JPS6033414B2 - Method for producing p-methylphenethyl alcohol - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing p-methylphenethyl alcohol from p-tolualdehyde.

More specifically, the present invention involves reacting p-tolualdehyde with carbon monoxide and water to produce p-methylphenylacetic acid;
The present invention relates to a method for producing p-methylphenethyl alcohol by reducing this with hydrogen. Conventionally known methods for producing p-methylphenethyl alcohol include p-methylphenethyl alcohol.
- The so-called Grignard method in which chlortoluene is reacted with magnesium and then ethylene oxide, and the method in which toluene is reacted with ethylene oxide in the presence of a Lewis acid catalyst are known, but in the former,
It requires the use of large amounts of expensive magnesium, and has the disadvantage of being dangerous when carried out industrially.

In the latter case, it is also necessary to use a large amount of expensive aluminum chloride, etc., and the regioselectivity with respect to aromatic moieties is insufficient, making it difficult to avoid the contamination of unnecessary isomers. Under these circumstances, there has been a demand for an industrially advantageous method for producing p-methylphenethyl alcohol, which is useful as an intermediate raw material for pharmaceuticals and agricultural chemicals.

As a result of various studies in order to overcome the above-mentioned drawbacks associated with conventionally known methods, the inventors of the present invention have developed a method that uses inexpensive p-tolualdehyde as a starting material in a relatively short process without using large amounts of reagents. The present invention was achieved by discovering a method for synthesizing pure p-methylphenethyl alcohol with good yield.
That is, in the present invention, p-tolualdehyde is reacted with carbon monoxide and water in the presence of a catalyst consisting of rhodium or a rhodium compound and hydrogen iodide to form p-methylphenylacetic acid, and then p-methylphenylacetic acid is reacted with rhenium or a rhenium compound. A new industrially useful manufacturing method for producing p-methylphenethyl alcohol from p-tolualdehyde, which comprises reacting hydrogen to synthesize p-methylphenethyl alcohol in the presence of a catalyst consisting of a chlorine and an organic base. It provides:

The starting material p-tolualdehyde in the present invention is easily produced from toluene and carbon monoxide according to a known method. (Hydmcar nPrOCeSSI increase Nov
．． 1978P147) A method for producing arylacetic acid from arylaldehyde is described in JP-A-52-13613.
There is an example described in Publication No. 3.

In this method, phenylacetic acid is obtained from benzaldehyde using a mixed gas consisting of carbon monoxide and hydrogen in the presence of a catalyst consisting of rhodium oxide and iodine.

However, the yield of phenylacetic acid is low and large amounts of high boiling products are created.

In addition, Japanese Patent Application Laid-Open No. 53-56633 discloses that carbon monoxide and water are mixed in the presence of a ternary catalyst consisting of a compound of a blood group noble metal of the periodic table, bromine, iodine or a halogen compound thereof, and a copper or silver compound. aryl acetic acid is obtained from aromatic aldehyde. In order to obtain a satisfactory yield with this method, it is necessary to add a copper or silver compound to the system as a third component of the catalyst, which has the disadvantage that handling of the product and catalyst becomes extremely complicated. Moreover, the yield is poor in systems that do not use the third component of the catalyst. In the synthesis of p-methylphenylacetic acid from p-tolualdehyde, we used hydrogen bromide to rhodium or a rhodium compound in a specific molar ratio to achieve the desired goal without adding any copper or silver compounds. We have found that the yield of aryl acetic acid is significantly increased.

That is, the method of the present invention can provide an industrially useful method for efficiently producing p-tolualdehyde and p-methylphenylacetic acid.

Next, the implementation method of this step will be explained in detail. The reaction is carried out in the presence of a catalyst consisting of rhodium or a rhodium compound and hydrogen iodide.

Here, rhodium compounds are rhodium halides,
oxides, oxoacid salts, carbonyl compounds, halogenocarbonyl compounds, nitrates, and other coordination compounds, such as compounds that are lead-bonded to at least one type of ligand such as a halogen atom, carbon monoxide, or a phosphorus compound. be. In principle, these rhodium compounds are known to form carbonyl compounds upon reaction.

Specific examples of preferred rhodium compounds include rhodium trichloride, dirhodium trioxide, rhodium (0) acetate dimer, dirhodium octacarbonyl, tetrarhodium dodetricarbonyl, hexalhodium hexadetricarbonyl, and chloro. carbonyl rhodium (0) dimer, rhodium nitrate,
Trichrome.

Tris (pyridine) rhodium (m), chlorocarbonylbis (triphenylphosphine) rhodium (1), chlorotris (triphenylphosphine) rhodium (1),
Hydridocarponyltris (triphenylphosphine)
Examples include rhodium (1). Among these, rhodium halides are particularly preferred.

These rhodium or rhodium compounds may be used as they are, but they can also be supported on porous substances such as activated carbon, alumina, silica alumina, and diatomaceous earth.

The preferred range of the amount of rhodium or rhodium compound used as a component of the catalyst is from 10-5 to 10-1, more preferably from 10-4 to 5 x 10-2 in molar ratio to p-tolualdehyde. range.

Similar ranges as above regarding the number of gram atoms of the metal when using rhodium. Hydrogen iodide, another component, can generally be used on its own, but in some cases it is also possible to use a compound that can generate hydrogen iodide during the reaction. The preferred range of the amount of hydrogen chloride used is from 1 to 1 in molar ratio to the rhodium compound.
It is 0.

When rhodium is used, the same range as above regarding the number of gram atoms of the metal is used. If the amount of hydrogen iodide used is out of this range, phenomena such as a decrease in the reaction rate and an increase in by-products will be observed. The yield of acetic acid is significantly reduced.

When carrying out the reaction, the components may be prepared outside the system prior to the reaction and then added to the system, or each component may be separately added to the system.

The amount of water as a reactant is in a molar ratio of 1 to 5, preferably 1 to 10, relative to the starting p-tolualdehyde.

The method of the present invention can be carried out without a solvent or in a solvent such as a hydrocarbon such as hexane, cyclohexane, benzene, toluene, or a chlorinated aromatic hydrocarbon such as chlorobenzene.

The reaction is 10%, 30% pressure, preferably 20%,
The test is carried out under a partial pressure of carbon monoxide of 15 p atm.

The carbon monoxide used may be a mixture with an inert gas. The reaction temperature ranges from 50 to 25,000 qo, preferably from 100 to 200 qo.

The reaction time mainly depends on the reaction temperature, but is generally 0.
．． The range is 1 without and 1 field time.

The reaction can be carried out either batchwise or continuously.
In order for the reaction to proceed smoothly, it is important to keep the system sufficiently homogeneous and to maintain it efficiently. Further, in order to prevent contamination of the system by metal compounds eluted from the reactor walls, it is desirable to use a reactor whose inner surface is protected by a glass lining or a corrosion-resistant material.

The generated p-methylphenylacetic acid is separated from the reaction mixture by common operations such as distillation, extraction, and crystallization.

The target p-methylphenethyl alcohol is produced by reducing the p-methylphenylacetic acid thus obtained.

A method known in principle for producing 2-arylethanols from arylacetic acids involves esterifying the arylacetic acids and reacting the ester with hydrogen in the presence of a reducing agent such as a metal hydride or a catalyst such as copper chromite. It is something that gives back.

In order to obtain 2-aryl ethyl according to these methods, it is necessary to use substantially equal moles or more of an expensive reducing agent to the arylacetate, or to use harsh reaction conditions in the presence of a catalyst. However, it cannot be said that this method is industrially advantageous. It is also an extremely uneconomical method in that it includes an extra step of converting into ester. The production of 2-arylevtanol from arylacetic acid in one step is as follows:
This is achieved by reduction with a metal hydride compound such as lithium aluminum hydride in the presence of an ethereal solvent. However, in order to substantially complete the reaction using this method, the amount of expensive metal hydride must be used in an equal or larger amount to the carboxylic acid to be treated, which is uneconomical and requires a large amount of aluminum compound. This involves complicated post-operations such as removal. Further, a catalytic reduction method is described in JP-A-52-136133. In this method, 2-phenylethanol and ethylbenzene are obtained from phenylacetic acid using a molybdenum-sulfur catalyst supported on charcoal.
It is necessary to carry out the reaction under high pressure of hydrogen for a long time. Others include J. ○rg. Chem. 24 1847 (195
When 9) is subjected to hydrogen reduction using a dirhenium heptoxide catalyst without a solvent, 2-phenylethanol and phenylacetic acid 2
- It is stated that a mixture of phenylethyl is obtained. However, according to experimental examples, a large amount of 2-phenylethyl phenylacetate, which is difficult to reduce, is produced as a by-product, and this method also
-This is an unsatisfactory method for producing arylethanol. As a result of various studies, the present inventors found that by coexisting an appropriate amount of an organic base with rhenium or a rhenium compound catalyst (hereinafter referred to as rhenium catalyst), the selectivity from p-methylphenylacetic acid to p-methylphenethyl alcohol was significantly improved. The second step of the method of the present invention was completed.

Next, the implementation method will be explained in detail. Although the reduction reaction can be carried out without using a solvent, it is desirable to use an appropriate solvent in order to carry out the reaction smoothly.

There are no particular restrictions on the solvent used as long as it is inert to the reaction, and organic solvents used in reduction reactions, such as ethers, aromatic hydrocarbons, alicyclic hydrocarbons, aliphatic hydrocarbons, or mixtures thereof can be used. . Specific examples of preferred solvents include dioxane, tetrahydrofuran, diphenyl ether, diglyme, benzene, toluene, and xylene.

The concentration of the raw material p-methylphenylacetic acid in the solvent is 1
It ranges from 5 to 8% by weight, preferably from 5 to 50% by weight.

The rhenium catalyst used in this step is rhenium or a rhenium compound catalyst, and the rhenium compound catalyst is not particularly limited as long as it undergoes a reduction treatment to produce rhenium or a low-valent rhenium oxide.

Examples of preferred rhenium compounds include dirhenium heptoxide,
Rhenium trioxide, rhenium dioxide, rhenium trioxide, rhenium monoxide, perrhenic acid, ammonium perrhenate, potassium perrhenate, dirhenium heptoxide/dioxane rust, dirhenium heptoxide/tetrahydropyran complex Examples include rhenium oxides such as rhenium oxides and their hydrates, oxoacids, oxoacid salts, and organic compound coordination complexes. Among these rhenium compounds, rhenium oxides are preferred, and low-valent rhenium oxides are particularly preferred because of their high catalytic activity.

The above-mentioned low valence state can be easily achieved by thermal decomposition of a high valence nium compound, reduction with a metal or hydrogen, or the like. Specific examples of preferred rhenium catalysts include rhenium, rhenium monoxide, dirhenium monoxide, dirhenium trioxide, rhenium dioxide, rhenium pentoxide, and mixtures thereof.

The rhenium compound catalyst may be used as it is, but it can also be supported on a porous material such as activated carbon, alumina, diatomaceous earth, or zeolite.

In the method of the present invention, if necessary, the reduction treatment of the rhenium compound may be carried out outside or in the system prior to the reaction, but if desired, it may be carried out simultaneously with pressurized hydrogen in the system during the reaction. You can also do it.

The effectiveness of these rhenium catalysts is significantly enhanced by the coexistence of an appropriate amount of an organic base.

That is, when reducing p-methylphenylacetic acid to p-methylphenethyl alcohol, excessive reduction to undesirable ethyl stalks or formation of esters is suppressed, and p-methylphenylacetic acid is reduced to p-methylphenethyl alcohol.
Selectivity to methylphenethyl alcohol is significantly improved. Examples of organic bases of the present invention include a wide range of organic compounds having lone pairs of electrons, including nitrogen, phosphorus, and the like.

Among these, nitrogen-containing compounds such as amine, imine, pyridine, and morpholine, and phosphorus compounds such as phosphine are preferred. Particularly preferred examples of nitrogen-containing compounds are aliphatic amines and aliphatic nitrogen-containing organic compounds that can be easily converted into aliphatic amines by hydrogen reduction, such as tolylamine and tri-n-butylamine.

Examples of preferable phosphorus-containing compounds include triphenylphosphine and tri-n-butylphosphine. The amount of organic base used in the present invention varies depending on the type of base, but generally ranges from 10-4 to 1, preferably from 10-2 to 1 in molar ratio to the rhenium catalyst.

These organic bases can be made to coexist in the system by adding them to the rhenium catalyst in advance prior to the reaction, or by adding them to the system separately from the rhenium catalyst during the reaction.

The reduction reaction is carried out under a hydrogen partial pressure of between 50 and 500 atmospheres, preferably between 80 and 20 atmospheres. The reaction temperature is 80 L, 25, preferably 100, 18
It is in the range of 0°C. The reaction time depends primarily on the reaction temperature, but is generally in the range of 0.1 to 1 mhr.
The reaction can be carried out either batchwise or continuously.
In the case of a batch system, the catalyst can be separated and recovered from the reaction solution by appropriate means such as filtration or sedimentation, and if necessary, can be recycled and used after regeneration treatment. Further, the catalyst can be used in either a fixed bed method or a slurry method. The produced p-methylphenethyl alcohol is separated and obtained from the reaction mixture by common operations such as distillation and extraction. The p-methylphenethyl alcohol produced according to the method of the present invention has high purity and is suitable for use as an intermediate raw material for agricultural chemicals and medicines.

Next, the method of the present invention will be specifically explained with reference to Examples, but the present invention is not limited thereto.

Fixation and quantification of products by IR, NMR and gasc.

By the matographic method. The yield and selectivity of each reaction product are based on the following formulas. Yield = Mitsubishi number X・oo (%) Number of moles of product Selectivity = Number of moles of reacted raw materials x 100 (%) Example
1 Into a 50cc stainless steel electromagnetic autoclave into which a glass intubation tube was inserted, p-tolualdehyde 1.20 hours, water 0.54 hours, rhodium trichloride 44, and 57% hydrogen iodide water 0.126 hours were added. After charging 5' of benzene and sufficiently purging the inside with nitrogen gas, carbon monoxide was pressurized to 5 atm.

Note that the molar ratio of hydrogen iodide to rhodium trichloride was 3.1. After heating at 150:00 for 4 hours, the contents were cooled to room temperature and the contents were analyzed by gas chromatography. The rate is 94.5 respectively.
% and place. It was 9%.

In addition, p-xylene was produced at a yield of 3.5%. Examples 2 to 4 The same operation as in Example 1 was carried out, except that the charging pressure of carbon monoxide was set to 10 atmospheres and the amount of hydrogen iodide charged was changed.

The results are shown in Table 1. Table 1 Example 5 In a 50 cc stainless steel electromagnetic autoclave into which a glass inner tube was inserted, 0.6 parts of p-methylphenylacetic acid, 10 parts of pre-dehydrated dioxane, 60 parts of dirhenium heptoxide, and 4 parts of triethylamine were added. After preparing 3 females and thoroughly purging the inside with nitrogen, hydrogen gas was pressurized until the pressure reached 10 pi atmosphere.

After heating at 160°C for 5 hours, the mixture was cooled to room temperature and the contents were analyzed by gas chromatography. The reaction rate of the charged raw material p-methylphenylacetic acid was 98.5%, p-
The yield and selectivity of methylphenethyl alcohol were 92.4% and 93.8%, respectively.

Furthermore, the yield of p-*ethyltoluene was 0.5%.
Comparative Example 1 The same operation as in Example 5 was performed except that triethylamine was not added. The reaction rate of p-methylphenylacetic acid was 99.2%, and the yield and selectivity of p-methylphenethyl alcohol were respectively 74.3
% and 74.9%. Furthermore, the yield of p-ethyltoluene was 10.2%. Examples 6-9 The procedure was exactly as in Example 5, except that various amounts of organic bases other than triethylamine were used.

The results are shown in Table 2. Table 2 Example 10 p-methylphenylacetic acid for 1 night, triethylamine for 7 days
．． When the same operation as in Example 5 was carried out except that toluene 5 (O) was added in place of dioxane 10 (9) and dioxane 10 (10), the reaction rate of p-methylphenylacetic acid was 98.
．． The yield and selectivity of 1% p-methylphenethyl alcohol were 85.2% and 86.8%, respectively.

Also, p-ethyltoluene, p-methylphenylacetic acid
-The yield of methyl phenethyl ester is 2.3% each.
and 4.7%. Comparative Example 2 The same operation as in Example 10 was carried out except that triethylamine was not added. 3%, the yield and selectivity of p-methylphenethyl alcohol were 73.7% and 7, respectively.
It was 5.0%.

Claims (1)

[Claims] 1. In producing p-methylphenethyl alcohol from p-tolualdehyde, p-tolualdehyde is mixed with rhodium or a rhodium compound and hydrogen iodide in a molar ratio (gram atomic ratio) of 1 to 10 to the rhodium or rhodium compound. After reacting with carbon monoxide and water to produce p-methylphenylacetic acid in the presence of a catalyst consisting of rhenium or a rhenium compound and hydrogen, A method for producing p-methylphenethyl alcohol, which comprises reacting it.