JPH03135938A - Production of 1-alkoxy-4-(substituted) benzyloxybenzene - Google Patents

Abstract

PURPOSE:To obtain both in high yield and purity the title compound useful as e.g. a raw material for highly sensitive heat-sensitive paper additives, medicines, pesticides etc. by reaction between a 4-alkoxyphenol and a (substituted) benzyl compound in an aprotic polar solvent in the presence of a base. CONSTITUTION:The objective compound of e.g. formula III can be advantageous ly obtained by reaction pref. at 60 - 100 deg.C under a pressure of 1 - 2 atm between (A) a 4-alkoxyphenol of e.g. formula I (R<1> is alkyl) and (B) a (substituted) benzyl compound of e.g. formula II (R<2> is H, halogen, alkyl, alkoxy, NO2 etc.; X is halogen. OSO2R<3> or OSO2Ar; R<3> is alkyl; Ar is aromatic group) in (C) an aprotic polar solvent such as N,N-dialkylacetamide, N,N-dimethylformamide, N- methylpyrrolidone or dimethylsulfoxide in the presence of (D) a base (pref. an alkali metal hydroxide or carbonate).

Description

Detailed Description of the Invention [Field of Industrial Application] The present invention relates to a method for producing l-alkoxy-4-(substituted)benzyloxybenzenes, which are used as highly sensitive thermal paper additives, medicines, agricultural chemical raw materials, etc. .

[Conventional technology]

Conventionally, as a method for producing 1-alkoxy-4-(substituted)benzyloxybenzenes, a method for producing 4-alkoxyphenols and a (substituted) benzyl compound has not been proposed.

On the other hand, in the presence of a base in a methanol/water mixed solution, 4
-(4'-halogenobenzyloxy)phenol (HO
60CH! ex, > Ni-a-Cl-geha-1-propanol (HOCH, CI, CB,
-(4'-halogenobenzyloxy)Hensen (HO(
A method for producing cut )a o ()ocnl(>r> is disclosed in JP-A-55-40651.

However, in this method, the obtained 1-alkoxy-4-(
Substituted) benzyloxybenzenes have low purity.

There are problems such as low yield.

[Problem to be solved by the invention]

The purpose of the present invention is to solve the above problems,
The object of the present invention is to propose a method for producing 1-alkoxy-4-(substituted)benzyloxybenzenes with high yield and high purity.

(Means for Solving the Problems) The present invention provides the following methods:
1-alkoxy-4- characterized by reacting a 4-alkoxyphenol with a (substituted) benzyl compound
This is a method for producing (substituted) benzyloxybenzenes.

In the present invention, the expression "(substituted)" includes both cases where there is substitution with a substituent group and cases where there is no substitution.

In the present invention, as the 4-alkoxyphenols serving as starting materials, those represented by the following general formula (1) can be used.

R'o-oOH-(1) (In the formula, R1 represents an alkyl group) Examples of the alkyl group for R1 in the general formula (I) include methyl, ethyl, propyl, etc. having 8 carbon atoms. chain alkyl group; a cycloalkyl group having 6 to 8 carbon atoms such as a cyclohexyl group; and the like. These alkyl groups may be substituted alkyl groups substituted with a substituent such as a hydroxyl group, or an alkyl group having an unsaturated bond (
However, it may be a vinyl group or a substituted vinyl group).

Specific examples of the 4-alkoxyphenols represented by the general formula (1) include 4-methoxyphenol, 4-ethoxyphenol, 4-butoxyphenol, 4-cyclohexyloxyphenol, 4-(3
-hydroxypropoxy) phenol, etc.

Known methods can be used to produce the 4-alkoxyphenols represented by the general formula (1).

For example, it can be produced by reacting hydroquinone with an alcohol such as methanol or ethanol, or an alkylating agent such as an alkyl halide, dimethyl sulfate, or diethyl sulfate.

In the present invention, a (substituted) benzyl compound represented by the following general formula (II) can be used as the (i!!-substituted) benzyl compound.

(In the formula, R2 is a hydrogen atom, a halogen atom or a substituent,
X is a halogen atom, -050, R3 group or -08O,
represents an Ar group, where R3 represents an alkyl group and Ar represents an aromatic hydrocarbon group) Examples of the halogen atom of R2 in the general formula [II) include fluorine, chlorine, bromine, and iodine.

Examples of the substituent for R1 in the general formula (II) include alkyl groups such as methyl and ethyl; alkoxy groups such as methoxy and ethoxy; and nitro.

Examples of the halogen atom for X in the general formula (n) include chlorine, bromine, and iodine. Also R3
Examples include alkyl groups such as methyl and ethyl groups. Examples of Ar include CH and @)- groups.

Specific examples of the (l[substituted)benzyl compound represented by the general formula (Il) include 1, for example, benzyl chloride, 4
-chlorobenzyl chloride, 4-methylbenzyl bromide, 4-methoxybenzyl chloride, 4-nitrobenzyl bromide and the like.

(W-substituted) benzyl compound is (substituted) benzyl compound/4
-Alkoxyphenols are preferably used in a molar ratio of 0.5 to 5, preferably 1 to 2.

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

Aprotic polar solvents are 4-alkoxyphenols 1
0.5 to 15 parts by weight, preferably 2 to 8 parts by weight
Preferably, they are used in parts by weight.

Examples of the base used in the present invention include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; alkali metal carbonates such as sodium carbonate and potassium carbonate; alkaline earth metals such as calcium hydroxide and barium hydroxide. Examples include hydroxides; alkaline earth metal carbonates such as calcium carbonate and barium carbonate; alkali metal hydrogen carbonates such as sodium hydrogen carbonate and potassium hydrogen carbonate;

Among them, 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 in its solid state, or it may be dissolved in a suitable solvent and used in the form of a solution.

The base has a base/4-alkoxyphenol molar ratio of 0.
．． It is preferable to use a proportion of 5 to 5, preferably 1 to 2.

In the present invention, when the 4-alkoxyphenol represented by the above general formula (1) is used as the (substituted) benzyl compound, the 4-alkoxyphenol represented by the above general formula (II) is used. 1-alkoxy-
4-(substituted)benzyloxybenzenes are produced.

(In the formula, R1 is the same as that of the general formula (13),
R2 is the same as in general formula (n) above. ) The reaction is a method in which 4-alkoxyphenols and a base are reacted in an aprotic polar solvent, and then a (substituted) benzyl compound is supplied and reacted, 4-alkoxyphenols and a (substituted) benzyl compound and An example of a method that can be adopted is to mix the two and then supply a base to cause the reaction.

The reaction conditions are: 1 reactor temperature is usually 30 to 150°C, preferably 60 to 100°C, 1 reaction pressure is usually 1 to 10 atm, preferably 1 to 2 atm, reaction time is usually 0.5 to 12 hours,
Preferably, it is appropriate to set the time in the range of 2 to 6 hours.

The reactor for carrying out the reaction is not particularly limited.

The reaction method, which is particularly preferably a tank type, is not particularly limited, and the reaction can be carried out as a slurry or liquid phase reaction by a batch method, a continuous method, or the like.

By the above method, the concentration of 1-alkoxy-4-(!substituted)benzyloxybenzenes in the reaction system is reduced to 1.
It can be produced at a concentration of 0 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 the reaction is complete, simply add water to the reaction mixture from which solids have been removed by filtration, etc., and filter out the precipitated crystals to obtain highly pure 1-benzyloxybenzenes. Alkoxy-4-(substituted)benzyloxybenzenes are obtained in high yield. Therefore, separation and purification after the completion of the reaction is extremely easy.1 For example, after the completion of the reaction, the reaction mixture is neutralized, the salt is filtered off, the reaction mixture is heated to about 60°C, and water is added dropwise to it. , 1-alkoxy with a yield of 90% or more and a purity of 99% or more is obtained by cooling to room temperature with stirring to precipitate crystals.
4-(substituted)benzyloxybenzenes can be produced.

1-alkoxy-4-(W exchanged) thus obtained
Benzyloxybenzenes can be used as highly sensitive thermal paper additives, pharmaceuticals, agricultural chemicals raw materials, etc.

〔Effect of the invention〕

According to the present invention, 1-alkoxy-4-(substituted) benzyloxybenzenes are produced by reacting 4-alkoxyphenols and (substituted) benzyl compounds in an aprotic polar solvent in the presence of a base. As a result, high yield and high purity 1-alkoxy-4-(substituted)
Benzyloxybenzenes can be produced.

〔Example〕

Next, examples of the present invention will be described.

Example 1 13.8 g (0.1 mol) of 4-ethoxyphenol and N,N-dimethylacetamide (hereinafter abbreviated as DMAC) were placed in a 200 mff 14-bottle flask equipped with a stirrer, a thermometer, a condenser, and a dropping funnel.40. 0g
After purging the reaction system with nitrogen, 16.1 g (0.1 mol) of 4-chlorobenzyl chloride was added, and the temperature was heated to 80°C.
After raising the temperature to 4.98% (solid) sodium hydroxide.
4 g (0.11 mol) was added in three portions at 15 minute intervals, and the mixture was further heated and stirred at 80° C. for 3 hours.

Next, after neutralizing by adding 1.7 g of 85% phosphoric acid, the reaction mixture was filtered and the salts were rinsed with DMACl0 mΩ. Combine the filtrate and rinse solution, heat to 60℃, and add 40℃ of water to this.
mfl was added dropwise over 1 hour, and the mixture was cooled to room temperature while stirring. The precipitated crystals were filtered, rinsed with 300 mQ of water, and then dried under reduced pressure to yield 1-nitoxy-4-(4'-chlorobenzyloxy)benzene (hereinafter abbreviated as ECBB) with a purity of 99.4%. 24.2g (yield 91.4
%) obtained.

Examples 2 to 5 The same procedure as in Example 1 was performed except that the solvent shown in Table 1 was used instead of DMAC in Example 1, and the results shown in Table 1 were obtained.

Table 1 Got the results.

Example 6 The procedure of Example 1 was repeated except that 12.6 g (0.1 mol) of benzyl chloride was used instead of 4-chlorobenzyl chloride, and 1-ethoxy-4 with a purity of 99.5% was prepared. -Benzyloxybenzene 21.1g (yield 92.
0%) was obtained.

Examples 7-8 In Example 1, in place of 4-nidoxyphenol, the second
Example 9 shown in Table 2 was carried out in the same manner as in Example 1 except that the phenols shown in the table were used in the amounts shown in Table 2. The same procedure as in Example 1 was carried out except that 0.6 g (0.12 mol) of EC with a purity of 99.6% was used.
824.8 g (yield 94.0%) of B was obtained.

Example 1O 20 equipped with stirrer, thermometer, cooler and feed port
0mff14 4-nitoxyphenol in a flask
After charging 3.8 g (0.1 mol) and DMAC40, Og and purging the reaction system with nitrogen, 4.8 g (0.12 mol) of 98% (solid) sodium hydroxide was added, and the mixture was heated at 70°C.
Then, 16.1 g (0.1 mol) of 4-chlorobenzyl chloride was added dropwise over 1 hour at 70 to 80°C, and the mixture was heated and stirred at 80°C for 2 hours. Thereafter, the same procedure as in Example 1 was carried out, and ECBB with a purity of 99.7% was obtained.
25. Og (yield 94.9%) was obtained.

Claims (1)

[Claims] (1) In an aprotic polar solvent, in the presence of a base, 4-
A method for producing 1-alkoxy-4-(substituted) benzyloxybenzenes, which comprises reacting an alkoxyphenol with a (substituted) benzyl compound.