JPH0784431B2 - 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] Among the above-mentioned methods for synthesizing allyl sulfone, a relatively well-used method having good operability is that in the method of (2) above, dimethylformamide or the like is used as a solvent, Alternatively, it is known that a reaction using a phase transfer catalyst, particularly a reaction of a primary allyl halide with a phenylsulfinate salt, gives the corresponding allyl sulfone almost quantitatively. As a method for inexpensively synthesizing this primary allyl halide, 1. Addition of hydrogen halide to diene (eg geranyl chloride synthesis by reaction of myrcene and hydrogen chloride) 2. Reaction of tertiary allyl alcohol with thionyl chloride (For example, geranyl chloride synthesis by reaction of linalool and thionyl chloride) and the like. However, in these reactions,
In addition to the primary allyl halide, a considerable proportion of tertiary allyl halide is by-produced. Moreover, the by-produced tertiary allyl halide hardly gives the target allyl sulfone under the reaction conditions of the primary allyl halide and phenylsulfinate, and the yield of allyl halide is diene or the 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 a raw material that is inexpensive and easily available.

[Means for solving problems]

According to the invention, the above object is (Wherein, X represents a chlorine atom, a bromine atom or an iodine atom) and a tertiary allyl halide represented by the general formula (III) (In the formula, R represents a hydrogen atom or a lower alkyl group, and
Is a sodium atom or a potassium atom) in the presence of a zinc halide and an iodine compound.

In the general formula (II), X represents a chlorine atom, 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), the above-mentioned 1) addition reaction of hydrogen chloride to myrcene (JP-A-60-41)
(See Japanese Patent Publication No. 623) 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 (main product) About 5 to 40% of the product), usually linalyl chloride and geranyl chloride are used in the form of a mixture.

Next, R and M in the general formula (III) 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, t-butyl group, etc., and these lower alkyl groups are in the ortho position (o) with respect to the position of the sulfinic acid salt.
-), The meta position (m-) and the para position (p-) may be substituted. Most preferred R
Is a methyl group located para to the hydrogen atom and the position of the sulfinate salt. M is a sodium atom and a potassium atom. The amount of the phenylsulfinate represented by the general formula (III) used is equimolar or more, preferably equimolar to 2 molar times with respect to the tertiary allyl halide of the general formula (II). In addition, the tertiary allyl halide
General formula (II ′) which is an isomer (Wherein, X represents a chlorine atom, a bromine atom or an iodine atom, and the double bond does not distinguish stereoisomerism), and a primary allyl halide represented by An equimolar amount or more, preferably an equimolar to 2 molar times amount of phenylsulfinic acid salt is used with respect to the total amount of the tertiary allyl halide.

Examples of the zinc halide used in the reaction according to the method of the present invention include zinc chloride, zinc bromide and zinc iodide, and zinc chloride is particularly preferable. The amount of zinc halide used is 1 mol% to equimolar amount with respect to the tertiary allyl halide of the general formula (II). As the iodine compound, an alkali metal salt of hydroiodic acid such as sodium iodide and potassium iodide is used, and the amount thereof is 1 mol% based on the tertiary allyl halide of the general formula (II).
To the equimolar amount. Although it is possible to use an iodine compound in excess of the equimolar amount, particularly good results are not obtained in terms of yield.

The reaction according to the method of the present invention is generally stable in a reaction system such as phenylsulfinate of the general formula (III), a zinc halide and an iodine compound which is easily dissolved, for example, dimethylformamide, diethylformamide, N-methylpyrrolidone and the like. In a polar solvent. The amount of the solvent used is 0. with respect to the tertiary allyl halide of the general formula (II).
5 to 50 times capacity. When the tertiary allyl halide of the general formula (II) is used as a mixture with the primary allyl allyl of the general formula (II ′), 0.5 is added to the total amount of the primary allyl halide and the tertiary allyl halide. ~ 50 volumes of solvent are used.

The reaction proceeds by stirring a predetermined amount of the above reaction product at an internal temperature of 0 ° C to 150 ° C, preferably 30 ° C to 100 ° C.
The reaction is preferably carried out under an inert gas atmosphere such as nitrogen, argon or helium. The reaction time varies greatly depending on the reaction conditions used, but for example, the internal temperature is 60 ° C.
When the reaction is carried out while maintaining at ~ 70 ° C, the reaction is completed within 10 hours.

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

Example 1 (1) Synthesis of Allyl Chloride 50 g (0.325 mol) of linalool in the three-necked flask of 1,
26.9 g (0.341 mol) of pyridine and 450 ml of hexane were added. Then, under vigorous stirring, 40.6 g (0.341 mol) of thionyl chloride was gradually added dropwise while keeping the internal temperature at 30 ° C. After completion of dropping, the mixture was stirred at the same temperature for 2.5 hours. The reaction solution was poured into 500 ml of ice water and the hexane layer was separated. The hexane layer was washed with 100 ml of 5% aqueous sodium hydrogen carbonate, 200 ml of water and 100 ml of saturated saline, and then dried over anhydrous magnesium sulfate. Remove anhydrous magnesium sulfate with a filter,
Hexane was distilled off under reduced pressure to give a pale yellow oil 5
0.6 g was obtained. As a result of gas chromatographic analysis, this was a mixture of linalyl chloride and geranyl chloride of linalyl chloride: geranyl chloride = 31: 69.

Gas chromatographic analysis conditions Column packing material PEG20M, 2m Column temperature 100 ° C (after 2 minutes, the temperature was raised to 150 ° C at 10 ° C / minute) (2) Synthesis of allyl sulfone Linalyl chloride obtained by the above method in the three-neck flask And geranyl chloride mixture 50.6 g, sodium phenylsulfinate 53.2 g, sodium iodide 4.77 g,
Zinc chloride (4.82 g) and dimethylformamide (450 ml) were added, and the mixture was stirred under a nitrogen gas atmosphere at an internal temperature of 60 to 70 ° C. for 5 hours. After completion of the reaction, dimethylformamide was distilled off under reduced pressure, and the remaining oil was poured into 500 ml of water. The separated oil was extracted 3 times with a total volume of 300 ml of ethyl acetate. The ethyl acetate extract was washed with 300 ml of water and 100 ml of saturated saline and then dried over anhydrous magnesium sulfate. Anhydrous magnesium sulfate was separated, and the solvent was distilled off under reduced pressure to obtain 76.4 g of a brown oily substance. As a result of liquid chromatography analysis, this product contained 72.1 g of geranylphenyl sulfone. 80% total yield from linalool.

Liquid Chromatographic Analysis Conditions Column μ-Polacil, 30 cm Developing solvent Ethyl acetate / hexane = 1/9 Flow rate 2 ml / min Comparative Example Using allyl chloride synthesized by the method described in Example 1, zinc chloride and sodium iodide were analyzed. Allyl sulfone was synthesized in the same manner as in Example 1 except that it was not added. After the same extraction operation, the result of liquid chromatography analysis,
The yield of geranylphenyl sulfone synthesis from linalool by this method was 67%.

Examples 2 to 4 50.6 g of a mixture of linalyl chloride and geranyl chloride obtained by the method of Example 1, 48.2 g of zinc chloride, 450 ml of dimethylformamide and a predetermined amount of a sulfinate salt and an iodine compound (the following table) were mixed in 1 of 3. The mixture was placed in a neck flask and the reaction was carried out under the same conditions as in Example 1. The results are summarized in the table below. In the table, the product yield is the total yield from linalool.

Example 5 50.0 g of a mixture of linalyl chloride and geranyl chloride synthesized by the method of Example 1 was distilled under reduced pressure using a glass bead packed column having a column length of 30 cm to give a boiling point of 45 to 50 ° / 0.3.
8.2 g of mmHg fraction was obtained. As a result of gas chromatography analysis, this product was a mixture of linalyl chloride and geranyl chloride: linalyl chloride: geranyl chloride = 95: 5.

Gas chromatographic analysis conditions Column packing material: PEG20M, 2m Column temperature: 100 ° C (after 2 minutes, the temperature was raised to 150 ° C at 10 ° C / minute) In a 200 ml three-necked flask, 8.2 g of the above mixture of linalyl chloride and geranyl chloride, phenyl Sodium sulfinate 8.6g, sodium iodide 1.4g, zinc chloride 2.6g
Then, 100 ml of dimethylformamide was taken and stirred under an atmosphere of nitrogen gas at an internal temperature of 60 ° to 70 ° C. for 5 hours. After completion of the reaction, dimethylformamide was distilled off under reduced pressure, and the remaining oil was poured into 200 ml of water. Total amount of separated oil is 100 ml
It was extracted 3 times with ethyl acetate. 200m of ethyl acetate extract
The extract was washed with 1 L of water and 100 ml of saturated saline and then dried over anhydrous magnesium sulfate. Anhydrous magnesium sulfate was separated, and the solvent was distilled off under reduced pressure to obtain 12.6 g of a brown oily substance. As a result of liquid chromatography analysis, this product contained 11.1 g of geranylphenyl sulfone. Yield 84%.

Liquid Chromatographic Analysis Column: μ-Polacil, 30 cm Developing solvent: Ethyl acetate / hexane = 1/9 Flow rate: 2 ml / min [Effect of the invention] According to the present invention, vitamin A can be obtained from a cheap and easily available raw material. Allyl sulfone represented by the general formula (I), which is useful as a synthetic intermediate for acetate, can be produced in good yield.

Claims (2)

[Claims] 1. A general formula (Wherein, X represents a chlorine atom, a bromine atom or an iodine atom) and a tertiary allyl halide represented by the general formula (III) (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 with phenylsulfinate in the presence of a zinc halide and an iodine compound. (In the formula, R represents a hydrogen atom or a lower alkyl group, and the double bond does not distinguish stereoisomerism). 2. The method according to claim 1, wherein X in the general formula (II) is a chlorine atom, zinc halide is zinc chloride, and iodine compound is sodium iodide.