JPH0822844B2 - Method for producing allyl sulfone - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial field of application] (In the formula, R represents a hydrogen atom or a lower alkyl group, and the double bond does not distinguish stereoisomerism).

The allyl sulfone of the general formula (I) produced by the method of the present invention can be converted into a synthetic intermediate of vitamin A acetate which is used as an additive for medicines and feeds, for example, after a ring closure reaction (Japanese Patent Publication No. Sho). 57-48549 and Odera et al., J. Org. Chem., 51 , 3834 (1986)).

[Conventional technology]

The conventionally known methods for producing allyl sulfone using phenylsulfinate are classified according to functional groups as follows.

[Problems to be Solved by the Invention] Of the above-mentioned methods for synthesizing allyl sulfone, the method having good operability and being relatively frequently used is (2), and particularly primary allyl halide and phenylsulfinic acid. It is known that the reaction with a salt produces the corresponding allyl sulfone almost quantitatively. However, the reaction shown in (2) requires the use of an expensive reaction solvent, or when the reaction is carried out using a water-soluble polar solvent, after the reaction, an extraction solvent is necessary to obtain a product. There are drawbacks such as requiring. Furthermore, as a method for inexpensively synthesizing the primary allyl halide which is a reaction raw material, 1. addition of hydrogen halide to diene (eg, geranyl chloride synthesis by reaction of myrcene and hydrogen chloride) 2. tertiary allyl alcohol And thionyl chloride (eg, geranyl chloride synthesis by the reaction of linalool and thionyl chloride) can be mentioned. In these reactions, a considerable proportion of tertiary allyl halide is by-produced in addition to the primary allyl halide. . This by-produced tertiary allyl halide gives almost no target allyl sulfone under the reaction conditions of the primary allyl halide and phenylsulfinate, and the yield of allyl halide is diene or tertiary On the basis of the grade allyl alcohol, it is never satisfactory.

Therefore, an object of the present invention is to provide an industrially advantageous method for producing an allyl sulfone represented by the general formula (I) in a high yield from raw materials that are inexpensive and easily available.

[Means for solving problems]

According to the present invention, the above-mentioned objects are represented by the general formula (II) (In the formula, X represents a chlorine atom, a bromine atom or an iodine atom) and / or a general formula (II
I) (Wherein, X is as defined above) and a primary allyl halide represented by the general formula (IV) (In the formula, R represents a hydrogen atom or a lower alkyl group, and
Is a sodium atom or a potassium atom) and is reacted in an anhydrous system in the presence of a halogenated tetraalkylammonium salt.

In the general formulas (II) and (III), X is a chlorine atom,
It represents a bromine atom and an iodine atom, but a chlorine atom is particularly preferable from the viewpoint of versatility. In the compound of the general formula (II) where X is a chlorine atom (hereinafter referred to as linalyl chloride), as described above, 1) addition reaction of hydrogen chloride to myrcene (see JP-A-60-41623). 2) Obtained as a by-product of the main products geranyl chloride and neryl chloride (hereinafter, both are collectively referred to as geranyl chloride) in a reaction such as a reaction between linalool and thionyl chloride (5 to the main product). About 40% produced), usually linalyl chloride and geranyl chloride are used in the form of a mixture.

Next, R and M in the general formula (IV) will be described. R
Is a hydrogen atom; methyl group, ethyl group, n-propyl group, i
A lower alkyl group such as -propyl group, n-butyl group, i-butyl group and t-butyl group, and these lower alkyl groups are in the ortho position (o) with respect to the position of the sulfinic acid salt.
It may be substituted at any position of-), meta position (m-), and para position (p-). The most preferable R among these is a hydrogen atom and a methyl group. M is a sodium atom and a potassium atom. The amount of the phenylsulfinic acid salt of the general formula (IV) used is equimolar or more, preferably the same amount as the tertiary allyl halide of the general formula (II) and / or the primary allylic halide of the general formula (III). It is a mole to 2 mole times.

The halogenated tetraalkylammonium salt used in the reaction according to the method of the present invention preferably has a total carbon number of four alkyl groups within a range of about 8 to 32,
Specific examples thereof include tetra-n-butylammonium halide, tetra-n-pentylammonium halide and stearyltrimethylammonium halide. Among the halogen atoms used for halogenation, an iodine atom is particularly preferable, and when an iodinated tetraalkylammonium salt is used, the compound represented by the general formula (V) (In the formula, R represents a hydrogen atom or a lower alkyl group) Generation of a tertiary allyl sulfone as represented by the formula is suppressed, and the intended primary allyl sulfone can be obtained in a high yield.

The halogenated tetraalkylammonium salt is a tertiary allyl halide of the general formula (II) and / or the general formula (II
It is used in a proportion of 0.1 to 30 mol%, preferably 0.5 to 10 mol%, based on the primary allyl halide of I).

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. A hydrogen-based solvent can be used. Of these, toluene is particularly suitable. When the reaction is carried out using a hydrocarbon solvent,
There are advantages as described below.

1. Since it is insoluble in water, it can be used as an extraction solvent as it is in the post-treatment after the reaction, and it is not necessary to use a new extraction solvent.

2. It is cheaper than polar solvents (such as dimethylformamide), and easy to collect and reuse.

3. The presence of water significantly reduces the yield of the target product, allyl sulfone (see Comparative Example 1). In the general formula, phenylsulfinate is commercially available in the form of a hydrate, but by using a hydrocarbon solvent such as toluene, it is entrained in phenylsulfinate by azeotropic dehydration treatment prior to the reaction. Water can be easily removed from the system.

The reaction temperature is selected from the range of 0 ° C to 150 ° C, preferably 50 ° C to 120 ° C. The reaction time varies greatly depending on the reaction conditions used, but when the reaction is carried out while maintaining the reaction temperature at around 100 ° C., the reaction is completed within 3 hours.

 Hereinafter, the present invention will be described in detail with reference to examples.

Example 1 (1) Synthesis of allyl chloride Myrcene 188.5 g (83% purity 1.16 mol) and copper (I) chloride
Hydrogen chloride gas was sucked into 0.7 g of the mixed solution at a temperature of 0 to 8 ° C. until myrcene disappeared, and the mixture was further stirred at that temperature for 20 hours. After pouring into 100 ml of water, add 100 ml of toluene for extraction, and extract the toluene layer with 100 ml of water, 100 ml of 5% sodium bicarbonate water, and 10 ml of water.
It was washed successively with 0 ml and the solvent was distilled off under reduced pressure to obtain 235.3 g of an oily substance. As a result of analysis by gas chromatography, this was a mixture of primary allyl chloride and tertiary allyl chloride in the ratio of 10.8 / 89.2.

Gas chromatography analysis conditions Column packing material PEG 20M, 2m column Column temperature 100 ° C (after 2 minutes, the temperature was raised to 150 ° C at 10 ° C / minute) (2) Synthesis of allyl sulfone Sodium benzenesulfinate dihydrate 21.5 g ( 1.07m
Toluene (1000 ml) was added to ol) and water was distilled off while heating from 90 ° C to 110 ° C using a water separator. Then 105 ° C
The mixture was cooled to room temperature, 3.76 g (10.2 mol) of iodinated tetra-n-butylammonium salt was added, and 278.2 g of a mixture of linalyl chloride and geranyl chloride obtained by the above method.
Was added dropwise over 20 minutes, and the mixture was stirred at the same temperature for 2 hours. After cooling, the solid substance was separated, the liquid was washed with 100 ml of 1% aqueous sodium thiosulfate and 100 ml of water, and the solvent was distilled off under reduced pressure to obtain 287.3 g of an oily substance. As a result of analysis by gas chromatography, the target geranylphenyl sulfone was 261.2 g (purity 90.9%), and the yield from myrcene was 81%. The ratio of primary allyl sulfone to tertiary allyl sulfone was 97.7 to 2.3.

Gas chromatography analysis conditions Column packing material Themon 1000, 1 m column Column temperature 100 ° C. (heated 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. Geranylphenyl sulfone was synthesized in the same manner as in Example 1 except that the water removal operation from sodium benzenesulfinate dihydrate was not performed. After a similar extraction operation, as a result of analysis by gas chromatography, the yield of geranylphenyl sulfone synthesis from myrcene was 53.8%, and the ratio of primary allyl sulfone to tertiary allyl sulfone was 89.9 / 10.1. .

Examples 2 to 5 Allylsulfones were synthesized by reacting various phenylsulfonate salts and tetraalkylammonium halide salts with the mixture of linalyl chloride and geranyl chloride obtained by the method described in Example 1. The results are shown in Table 1. The yield is calculated based on Myrcene.

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

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Claims (1)

[Claims] 1. General formula (II) (In the formula, X represents a chlorine atom, a bromine atom or an iodine atom) and / or a general formula (II
I) (Wherein, X is as defined above) and a primary allyl halide represented by the general formula (IV) (In the formula, R represents a hydrogen atom or a lower alkyl group, and
Is a sodium atom or a potassium atom) and is reacted in an anhydrous system in the presence of a tetraalkylammonium halide salt. (Wherein R represents a hydrogen atom or a lower alkyl group, and the double bond does not distinguish stereoisomerism).