JP2847813B2 - Method for producing 1-alkoxy-4- (substituted) benzyloxybenzenes - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to a method for producing 1-alkoxy-4- (substituted) benzyloxybenzenes used as additives for high-sensitivity thermal paper, raw materials for pharmaceuticals and agricultural chemicals, and the like. .

[Conventional technology]

Conventionally, as a method for producing 1-alkoxy-4- (substituted) benzyloxybenzenes, 4- (4′-halogenobenzyloxy) phenol is used in a mixed solution of methanol and water in the presence of a base. 3-halogeno-1-propanol (HOCH ₂ CH ₂ CH ₂ X ² )
To give 1- (3-hydroxypropoxy) -4-
(4'-halogenobenzyloxy) benzene Is disclosed in JP-A-55-40651. However, in this method, the resulting 1-alkoxy-
Low purity of 4- (substituted) benzyloxybenzenes,
There are problems such as a low yield.

[Problems to be solved by the invention]

SUMMARY OF THE INVENTION An object of the present invention is to solve the above-mentioned problems by providing a high-yield and high-purity 1-alkoxy-4-
It is to propose a method for producing (substituted) benzyloxybenzenes.

[Means for solving the problem]

The present invention provides a method for reacting a 4- (substituted) benzyloxyphenol with an alkylating agent in an aprotic polar solvent in the presence of a base. This is a method for producing benzenes.

In the present invention, the notation “(substituted)” indicates that it includes both cases with and without substitution by a substituent.

In the present invention, as the starting material, 4- (substituted) benzyloxyphenols represented by the following general formula [I] can be used.

(In the formula, R ¹ represents a hydrogen atom, a halogen atom or a substituent.) Examples of the halogen atom of R ^{1 in} the general formula [I] include fluorine, chlorine, bromine and iodine.

Examples of the substituent of R ^{1 in} the general formula [I] include an alkyl group such as a methyl group and an ethyl group; an alkoxy group such as a methoxy group and an ethoxy group; and a nitro group.

Specific examples of 4- (substituted) benzyloxyphenols represented by the general formula [I] include, for example, 4
-(4'-chlorobenzyloxy) phenol, 4-benzyloxyphenol, 4- (4'-methoxybenzyloxy) phenol, 4- (4'-methylbenzyloxy) phenol, 4- (4'-nitrobenzyloxy) ) Phenol and the like.

A known method can be employed for producing the 4- (substituted) benzyloxyphenol represented by the general formula [I]. For example, a base such as sodium hydroxide is dissolved in a solvent such as methanol, and then this solution is dissolved. And halogenated 4- such as hydroxynon and 4-chlorobenzyl chloride.
By adding (substituted) benzyl and heating to reflux with stirring, 4- (substituted) benzyloxyphenols are produced. After the completion of the reaction, the insoluble substance is separated into solid and liquid by filtration or the like, and then the solvent from which the solvent has been removed by distillation or the like, or recrystallized using methanol, acetone, etc. and water, toluene, hexane, etc. Can be used as a raw material for the production method of the present invention.

In the present invention, an alkylating agent represented by the following general formula [II] can be used as the alkylating agent.

R ² X ... [II] (wherein, R ² is an alkyl group, X is a halogen atom, -OSO ₃ R ³
Group or —OSO ₂ Ar group. Where R ³ is an alkyl group, Ar
Represents an aromatic hydrocarbon group. Examples of the alkyl group of R ^{2 in} the general formula [II] include an alkyl group having 1 to 8 carbon atoms such as a methyl group, an ethyl group, and a propyl group; a cycloalkyl group having 6 to 8 carbon atoms such as a cyclohexyl group; Can be given. These alkyl groups may be substituted alkyl groups substituted with a substituent such as a hydroxyl group, or may be alkyl groups having an unsaturated bond (however, vinyl groups and substituted vinyl groups are excluded).

Examples of the halogen atom of X in the general formula [II] include chlorine, bromine, and iodine. R ³ may be an alkyl group such as a methyl group and an ethyl group. As Ar Groups and the like.

Specific examples of the alkylating agent represented by the general formula [II] include, for example, methyl chloride, ethyl chloride, propyl chloride, methyl bromide, ethyl bromide, propyl bromide, n-butyl bromide, iodide Methyl, dimethyl sulfate, diethyl sulfate, HOCH ₂ CH ₂ CH ₂ Cl and the like.

The alkylating agent is used in a molar ratio of alkylating agent / 4- (substituted) benzyloxyphenols of 0.5 to 5, preferably 1 to 5.
It is preferred to use at a ratio of 2.

Examples of the aprotic polar solvent used in the present invention include N, N-dimethylacetamide, N, N-dialkylacetamide such as N, N-diethylacetamide, N, N-dimethylformamide, N-methylpyrrolidone, N, N ', N'
-Tetramethylurea, 1,3-dimethyl-2-imidazolidinone, dimethylsulfoxide, sulfolane, hexamethylphosphoric triamide and the like.

The aprotic polar solvent is preferably used in an amount of 0.5 to 15 parts by weight, preferably 2 to 8 parts by weight, based on 1 part by weight of 4- (substituted) benzyloxyphenols.

Examples of the base used in the present invention include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; alkali metal carbon salts such as sodium carbonate and potassium carbonate; alkaline earth metals such as calcium hydroxide and barium hydroxide. Hydroxides; alkaline earth metal carbonates such as calcium carbonate and barium carbonate; and alkali metal bicarbonates such as sodium bicarbonate and potassium bicarbonate. Among these, alkali metal hydroxides and alkali metal carbonates are preferred, and sodium hydroxide, potassium hydroxide and potassium carbonate are particularly preferred.

The base may be used as it is, or may be dissolved in an appropriate solvent and used in a solution.

The base is preferably used in a molar ratio of base / 4- (substituted) benzyloxyphenols of 0.5 to 5, preferably 1 to 2.

In the present invention, when 4- (substituted) benzyloxyphenols represented by the general formula [I] are used and alkylating agents represented by the general formula [II] are used, the following general formula [III] 1-alkoxy-4- (substituted) benzyloxybenzenes represented by the formula are produced.

(In the formula, R ¹ is the same as in the general formula (I), R ²
Is the same as that of the general formula [II]. The reaction is carried out by reacting 4- (substituted) benzyloxyphenols with a base in an aprotic polar solvent and then reacting by supplying an alkylating agent. A method in which an alkylating agent is mixed and then a base is supplied to cause a reaction can be employed.

The reaction conditions are such that the reaction temperature is usually 30 to 150 ° C, preferably 6
0 to 100 ° C, reaction pressure is usually 1 to 10 atm, preferably 1 to 10 atm
2 atm, reaction time is usually 0.5 to 12 hours, preferably 2 to
It is appropriate to set within the range of 6 hours.

The reactor for carrying out the reaction is not particularly limited, but a tank type is particularly preferred. The reaction system is not particularly limited, and the reaction can be carried out as a slurry or liquid phase reaction by a system such as a batch system or a continuous system.

According to the method as described above, 1-alkoxy-4- (substituted) benzyloxybenzenes are used as the concentration in the reaction system.
It can be manufactured at a concentration of 10 to 40% by weight.

In the production method of the present invention, most of the raw materials used are 1-
Since it is converted to alkoxy-4- (substituted) benzyloxybenzenes, after completion of the reaction, water and the like are added to the reaction mixture from which solids have been removed by filtration or the like, and only crystals that precipitate are filtered and filtered. Alkoxy-4- (substituted) benzyloxybenzenes are obtained in high yield. Therefore, separation and purification after the completion of the reaction are extremely easy. For example, after completion of the reaction, after neutralizing the reaction mixture, the salt is filtered off, the reaction mixture is heated to about 60 ° C., water is added dropwise thereto, and the mixture is cooled to room temperature with stirring to precipitate crystals. By such a method, 1-alkoxy-4- (substituted) benzyloxybenzenes having a yield of 90% or more and a purity of usually 99% or more can be produced.

The thus obtained 1-alkoxy-4- (substituted) benzyloxybenzenes are highly sensitive thermal paper additives,
It can be used as a raw material for medicines and agricultural chemicals.

〔The invention's effect〕

According to the present invention, 4- (substituted) benzyloxyphenols are reacted with an alkylating agent in an aprotic polar solvent in the presence of a base to form 1-alkoxy-4- (substituted) benzyloxybenzenes. To produce 1-alkoxy-4- with high yield and high purity.
(Substituted) benzyloxybenzenes can be produced.

Example Next, an example of the present invention will be described.

Example 1 30 equipped with a stirrer, thermometer, cooler and supply port
23.5 g (0.1 mol) of 4- (4'-chlorobenzyloxy) phenol (hereinafter abbreviated as CBP) and 80.0 g of N, N-dimethylacetamide (hereinafter abbreviated as DMAC) were charged into a 0 ml four-necked flask, After replacing the inside of the reaction system with nitrogen, 4.8 g (0.12 mol) of 98% (solid) sodium hydroxide was added, and the mixture was stirred at 70 ° C. for 1 hour. Then 7.8 g of ethyl chloride (0.
12 mol) at 70-75 ° C over 1 hour, and then heated and stirred at 70 ° C for 2 hours.

The reaction mixture was filtered after neutralization by adding 1.7 g of 85% phosphoric acid, and the salt was rinsed with 10 ml of DMAC. The filtrate and the rinsing solution were combined and heated to 60 ° C., to which 40 ml of water was added dropwise over 1 hour, and cooled to room temperature with stirring. The precipitated crystals were filtered, rinsed with 300 ml of water, and dried under reduced pressure to give 99.8% pure 1-ethoxy-4- (4'-chlorobenzyloxy) benzene (hereinafter abbreviated as ECBB).
4.0 g (91.4% yield) was obtained.

Examples 2 to 4 The same procedures as in Example 1 were carried out except that the solvents shown in Table 1 were used instead of DMAC, and the results shown in Table 1 were obtained.

Examples 5 to 7 The same procedure as in Example 1 was carried out except that the alkylating agent shown in Table 2 was used in place of ethyl chloride in the amount shown in Table 2, and the results shown in Table 2 were obtained. .

Examples 8 to 9 The same procedures as in Example 1 were carried out except that the phenols shown in Table 3 were used in place of CBP in the amounts shown in Table 3, and the results shown in Table 3 were obtained.

Example 10 30 equipped with a stirrer, thermometer, cooler and supply port
In a 0 ml four-necked flask, 23.5 g (0.1 mol) of CBP and DMAC 6
After charging 0.0 g, the inside of the reaction system was replaced with nitrogen, 13.7 g (0.1 mol) of n-butyl bromide was added, and the temperature was raised to 80 ° C., and 13.8 g (0.1 mol) of potassium carbonate was added 4 times at intervals of 15 minutes. And stirred under heating at 80 ° C. for 5 hours. The reaction mixture was filtered, the salt was rinsed with 20 ml of DMAC, the combined filtrate and rinse were heated to 60 ° C., to which 40 ml of water was added dropwise over 1 hour and cooled to room temperature with stirring. The precipitated crystals were filtered, rinsed with 200 ml of water, and dried under reduced pressure to obtain 26.5 g (91.0% yield) of 19.8% pure 1-butoxy-4- (4'-chlorobenzyloxy) benzene. .

──────────────────────────────────────────────────の Continued on the front page (58) Field surveyed (Int. Cl. ⁶ , DB name) C07C 43/205 C07C 41/16 CA (STN) CAOLD (STN) REGISTRY (STN)

Claims (1)

(57) [Claims] 1. A 1-alkoxy-4- (substituted) benzyl, which comprises reacting a 4- (substituted) benzyloxyphenol with an alkylating agent in an aprotic polar solvent in the presence of a base. A method for producing oxybenzenes.