Process for producing vitamin A or its carboxylic acid esters, and itermediate compounds useful for the process

A process for producing vitamin A represented by the formula ##STR1## which comprises treating a compound represented by the formula ##STR2## wherein R.sup.1 represents an aryl group which may be substituted, R.sup.21 and R.sup.22 each represent a hydrogen atom or a lower alkanoyl group, R.sup.3 represents an acetal-type protective group for a hydroxyl group, and X represents a halogen atom, with a base; and novel intermediate compounds useful for the above 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. 
EXAMPLE 1 
##STR18## 
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%. 
EXAMPLE 2 
##STR22## 
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%. 
EXAMPLE 3 
##STR24## 
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%. 
EXAMPLE 4 
##STR25## 
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%. 
EXAMPLES 5-7 
##STR28## 
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. 
__________________________________________________________________________ 
Reaction 
Reaction 
Vinylic ether 
Acid catalyst 
temperature 
time R Yield 
Example 
(mole ratio to 3) 
(mole ratio to 3) 
(.degree.C.) 
(hours) 
(Comp. No.) 
(%) 
__________________________________________________________________________ 
##STR29## p-TsOH H.sub.2 O (0.01) 
5 2.4 
##STR30## 99 
6 
##STR31## p-TsOH H.sub.2 O (0.01) 
5 2.4 
##STR32## 97 
7 
##STR33## p-TsOH pyridine (0.04) 
26 5.8 
##STR34## 94 
__________________________________________________________________________ 
EXAMPLES 8-10 
##STR35## 
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. 
__________________________________________________________________________ 
Yield of 
vitamin A 
Com- 
Potassium Reaction acetate 
All-trans 
Ex- pound 
methoxide 
Toluene 
temperature 
(total from 
content 
ample 
No. (mole ratio) 
(ml) and time 12-14) 
(%) 
__________________________________________________________________________ 
(1) 
at 27.degree. C. for 
8 12 5.0 6.0 0.3 hour 
78 95 
(2) 
at 38.degree. C. for 
1.5 hours 
9 13 5.0 5.7 " 74 95 
(1) 
at 25.degree. C. for 
10 14 5.0 4.7 0.3 hour 
83 95 
(2) 
at 39.degree. C. for 
1.5 hours 
__________________________________________________________________________ 
EXAMPLE 11 
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. 
EXAMPLE 12 
##STR36## 
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). 
EXAMPLE 13 
##STR38## 
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). 
EXAMPLE 14 
##STR39## 
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). 
EXAMPLE 15 
##STR40## 
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). 
EXAMPLE 16 
##STR41## 
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%. 
EXAMPLE 17 
##STR42## 
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%. 
EXAMPLE 18 
##STR43## 
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. 
EXAMPLE 19 
##STR45## 
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%. 
EXAMPLE 20 
##STR46## 
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%. 
EXAMPLE 21 
##STR47## 
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%. 
EXAMPLE 22 
##STR48## 
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). 
EXAMPLE 23 
##STR49## 
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). 
EXAMPLE 24 
##STR50## 
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). 
EXAMPLE 25 
##STR51## 
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. 
EXAMPLE 26 
##STR52## 
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). 
EXAMPLE 27 
##STR55## 
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%. 
EXAMPLE 28 
##STR56## 
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%. 
EXAMPLE 29 
##STR57## 
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%. 
EXAMPLE 30 
##STR58## 
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%. 
EXAMPLE 31 
##STR59## 
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%. 
EXAMPLE 32 
##STR60## 
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). 
EXAMPLE 33 
##STR61## 
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%.