s, 3H); 3.95-5.60 (m, 8H); 7.40-8.00 (m, 5H).

IR (film) .nu. (cm.sup.-1 ): 3500 (C.dbd.O), 1140 (SO.sub.2). ##STR21##

Under a nitrogen gas atmosphere, a 50 ml brown flask was charged with 0.5121 g (1.05 mmoles) of compound (5) and 5 ml of toluene, and the mixture was stirred to form a solution. To the solution was added 0.21 g (3.15 mmoles) of potassium methoxide, and the mixture was stirred at room temperature for 5 minutes and further at 40.degree. C. for 2 hours.

Hexane (20 ml) and 15 ml of water were added to the reaction mixture, and the mixture was transferred to a separating tunnel. The separated aqueous layer was extracted with 15 ml of hexane, and the extract was combined with the hexane layer. The mixture was washed twice with water, and dried over anhydrous magnesium sulfate. The anhydrous magnesium sulfate was removed by filtration, and the solvent was evaporated at 35.degree. C. under reduced pressure to give an orange oily product. The IR spectrum of this product agreed with that of commercial vitamin A (6).

Under a nitrogen atmosphere, a 100 ml brown flask was charged with the oily product obtained above, 4 ml of hexane and 1.1 ml of triethylamine, and cooled with an ice water bath. Acetic anhydride (0.68 ml) was added, and the mixture was stirred at the same temperature for 20 minutes and further at room temperature for 16 hours.

Hexane (25 ml) was added to the reaction mixture, and the mixture was cooled with an ice water bath. Then, 10 ml of a saturated aqueous solution of sodium bicarbonate was added. The mixture was stirred for 15 minutes and transferred to a separating funnel. It was separated by adding 15 ml of hexane and 10 ml of a saturated aqueous solution of sodium bicarbonate. The hexane layer was washed with a saturated aqueous solution of sodium bicarbonate, and dried over anhydrous magnesium sulfate.

The anhydrous magnesium sulfate was removed by filtration, and the solvent was evaporated at 35.degree. C. under reduced pressure to give 0.3723 g of an orange oily product. By high-performance liquid chromatography (column: .mu.-porasil; mobile phase: a 9:1 mixture of hexane and diisopropyl ether), the oily product was found to contain 0.2755 g (all-trans content: 95%) of vitamin A acetate (7). The total yield based on the compound (5) was 80%.

A 200 ml flask purged with argon gas was charged with 5.00 g (18.0 mmole) of beta-cyclogeranyl phenyl sulfone (1) and 60 ml of tetrahydrofuran, and cooled to -78.degree. C. Then, 6.6 ml (9.9 mmoles) of a hexane solution of n-butyllithium (1.5 moles/liter) was added dropwise, and the mixture was stirred at the above temperature for 3 hours. Then, a solution of 1.89 g (9.0 mmoles) of 8-acetoxy-2,6-dimethyl-2(E),6(E)-octadien-1-al(2-1) in 15 ml of tetrahydrofuran was added dropwise at -78.degree. C., and the mixture was stirred at this temperature for 2 hours and further at -50.degree. C. for 2 hours. The reaction mixture was cooled to -78.degree. C., and water was added to it. The temperature of the mixture was then raised to room temperature. The mixture was extracted with three 100 ml portions of benzene. The extracts were washed with water, and dried over anhydrous sodium sulfate. Benzene was evaporated from the extracts, and the residue was chromatographed on a silica gel column using an eluent composed of a 5:1 by volume mixture of hexane and ethyl acetate to give 4.01 g of a colorless transparent oil By the following analytical data, the product was determined to be 1-acetoxy-8-hydroxy-3,7-dimethyl- 9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-phenylsulfonyl-2(E),6(E)-nonadiene (3). Yield 93%.

NMR .delta. CDCl.sub.3 (CH.sub.3).sub.3 (SiOSi(CH.sub.3).sub.3 : 0.62-1.94 (m, 28H); 3.73 (br, 1H); 3.81 (d, 1H); 4.41 (d, 2H); 4.90 (d, 1H); 5.21 (m, 2H); 7.38-7.00 (m, 5H).

IR (film) .nu. (cm.sup.-1 ): 3500 (OH), 1735 (C.dbd.O), 1140 (SO.sub.2).

FD-MASS m/e: 488 (M.sup.+). ##STR23##

A 100 ml flask was charged with 1.36 g (2.8 mmoles) of 1-acetoxy-3,7-dimethyl-8-hydroxy-9-phenylsulfonyl-9-(2,6,6-trimethyl-1-cyc lohexen-1-yl)-2(E),6(E)-nonadiene (3), a catalytic amount of pyridinium p-toluenesulfonate and 15 ml of methylene chloride, and cooled with an ice water bath. To the solution was added dropwise 0.73 ml (8.4 mmoles) of 3,4-dihydro-2H-pyran, and the mixture was stirred for 3 hours with cooling in the bath. An aqueous sodium bicarbonate solution was poured into the reaction mixture, and the mixture was extracted with methylene chloride. The methylene chlorine extract was washed with water, and dried over anhydrous sodium sulfate. Methylene chloride was evaporated from the extract by an evaporator, and the remaining oil was chromatographed on a silica gel column using an eluent composed of a 1:5 mixture of ethyl acetate and n-hexane to give 1.59 g of 1-acetoxy-3,7-dimethyl-8-(tetrahydropyran-2-yl)oxy-9phenylsulfonyl-9-(2,6, 6-trimethyl-1-cyclohexen-1-yl)2(E),6(E)-nonadiene (8). Yield 99%. The analytical data of the product were as follows:

NMR .delta. CDCl.sub.3 (CH.sub.3).sub.3 SiOSi(CH.sub.3).sub.3 : 0.62-2.03 (m, 34H); 3.23-5.36 (m, 9H); 7.43-8.15 (m, 5H).

IR (film) .nu. (cm.sup.-1 ): 1150 (SO.sub.2).

FD-MASS m/e: 573 (M.sup.+ +1), 572 (M.sup.+).

Under a nitrogen gas atmosphere, a 100 ml brown flask was charged with 1.59 g of compound (8) and 15.9 ml of toluene, and the mixture was stirred to form a solution. While the inside temperature was maintained at 27.degree. C., 0.97 g of potassium methoxide was added. The mixture was stirred at this temperature for 0.3 hour, and then at an inside temperature of 38.degree. C. for 1.5 hours.

Hexane (60 ml) and 45 ml of water were added to the reaction mixture, and the hexane layer was separated by a separating funnel. The aqueous layer was extracted with 45 ml of hexane, and the extract was combined with the separated hexane layer. The mixture was washed twice with water, and dried over anhydrous magnesium sulfate. The anhydrous magnesium sulfate was removed by filtration, and the solvent was evaporated at 35.degree. C. under reduced pressure to give an orange oily product (6).

Under a nitrogen gas atmosphere, a 100 ml brown flask was charged with the above oily product (6), 10.6 ml of hexane and 2.9 ml of triethylamine, and cooled with an ice water bath. Acetic anhydride (1.8 ml) was added, and the mixture was stirred at the same temperature for 20 minutes and further at room temperature for 16 hours.

Hexane (70 ml) was added to the reaction mixture, and the mixture was cooled with an ice water bath. To the mixture was added 27 ml of a saturated aqueous solution of sodium bicarbonate, and the mixture was stirred for 15 minutes. The reaction mixture was transferred to a separating funnel, and separated by adding 40 ml of hexane and 27 ml of a saturated aqueous solution of sodium bicarbonate. The hexane layer was washed with a saturated aqueous solution of sodium bicarbonate, and dried over anhydrous magnesium sulfate.

The anhydrous magnesium sulfate was removed by filtration, and the solvent was evaporated at 35.degree. C. under reduced pressure to give an orange-colored oily product. By high-performance liquid chromatography (column: .mu.-porasil; mobile phase: a 9:1 mixture of hexane and diisopropyl ether), this product was found to contain 0.70 g (all trans content: 95%) of vitamin A acetate (7). The yield of the product based on compound (8) was 77%.

Under a nitrogen gas atmosphere, a 100 ml brown flask was charged with 2.68 g of 1-acetoxy-3,7-dimethyl-8-methoxymethoxy-9-phenylsulfonyl-9-(2,6,6-trimethy l-1-cyclohexen-1-yl)-2(E),6(E)-nonadiene(4) obtained in Example 1, (B) and 80 ml of cyclohexane, and the mixture was stirred to form a solution. Then, 3.53 g of potassium methoxide was added, and the mixture was stirred at an inside temperature of 39.degree. C. for 1.8 hours.

Hexane (96 ml) and 72 ml of water were added to the reaction mixture, and the mixture was transferred to a separating funnel. The aqueous layer separated was extracted with 96 ml of hexane, and the extract was combined with the separated hexane layer. The mixture was washed twice with water, and then dried over anhydrous magnesium sulfate. The anhydrous magnesium sulfate was removed by filtration, and the solvent was evaporated at 35.degree. C. under reduced pressure to give an orange-colored oily product.

Under a nitrogen gas atmosphere, a 300 mol brown flask was charged with the above oily product, 19.2 ml of hexane and 5.3 ml of triethylamine, and cooled with an ice water bath. Acetic anhydride (3.26 ml) was added, and the mixture was stirred at this temperature for 20 minutes and further at room temperature for 16 hours. Hexane (120 ml) was added to the reaction mixture, and the mixture was cooled with an ice water bath. Then, 48 ml of a saturated aqueous solution of sodium bicarbonate was added, and the mixture was stirred for 15 minutes. The mixture was then transferred to a separating funnel, and 72 ml of hexane and 48 ml of an aqueous sodium bicarbonate solution was added to separate the mixture into layers. The hexane layer was washed with a saturated aqueous solution of sodium bicarbonate, and dried over anhydrous magnesium sulfate.

The magnesium sulfate was removed by filtration, and the solvent was evaporated at 35.degree. C. under reduced pressure to give an orange-colored oily product. By high-performance liquid chromatography (column: .mu.-porasil; mobile phase: a 9:1 mixture of hexane and diisopropyl ether), this product was found to contain 1.29 g (all-trans content: 95%) of vitamin A acetate (7). The yield of the product based on the compound (4) was 78%.

A 200 ml three-necked flask purged with argon gas was charged with 7.01 g (24.0 mmoles) of beta-cyclogeranyl p-tolyl sulfone and 70 ml of tetrahydrofuran, and cooled to -78.degree. C. Then, 9.6 ml (14.4 mmoles) of a hexane solution of n-butyllithium (1.5 moles/liter) was added dropwise, and the mixture was stirred at the above temperature for 2 hours. A solution of 2.52 g (12.0 mmoles) of 8-acetoxy2,6-dimethyl-2(E),6(E)-octadien-1-al (2-1) in 15 ml of tetrahydrofuran was added dropwise to the solution at -78.degree. C., and the mixture was stirred at this temperature for 3 hours. Water was added to the reaction mixture, and the temperature of the mixture was raised to room temperature. The mixture was extracted successively with three 50 ml portions of benzene. The benzene extracts were washed with water, and dried over anhydrous magnesium sulfate. The solvent was evaporated from the extracts, and the residue was chromatographed on a silica gel column using an eluent composed of a mixture of hexane and ethyl acetate in a volume ratio of from 5:1 to 3:1 to give 4.88 g of a white solid. By the following analytical data, this product was determined to be 1-acetoxy-8-hydroxy-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-( p-tolyl)sulfonyl-2(E),6(E)-nonadiene (10). Yield 81%.

NMR .delta. CDCl.sub.3 (CH.sub.3).sub.3 SiOSi(CH.sub.3).sub.3 : 0.61-2.01 (m, 28H); 2.37 (s, 3H); 3.71 (br., 1H); 3.94 (d, 1H); 4.49 (d, 2H); 4.97 (d, 1H); 5.16 (m, 2H); 7.26 (d, 2H); 7.86 (d, 2H).

IR (film) .nu. (cm.sup.-1 ): 3480 (OH), 1735 (C.dbd.O), 1140 (SO.sub.2). ##STR26##

A 100 ml flask was charged with 1.00 g (1.99 mmoles) of compound (10), 0.52 ml of 3,4-dihydro-2H-pyran, 10 ml of methylene chloride, and a catalytic amount of p-toluenesulfonic acid, and the mixture was stirred at 0.degree. C. for 6 hours.

A saturated aqueous solution of sodium bicarbonate was put in a separating funnel, and the solution portion of the reaction mixture was added to it. The methylene chloride layer was separated. The aqueous layer was extracted with methylene chloride, and the extract was combined with the separated methylene chloride layer. The mixture was washed with water and dried over anhydrous magnesium sulfate.

The magnesium sulfate was removed by filtration, and methylene chloride was evaporated by an evaporator to give 1.47 g of a viscous oil. The oil was chromatographed on a silica gel column using an eluent composed of a 1:3 mixture of ethyl acetate and hexane to give 1.09 g of a product. By the IR analysis, this product was determined to be 1-acetoxy-3,7-dimethyl-8-(tetrahydropyran-2-yl)oxy-9-(p-tolyl)sulfonyl-9-( 2,6,6-trimethyl-2-cyclohexen-1-yl)-2(E),6(E)-nonadiene (11). Yield 93%.

IR (film) .nu. (cm.sup.-1 ): 2930, 1740, 1600, 1450, 1380, 1365, 1300, 1230, 1140, 1080, 1020, 960, 815. ##STR27##

A 100 ml brown flask was charged with 0.60 g (8.53 mmoles) of potassium methoxide and 25 ml of toluene, and in an argon atmosphere, a solution of 1.00 g (1.71 mmoles) of compound (11) in 5 ml of toluene was added at room temperature. The mixture was stirred at room temperature for 30 minutes, and further at 40.degree. C. for 2 hours.

The reaction mixture was poured into an aqueous solution of ammonium chloride, and extracted with diethyl ether. The extract was washed with water and then with a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate. The magnesium sulfate was removed by filtration, and then the diethyl ether and toluene were evaporated to give 0.76 g of a reddish yellow oil (6).

The oil was dissolved in 5 ml of pyridine, and 5 ml of acetic anhydride and a analytic amount of dimethylaminopyridine were added. The mixture was stirred at room temperature for 2 hours.

The reaction mixture was poured into a large amount of water, and extracted with n-hexane. The hexane extract was washed with an 80% aqueous solution of methanol and further three times with water, and dried over anhydrous magnesium sulfate. The anhydrous magnesium sulfate was removed by filtration, and n-hexane was evaporated to give 0.64 g of a reddish yellow oil. By liquid chromatography, this oil was found to contain 0.34 g (all-trans content: 95%) of vitamin A acetate. The total yield of the product based on the compound (11) was 61%.

1.36 g (2.8 mmoles) of 1-acetoxy-3,7-dimethyl-8-hydroxy-9-phenylsulfonyl-9-(2,6,6-trimethyl-1-cyc lohexen-1-yl)-2(E),6(E)-nonadiene (3) obtained in Example 2 in 15 ml of methylene chloride was subjected to the following reaction conditions, and the reaction mixture was worked up in the same way as in Example 2 to give the corresponding acetals. The results are shown in the following table.

The same reaction as in Example 1 was carried out under the conditions shown in the following table using 1.05 mmoles of each of the compounds (12), (13) and (14) obtained in Examples 5 to 7 to obtain vitamin A acetate (7). The results are shown in the following table.

0.76 g of the reddish yellow oil (6) obtained by the reaction of compound (11) with potassium methoxide in toluene in Example 4 was dissolved in 5 ml of pyridine, and the solution was cooled with ice water. Then, 0.71 g (2.58 mmoles) of palmitoyl chloride was added to the solution, and the mixture was stirred at the same temperature for 0.5 hour, the further at room temperature for 5 hours.

The reaction mixture was poured into a large amount of water, and extracted with n-hexane. The hexane extract was washed three times with water, and dried over anhydrous magnesium sulfate. The magnesium sulfate was removed by filtration, and hexane was evaporated under reduced pressure to give 0.73 g of reddish yellow oil. By liquid chromatography (column: .mu.-porasil: mobile phase: a 2:98 mixture of diisopropyl ether and hexane), this oil was found to contain 0.55 g (all-trans content: 95%) of vitamin A palmitate.

A 100 ml flask was charged with 7.38 g (15 mmoles) of 1-acetoxy-8-hydroxy-3,7-dimethyl-9-(2,6,6,-trimethyl-1-cyclohexen-1-yl)-9- phenylsulfonyl-2(E),6(E)-nonadiene (3) obtained in Example 1, (A), 60 ml of benzene and 12 ml of pyridine, and while the flask was cooled on an ice water bath, 1.32 ml of thionyl chloride was added dropwise. Then, the mixture was stirred at room temperature for 16 hours. A 3% aqueous solution of sulfuric acid cooled with ice was added to the reaction mixture, and the organic layer was separated. The aqueous layer was extracted with two 70 ml portions of diethyl ether. The extracts were combined with the organic layer, and the mixture was successively washed with a 3% aqueous sulfuric acid solution cooled with ice, a saturated aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate. The solvent was evaporated from the organic layer. The residue was chromatographed on a silica gel column using an eluent composed of a 5:1 by volume mixture of hexane and ethyl acetate to give 7.18 g of a white waxy product. By the following analytical data, this product was determined to be 1-acetoxy-6-chloro-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-ph enylsulfonyl-2,7-nonadiene (15). Yield 94%.

NMR .delta. CDCl.sub.3 (CH.sub.3).sub.3 /CDCl.sub.3 SiOSi(CH.sub.3).sub.3 : 0.72-2.05 (m, 28H); 4.17-4.57 (m, 4H); 5.23 (t, 1H); 5.88 (m, 1H); 7.35-7.91 (m, 5H).

IR (film) .nu. (cm.sup.-1 ): 1745 (C.dbd.O), 1150 (SO.sub.2), 685 (C.sub.6 H.sub.5).

RD-MASS m/e: 506 (M.sup.+), 507 (M.sup.+ +1), 470 (M.sup.+ --HCl), 365 (M.sup.+ --C.sub.6 H.sub.5 SO.sub.2). ##STR37##

A 10 ml flask was charged with 0.0226 g (0.342 mmole) of potassium hydroxide having a purity of 85% and 1 ml of methanol The mixture was stirred at room temperature to prepare a methanol solution of potassium hydroxide. To the solution was added a solution of 0.0373 g (0.0736 mmole) of 1-acetoxy-6-chloro-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-ph enylsulfonyl-2,7-nonadiene (15) in a mixture of 2 ml of methanol and 0.2 ml of benzene. The mixture was stirred in an ice water bath for 30 minutes. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, and the solvent was evaporated from it. Water was added to the residue, followed by extraction with diethyl ether. The extract was washed with a saturated aqueous solution of ammonium chloride, and dried over anhydrous magnesium sulfate. The solvent was evaporated from the extract to give 0.0297 g of a yellow oil. By the following analytical data, this product was identified as 6 -chloro-1-hydroxy-3.7-dimethyl9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-phen ylsulfonyl-2,7-nonadiene (16). Yield 87%.

NMR .delta. CDCl.sub.3 (CH.sub.3).sub.3 SiOSi(CH.sub.3).sub.3 :/CDCl.sub.3

0.75-2.20 (m, 26H); 4.06 (d, 2H); 4.21-4.55 (m, 2H); 5.30 (t, 1H); 5.91 (m, 1H); 7.36-7.90 (m, 5H).

IR (film) .nu. (cm.sup.-1 ): 3300 (OH), 1150 (SO.sub.2), 685 (C.sub.6 H.sub.5).

FD-MASS m/e: 465 (M.sup.+ +1), 428 (M.sup.+ --HCl), 323 (M.sup.+ --C.sub.6 H.sub.5 SO.sub.2).

A 50 ml flask was charged with 2.44 g (5.00 mmoles) of 1-acetoxy-8-hydroxy-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-p henylsulfonyl-2(E),6(E)-nonadiene (3), 0.12 g of pyridine and 20 ml of methylene chloride. While the flask was cooled with an ice water bath, 0.29 ml (3.3 mmoles) of phosphorus trichloride was added dropwise. The mixture was then stirred at the above temperature for 6 hours. To the reaction mixture was added a saturated aqueous solution of sodium bicarbonate, and the mixture was extracted with diethyl ether. The extract was washed with a saturated aqueous solution of sodium bicarbonate, and dried over anhydrous magnesium sulfate. The solvent was evaporated from the extract, and the residue was chromatographed on a silica gel column using an eluent composed of a mixture of hexane and ethyl acetate in a volume ratio of from 9:1 to 5:1 to give 1.27 g (yield 50%) of 1-acetoxy-6-chloro-3,7-dimethyl-9-(2,6,6-trimethyl-1 -cyclohexen-1-yl)-9-phenylsulfonyl-2,7-nonadiene (15).

A 50 ml flask was charged with 2.44 g (5.0 mmoles) of 1-acetoxy-8-hydroxy-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-p henlsulfonyl-2(E),6(E)-nonadiene (3) obtained in Example 2, (A), 0.12 g of pyridine and 20 ml of methylene chloride, and while the flask was cooled with an ice water bath, 0.31 ml (3.3 mmoles) of phosphorus tribromide was added dropwise, and the mixture was stirred at this temperature for 1.5 hours. To the reaction mixture was added a saturated aqueous solution of sodium bicarbonate, followed by extraction with diethyl ether. The extract was washed successively with a saturated aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate. The solvent was evaporated from the extract, and the residue was chromatographed on a silica gel column using an eluent composed of a mixture of hexane and ethyl acetate in a volume ratio of the from 9:1 to 3:1 to give 2`34 g of a white waxy product. By the following analytical data, this product was determined to be 1-acetoxy-6-bromo-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-phe nylsulfonyl-2,7-nonadiene (17). Yield 85%.

NMR .delta. CDCl.sub.3 (CH.sub.3).sub.3 SiOSi(CH.sub.3).sub.3 : 1.71-2.03 (m, 28H); 4.32-4.57 (m, 4H); 5.24 (m, 1H); 5.90 (m, 1H); 7.43-7.90 (m, 5H).

IR (film) .nu. (cm.sup.-1 ): 1730 (C.dbd.O), 1135 (SO.sub.2), 670 (C.sub.6 H.sub.5).

FD-MASS m/e: 550 (M.sup.+), 470 (M.sup.+ --HBr), 409 (M.sup.+ --C.sub.6 H.sub.5 SO.sub.2).

A 50 ml flask was charged with 610 mg (1.26 mmoles) of 1-acetoxy-8-hydroxy-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-( p-tolyl)sulfonyl-2(E),6(E)nonadiene (10) obtained in Example 4, (A), 0.96 ml (12 mmoles) of pyridine and 15 ml of benzene. While the flask was cooled with an ice water bath, 0.11 ml (1.5 mmoles) of thionyl chloride was added, and the mixture was stirred at room temperature for 16 hours. The reaction mixture was partitioned between 1N hydrochloric acid and benzene. The organic layer was washed with water, and dried over anhydrous magnesium sulfate; and the solvent was evaporated to give 630 g of a yellow oil. By the following analytical data, this product was determined to be 1-acetoxy6-chloro-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen- 1-yl)-9-(p-tolyl)sulfonyl-2,7-nonadiene (18). It was found that from the NMR analysis, the oily product had a purity of 89%. Yield 88%.

NMR .delta. CDCl.sub.3 (CH.sub.3).sub.3 SiOSi (CH.sub.3).sub.3 : 0.70-1.93 (m, 28H); 2.40 (s, 3H); 4.15-4.43 (m, 4H); 5.17 (t, 1H); 5.82 (d, 1H); 7.21 (d, 2H); 7.64 (d, 2H).

IR (film) .nu. (cm.sup.-1 ): 1740 (C.dbd.O), 1150 (SO.sub.2).

A 50 ml flask purged with argon gas was charged with 0.4951 g (0.977 mmole) of 1-acetoxy-6-chloro-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-ph enylsulfonyl-2,7-nonadiene (15) and 15 ml of cyclohexane. After the mixture was stirred for a while, 0.70 g (10 mmoles) of potassium methoxide was added, and the mixture was stirred at 38.degree. C. for 2 hours. To the reaction mixture were added 30 ml of diisopropyl ether and 15 ml of a saturated aqueous solution of ammonium chloride. The organic layer was separated, and the aqueous layer was extracted with 20 ml of diisopropyl ether. The extract was combined with the organic layer, and the mixture was washed with a saturated aqueous solution of ammonium chloride and dried over anhydrous magnesium sulfate. The organic solvent was evaporated from the organic layer, and the residue, together with 4 ml of a 0.05% by weight hexane solution of 2,6-di-t-butyl-4-methylphenol and 1.1 ml of triethylamine, was put in a 100 ml flask purged with argon. Under ice base cooling, 0.68 ml of acetic anhydride was added to the mixture, and the mixture was stirred for one day at room temperature. To the reaction mixture were added 50 ml of hexane and 10 ml of a saturated aqueous solution of sodium bicarbonate. The mixture was stirred for a while, and the hexane layer was separated. The hexane layer was washed with a saturated aqueous solution of sodium bicarbonate, and dried over anhydrous magnesium sulfate, By evaporating hexane from the hexane layer, 0.3462 g of a red oil was obtained. The FD-MASS analysis of this oily product revealed a peak at m/e=328. This led to the determination that the main component of the oily product was vitamin A acetate (7).

The vitamin A acetate was then quantified by high-performance liquid chromatography using methyl stearate as an internal standard. It was consequently found that the yield of vitamin A acetate was 70% based on 1-acetoxy-6-chloro-3,7- dimethyl-9-(2,6,6-trimethyl-1-cycloexen-1-yl)-9-phenylsulfonyl-2,7-nonadie ne (15), and its all-trans content was 93%.

The same reaction and separating operations as in Example 16 were carried out except that 0.5538 g (1.01 mmoles) of 1-acetoxy-6-bromo-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-phe nylsulfonyl-2,7-nonadiene 1-cyclohexen-1-yl)-9-phenylsulfonyl-2,7-nonadiene (17) obtained in Example 14 was used instead of 0.4951 g (0.977 mmole) of 1-acetoxy-6-chloro-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclphexen-1-yl)-9-ph enylsulfonyl-2,7-nonadiene, and a mixture of 10 ml of cyclohexane and 5 ml of toluene was used instead of 15 ml of cyclohexane. As a result, 0.3195 g of a red oily product was obtained. The FD-MASS analysis of the oily product revealed a peak at m/e=328, and this led to the determination that the main component of the oily product was vitamin A acetate (7).

The resulting vitamin A acetate was quantified by high-performance liquid chromatography in the same way as in Example 16. It was found that the yield of vitamin A acetate was 70% based on 1-acetoxy-6-bromo-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-phe nylsulfonyl-2,7-nonadiene (17), and its all-trans content was 93%.

A 10 ml flask purged with argon gas was charged with 0.0232 g (0.050 mmole) of 6-chloro-1-hydroxy-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-ph enylsulfonyl-2,7-nonadiene (16) obtained in Example 12, (B) and 5 ml of cyclohexane, and then 0.0352 g (0.50 mmole) of potassium methoxide was added. The mixture was stirred at 35.degree. C. for 2 hours. The reaction mixture was added to a mixture of 20 ml of diisopropyl ether and 10 ml of a saturated aqueous solution of ammonium chloride. The organic layer was separated, dried over anhydrous magnesium sulfate, and concentrated to about 1 ml. The FD-MASS analysis of the concentrate revealed a peak at m/e=286. This led to the determination that the concentrate contained vitamin A (6). ##STR44##

The above concentrate was dissolved in 2 ml of pyridine, and the solution was cooled with an ice water bath. Then, 0.0137 g (0.05 mmole) of palmitoyl chloride was added to the solution, and the mixture was stirred under ice bath cooling for 0.5 hour and then at room temperature for 5 hours. The reaction mixture was poured into a large amount of water, and extracted with hexane. The hexane extract was washed with water, and dried over anhydrous magnesium sulfate. The magnesium sulfate was removed by filtration, and hexane was evaporated from the filtrate under reduced pressure. As a result, 0.0282 g of a reddish yellow oil was obtained. The oil was determined, by liquid chromatography (column: .mu.-porasil; mobile phase: a 2:98 by volume mixture of diisopropyl ether and hexane), to contain 0.0183 g of vitamin A palmitate.

The same reaction and separating operations as in Example 17 were carried out except that 0.5127 g (0.985 mmole) of 1-acetoxy-6-chloro-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-(p -tolyl)sulfonyl-2,7-nonadiene (18) was used instead of 0.5538 g (1.01 mmoles) of 1-acetoxy-6-bromo-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-phe nyl-sulfonyl-2,7-nonadiene. As a result, 0.3325 g of a red oily product was obtained. The FD-MASS analysis of the oily product revealed a peak at m/e=328. This led to the determination that the main component at the oily product was vitamin A acetate. Then, in the same way as in Example 16, the resulting vitamin A acetate was quantified by high-performance liquid chromatography. It was found that the yield of vitamin A acetate (7) was 68% based on 1-acetoxy-6-chloro-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-(p -tolyl)sulfonyl-2,7-nonadiene (18), and its all-trans content was 93%.

The same reaction and separating operations as in Example 16 were carried out except that 1.12 g (10 mmoles) of potassium n-butoxide was used instead of 0.70 g (10 mmoles) of potassium methoxide. As a result, 0.3481 g of a red oily product was obtained. In the same way as in Example 16, the resulting vitamin A acetate was quantified by high-performance liquid chromatography. It was found that the yield of vitamin A acetate (7) was 72% based on 1-acetoxy-6-chloro-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-ph enylsulfonyl-2,7-nonadiene (15), and its all-trans content was 92%.

A 50 ml flask purged with argon gas was charged with 0.4913 g (0.970 mmole) of 1-acetoxy-6-chloro-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-ph enylsulfonyl-2,7-nonadiene (15) obtained in Example 12, (A) and 15 ml of cyclohexane. The mixture was stirred for a while, and 0.55 g (10 mmoles) of potassium hydroxide (purity 85%) was added. The mixture was stirred at 65.degree. C. for 1.5 hours, and further at the refluxing temperature for 2 hours. After cooling, 30 ml of diisopropyl ether and 15 mml of a saturated aqueous solution of ammonium chloride were added to the reaction mixture. The organic layer was separated, and the aqueous layer was extracted with 20 ml of diisopropyl ether. The extract was combined with the organic layer, and the mixture was washed with a saturated aqueous solution of ammonium chloride, and dried over anhydrous magnesium sulfate. The organic solvent was evaporated from the organic layer, and the residue, together with 5 ml of a 0.05% by weight hexane solution of 2,6-di-t-butyl-4-methylphenol and 1.1 ml of triethylamine, was put in a 100 ml flask purged with argon. Under ice bath cooling, 0.68 ml of acetic anhydride was added to the mixture. The mixture was stirred at room temperature for 1 day. To the reaction mixture were added 50 ml of hexane and 10 l of a saturated aqueous solution of sodium bicarbonate. The mixture was stirred for a while, and the hexane layer was separated. The hexane layer was washed with a saturated aqueous solution of sodium bicarbonate, and dried over anhydrous magnesium sulfate. Hexane was evaporated from the hexane solution to give 0.3577 g of a red oily product. The resulting vitamin A acetate was quantified by high-performance liquid chromatography in the same way as in Example 16. It was found that the yield of vitamin A acetate (7) was 64% based on 1-acetoxy-6-chloro-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-ph enylsulfonyl-2,7-nonadiene, and its all-trans content was 90%.

A 50 ml flask was charged with 1.55 g (3.1 mmoles) of 1-acetoxy-6-chloro-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-ph enylsulfonyl-2,7-nonadiene (15) obtained in Example 12, (A), 30 ml of diethyl ether and 0.85 ml (6.0 mmoles) of 1,8-diazabicyclo[5.4.0]undec-7-ene, and the mixture was stirred for 10 hours under reflux. The reaction mixture was partitioned between diethyl ether and water. The ether layer was washed successively with 5% sulfuric acid and a saturated aqueous solution of sodium bicarbonate, and dried over anhydrous magnesium sulfate. The solvent was evaporated from the ether solution, and the residue was chromatographed on a silica gel column using an eluent composed of a 3:1 by volume mixture of hexane and ethyl acetate to give 1.23 g of a yellow oily product. By the following analytical data, this product was determined to be 1-acetoxy-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-phenylsulfo nyl-2,6,8-nonatriene (19). Yield 86%.

NMR .delta. CDCl.sub.3 (CH.sub.3).sub.3 SiOSi(CH.sub.3).sub.3 : 0.86-2.27 (m, 28H); 4.51 (d, 2H); 5.25 (t, 1H); 5.67-5,90 (m, 1H); 7.14-7.90 (m, 6H).

IR (film) .nu. (cm.sup.-1 ): 1745 (C.dbd.O), 1150 (SO.sub.2).

FD-MASS m/e: 470 (M.sup.+), 328 (M.sup.+ --C.sub.6 H.sub.5 SO.sub.2).

A 100 ml flask was charged with 2.5347 g (5.00 mmoles) of 1-acetoxy-6-chloro-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-ph enylsulfonyl-2,7-nonadiene (15) obtained in Example 12, (A), 6 ml of benzene and 20 ml of methanol, and the mixture was stirred to form a solution. The solution was cooled with an ice water bath, and a solution of 1.35 g (20 mmoles) of potassium hydroxide (purity 85%) in 15 ml of methanol was added. The mixture was stirred in an ice water bath for 5 minutes, and further at room temperature for 18 hours. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, and the mixture was extracted successively with three 100 ml portions of diethyl ether. The extracts were washed with a saturated aqueous solution of ammonium chloride and dried over anhydrous magnesium sulfate. The solvent was evaporated from the ether solution, and the residue was chromatographed on a silica gel column using an eluent composed of a mixture of hexane and ethyl acetate in a volume ratio of from 4:1 to 3:1 to give 1.5071 g of a yellow oily product. By the following analytical data, the product was determined to be 1-hydroxy-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-phenylsulfo nyl-2,6,8nonatriene (20). Yield 70%.

NMR .delta. CDCl.sub.3 (CH.sub.3).sub.3 SiOSi(CH.sub.3).sub.3): 0.90-2.28 (m, 26H); 4.07 (m, 2H); 5.35 (t, 1H0; 5.67-5.89 (m, 1H); 7.13-7.90 (m, 6H).

IR (film) .nu. (cm.sup.-1 ): 3450 (OH), 1140 (SO.sub.2).

FD-MASS m/e: 428 (M.sub.+), 287 (M.sup.+ --C.sub.6 H.sub.5 SO.sub.2).

A 50 ml flask was charged with 1.38 g (2.5 mmoles) of 1-acetoxy-6-bromo-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-phe nylsulfonyl-2,7-nonadiene (17) obtained in Example 14, 15 ml of methylene chloride, and 0.6 ml (5 mmoles) of 1,5-diazabicyclo[4.3.0]non-5-ene. The mixture was stirred for 5 hours under reflux. The reaction mixture was worked up by the same operation as in Example 22, to give 0.99 g (yield 84%) of 1-acetoxy-3,7-dimethyl- 9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-phenylsulfonyl-2,6,8-nonatriene (19).

The same reaction and separating operations as in Example 23 were carried out except that 1.36 g (2.6 mmoles) of 1-acetoxy-6-bromo-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-phe nylsulfonyl-2,7-nonadiene (17) obtained in Example 14 was used instead of 2.5347 g (5.00 mmoles) of 1-acetoxy-6-chloro-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-ph enylsulfonyl-2,7-nonadiene (15). As a result, 0.87 g (yield 73%) of 1-hydroxy-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-phenylsulfo nyl-2,6,8-nonatriene was obtained.

A 100 ml flask was charged with 4.27 g (8.82 mmoles) of 1-acetoxy-8-hydroxy-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-( p-tolyl)sulfonyl-2,6-nonadiene (10) obtained in Example 4, (A), 6.7 ml (84 mmoles) of pyridine and 50 ml of benzene. While the flask was cooled with an ice water bath, 0.77 ml (11 mmoles) of thionyl chloride was added, and the mixture was then stirred at room temperature for 16 hours. The reaction mixture was partitioned between 1N hydrochloric acid and benzene. The organic layer was washed with water, and dried over anhydrous magnesium sulfate. The solvent was evaporated to give 4.41 g of a yellow oily product. By the following analytical data, this product was determined to the 1-acetoxy-6-chloro-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-(p -tolyl)sulfonyl-2,7-nonadiene (18). From the NMR analysis, the purity of the oily product was found to be 89%. Yield 88%.

NMR .delta. CDCl.sub.3 (CH.sub.3).sub.3 SiOSi(CH.sub.3).sub.3 : 0.70-1.93 (m, 28H); 2.40 (s, 3H); 4.15-4.43 (m, 4H); 5.17 (t, 1H); 5.82 (d, 1H); 7.21 (d, 2H); 7.64 (d, 2H).

IR (film) .nu. (cm.sup.-1 ): 1740 (C.dbd.O), 1150 (SO.sub.2). ##STR53##

The same reaction and separating operations as in Example 22 were carried out except that 1.75 g (3.0 mmoles) of 1-acetoxy-6-chloro-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-(p -tolyl)sulfonyl-2,7-nonadiene (18) (purity 89%) was used instead of 1.55 g (3.1 mmoles) of 1-acetoxy-6-chloro-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-ph enylsulfonyl-2,7-nonadiene (15). As a result, 1.19 g of a yellow oily product was obtained. By the following analytical data, this product was determined to be 1-acetoxy-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-(p-tolyl)su lfonyl2-6,8-nonatriene (21). Yield 82%.

NMR .delta. CDCl.sub.3 (CH.sub.3).sub.3 SiOSi(CH.sub.3).sub.3 : 0.87-2.25 (m, 28H); 2.40 (s, 3H0; 4.51 (d, 2H); 5.24 (t, 1H); 5.66-5.90 (m, 1H); 7.14-7.98 (m, 5H).

IR (film) .nu. (cm.sup.-1): 1745 (C.dbd.O), 1150 (SO.sub.2).

FD-MASS m/e: 484 (M.sup.+), 328 (M.sup.+ --CH.sub.3 C.sub.6 H.sub.4 SO.sub.2 H). ##STR54##

The same reaction and separating operations as in Example 23 were carried except that 2.92 g (5.0 mmoles) of 1-acetoxy-6-chloro-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-1yl)-9-( p-tolyl)sulfonyl-2,7-nonadiene (18) (purity 89%) was used instead of 2.5347 g (5.00 mmoles) of 1-acetoxy-6-chloro-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl) 9-phenylsulfonyl-2,7-nonadiene (15). As a result, 1.45 g of a yellow oil was obtained. By the following analytical data, the oil was determined to be 1-hydroxy-3,7-dimethyl9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-(p-tolyl)sul fonyl2,6,8-nontriene (22). Yield 66%.

NMR .delta. CDCl.sub.3 (CH.sub.3).sub.3 SiOSi(CH.sub.3).sub.3 :

0.89-2.27 (m, 26H); 2.40 (s, 3H); 4.06 (m, 2H); 5.33 (t, 1H); 5.67-5.89 (m, 1H); 7.13-7.99 (m, 5H).

IR (film) .nu. (cm.sup.-1 ): 3450 (OH), 1140 (SO.sub.2).

FD-MASS m/e: 442 (M.sup.+), 287 (M.sup.+ --CH.sub.3 C.sub.6 H.sub.4 SO.sub.2).

A 50 ml flask purged with argon gas was charged with 0.4812 g (1.02 mmoles) of 1-acetoxy-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-phenylsulfo nyl2,6,8-nonatriene (19), 15 ml of cyclohexane and 0.70 g (10 mmoles) of potassium methoxide, and the mixture was stirred at 38.degree. C. for 2 hours. The reaction mixture was partitioned between 30 ml of diisopropyl ether and 15 ml of a saturated aqueous solution of ammonium chloride. The aqueous layer was extracted with 20 ml of diisopropyl ether, and the extract was combined with the organic layer. The mixture was washed with a saturated aqueous solution of ammonium chloride, and dried over anhydrous magnesium sulfate. The solvent was removed from the organic layer, and the residue, together with 4 ml of a 0.05% by weight hexane solution of 2,6-di-t-butyl-4-methylphenol and 1.1 ml of triethylamine, was put in a 100 ml flask purged with argon gas. To the mixture was added 0.68 ml of acetic anhydride, and the entire mixture was stirred at room temperature for one day. The reaction mixture was stirred for a while together with 50 ml of hexane and 10 ml of a saturated aqueous solution of sodium bicarbonate, and the hexane layer was separated. The hexane layer was washed with a saturated aqueous solution of sodium bicarbonate, and dried over anhydrous magnesium sulfate. Hexane was evaporated from the hexane solution to give 0.3276 g of a red oily product. The FD-MASS analysis of the oily product revealed a peak at m/e=328. This led to the determination that the main component of the oily product was vitamin A acetate (7). The resulting vitamin A acetate was quantified by high-performance liquid chromatography using methyl stearate as an internal standard. It was found that the yield of vitamin A acetate was 74% based on 1-acetoxy-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-phenylsulfo nyl-2,6,8-nonatriene (19), and its all-trans content was 93%.

The same reaction and separating operations as in Example 27 were carried out except that 0.4495 g (1.05 mmoles) of 1-hydroxy-3,7-dimethyl-9-(2,6,6-trimethyl-1cyclohexen-1-yl)-9-phenylsulfon yl-2,6,8-nonatriene (20) obtained in Example 23 was used instead of 0.4812 g (1.02 mmoles) of 1-acetoxy-3,7-dimethyl-9-(2,6,6-trimethyl-1cyclohexen-1-yl)-9-phenylsulfon yl-2,6,8-nonatriene (19). As a result, 0.3285 g of a red oily product was obtained. In the same way as in Example 27, the resulting vitamin A acetate (7) was quantified by high-performance liquid chromatography. It was found that the yield of vitamin A acetate was 77% based on 1-hydroxy-3,7-dimethyl-9-(2,6,6trimethyl-1-cyclohexen-1-yl)-9-phenylsulfon yl-2,6-8-nonatriene (20), and its all-trans content was 93%.

The same reaction and separating operations as in Example 27 were carries out except that 0.5227 g (1.08 mmoles) of 1-acetoxy-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-(p-tolyl)su lfonyl-2,6,8-nonatriene (21) obtained in Example 26, (B-1) was used instead of 0.4812 g (1.02 mmoles) of 1-acetoxy-3,7-dimethyl-9-(2,6,6-trimethyl1-cyclohexen-1-yl)-9-phenylsulfon yl-2,6,8-nonatriene (19). As a result, 0.3156 g of a red oily product was obtained. The resulting vitamin A acetate (7) was quantified by high-performance liquid chromatography in the same way as in Example 27. It was found that the yield of vitamin A acetate was 70% based on 1-acetoxy-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-(p-tolyl)su lfonyl-2,6,8-nonatriene (21), and its all-trans content was 93%.

The same reaction and separating operations as in Example 27 were carried out except that 0.4464 g (1.01 mmoles) of 1-hydroxy-3,7-dimethyl-9-(2,6,6-trimethyl-1cyclohexen-1-yl)-9-(p-tolyl)sul fonyl-2,6,8-nonatriene (22) obtained in Example 26, (B-1) was used instead of 0.4812 g (1.02 mmoles) of 1-acetoxy-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-phenylsulfo nyl-2,6,8-nonatriene (19). As a result, 0.3201 g of a red oily product was obtained. In the same way as in Example 27, the resulting vitamin A acetate (7) was quantified by high-performance liquid chromatography. It was found that the yield of vitamin A acetate was 74% based on 1-hydroxy-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-(p-tolyl)-s ulfonyl-2,6,8-nonatriene (22), and its all-trans content was 93%.

The same reaction and separating operations as in Example 27 were carried out except that 1.12 g (10 mmoles) of potassium n-butoxide was used instead of 0.70 g (10 mmoles) of potassium methoxide. As a result, 0.3481 g of a red oily product was obtained. In the same way as in Example 27, the resulting vitamin A acetate (7) was quantified by high-performance liquid chromatography. It was found that the yield of vitamin A acetate was 72% based on 1-acetoxy-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-phenylsulfo nyl-2,6,8-nonatriene (19), and its all trans content was 92%.

A 10 ml flask purged with argon gas was charged with 0.0235 g (0.050 mmole) of 1-acetoxy-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-phenylsulfo nyl-2,6,8-nonatriene (19) obtained in Example 22 and 6 ml of cyclohexane, and then 0.07 g (1 mmole) of potassium hydroxide (purity 85 %) was added. The mixture was stirred for 2 hours at the refluxing temperature. The reaction mixture was added to a mixture of 20 ml of diisopropyl ether and 10 ml of a saturated aqueous solution of ammonium chloride. The organic layer was separated, dried over anhydrous magnesium sulfate, and concentrated to about 1 ml. The FD-MASS analysis of the concentrate revealed a peak at m/e=286. This led to the determination that the concentrate contained vitamin A (6).

The concentrate was dissolved in 2 ml of pyridine, and cooled in an ice bath. Palmitoyl chloride (0.0137 g; 0.05 mmole) was added to the solution, and the mixture was stirred under ice bath cooling for 0.5 hour, and further at room temperature for 5 hours. The reaction mixture was poured into a large amount of water, and extracted with hexane. The hexane extract was washed with water, and then dried over anhydrous magnesium sulfate. The magnesium sulfate was separated by filtration, and hexane was evaporated from the filtrate under reduced pressure. As a result, 0.0282 g of a reddish yellow oil was obtained. The oil was determined to contain 0.0183 g of vitamin A palmitate from the results of analysis by liquid chromatography (column: .mu.-porasil; mobile phase: a 2:98 by volume mixture of diisopropyl ether and hexane).

A 200 ml flask purged with argon gas was charged with 8.70 g (31.2 mmoles) of beta-cyclogeranyl phenyl sulfone and 60 ml of tetrahydrofuran, and cooled to -78.degree. C. Then, 20.8 ml (31.2 mmoles) of a hexane solution of n-butyllithium (1.5 moles/liter) was added dropwise, and the mixture was stirred at the above temperature for 3 hours. Then, a solution of 6.59 g (31.3 mmoles) of 8-acetoxy-2,6-dimethyl-2(E),6(Z)-octadien-1-al in 15 ml of tetrahydrofuran was added dropwise at -78.degree. C., and the mixture was stirred at this temperature for 2 hours. The mixture was further stirred at -50.degree. C. for 2 hours. The reaction mixture was cooled to -78.degree. C., and water was added. The temperature of the mixture was raised to room temperature. The resulting mixture was extracted with three 100 ml portions of benzene. The extracts were washed with water, and dried over anhydrous sodium sulfate. Benzene was evaporated from the extract, and the residue was chromatographed on a silica gel column using an eluent composed of a mixture of hexane and ethyl acetate in a volume ratio of 5:1 to give 13.87 g of a colorless transparent oil. By the following analytical data, this product was determined to be 1-acetoxy-8-hydroxy-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-p henylsulfonyl-2(Z),6(E)-nonadiene (23).

Yield 91%.

NMR .delta. CDCl.sub.3 (CH.sub.3).sub.3 SiOSi(CH.sub.3).sub.3 : 0.60-2.20 (m, 28H); 3.67 (br, 1H); 3.98 (d, 1H); 4.50 (d, 2H); 5.00 (d, 1H); 5.34 (m, 2H); 7.66-8.20 (m, 5H).

IR (film) (cm.sup.-1 ): 3500 (OH), 1735 (C.dbd.O), 1140 (SO.sub.2).

FD-MASS m/e: 488 (M.sup.+). ##STR62##

A 100 ml flask was charged with 4.88 g (10 mmoles) of compound (23), 0.02 g (0.1 mmole) of p-toluenesulfonic acid monohydrate and 30 ml of methylene chloride, and cooled with an ice water bath. 2.6 ml (30 mmoles) of 3,4-dihydro-2H-pyran was added dropwise. After the addition, the mixture was stirred at the above temperature for 2 hours.

Sodium bicarbonate (0.52 g) was added to the reaction mixture. The mixture was stirred for 5 minutes, and then 20 ml of a saturated aqueous solution of sodium bicarbonate was added. The resulting mixture was extracted with 100 ml of diethyl ether. The extract was washed with 20 ml of a saturated aqueous solution of sodium bicarbonate, and dried over anhydrous magnetism sulfate. The solvent was evaporated by an evaporator, and the residue was chromatographed on a silica gel column using an eluent composed of a 1:5 mixture of ethyl acetate and n-hexane to give 5.75 g of compound (24). Yield 100%. The analytical data of the product were as follows:

NMR .delta. CDCl.sub.3 (CH.sub.3).sub.3 SiOSi(CH.sub.3).sub.3 : 0.60-2.02 (m, 34H); 3.17-5.40 (m, 9H); 7.38-8.11 (m, 5H).

IR (film) .nu. (cm.sup.-1 ): 1745 (C.dbd.O), 1150 (SO.sub.2) ##STR63##

Under an argon gas atmosphere, a 50 ml flask was charged with 0.5678 g (0.993 mmole) of compound (24), 15 ml of cyclohexane and 0.70 g (10 mmoles) of potassium methoxide, and the mixture was stirred for 1.5 hours at 40.degree. C.

The reaction mixture was poured into a mixture of 50 ml of diisopropyl ether and 15 ml of a saturated aqueous solution of ammonium chloride, and the organic layer was separated. The organic layer was washed with 10 ml of a saturated aqueous solution of ammonium chloride, and dried over anhydrous magnesium sulfate. The solvent was evaporated by an evaporator. The residue was dissolved in 4 ml of hexane and transferred to a 50 ml brown flask.

The flask was cooled in an ice water bath, and 1.1 ml of triethylamine and 0.68 ml of acetic anhydride were added. The mixture was stirred for one day at room temperature.

The reaction mixture was poured into a mixture composed of 50 ml of hexane and 10 ml of saturated aqueous solution of sodium bicarbonate, and the organic layer was separated. The organic layer was washed twice with 10 ml of a saturated aqueous solution of sodium bicarbonate, and dried over anhydrous magnesium sulfate. The solvent was evaporated by an evaporator to give 0.3535 g of an orange-colored oily product. By high-performance liquid chromatography (column: .mu.-porasil; mobile phase: a 9:1 mixture of hexane and diisopropyl ether), this oily product was found to contain 0.248 g of vitamin A acetate (7). Yield 76%. The content of the 13-cis isomer in the vitamin A acetate was 90%.