JPS6289652A - Novel vinyl sulfone and production thereof - Google Patents

Abstract

NEW MATERIAL:A compound expressed by formula I (R<1> is phenyl; R<2> represents H or lower acyl). EXAMPLE:1-Acetoxy-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen--1-yl)- 9-phenylsul fonyl-2,6,8-nonatriene. USE:An intermediate for synthesis of vitamin A or acetate thereof used as a medicine or feed additive, obtainable from an inexpensive and readily available raw material in good yield. PREPARATION:A novel halosulfone expressed by formula II (X represents halogen atom) is treated with a dehydrohalogenating agent (example; 1,8- diazabicyclo[5.4.0]undec-7-ene) to obtain the compound expressed by formula I. The reaction is carried out by using 1-5mol, based on 1mol halosulfone expressed by formula II, dehydrohalogenating agent.

Description

Detailed Description of the Invention [Industrial Application Field] The present invention provides a compound represented by the general formula (wherein R1 represents an optionally substituted phenyl group, and R2 represents a hydrogen atom or a lower acyl group) This invention relates to vinyl sulfone and its manufacturing method.

The vinyl sulfone represented by the general formula (1) provided by the present invention is useful as a synthetic intermediate for vitamin A or its acetate, which is used as a medicine and feed additive, as described below.

[Conventional technology]

Conventionally, it has been known that vitamin A or its acetate is produced by the following method [wherein, AC represents an acetyl group;
caChemieaActa, 30.1911 (19
47) Reference] “Vitamin A” Lukibonbo-1. Mi, A Acetate [In the formula, Ph represents a phenyl group, X represents a...rogen atom, and AC represents an acetyl group; Chemie
Ingeniuor Technik, 45.64
6 (1973)] [Problems to be Solved by the Invention] The above-mentioned conventional methods for producing vitamin C or its acetate all use β-ionone as a starting material. This β-ionone is produced industrially by subjecting pseudoionone to a ring-closing reaction using a large amount of concentrated sulfuric acid, but the yield is not very high and it is difficult to separate it from by-products such as α-ionone by distillation. It is not necessarily an industrial raw material that can be obtained at low cost.

Therefore, one object of the present invention is to develop a new vitamin A1 and its acetate which can be easily produced in good yield from inexpensive and easily available industrial raw materials and which can be easily derived in good yield and into vitamin A1 and its acetate. to provide the compound. Another object of the invention is to provide a method for producing the new compounds.

[Means for solving problems]

According to the present invention, the above object is achieved by providing a vinyl sulfone represented by the general formula (1), wherein R1 and R2 are as defined above, and X is・A method for producing vinyl sulfone represented by the general formula (■), which is characterized by treating a halosulfone represented by (representing a halogen atom) with a dehydrohalogenating agent, and a halosulfone represented by the above general formula (n). , by reacting a halogenating agent with a hydroxysulfone represented by the general formula (wherein R1 is as defined above and R3 represents a lower acyl group), and optionally hydrolyzing the product. This is achieved by providing a method for producing the above-mentioned vinyl sulfone using the produced product.

RL, 12, Ha and X in the above general formula will be explained in detail. R1 represents an optionally substituted phenyl group, where the substituent is a lower alkyl group such as methyl, ethyl, i-propyl, n-7'robyl, n-butyl; Chlorine, bromine, iodine, etc... rogen atoms; and methoxy, ethoxy, i-propoxy, n
Examples include lower alkoxy groups such as -propoxy, i-butoxy, and n-butoxy. In addition, the substituent is at the ortho position,
It may be located at either the meta or para position, and may be one or two or more. R2 represents a hydrogen atom or a lower acyl group such as formyl, acetyl, propionyl, etc. R3 represents the same lower acyl group as R2. Moreover, X represents a halogen atom such as chlorine, bromine, or iodine.

Examples of the dehydrogenation agent to be present in the reaction system in the reaction of inducing the no-rosulfone represented by the general formula (II) to the vinyl sulfone represented by the general formula (I) according to the present invention include 1. 8-diazabicyclo(5,4,
0) undec-7-ene, 1,5-diazabicyclo[:
4.3.0] tertiary amines such as nona-5-dine, 1,4-diazabicyclo(2,2,2)octane, N-methylmorpholine; alkali metals such as sodium hydroxide, potassium hydroxide, etc. Hydroxide etc. are used. General formula (
In n), when R2 is a lower acyl group and a tertiary amine is used as a dehydrohalogenation agent to act on an alhalosulfone, a vinyl sulfone in which R2 is a lower acyl group in general formula (I) is obtained, and the dehydrogenation When an alkali metal hydroxide is used as a hydrogen chloride agent in a solvent containing alcohol, a vinyl sulfone in which R2 is a hydrogen atom in the general formula (1) is obtained. Also, the general formula (n
), R2 is a hydrogen atom...When the above dehydrohalogenating agent is applied to rosulfone, the general formula (1
), a vinyl sulfone in which R2 is a hydrogen atom is obtained. The amount of the dehydrohalogenating agent to be used is preferably about 1 to 5 mol per 1 mol of the halosulfone represented by general formula (II). Advantageous results are obtained when this reaction is carried out in a solvent.

The solvent is appropriately selected in combination with the dehydrohalogenating agent. When using a tertiary amine as a dehydrohalogenation agent, examples of solvents include hydrocarbons such as benzene and toluene; halogenated hydrocarbons such as methylene chloride and 1,2-dichloroethane; diethyl ether, tetrahydro-7rane, etc. ethers; Amides such as N,N-dimethylformamide and N-methylpyrrolidone are preferably used, and the amount used is determined by the general formula (It)
The concentration of halosulfone is approximately 0.1 to 5 mol/l.
It is preferable that the amount is such that. In this case, the reaction is suitably carried out within a temperature range of about 0 to 100°C. In addition, when using an alkali metal hydroxide as a dehydrohalogenation agent, the solvent may be an alcohol such as methanol or ethanol, or a mixture of these alcohols with water and/or a hydrocarbon such as benzene or toluene. It is preferable to use the following, and the amount used is such that the concentration of halosulfone represented by the general formula (l[) is approximately 0.1
The amount is preferably 5 mol/j.

When a mixture of alcohols and water and/or hydrocarbons is used as a solvent, it is preferable to use the water and/or hydrocarbons to such an extent that phase separation does not occur in the reaction system. In this case, the reaction is suitably carried out within a temperature range of about -20°C to +30°C.

The vinyl sulfone represented by the general formula (I) obtained by the above dehydrohalogenation reaction can be separated and purified by a conventional method. For example, dilute sulfuric acid in the reaction mixture,
Neutralize the remaining dehydrohalogenating agent by adding ammonium chloride aqueous solution, etc., distill off the solvent if necessary, add water to the residue, and then extract with benzene, toluene, methylene chloride, ethyl acetate, etc. Then, the extract is washed with water and dried with anhydrous sodium sulfate, etc., then the solvent is distilled off from the extract, and the residue is subjected to column chromatography, for example. Nilsulfone can be isolated.

The halosulfone represented by the general formula (■) used as a raw material is a new compound.
It is produced if necessary by hydrolyzing the product. First, by treating the hydroxysulfone represented by the general formula (n) with a halogenating agent, the general formula (n
) in which R2 is a lower acyl group can be produced. As the halogenating agent, for example,
Thionyl chloride, thionyl bromide, phosphorus trichloride, phosphorus tribromide, etc. are used. The amount of the halogenating agent used is determined by the general formula (I
About 1 to 3 for the hydroxysulfone represented by II)
Equivalent amounts are preferred. This reaction is preferably carried out in an organic solvent.
It is carried out in the presence of a grade amine.

Examples of organic solvents include hydrocarbons such as benzene and toluene; halogenated hydrocarbons such as methylene chloride and 1,2-dichloroethane; ethers such as diethyl ether and diinoprobyl ether; ethyl acetate and butyl acetate. Esters such as are used. The amount of the organic solvent used is preferably 1, such that the concentration of the hydroxysulfone represented by the general formula ([) is about 0.1 to 5 mol/J.

As the tertiary amine, for example, pyridine, triethylamine, etc. are advantageously used. It is preferable to use these tertiary amines in an amount of about 0.01 to 50 equivalents relative to the hydroxysulfone represented by the general formula (1), but by using an excess amount, the tertiary amines can be used as an organic solvent. It can also serve as a role. The reaction is about -1
Preferably, the reaction is carried out within a temperature range of 0°C to 30°C. The halosulfone obtained by this reaction in general formula (11) in which R2 is a lower acyl group can be separated by a conventional method. For example, after pouring the reaction mixture into water, saturated aqueous sodium bicarbonate solution, dilute sulfuric acid, etc.
Extract with benzene, methylene chloride, diethyl ether, ethyl acetate, etc., wash the extract with water and dilute with anhydrous sulfuric acid) IJ
Dry with um. Next, by distilling off low-boiling substances from the extract under reduced pressure and subjecting the residue to silica gel column chromatography, a halosulfone in which R2 is a lower acyl group in general formula (It) can be isolated. can.

Further, a halosulfone in which R2 is a hydrogen atom in general formula (n) is produced by hydrolyzing a halosulfone in which R2 is a lower acyl group in general formula (H) obtained by the above method. This hydrolysis reaction can be carried out by reacting a halosulfone in which R2 is a lower acyl group in general formula (n) with an alkali metal hydroxide or carbonate. As the alkali metal hydroxide or carbonate, for example, potassium hydroxide, sodium hydroxide, lithium hydroxide, potassium carbonate, etc. are used. The amount of the alkali metal hydroxide or carbonate to be used is preferably about 1 to 2 equivalents relative to the sulfone in which R2 is a lower acyl group in general formula (11).

This reaction is preferably carried out in a solvent, such as alcohols such as methanol and ethanol, or mixtures of these alcohols with water and/or hydrocarbons such as benzene and toluene. The amount of solvent used is preferably such that the concentration of halosulfone in which R2 is a lower acyl group in general formula (n) is about 0.1 to 10 mol/l. When a mixture of alcohols and water and/or hydrocarbons is used as a solvent, it is preferable to use the water and/or hydrocarbons to such an extent that phase separation does not occur in the reaction system. The reaction is about -10°
It is suitable to carry out within the temperature range of 30°C to 30°C. The halosulfone of general formula (n) in which R2 is a hydrogen atom obtained by this reaction can be separated by a conventional method. For example, saturated ammonium chloride aqueous solution, dilute hydrochloric acid, dilute sulfuric acid, etc. are added to the reaction mixture to neutralize the remaining alkali metal hydroxide or carbonate, and if necessary, the alcohol used as a solvent is distilled off. After adding water to the residue, it is extracted with benzene, methylene chloride, diethyl ether, ethyl acetate, etc., and the extract is washed with water and dried over anhydrous sodium sulfate. Next, by distilling off low-boiling substances from the extract under reduced pressure and subjecting the residue to silica gel column chromatography, the halosulfone in which R2 is a hydrogen atom in general formula (II) can be isolated. .

Hydroxysulfone represented by the general formula (III) is also a new compound, for example, a compound represented by the general formula (wherein R1 is as defined above) and a compound represented by the general formula % formula% (wherein R3 is as defined above). It is produced by reacting the compound shown in (as defined in the following) in the presence of an anionizing agent. The anionizing agent used has the general formula (I
A base that generates a carbanion at the α-position of -8O2R'M in the compound represented by V), for example, an organic lithium such as methyllithium and n-butyllithium;
Grignard reagents such as methylmagnesium chloride, ethylmagnesium chloride, and ethylmagnesium bromide; alkali metal hydrides such as lithium hydride, sodium hydride, and potassium hydride; lithium amide,
Alkali metal amides such as sodium amide and potassium amide; lithium methoxide, sodium methoxide,
potassium methoxide, potassium ethoxide, potassium t
- Lower alkoxides of alkali metals such as butoxide.

The amount of anionizing agent used is about 0.2 to 1 molar equivalent relative to the compound represented by general formula (IV). This reaction reacts with aliphatic or aromatic hydrocarbons such as hexane, heptane, benzene, and toluene; linear or cyclic ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, and dioxane; dimethylformamide, N-methylpyrrolidone, dimethylsulfoxide, and hexamethyl Preferably, it is carried out in an organic solvent such as phosphoryltriamide. The solvent is appropriately selected in combination with the anionizing agent. The reaction is normally carried out within a temperature range of about -100 DEG C. to 150 DEG C., and is advantageously carried out under an atmosphere of an inert gas such as helium, nitrogen or argon.

The reaction time varies depending on the anionizing agent, solvent, reaction temperature, etc. used, but for example, n-butyllithium is used as the anionizing agent and the reaction is carried out at a temperature of about -78°C to -50°C in a tetrahydro7rane solvent. Approximately 4
It's time.

The compound represented by the general formula (IV) can be easily produced in good yield from linalool, which is an inexpensive industrial raw material. For example, a compound in which R1 is a phenyl group in general formula (IV) can be produced by the following method: geranyl chloride is obtained by reacting linalool with thionyl chloride, and the geranyl chloride is reacted with sodium benzenesulfinate. By doing this, geranylphenyl sulfone is obtained. β-cyclogeranylphenyl sulfone is obtained by subjecting geranylphenyl sulfone to a ring-closing reaction in the presence of an acid catalyst 1, such as a mixed acid of sulfuric acid and acetic acid. In addition, during the ring-closing reaction, the 41 body of β-cyclokeranylphenyl sulfone-1? A certain α-cyclogeranylphenylsulfone may be present, but highly pure β-cyclogeranyl A/phenylsulfone can be obtained by crystallizing the resulting mixture of both in a solvent such as hexane. . The target β-cyclogeranylphenyl sulfone Kffi can be converted by returning the α-cyclogeranylphenyl sulfone to the above-mentioned ring-closing reaction system.

The total yield of β-cyclogeranylphenyl sulfone from linalool is typically about 80%.

Further, the compound represented by the general formula (V) can be easily produced by reacting, for example, selenium dioxide with a lower carboxylic acid ester of geraniol (Tetrahed
ron Letters, 281 (1973)].

Vinyl sulfone represented by the general formula (1) can be easily converted into vitamin A1 and further into vitamin A acetate in good yield by the following method.

(In the above formula, R1 and R2 are as defined above.

) That is, sivitamin A can be obtained by treating halosulfone represented by general formula (1) with a base. As the base, for example, potassium alkoxide such as potassium methoxide, potassium ethoxide, potassium n-butoxide, potassium hydroxide, etc. are used. The amount of the base to be used is preferably about 2 to 20 mol per 1 mol of the halosulfone represented by general formula (1). This reaction is preferably carried out in an organic solvent, and hydrocarbons such as hexane, cyclohexane, benzene, and toluene are used as the organic solvent. The amount of organic solvent used is such that the concentration of halosulfone represented by general formula (1) is approximately 0.05 to 1 mol/! The amount of 0 reaction is preferably about 10 to 1
Preferably it is carried out within a temperature range of 20°C. After the reaction is completed, a precipitate is filtered from the reaction mixture as required, and then water, a saturated ammonium chloride aqueous solution, etc. are added to the reaction mixture, and the organic layer is separated. Recrystallize the obtained organic layer 1
Vitamin A can be obtained by subjecting it to purification means such as column chromatography.

Vitamin A thus obtained can be converted into vitamin A acetate by diacetylation using a conventional method. This acetylation reaction is preferably performed on the organic layer containing vitamin A separated from the reaction mixture obtained by the above-mentioned vitamin A production reaction or on the vitamin A separated and purified from the organic layer, preferably in an organic solvent. This is carried out by using an acetylating agent in the presence of a class amine. Examples of acetylating agents include acetic anhydride,
Acetyl chloride etc. are used. The amount of the acetylating agent used is preferably about 1 to 10 equivalents relative to vitamin A. Examples of organic solvents include hydrocarbons such as benzene and toluene; halogenated hydrocarbons such as methylene chloride and 1,2-dichloroethane; ethers such as diethyl ether and diisopropyl ether; and esters such as ethyl acetate and butyl acetate. It is preferable to use such organic solvents that the concentration of vitamin A is about 0.1 to 5 mol/I. As the tertiary amine, for example, triethylamine, pyridine, etc. are used. These tertiary amines have a ratio of about 1 to
Although it is preferable to use 10 equivalents, by using an excess amount, the tertiary amine can also serve as an organic solvent. The reaction is about -10℃~30℃
It is preferable to carry out the test in a temperature range of . After the reaction is completed, the precipitate is filtered from the reaction mixture if necessary, and then dilute sulfuric acid, water, a saturated aqueous sodium bicarbonate solution, etc. are added to the kernel mixture to separate the organic layer. Vitamin A acetate can be obtained by subjecting the obtained organic layer to purification means such as recrystallization and column chromatography.

〔Example〕

The present invention will be explained below with reference to Examples, but the present invention is not limited to these Examples. ,6,6-drimethyl-1-cyclohexen-1-yl)-9-phenylsulfonyl-2,7-/f dixene 1.55F (3,1mmo
l), dix5-A/x-chill 30IILl and 1
．． 0.85 aJ (6.0 mmol) of 8-diazabicyclo[5°4.0)undec-7-ene was added, and the mixture was heated and stirred under reflux for 10 hours. Diethyl ether and water were added to the reaction mixture to separate the layers. ether layer 5
% sulfuric acid and saturated hydrogen carbonate) and IJum water, and dried over anhydrous magnesium sulfate.

The solvent was distilled off from the ether solution, and the residue was purified by column chromatography using silica gel (elution &: a mixture of hexane and ethyl acetate in a volume ratio of 3:1) to obtain 1.23 r of a yellow oil. I got it. According to the following instrumental analysis data, this product was found to be 1-acedoxy-3,7-dimether-9-(2,6,6-drimethyl-1-cyclohexen-1-yl)-9-phenylsulfonyl-2,6,8
-/f) Confirmed that it was Lien. Yield 86
%0 0.86-2.27Cm, 28H), 4.51(d
, 2H).

5.25 (t, II(), 5.67-5.9
0 (m, II().

7.14-7.90 (rn, 6H) IR (film) v (crn-1): 1745 (C=0), 115
0(802)FD-MASS m/e: 47
0 (M”), 328 (M+-CsHsSOzH)
1-acetoxy-6-chloro-3,7-dimethyl-9-(2,6,6-)dimethyl-1-cyclohexen-1-yl)-9-phenylsulfonyl-2,7-nonadiene in a 100 d round-bottom flask. 2.5347? (5, O
Qmmol), Buff 9f 6ml and U Meta/
-A.

20d and stirred to prepare a solution. This bath number was cooled in an ice water bath, and 1 1/2 potassium hydroxide (purity 85%) was added to it.
．． Add a solution of 15 rnl of 35F (20 mmol) methanol. The mixture was stirred in an ice water bath for 5 minutes and then at room temperature for 18 hours. A saturated aqueous ammonium chloride solution was added to the reaction mixture, and the mixture was extracted with 100 rnl of diethyl ether three times at 300 m. This extract was washed with a saturated aqueous ammonium chloride solution and dried over anhydrous magnesium sulfate. The solvent was distilled off from the ether solution, and the residue was purified by column chromatography using silica gel (eluent: a mixture of hexane and ethyl acetate in a volume ratio of 4:1 to 3:1) to give a yellow color. 1.50712 of an oil was obtained.

According to the following instrumental analysis data, this product is l-hydroxy-3,7-dimethyl-9-(2°6,6-)! j
The yield was 70%, which was confirmed to be methyl-1-cyclohexen-1-yl)-9-phenylsulfonyl-2,6,8-nonatriene.

0.90-2.28 (m, 26H), 4.07 (m
, 2M).

5.35 (t, LH), 5.67-5.89
(m, tH).

7.1:3-7.90 (m, 6H) IR (film) y (crn'): 3450 (OH),
1140(SO2)FD-MASS m/e:428
(M”), 287 (M”-CsHsSO2) 3.7 1-acetoxy-6-bromo in a 50 d round-bottom flask.
-Simethyl-9-(2,6,6-)dimethyl-1-cyclohexen-1-yl)-9-phenylsulfonyl-2
, 7-nonadiene 2.75 f (5.0 mmol),
Methyl chloride L/730 ml and 1,5-diazabicyclo(4,3,0)non-5-ene 71.2 rnl (10
mmol), and the mixture was stirred under heating and reflux for 5 hours. The reaction mixture was treated as in Example 1 to give 1-acetoxy-3,7-dimethyl-9-(2,6,6-drimether-1-cyclohexen-1-yl)-9-phenylsulfonyl- 2,
6,8-/f) IJ engineering 1.98F was obtained. Yield 84%.

In Example 2 l-acetoxy-6-chloro-3,7
-Simethyl-9-(2,6,6-)rimether-1-cyclohexen-1-yl)-9-phenylsulfonyl-2
, 7-nonadiene 2.5347fC5,0Qmmol)
1-acetoxy-6-bromo-3゜7-dimethyl-9-(2,6,6-)dimethyl-1-cyclohexen-1-yl)-9-7enylsulfonyl-2,7-nonadi, The reaction and separation procedure was carried out in the same manner except that Z72,75 f (5,Qmmol) was used, and 1-hydroxy-3,7-dimethyl-9-(2゜6,6-t!J
Methyl-1-cyclohexen-1-yl)-9-phenylsulfonyl-2,6,8-/ 1.7
I got 3F. Yield 73%.

In Example 1, 1-acetoxy-6-chloro-3,7
-Simethyl-9-(2,6,6-)rimether-1-cyclohexen-1-yl)-9-phenylsulfonyl-2
,7-nonadiene 1.55 t (3,1 mmol)
1-acetoxy-6-chloro-3,7-cymeter-9-(2,6,6-drimethyl-1-cyclohexen-1-yl)-9-(p-)lyl)sulfonyl-2,
7-nonadiene (purity 89%) 1.759 (3,□m
The reaction and separation procedure was carried out in the same manner except that 1.19F of yellow oil was obtained. According to the following instrumental analysis data, this product is l-acetoxy-3,7-
It was confirmed that it was dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-(p-tolyl)sulfonyl-2,6,8-nonatriene.

Yield 82%.

0.87-2.25 (rn, 28FL), 2.40 (3
, 3H).

4.51(d, 2H), 5.24(t, 1)i),
5.66-5.90 (m, lJ, 7.14-7.98 (
m, 5H) IR (film) ν (i=), 1) 217
45 (C=0), 1150 (SO2) FD-MASS
m/e: 484 (M”), 328 (M+-CH
5C6H4SO2H) Example 6 In Example 2, 1-acetoxy-6-chloro-3,7
-dimeteru 9-(2,6,6-)rimetheru 1-'/
Chlohexen-1-yl)-9-phenylnurbonyl-
2, Funonadiene 2.5347F (5,00 mmol
) instead of 1-acetoxy-6-ri o o -3゜7-
Dimeter-9-(2,6,6-drimethyl-1-7chlorohexen-1-yl)-9-(p-1lyl)sulfonyl-2,7-/f dixeneltl! 89%) 2.92?
(5.0 mmol) was used, but the reaction and separation operations were carried out in the same manner to obtain 1.452 of a yellow oil.

According to the following instrumental analysis data, this product is 1-hydroxy-3,7-dimethyl-9-(2°6.6-drimethyl-1-cyclohexen-1-yl)-9-(p-tolyl)sulfonyl-2, It was confirmed that it was 6,8-nonatriene. Yield 66%.

0.89-2.27 (m, 26H), 2.40
(8, 3H).

4.06 (m, 2H), 5.33 (t, LH), 5
．． 67-5.89 (m, l), 7.13-7.99 (
m, 5H) IR (film) ν(crn'): 34
50 (OR), 1140 (802) FD-MASS m
/e: 442(M), 287(M-Cf(a
csH4SO2) Reference Example 1 β-Cyclogeranylphenyl sulfone lO, 8cl (3
8.8 mmol) and 100ml of toluene,
Next, diethyl ether iG solution of ethylmagnesium bromide (1,06 mol/A') 24.2rrLI!
(25.6 mmol) was added dropwise at an internal temperature of 20 to 25°C.

After the dropwise addition was completed, the mixture was stirred for 3 hours at an internal temperature of 40 to 45°C. Next, the solution was cooled to an internal temperature of -40 to -30°C and added with 8-acetoxy-2,6-dimethyl-2,6-octadix7-1-ark4.02? (19,1
mmol) in 1 om toluene was added dropwise. After the dropwise addition was completed, the mixture was vigorously stirred for another 2 hours at the same temperature. A 10% aqueous hydrochloric acid solution was added to the reaction mixture, and the toluene layer was separated. This toluene layer was washed with water, further washed with a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate.

Toluene was distilled off from this toluene layer, and the residue was purified by column chromatography using silica gel (eluent: a mixture of hexane and ethyl acetate in a volume ratio of 7:3) to obtain a colorless and transparent oil with a volume of 8.469 g. I got it. According to the following instrumental analysis data, this product is 1-acetoxy-8-
It was confirmed that it was a mixture of hydroxy-3,7-dimethe-9-(2,6,6-dimethe-1-cyclohexen-1-yl)-9-phenylsulfonyl-2,6-nonacyennosia stereomer. Yield 91%.

0.61-2.03 (m, 28H) i 2.87
(br, 1)i) ;3.95 ,4.20 (d
, together with IH); 4.50 (d, 21()i4.85
, 4.97 (d, together with LH): 5.25.5
．． 62 (m.

Total 2H); 7.40-8.03 (m, 5
H) IR (film) v (crR-1): 3500 (
OH), 1735 (C=0).

1140 (SO2) FD-FviAS S m/e: 488 CM)
1-acetoxy-8 in a 100ml eggplant flask
-Hydroxy-3,7-dimethyl-9-(2,6,6=
trimethyl-1-cyclohexen-1-yl)-9-phenylsulfonyl-2,6-/fShen7.381 (
15 mmol), benzene 60 rnl and pyridine 12
Add thionyl chloride and add thionyl chloride while cooling in an ice water bath.
32 rnl was added dropwise and then stirred at room temperature for 16 hours. An ice-cooled FC3% sulfuric acid aqueous solution was added to the reaction mixture, and the organic layer was separated. The aqueous layer was diluted with 70rnl of diethyl ether.
Extracted by diffraction 140d. These organic layers were combined and added with an ice-cooled 3% aqueous sulfuric acid solution, a saturated aqueous sodium bicarbonate solution,
The mixture was washed successively with saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate. The solvent was distilled off from the organic layer, and the residue was purified by column chromatography using silica gel (eluent: a mixture of hexane and ethyl acetate in a volume ratio of 5:1) to obtain a white waxy substance.7. I got 182. This product was found to be 1-acetoquine-6-chloro-3,7-dimether-9-(2,
6,6-)rifthyl-l-cyclohexen-1-yl)
It was confirmed that it was -9-phenylsulfonyl-2,7-nonadiene. Yield 94%.

0.72-2.05 (m, 28) I), 4.17-4.
57 (m, 4H).

5.23 (t, IH), 5.88 (m, LH), 7
．． 35-7.91 (m, 5H) IR (film), ν (m'): 1745 (C=O),
1150 (SO2).

685 (CsHs) FD-MASS m/e: 506 (M”) + 507
(M”+1).

470 (M4α), 365 (M-C6H5SO2)1
Potassium hydroxide (purity 85
%) 0.0226f (0,342 mmol) and 1 rnl of methanol were added and stirred at room temperature to prepare the methanol bath number of potassium hydroxide. Add 1-acetoxy-6-chloro-3,7-dimethyl-9-(2°6.
6-drimethyl-1-cyclohexen-1-yl)-9
-Phenylsulfonyl-2,7-nonadiene 0.037
A solution prepared by dissolving 3tC0,0736mmol) of meta,/-A,2go in a mixed solution of 0.2ml of benzene was added, and the mixture was stirred in an ice-water bath for 30 minutes. A saturated aqueous ammonium chloride solution was added to the reaction mixture, and the solvent was distilled off.
Water was added to the residue and then extracted with diethyl ether. The extract was washed with a saturated aqueous ammonium chloride solution and dried over anhydrous magnesium sulfate. The solvent was distilled off from this extract to obtain a yellow oil of 0.0297F. According to the instrumental analysis data shown below, this product is 6-chloro-1-
It was confirmed that it was hydroxy-3,7-dimethyl-9-(2,6,6-drimethyl-1-cyclohexen-1-yl)-9-phenylsulfonyl-2,7-nonadiene. Yield 87%.

CDα3 NMR'(CHs)3SiOSi(CHa)3'0.
75-2.20 (m, 26H), 4.06 (
d, 2H).

4.21-4.55 (m, 2H), 5.30 (t, L
H).

5.91 (m, IH), 7.36-7.90 (
m, 5H) IR (film) ν(z 1): 33
00COK), #-1 #5yo average; 1150 (SO2),
685 (C6H5) FD-MASS m/e: 4
65 (M +1), 428 (M - Hα).

323 (M -C6H5SO2) Reference Example 2 β-
Cyclogeranylphenyl sulfone 5.0 Of(18,
0 mmol) and 60 rrLl of tetrahydro7ran were added, and after cooling to -78°C, a hexane solution of n-butyllithium W (1.5 mol/l) 6.6rILl (
9.9 mmol) was added dropwise, and the mixture was stirred at the same temperature for 3 hours.

next.

In this solution, 8-acetoxy-2,6-dimethyl-2,
6-octarenine-1-al 1.89 f (9,O
A solution of 15 rnl of tetrahydrofuran (mmol) in tetrahydrofuran was added dropwise at -78°C, stirred at the same temperature for 2 hours, and then -
The mixture was stirred at 50°C for 2 hours. After cooling to -78°C, water was added to one reaction mixture, and then the temperature was raised to room temperature. The resulting mixture was diffracted 300r ILI with benzene 100d.
! Extracted with. Wash the extract with water.

It was dried with anhydrous sodium sulfate. Benzene was distilled off from this extract, and the residue was purified by nine column chromatography using silica gel (eluent: a mixture of hexane and ethyl acetate at a volume ratio of 5:1). According to the following instrumental analysis data, this product is 1-7cetoxy-8-hydroxy-3,7-dimethyl-9-(2°6.6-dolimethyl-1-cyclohexen-1-yl)-9- Phenylsulfonyl-2,6-
It was confirmed that it was Nonagene. Yield: 93 cm.

DCIs NMR'(CHa)3SiO8i(Cout)3'0.62
~1.94 (m, 28H), 3.73 (br
, IH) 13.5x (d, IH), t4x (d,
2H) t4.90 (d+IH) + 5.21 (
m * 2H) *7.38~7.99 (m, 5H) IR (Finim') W (cm 1): 3500 (OI (
), 1735 (C=0).

1140 (SO2) FD-MASS m/e: 488 (M) Example 8 1-acetoxy-8-hydroxy-3,7-dimethyl-9-(2,6,6-drimethyl-1-cyclohexene) was added to a 50 d round-bottom flask. -1-yl)-9-phenylsulfonyl-2,6-nonadiene 2.44P (5, Omm
ol), viridi 10.12F and methylene chloride 201L
0.31 phosphorus tribromide while cooling in an ice water bath.
ml (3.3 mmol) was added dropwise.
The mixture was stirred at the same temperature for 1.5 hours. A saturated aqueous sodium hydrogen carbonate solution was added to the reaction mixture, and the mixture was extracted with diethyl ether. The extract was washed with a saturated aqueous sodium bicarbonate solution and a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate. The solvent was distilled off from the extract, and the residue was subjected to column chromatography using silica gel (elution g:
A mixture of hexane and ethyl acetate in a volume ratio of 9:1 to 3:1) was purified to obtain 2.34 F of a white waxy substance.

According to the following instrumental analysis data, this product is 1-7 setoxy-6-promo 3,7-cymethyl-9-(2°6.6
-T! jMethyl-1-cyclohexen-1-yl)-9
-Phenylsulfonyl-2,7-nonadiene was confirmed. Yield F3596゜CDα3 NMRδ(CHs)3SiO8i(CHa)3'1.7
1-2.03 (m, 28H), 4.32-4.5
7 (m, 4H).

5.24 (m, LH), 5.90 (m, IH),
7.43-7.90 (rn, 5H) IR (Fill A) ν (Crn'): 1730 (C=
0), 1135 (802) + 670 (CsHa) FD-MASS m/e: sso (M+), 470
(M”-Hnr).

409 (M -CsHsSO2) Reference Example 3 β-cyclogeranyl-p-IJ sulfone 7.0 was added to a 200 WL 3-bottle flask purged with argon gas.
1? (24,0 mmol) and 70 d of tetrahydrofuran were added, and after cooling to -78°C, a hexane solution of n-butyllithium (1,5 mol/J) 9
．． 6 td (14.4 mmol) was added dropwise and stirred at the same temperature for 2 hours. Next, in this solution, 8-7cetoxy-2,6-dimethyl-2,6-octarenine-1-al 2.529 (12,0 mmol) of tetrahydro7
A solution of Uy15y was added dropwise at -78°C, and the mixture was stirred at the same temperature for 3 hours. Water was added to the anti-stone mixture and the temperature was raised to room temperature.

The resulting mixture was extracted with 50° of benzene and 150° by diffraction three times, and the benzene extract was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off from this extract, and the residue was purified by column chromatography using silica gel (eluent: a mixture of hexane and ethyl acetate in a volume ratio of 5:1 to 3:1) to obtain a white solid. A mold of 4.88F was obtained.

According to the following instrumental analysis data, this product is 1-acetoxyl 8-hydroxy-3,7-cymethyl-9-(2,6
,6-drimethyl-1-cyclohexen-1-yl)-
It was confirmed that it was 9-(P-)lyl)sulfonyl-2,6-nonadiene. Yield: 81 cm.

0.61-2.01 (m, 28H), 2.37
(S, 3H).

3.71 (br,, IH), 3.94 (d, I
H), 4.49(d, 2H) 14.97(d,
IH), 5.16 (mt2H), 7.26 (d, 2H
) t7.86 (ci, 2H) IR (film) ν (cWv'): 3480 (OH)
, 1735 (C=O)*1140 (SO2) Example 9 1-acetoxy-8-hydroxy-3,7-dimethyl-9-(2,6,6-drimethyl-1-cyclohexene-1- yl)-9-(p-tolyl)sulfonyl-2,6-nonadiene 74.27 t
(8,82 mmos, pyridine 6,7 MI (34 m+
0.77 m/(11 mmo
1) was added and then stirred at room temperature for 16 hours. IN hydrochloric acid and benzene were added to the reaction mixture to separate the layers.

The organic layer was washed with water, dried over 2 ml of anhydrous sulfuric acid magnesium, and then the solvent was distilled off to obtain a yellow oily substance 4.41F. According to the following instrumental analysis data, this product is 1-acetoxy-6-chloro-3,7-cymethyl-9-(2,6
,6-drimethyl-1-cyclohexen-1-yl)-
It was confirmed that it was 9-(p-)lyl)sulfonyl-2,7-nonadiene. In addition, NMR analysis revealed that the purity of the oily substance was 89%. Yield 88%.

0.70-1.93 (m, 28H), 2.40 (
a, 3H).

4.15-4.43 (m, 4H), 5.17 (t, I
H).

5.82 (d, 1) 1), 7.21 (d, 2H).

7.64 (d, 2H) IR (film) ν (m-1): 1740 (C=0)
, 1150 (SOz) Reference Example 4 1-acetoxy-3,7-dimethyl-9-(2,6,6-drimethyl-1-cyclohexen-1-yl)-9-phenylsulfonyl was added to a 50a # flask purged with argon gas. -2,6,8-/su)sl-: 10.481
2F (1.02 mmol), 15 d of cyclohexane, and 0.70 f of potassium methoxide were added, and this mixture was
The mixture was stirred at 8°C for 2 hours. Add 30 d of diimpropyl ether and 15 g of saturated ammonium chloride aqueous solution to the reaction mixture.
was added and the liquid was separated. The aqueous layer was diisopropyl ether 20
Extracted with WLL. The organic layers were combined, washed with saturated aqueous ammonium chloride solution, and diluted with 0.05% of -4-methylphenol.
4 d of hexane solution and triethylamine 1.1-wt. % with 100 liters purged with argon gas.
I put it in a flask. Add 0.68 acetic anhydride to this mixture.
zl was added and stirred at room temperature for 1 day. To the reaction mixture were added 50 g of hexane and 10 g of a saturated aqueous solution of hydrogen carbonate, and after stirring for a while, the hexane layer was separated. This hexane layer was washed with a saturated aqueous sodium bicarbonate solution and dried over anhydrous magnesium sulfate. By distilling off hexane from this hexane solution, a red oily substance 0.3276F was obtained. When this oily substance was subjected to FD-MASS analysis, a peak of m/e=328 was detected. From this, it was confirmed that the main component of the oily substance was vitamin A acetate. Next, we quantified vitamin A acetate produced using methyl stearate as an internal standard using high-performance liquid chromatography. 6-)dimethyl-1-cyclohexen-1-yl)-9-phenylsulfonyl-2,6
, 8-nona) 92-n-t-reference value was 74%.

) Reference Example 5 In Reference Example 4, 1-acetoxy-3,7-dimethyl-9-(2,6,6-)trimethyl-1-cyclohexene-
1-Hydroxy-3,7-dimethyl-9-(2,
6,6-)methyl-1-cyclohexen-1-yl)
-9-Phenylsulfonyl-2,6,8-nonatri! 7
The reaction and separation operations were carried out in the same manner except that 0.4495F (1.05 mmol) was used, and red oily 4io
, 32s5r was obtained. When the vitamin A acetate produced was quantified by high performance liquid chromatography in the same manner as in Reference Example 4, the yield of vitamin A acetate was l-
It was 77% based on hydroxy-3,7-dimethyl-9-(2,6,6-drimethyl-1-cyclohexen-1-yl)-9-phenylsulfonyl-2,6,8-nonatriene.

In Reference Example 4, 1-acetoxy-3,7-dimethyl-9-(2,6,6-)trimethyl-1-cyclohexene-
1-yl)-9-phenylsulfonyl-2,6,8-nonatri:r-:/0.4812? (1.02mm
ol ) instead of 1-acetoxy-3,7-dimethyl-9-(2,6,6-)trimethyl-1-cyclohexene-
1-yl)-9-(p-)lyl)sulfonyl-2,6°8-nonatriene 0.5227P (1, Q$mmol)
The reaction and separation operations were carried out in the same manner except that
A red oil 0.3156F was obtained. When the vitamin A acetate produced by commercial liquid chromatography was quantified in the same manner as in Reference Example 4, the yield of vitamin A acetate was 1-acetoxy-3,7-dimethyl-9-(
It was 70% based on 2,6,6-)trimethyl-1-cyclohexen-1-yl)-9-(P-tolyl)sulfonyl-2,6,8-nonatriene.

In Reference Example 4, l-acetoxy-3,7-dimethyl-9-(2,6,6-1-limethyl-1-cyclohexene-
1-Hydroquine-3,7-dimether-9-(2,6,
6-trimethyl-1-cyclohexen-1-yl)-9
-(p-)lyl)sulfonyl-2,6°8-nonatriene0.4464? The reaction and separation operations were carried out in the same manner except that (1, Olmmol) was used, and a red oily substance 0.3201F was obtained. When the vitamin A acetate produced by high performance liquid chromatography was quantified in the same manner as in Reference Example 4, the yield of vitamin A acetate was 1.
-Hydroxy-3,7-dimethyl-9-(2,6,6-
Dolimethyl-1-cyclohexen-1-yl)-9-(
It was 74 cases based on p-)lyl)sulfonyl-2,6,8-nonatriene.

〔Effect of the invention〕

According to the method of the present invention, the vinyl sulfone represented by the general formula (1) can be easily produced in good yield from inexpensive and easily available industrial raw materials, as is clear from the above examples. Further, the vinyl sulfone represented by the general formula (1) of the present invention can be easily derived into vitamin A1 and its acetate with good yield as is clear from the above-mentioned reference examples.

Claims (1)

[Claims] 1. General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (In the formula, R^1 represents an optionally substituted phenyl group, and R^2 represents a hydrogen atom or a lower acyl group. vinyl sulfone represented by ). 2. General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (II) (In the formula, R^1 represents an optionally substituted phenyl group, R^2 represents a hydrogen atom or a lower acyl group,
represents a halogen atom. ) A general formula characterized by treating a halosulfone represented by the above with a dehydrohalogenating agent ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (I) (In the formula, R^1 and R^2 are as defined above. ) A method for producing vinyl sulfone. 3. Halosulfone represented by the general formula (II) has the general formula ▲ mathematical formula, chemical formula, table, etc. ▼ (In the formula, R^1 represents an optionally substituted phenyl group, and R^3 represents a lower acyl group. 3. The method according to claim 2, which is produced by reacting a halogenating agent with a hydroxysulfone (representing a group) and, if necessary, hydrolyzing the product.