JPH11158097A - Production of alcohols - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject compound useful as an intermediate for medicines and agrochemicals, by reacting a specific organic halide with magnesium and paraformaldehyde and hydrolyzing the reaction product. SOLUTION: Magnesium and paraformaldehyde are suspended in a reaction solvent (e.g. diethyl ether; tetrahydrofuran or the like) at preferably 20-70 deg.C with stirring and is reacted with an organic halide of the formula RXn (R is an aromatic residue, an unsaturated aliphatic residue or the like; X is a halogen; (n) is >=1) preferably at 20-70 deg.C and then the reaction product is hydrolyzed at preferably 5-50 deg.C to give an alcohol of the formula R(CH2 OH)n . The organic halide is preferably a styrene derivative of the formula [A is a (substituted) benzene ring]. The amount of magnesium used is preferably 80-150 mol.% based on the organic halide.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for producing alcohols from an organic halide, magnesium and paraformaldehyde. More specifically, the present invention relates to a method for producing alcohols useful as intermediates of medicines and agricultural chemicals by the Grignard reaction.

[0002]

2. Description of the Related Art Methods for producing alcohols by reacting Grignard reagents with aldehydes are already known. For example, JP-A-9-30998 discloses that a Grignard reagent obtained by reacting m-substituted α-bromostyrene with metallic magnesium is reacted with formaldehyde, and then hydrolyzed to form an m-substituted useful as an intermediate for pesticides. A method for producing α-hydroxymethylstyrene is disclosed.

[0003]

However, in order to produce alcohol on an industrial scale by this method, there are various problems to be solved. That is, since formaldehyde is easily polymerized, paraformaldehyde is used in industrial applications where a large amount is handled. Since this reaction is performed in an inert atmosphere, it is necessary to sufficiently replace the inside of the reactor with nitrogen gas or the like. Thus, paraformaldehyde is a solid and has very low solubility in solvents. When paraformaldehyde is added to a Grignard reagent solution in a solid state, the addition operation becomes very complicated in terms of inert gas replacement and reaction control. In addition, it is conceivable to dissolve paraformaldehyde in a solvent and add it to the Grignard reagent.However, since the solubility of paraformaldehyde is low, it becomes a suspension and it is difficult to uniformly control the addition concentration of paraformaldehyde. It is difficult to control the reaction. On the other hand, the method of adding a Grignard reagent solution to a suspension of paraformaldehyde is relatively easy to control the reaction.However, in order to smoothly add the Grignard reagent solution, solid components in the solution are removed in advance. In addition to this, an additional reactor is required for the reaction, compared to the case where paraformaldehyde is added. Therefore, an operation of removing unreacted magnesium by means such as filtering a reaction product liquid of the organic halide and magnesium is required.

[0004] Therefore, it has been strongly desired to simplify an industrial reaction procedure for producing alcohols from an organic halide, magnesium and paraformaldehyde by utilizing the Grignard reaction. The present invention has been made in view of such circumstances, and has as its object to provide a method for industrially producing alcohols from an organic halide, magnesium, and paraformaldehyde.

[0005]

The present inventors have conducted intensive studies to solve the above-mentioned problems, and as a result, by selecting the order of adding magnesium, paraformaldehyde and an organic halide, the same order as in a normal reaction method is obtained. It has been found that reaction operation and management can be facilitated while maintaining reaction results.

That is, the gist of the present invention is the following general formula (1)

Embedded image RX _n (1) (wherein, R is an aromatic residue, an unsaturated aliphatic residue or a saturated aliphatic residue, X is a halogen atom, and n is an integer of 1 or more). After reacting the organic halide to be reacted with magnesium and paraformaldehyde, the reaction product is hydrolyzed to give the following general formula (2)

[0007]

In a reaction for producing an alcohol represented by R (CH ₂ OH) _n (2) (wherein R and n are as defined in the general formula (1)), magnesium and paraformaldehyde are used. Mixing, and then adding an organic halide represented by the general formula (1).

[0008]

DESCRIPTION OF THE PREFERRED EMBODIMENTS Preferred embodiments of the present invention will be described below. In the above general formula (1), R represents an aromatic residue such as variously substituted phenyl groups and various optionally substituted benzyl groups, such as various optionally substituted vinyl groups and various substituted groups. Represents an unsaturated aliphatic residue such as an allyl group which may be substituted, or a saturated aliphatic residue such as an alkyl group which may be variously substituted, X represents a halogen atom, and a bromine atom or an iodine atom Particularly preferred. n represents an integer of 1 or more, and 1 is most preferable.

The halide represented by the general formula (1) is not particularly limited, but is preferably a compound represented by the following general formula (3)

Embedded image (Wherein, X represents a halogen atom, and A represents a benzene ring which may be substituted with an electron-withdrawing group). Examples of the electron withdrawing group which may be substituted on the ring A in the general formula (3) include a halogen atom such as a chlorine atom and a fluorine atom, and an alkyl group such as a nitro group, a cyano group, a trifluoromethyl group, a methyl group and an ethyl group. , A methoxy group and an ethoxy group.

The present invention is characterized in that magnesium and paraformaldehyde are suspended in a reaction solvent, and an organic halide represented by the general formula (1) is added thereto to carry out the reaction. In this reaction, the amount of metal magnesium used is 50 to 300 mol%, preferably 80 to 15 mol%, based on the organic halide represented by the general formula (1).
0 mol%. In this reaction, the amount of paraformaldehyde to be used is not particularly limited, but is 0.1 to 1 equivalent of the organic halide represented by the general formula (1).
5 to 2 equivalents, preferably 0.8 to 1.5 equivalents are used.

In this reaction, magnesium and paraformaldehyde are added to a reaction solvent in advance and suspended with stirring. The temperature for stirring and suspending is usually -10 to 100.
° C, preferably 20-70 ° C. Examples of the solvent to be used include ether solvents such as diethyl ether, tetrahydrofuran and dibutyl ether, or mixed solvents of the above ether solvents and aromatic hydrocarbons such as benzene, toluene and xylene. The amount of the solvent used is usually 1 to 1 with respect to the organic halide represented by the general formula (1).
The amount is 00 times (weight), preferably 1 to 15 times.

Next, an organic halide of the general formula (1) is added to the above suspension to carry out a reaction. The reaction temperature is usually −10 to 100 ° C., preferably 20 to 70 ° C., and the reaction is further maintained for 5 minutes to 10 hours after completion of the addition to complete the Grignard reaction. During the reaction, a small amount of iodine, dibromoethane or the like may be added to activate magnesium. The organic halide of the general formula (1) may be added after being diluted with a solvent. Examples of the solvent include the solvents used for suspending magnesium and paraformaldehyde. The amount of solvent used for dilution is
The amount is usually 1 to 100 times (weight), preferably 1 to 15 times the amount of the organic halide represented by the general formula (1). By this reaction, the following general formula (4)

[0013]

## STR7 ## An intermediate represented by R (CH ₂ OMgX) _n (4) (where R, X and n are as defined in the general formula (1)) is produced. Next, an acidic aqueous solution is added to the reaction solution to hydrolyze the intermediate, whereby an alcohol represented by the general formula (2) can be produced. The acidic aqueous solution used for the hydrolysis is not particularly limited, and examples thereof include diluted hydrochloric acid and diluted sulfuric acid. The hydrolysis is carried out in a temperature range of 0 to 100 ° C, preferably 5 to 50 ° C.
The temperature range is as follows. Separation of the alcohol represented by the general formula (2) from the reaction solution is performed by a method such as solvent extraction, and if necessary, purification is performed by means such as distillation.

[0014]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited to the following Examples unless it exceeds the gist thereof.

Example 1 In a 100 ml flask, 1.23 g (0.051 mol) of magnesium, 1.52 g (0.051 mol) of paraformaldehyde, 10 ml of tetrahydrofuran (THF), 10 ml of toluene, and 0.02 g of iodine were placed under a nitrogen atmosphere. added. While stirring this mixture under cooling in a water bath, a solution prepared by dissolving 10 g (0.046 mol) of 3-chloro-α-bromostyrene in 5 ml of THF and 5 ml of toluene was added dropwise at 30 ° C. over 2 hours. The reaction was performed for 2 hours to complete the reaction. After completion of the reaction, THF was distilled off under reduced pressure and toluene was added to replace the solvent. Further, 40 ml of a 3N hydrochloric acid aqueous solution was added to the reaction solution at 25 ° C., and the mixture was hydrolyzed to separate an organic phase. The organic phase was washed sequentially with water, a 1% aqueous NaOH solution and water, and then quantitatively analyzed by gas chromatography (GC). As a result, the yield of 3-chloro-α-hydroxymethylstyrene was 70%. In this reaction method, the minimum number of reactors required was one, and the reaction operations such as charging of raw materials, addition, and replacement of inert gas could be easily performed.

Comparative Example 1 1.23 g (0.051 mol) of magnesium, 10 ml of THF,
Toluene (10 ml) and iodine (0.02 g) were added, and while stirring in a water bath under cooling, 10 g (0.046 mol) of 3-chloro-α-bromostyrene was added at 30 ° C. in THF (5 m).
and 1 ml of a solution dissolved in 5 ml of toluene were added dropwise over 30 minutes, and the reaction was further performed for 1 hour. Then, the reaction solution from which magnesium in the solution was removed by filtration was added to a separately prepared suspension of 1.52 g (0.051 mol) of paraformaldehyde in 10 ml of THF and 10 ml of toluene.
The mixture was added dropwise at 30 ° C. over 2 hours, and the reaction was further performed for 2 hours to complete the reaction. After completion of the reaction, the same operation as in Example 1 was performed, and quantitative analysis was performed by GC. As a result, the yield of 3-chloro-α-hydroxymethylstyrene was 70%. In this reaction method, at least two reactors are required, and the Grignard reagent solution needs to be filtered, so that the reaction operation is complicated.

Comparative Example 2 1.23 g (0.051 mol) of magnesium, 10 ml of THF, and 100 ml of a flask were placed under a nitrogen atmosphere.
Toluene (10 ml) and iodine (0.02 g) were added, and while stirring in a water bath under cooling, 10 g (0.046 mol) of 3-chloro-α-bromostyrene was added at 30 ° C. in THF (5 m).
and 1 ml of a solution dissolved in 5 ml of toluene were added dropwise over 30 minutes, and the reaction was further performed for 1 hour. Next, 1.52 g (0.051 mol) of paraformaldehyde was added to the reaction solution, and the reaction was carried out for 4 hours to complete the reaction. After completion of the reaction, the same operation as in Example 1 was performed, and quantitative analysis was performed by GC. As a result, the yield of 3-chloro-α-hydroxymethylstyrene was 70%. In this reaction method, it is necessary to add paraformaldehyde powder to the reactor during the reaction, but when the powder is charged, air is easily entrained,
Inert gas replacement in the reactor becomes difficult. In addition, a special device is required to control the rate of powder addition.

[0018]

INDUSTRIAL APPLICABILITY According to the present invention, in producing alcohols useful as medicines and agricultural chemicals by the Grignard reaction using paraformaldehyde, the reaction operation and control can be made very easy.

 ────────────────────────────────────────────────── ─── Continuing on the front page (72) Inventor Yuichi Tanikawa 1-1 Kurosaki Castle Stone, Yawatanishi-ku, Kitakyushu City Inside the Mitsubishi Chemical Corporation Kurosaki Office

Claims (2)

[Claims] 1. A compound represented by the following general formula (1): RX _n (1) wherein R is an aromatic residue, an unsaturated aliphatic residue or a saturated aliphatic residue, X is a halogen atom, n Represents an integer of 1 or more.) After reacting an organic halide represented by the formula (1) with magnesium and paraformaldehyde, the reaction product is hydrolyzed to give the following general formula (2): R (CH ₂₎ OH) _n (2) In the reaction for producing an alcohol represented by the formula (1), R and n are mixed with magnesium and paraformaldehyde. A method for producing alcohols, comprising adding an organic halide represented by the formula (1). 2. An organic halide represented by the general formula (1) is converted to a compound represented by the general formula (3): (Wherein X represents a halogen atom, and A represents a benzene ring which may be substituted with an electron-withdrawing group). Law.