JPS63227564A - Production of allylsulfone - Google Patents

Abstract

PURPOSE:To obtain the titled compound useful as a drug intermediate in high yield, by reacting a readily obtainable tertiary allyl halide with a phenylsulfinate in the presence of a halogenated tetraalkylammonium salt in an anhydrous system. CONSTITUTION:A tertiary allyl halide shown by formula I (X is Cl, Br or I) and/or a primary allyl halide shown by formula II is reacted with a phenylsulfinate shown by formula III (R is H or lower alkyl; m is Na or K) in the presence of a halogenated tetraalkylammonium salt in an anhydrous system to give an allylsulfone shown by formula IV (double bond does not distinguish stereospecificity). The compound shown by formula IV is useful as a synthetic intermediate for vitamin A acetate.

Description

Detailed Description of the Invention [Field of Industrial Application] The present invention relates to allyl sulfones represented by the general formula (wherein R represents a hydrogen atom or a lower alkyl group, and the double bond does not distinguish stereoisomerism). Regarding the manufacturing method.

The allyl sulfone of general formula (1) produced by the method of the present invention can be converted into a synthetic intermediate for vitamin A acetate, which is used as a pharmaceutical and feed additive, for example, after a ring-closing reaction (especially Publication No. 57-48549 and Tenju et al., J-Org*Chsm, @51.3
834 (1986)).

[Conventional technology]

The conventionally known method for producing allyl sulfone using phenyl sulfinate can be classified as functional as shown below.

(J, Wildeman, at at, , Syn
thesig, 733 (1979)) (J, Org.
, Chem, 50.1327 (1985) ) (Japanese Unexamined Patent Publication No. 58-52267) (% Kokai No. 56-86149)
981)) [Problems to be Solved by the Invention] Among the above-mentioned methods for synthesizing allyl sulfone, the method (2) is one that is easy to operate and is relatively commonly used, especially for primary allyl halides. It is known that the reaction between phenylsulfinate and phenylsulfinate produces the corresponding allylsulfone quantitatively.

However, from the table, the reaction shown in (2) requires the use of a high-potency reaction solvent, or if the reaction is carried out using a water-soluble polar solvent, it is difficult to obtain the product after the reaction. There are drawbacks such as the need for an extraction solvent. Furthermore, as a method for inexpensively synthesizing primary allyl halide, which is a reaction raw material, 1. Addition of hydrogen halide to diene (for example, synthesis of geranyl chloride by reaction of myrcene and hydrogen chloride) 2. Tertiary allyl alcohol and thionyl chloride (for example, synthesis of geranyl chloride by the reaction of linalool and thionyl chloride), but in these reactions, in addition to the primary allyl halide, 3R allyl halide is produced as a by-product in a small proportion. This by-produced tertiary allyl halide hardly yields the target allyl sulfone under the reaction conditions of the primary allyl halide and the 7-enyl sulfinate, and the yield of allylno-ride is reduced by the diene or 7-enyl sulfinate. If you look at it based on tertiary allyl alcohol standards, it's definitely not satisfactory, but it's strong.

SUMMARY OF THE INVENTION Therefore, an object of the present invention is to provide an industrially advantageous method for producing allyl sulfone represented by the general formula (Il) in good yield from inexpensive and easily available raw materials.

[Means for solving problems]

According to the present invention, the above object is achieved by the tertiary allyl halide represented by the general formula (IF) (wherein X represents a chlorine atom, a bromine atom or an iodine atom) and/or by the general formula (2
) (wherein, X is as defined above) and b first
A class allyl halide and a phenyl sulfinate represented by the general formula (IV) (wherein R represents a hydrogen atom or a lower alkyl group, and M is a sodium atom or a potassium atom) are combined into a halogenated tetraalkylammonium salt. This is achieved by reacting in an anhydrous system in the presence of

In the general formulas (1) and (II), X represents a chlorine atom, a bromine atom, or an iodine atom, and from the viewpoint of versatility, a chlorine atom is particularly preferred. Compounds in which X is a chlorine atom in the general formula (If) (hereinafter referred to as linalyl chloride) is produced by 1) addition reaction of hydrogen chloride to myrcene (see JP-A No. 60-41623), 2)
Dalanyl chloride and neryl chloride, which are the main products in reactions such as the reaction between linalool and thionyl chloride (hereinafter, both are collectively referred to as r-ranyl chloride)
linalyl chloride and dalanyl chloride are usually used in the form of a mixture.

Next, R and M in general formula (IV) will be explained.

R is a hydrogen atom: methyl group, ethyl group, n-fa pyl group,
It can be any lower alkyl group such as l-propyl group, n-butyl group, l-butyl group, or t-butyl group, and these lower alkyl groups are in the ortho position (o
It may be substituted at either the L-meta position (m-) or the A/o-position (p-). Among these, the most preferable R
are hydrogen atoms and methyl groups. M is at least the equivalent molar amount, preferably from the equivalent molar amount to 2 times the molar amount, relative to the sodium atom and the carido (2) and/or the primary allyl halide of the general formula (2).

In addition, in the halogenated tetraalkylammonium salt used in the reaction according to the method of the present invention, the total number of carbon atoms in the four alkyl groups is preferably within the range of about 8 to 32,
Specific examples include tetra-n-butylammonium halide, tetra-n-pentylammonium halide, and stearyltrimethylammonium halide.

Among the halogen atoms used for halodination, an iodine atom is particularly preferred, and when an iodinated tetraalkylammonium salt is used, it is represented by the general formula (wherein R represents a hydrogen atom or a lower alkyl group). This suppresses the formation of tertiary allyl sulfone, which would otherwise occur, and allows the desired primary allyl sulfone to be obtained in high yield.

The following margin halodanated tetraalkylammonium salts are represented by the general formula (I
The tertiary prill halide of I) and/or the first of general formula ■
It is used in a proportion of 0.1 to 30 mol, preferably 0.5 to 10 mol, based on the class allyl halide.

A reaction solvent can be used in this reaction, and examples of usable reaction solvents include aliphatic hydrocarbons such as hexane, heptane, and octane, and aromatic hydrocarbons such as benzene, toluene, and xylene. Examples include hydrogen-based solvents.

Among these, toluene is particularly suitable. There are several advantages when the reaction is carried out using a hydrocarbon solvent.

1. Since it is insoluble in water, it can be used as it is as an extraction solvent during post-treatment after the reaction, and there is no need to use a new extraction solvent.

2. It is available at a lower cost than polar solvents (dimethylformamide, etc.) and is easy to recover and reuse.

3. The presence of water greatly reduces the yield of the target allylsulfone (see Comparative Example 1). Generally, phenylsulfinate is commercially available in the form of a hydrate, but it can be converted to diphenylsulfinate by using a hydrocarbon solvent such as toluene or by performing azeotropic dehydration treatment prior to the reaction. Entrained water can be easily removed from the system.

The reaction temperature is θ°C to 150°C, preferably 50°C to 120°C.
Selected from within the range of ℃. The reaction time varies greatly depending on the reaction conditions employed, but for example, if the reaction temperature is
When the reaction is carried out while being maintained at around 0.degree. C., the reaction is completed within 3 hours.

Hereinafter, the present invention will be explained in detail by way of examples.

Example 1 (1) Synthesis of allyl chloride Myrcene 188.5& (83fy purity 1.16 mol)
Hydrogen chloride gas was sucked into a mixture of 0.7 g of copper chloride (1) and copper chloride (1) at a temperature of 0 to 8°C until myrcene disappeared.
Stirring was continued at that temperature for an additional 20 hours. After pouring into 100ml of water, extract by adding 100ml of toluene, and extract the toluene layer with 100N of water, 5ml of sodium bicarbonate solution IQQmA', and 100ml of water.
After successively washing with Lt and further distilling off the solvent under reduced pressure, oily substance 235.3Ii was obtained. As a result of gas chromatography analysis, this product was a mixture of primary allyl chloride and tertiary allyl chloride in a ratio of 10.8/89.2.

Gas chromatography analysis conditions Column packing material PEG 20M, 2 m column Column temperature 100°C (After 2 minutes, the temperature was raised to 150°C at a rate of 10°C/min) (2) Synthesis of allyl sulfone Sodium benzenesulfinate dihydrate 21. 5,! i
'Toluene 1000Jl17 for (1,07mot)!
was added, and water was distilled off while heating from 90°C to 110°C using a water separator. Then cooled to 105℃,
Iodine Tetra n-butylammonium salt 3.769
(10.2 mmot), and then the mixture 2 of nalyl chloride and geranyl chloride obtained by the above method.
78.2 g was added dropwise over 20 minutes, and the mixture was stirred at the same temperature for 2 hours. After cooling, the solid matter was separated in a furnace, and the filtrate was washed with 100 JI of 1% sodium thiosulfate water and 100 d of water, and the solvent was distilled off under reduced pressure, resulting in an oily substance of 287.3
．． I got a 9. As a result of gas chromatography analysis, the target geranyl phenyl sulfone was 261.2 g.
(Purity 9o, 9%) The yield from myrcene is 81
It was Chi. The ratio of primary allyl sulfone to tertiary allyl sulfone was 97.7:2.3.

Gas chromatography analysis conditions Column packing material Themon 1000.1m column Column temperature 100°C (heated up to 250°C at 10°C/min) Comparative example 1 Allyl chloride synthesized by the method described in Example 1 was used, and toluene was used. Geranyl phenyl sulfone was synthesized in the same manner as in Example 1 except that the water removal operation from sodium benzenesulfinate dihydrate using was not performed. After a similar extraction operation, gas chromatography analysis revealed that the yield of geranylphenyl sulfone synthesis from myrcene was 53.81, and the ratio of primary allyl sulfone to tertiary allyl sulfone was 89.9/ 1
It was 0.1.

Examples 2 to 5 Allyl sulfones obtained by the method described in Example 1 or by reacting various phenyl sulfonates and tetraalkylammonium halide salts with a mixture of nalyl chloride and geranyl chloride were synthesized. The results are shown in Table 1. Note that the yield is calculated based on myrcene.

[Effects of the Invention] According to the present invention, allyl sulfone represented by the general formula (1), which is useful as a synthetic intermediate for vitamin A acetate, can be produced in good yield from raw materials that are inexpensive and easily available. can be manufactured.

Claims (1)

[Claims] 1. Tertiary allyl represented by general formula (II) ▲Mathematical formulas, chemical formulas, tables, etc.▼(II) (in the formula, X represents a chlorine atom, a bromine atom, or an iodine atom) halide and/or general formula (I
II) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(III) (In the formula, X is as defined above) ▼(IV) (In the formula, R represents a hydrogen atom or a lower alkyl group, and M
is a sodium atom or a potassium atom) in an anhydrous system in the presence of a halogenated tetraalkylammonium salt. ▼ (In the formula, R represents a hydrogen atom or a lower alkyl group, and the double bond does not distinguish stereoisomerism.) A method for producing allyl sulfone.