JPS63192883A - Production of m-substituted benzyl alcohol - Google Patents

Abstract

PURPOSE:To produce specified m-substd. benzyl alcohol with high current efficiency in a high yield by electrolytically reducing a specified benzoic acid deriv. with a highly acidic aq. soln. as a catholyte and a specified amt. of quat. ammonium salts. CONSTITUTION:An m-substd. benzoic acid deriv. represented by general formula I (where R<1> is phenyl or lower alkyl which may be substd. by halogen and R<2> is H or alkyl) is electrolytically reduced with a highly acidic aq. soln. as a catholyte and 3-60wt.% quat. ammonium salts represented by formula III (where each of R1-R4 is lower alkyl and X is a residue of p-toluenesulfonic acid, sulfuric acid, hydrochloric acid or oxalic acid) based on the amt. of the highly acidic aq. soln. An aq. soln. contg. about 10-70wt.% sulfuric acid or the like and adjusted to <=1 pH is suitable for use as the highly acidic aq. soln. By the reduction, m-substd. benzyl alcohol represented by general formula II is obtd. with high current efficiency in a high yield.

Description

[Detailed description of the invention] Meaning! The present invention relates to a method for producing m-substituted benzyl alcohol.

More specifically, the present invention provides the general formula (2) by an electrolytic reduction method.
) (In the formula, R1 represents a phenyl group or an alkyl group which may be substituted with a halogen atom.)
-phenoxybenzyl alcohols according to the corresponding general formula (1) (R' is the same as R1 in the general formula (2), and Rt is -
The present invention relates to a novel synthetic method for obtaining a m-substituted benzoic acid derivative represented by H1 or an alkyl group in good yield.

The m-H substituted benzyl alcohol represented by the above formula (2) is a compound useful as an intermediate for medicines, agricultural chemicals, and industrial chemicals.

The conventional method for producing m-phenoxybenzyl alcohol, for example, expressed by formula (2), is to halogenate m-phenoxytoluene and then hydrolyze it. However, in this method, if the conversion rate of halogenation is increased, the selectivity decreases.In other words, in industrial practice where the conversion rate is maintained, the production of by-products cannot be avoided.
It is necessary to separate and purify it.

Furthermore, the next step of hydrolysis is also complicated. Furthermore, a method of hydrogenating alkyl m-phenoxybenzoate has been proposed (Japanese Patent Application Laid-Open No. 60-214753), but the reaction is carried out under pressure in a high-temperature oven, and there are various problems with the industrial production method.

Methods using electrolytic reduction are also known, and a method has been proposed in which m-phenoxybenzoic acid is electrolytically reduced in an acidic aqueous solution containing ethanol to obtain m-phenoxybenzyl alcohol (Synthetic Comunication 5ynthe
tic Co+w+wunication, 11(6)
.

439 (1981), but there is no description of substrates, concentrations, current efficiency, etc., which are important factors in industrializing electrolytic reduction reactions.

When the present inventors tried this method again, it was found that in order to obtain m-phenoxybenzyl alcohol in a good yield, it was necessary to apply a large amount of electricity, and the current efficiency was low (
(See Comparative Example 2).

Furthermore, the above-mentioned literature describes m- other than m-phenoxybenzoic acid.
There is no description whatsoever regarding the electrolytic reduction of alkoxybenzoic acids, and when the present inventors carried out an electrolytic reduction reaction in accordance with the reaction conditions of the above-mentioned document, the current efficiency was similarly low.

Furthermore, in JP-A-60-234987, a metal material with high hydrogen overvoltage is used as a cathode, and m-hydroxybenzoic acid is Alternatively, a method for producing m-hydroxybenzyl alcohol by electrolytically reducing an ester of m-hydroxybenzoic acid has been disclosed. However, even when this method was applied to the present invention, the current efficiency was poor as in the above-mentioned literature.

That is, the electrolytic reduction reaction of m-alkoxybenzoic acid of the present invention is completely different from the electrolysis of m-hydroxybenzoic acid, and it was necessary to newly design reaction conditions.

For example, in the method of JP-A-60-234987, m
-Hydroxybenzoic acid has low solubility in water, but
Since m-hydroxyhensyl alcohol, which is sequentially produced in the reaction, exhibits high solubility in water, a quaternary ammonium salt is not necessarily required since mutual solubility with water can be utilized; however, in the electrolytic reaction of the present invention, target compound m
-Hydroxy compounds to the formulas (1) and (2) of the present invention
It has been found that when the m-alkoxy compounds shown in the following are used, the solubility in water of both becomes extremely poor, and the reaction does not proceed well.

The present inventors conducted intensive studies to solve the above problems, and found that if electrolytic reduction is carried out in a strongly acidic aqueous solution with a specific amount of quaternary ammonium salt coexisting, the reaction current will be reduced. They discovered that the efficiency was dramatically improved and completed the present invention.

That is, in the electrolytic reduction of the m-substituted benzoic acid derivative represented by the general formula (1) of the present invention, a diaphragm is usually provided in the center:
: An electrolytic layer consisting of an anode chamber and a cathode chamber is used, and the reaction is carried out in the cathode chamber. In this case, the present invention uses a quaternary ammonium salt in a strongly acidic aqueous solution as a catholyte at a concentration of 3 to 6
This is a method for producing m-substituted benzyl alcohol, in which electrolysis is carried out in the coexistence of 1%, preferably 5 to 30% by weight of m-substituted benzyl alcohol.

In the present invention, the acidic substance added to make the strong aqueous solution is not particularly limited as long as it is inert to the electrolytic reaction at the cathode, but from the viewpoint of cost, sulfuric acid, hydrochloric acid, etc. are usually used. Preferably, mineral acids are used. The concentration of the acidic aqueous solution is 10 to 10 M%, and is strongly acidic, preferably adjusted to below Pill level. P) Below 11,
Current efficiency deteriorates considerably.

In the present invention, a water-soluble organic solvent may be added to the strong acid water and used as a mixing medium.

Furthermore, as the quaternary ammonium salt used in the method of the present invention,
It is represented by the general formula (wherein R+, Rx, R3+ R4 are lower alkyl groups, and X represents a residue of pt-toluenesulfonic acid, sulfuric acid, hydrochloric acid or hydrobromic acid), and these Examples of ammonium salts include tetraethylammonium P-) toluenesulfonate, tetramethylammonium P-toluenesulfonate, tetrapropylammonium p-toluenesulfonate, tetrabutylammonium p-toluenesulfonate, and sulfuric acid in place of these P-)toluenesulfonates. Examples include salt, hydrochloride, and bromate. These salts have a concentration of 3 to 60% of the acidic water used.
Use % by weight.

If the amount used is less than 3% by weight, the reaction will be slow and the current efficiency will not be sufficient, and if the amount used is more than 60% by weight, the reaction liquid will increase in viscosity and become difficult to handle.

In addition, in the method of the present invention, the compounds represented by -M formula (2) include m-methoxybenzyl alcohol, m-ethoxybenzyl alcohol, m-phenoxybenzyl alcohol, m-(3-chloro)phenoxybenzyl alcohol, m-( Examples include 4-chloro)phenoxybenzyl alcohol.

Water-soluble solvents that can coexist with strong acids include alcohols such as methanol, ethanol, propatool, and buknol, acetonitrile, N, JJ'-dimethylimidazolidinone, N, N'-dimethylformamide, N-
Examples include methyl-2-pyrrolidone and sulfolane.

In the method of the present invention, the electrolytic reduction reaction is carried out at a temperature range of 20 to 70°C. In addition, among the electrodes used for electrolysis, the cathode material is one with a high hydrogen overvoltage, specifically zinc, lead,
Uses cadmium and mercury. The anode, on the other hand, is not particularly limited as long as it is made of a normal electrode material.

As the material of the diaphragm, ion exchange membrane, asbestos, salamix, cinder glass, etc. can be used.

Further, in the reaction, if a surfactant, an antifoaming agent, etc. are used in combination, the current efficiency is further improved.

In the electrolytic reduction of the present invention, the current density is preferably 1 to
30^/drrf. Theoretically, it is a 4-electron reduction and the amount of current is 4 Fr/mole, but the current efficiency is 4
Since it is 0 to 60%, it takes 6 to 8 F to complete the reaction.
There is an electric furnace that runs the r/mole electric spear.

EXAMPLES The method of the present invention will now be explained in detail with reference to Examples. Hereinafter, "%" indicates weight %.

Example 1 Both electrode chambers had a capacity of 300,111 cm, and 50 cm was used as a cathode in an H-type electrolytic cell separated by Selemion CMV (cation exchange membrane, trade name of Asahi Glass Co., Ltd.) as a diaphragm.
A platinum plate of 50 cd was attached as the anode.

10% sulfuric acid water (200 sN) was charged in both the anode and cathode chambers, and tetraethylammonium P-) was added in the cathode chamber.
20g of luenesulfonate was charged.

While maintaining the electrolytic cell at 40° C., 5 g of m-methoxybenzoic acid methyl ester was added to the cathode chamber, and a constant DC current of 3 A was applied for 100 minutes (6.2 Fr 1 mol).

After the electrolysis was completed, the catholyte was taken out and extracted with ether.

The ether layer is high performance liquid chromatography () IPLC.
) Analysis showed that the conversion rate of m-methoxybenzoic acid methyl ester was 95% and the yield of m-methoxybenzyl alcohol was 93%.

Next, after distilling off the ether solvent, the residue was purified with a silica gel column, and m-methoxybenzyl alcohol was obtained by 3.0% m-methoxybenzyl alcohol.
82 g (isolated yield 92%) was obtained (current efficiency 61
%).

Example 2 20 ml of 15% sulfuric acid water was placed in the anode chamber of the same reactor as in Example 1.
0rI11 is charged, and 150 Jt of 30% sulfuric acid water is placed in the cathode chamber.
j! and 50 g of acetonitrile, and further 20 g of tetramethylammonium sulfate.

While keeping the electrolytic cell at 40°C, 5g of m-(3-chloro)phenoxybenzoic acid was added and a DC current of 2.5A was applied to the cell at 100°C.
Electricity was applied for a minute (7.5Fr 1 mol).

After the electrolysis was completed, the same post-treatment as in Example 1 was performed, and IIPLc analysis of the ether layer showed that the conversion rate of m-(3-chloro)phenoxybenzoic acid was 99%, and the conversion rate of m-(3-chloro)phenoxybenzoic acid was 99%.
The yield of phenoxybenzyl alcohol was 94%. After distilling off the ether solvent, further purification with a silica gel column yielded 4.3 g (isolated yield: 92%) of m-(3-chloro)phenoxybenzyl alcohol (with a flow rate of 5).
3%).

Example 3 In the anode chamber of the same reactor as in Example 1, 15% sulfuric acid water was charged, and in the cathode chamber, 100 d of 30% sulfuric acid water and 1 d of methanol were charged.
0 (I prepared ld.

m-ethoxybenzoic acid 5 while keeping the electrolytic cell at 50°C.
g was added and a 3A direct current was applied for 120 minutes (7.
5Fr1 mole).

After the electrolysis was completed, the catholyte was extracted with ether. From the IPLC analysis of the ether layer, the conversion rate of m-ethoxybenzoic acid was 9.
7%, yield of m-ethoxybenzyl alcohol is 91%
Met.

After further distilling off the ether solvent, the residue was purified using a silica gel column, and m-ethoxybenzyl alcohol was
．． 2g (isolated yield 92%) was obtained (current effect 52%).
).

Example 4 Distearyldimethylammonium chloride (surfactant Cortamine 24P, Kao product) was added to the cathode chamber.
The same reaction as in Example 1 was carried out except that 2 g and 0.01 g of Tomu Silicone 5R-200 (Toshi product) were further added.

After the electrolysis was completed, the catholyte was extracted with ether. H of the ether layer
PLC analysis showed that the conversion rate of m-methoxybenzoic acid methyl ester was 98% and the yield of m-methoxybenzyl alcohol was 94%.

Next, after distilling off the ether solvent, the residue was purified using a silica gel column, and m-methoxybenzyl alcohol was obtained by 3.0% m-methoxybenzyl alcohol.
90 g (isolated yield 94%) was obtained (current efficiency 63
%).

Example 5.6 and Comparative Example 1.2.3 10% sulfuric acid water 2 was placed in the anode chamber of the same reactor as in Example 1.
00d was charged, and the electrolytic reduction reaction of m-phenoxybenzoic acid was attempted by changing the catholyte.

That is, while maintaining the electrolytic cell at 40° C., a constant LA DC current was applied. 5g of m-phenoxybenzoic acid in the cathode chamber
was slowly added over 4 hours, and then electricity was applied for another 1 hour (total 5 hours, 1 mol of 8.0Fr).

After electrolysis, the catholyte is extracted and extracted with ether) IPL
Analyzed at c. The results are shown in the table.

As is clear from the results of Examples and Comparative Examples, general formula (1)
In the production of meta-substituted hensyl alcohol represented by the general formula (2), which is reacted by electrolytic reduction of the meta-substituted benzoic acid derivative represented by Meta-substituted hensyl alcohol can be obtained with high current efficiency and high yield.

As described above, the present invention is extremely valuable industrially.

Claims (2)

[Claims] (1) General formula (1) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (1) (In the formula, R^1 is a phenyl group or a lower alkyl group that may be substituted with a halogen atom, and R^ 2 represents a hydrogen atom or an alkyl group.) A benzoic acid derivative represented by the general formula (2) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(2) (In the formula, R^1 is the formula ( 1) When obtaining the m-substituted benzyl alcohol shown by % of m-substituted benzyl alcohol. ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R_1 to R_4 are lower alkyl groups, and X represents a residue of p-toluenesulfonic acid, sulfuric acid, hydrochloric acid, or hydrobromic acid.) (2) The method according to claim (1), wherein the strongly acidic aqueous solution has a pH of 1 or less.