JPS6234745B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a process for preparing arylacetic acid alkyl esters.

More specifically, it is a method for producing an arylacetic acid alkyl ester by reacting an aromatic halogenated methyl compound, carbon monoxide, and alcohol in the presence of a cobalt carbonyl catalyst and a basic reagent. Several methods for producing phenyl acetate using cobalt carbonyl catalysts have been known so far. For example, carbonylation of benzyl halide with Na salt of cobalt hydrocarbonyl provides phenyl acetate (RFHeck et al., J. Amer. Chem.
Soc. vol. 85 (1963) pp. 2779-82). However, in this method, cobalt carbonyl Na
The use of salt is difficult to implement industrially, and the yield of the desired product is extremely low, making it unsatisfactory as a manufacturing method. Phenyl acetate esters can also be produced by carbonylating benzyl halides in the presence of cobalt carbonyl and alkali alcoholates (Japanese Patent Application Laid-open No. 108041/1983). This method requires a very complicated operation because the alkali alcoholate is gradually introduced as the reaction progresses. Furthermore, when the alkali alcoholate and the alcohol used as the solvent are different types, a mixture is produced. Therefore, it cannot be said that it is an industrially advantageous manufacturing method.

An object of the present invention is to provide a method for producing arylacetic acid alkyl esters in high yield and in an easy industrial manner.

As a result of various studies to overcome the above-mentioned drawbacks of conventionally known methods, it has been found that the above object can be achieved by using an appropriate basic reagent.

In other words, various basic reagents have conventionally been used for this reaction, but if a strong base such as an alkali metal alcoholate is introduced into the reaction system at once, a large amount of undesirable ether compounds will be produced as by-products, and the desired alkyl arylacetate This results in a decrease in ester yield. Furthermore, the use of organic nitrogen bases such as pyridine and triethylamine is uneconomical, and also causes an undesirable reaction with the aromatic halogenated methyl compound as a raw material, making it unusable.

However, the present inventors have surprisingly found that when using an alkali metal salt of an inorganic weak acid, especially an alkali metal carbonate, as a basic reagent, the above-mentioned drawbacks are not present and arylacetic acid alkyl esters can be obtained in high yields. They discovered this and completed the present invention.

That is, the present invention relates to a method for producing an arylacetic acid alkyl ester by reacting an aromatic halogenated methyl compound, carbon monoxide, and an alcohol in the presence of a cobalt carbonyl catalyst and a basic reagent, in which an inorganic weak acid is used as the basic reagent. The purpose of the present invention is to provide an industrially useful manufacturing method for obtaining arylacetic acid alkyl esters in high yield by using an alkali metal salt of.

Next, a method of implementing the present invention will be explained in detail.

The aromatic halogenated methyl compound as a raw material is a fused cyclic or non-fused cyclic aromatic compound having one or more CH ₂ X (X represents a halogen atom) atomic group. These contain one or more other substituents on the aromatic ring, such as alkyl groups having 1 to 6 carbon atoms, alkoxyl groups having 1 to 6 carbon atoms, halogen atoms such as fluorine, chlorine, etc. You can stay there.

Preferred aromatic halogenated methyl compounds have the general formula [In the formula, X represents a halogen atom, R ₁ and R ₂
are the same or different substituents and represent a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, an alkoxyl group having 1 to 6 carbon atoms, or a halogen atom. ] It is an unsubstituted or substituted benzyl halide represented by the following.

Among these, unsubstituted or substituted benzyl chloride is particularly preferred, and specific examples include benzyl chloride, p-chlorobenzyl chloride, p-methylbenzyl chloride, p-methoxybenzyl chloride, and 2,4-dimethylbenzyl chloride. It will be done.

Alkali metal salts of inorganic weak acids used as basic reagents include alkali metal carbonates, bicarbonates, phosphates, silicates or borates. In addition, sodium and potassium are preferable as alkali metals. Among these salts, carbonates are preferably used, more preferably sodium carbonate.

The basic reagents mentioned above are added all at once at the beginning of the reaction. Usually, the amount thereof is equimolar to the aromatic halogenated methyl compound or is used in a very small excess.

As the alcohol, lower alcohols having 1 to 6 carbon atoms, especially methanol and ethanol are preferred.

The amount thereof is at least 1 mole per mole of the aromatic halogenated methyl compound, but it is usually used in excess as a solvent.

Catalysts include well-known cobalt carbonyl catalysts used in conventional carbonylation reactions and hydroformylation reactions, i.e. cobalt carbonyl catalysts with the formula H [Co(CO) ₄ ], M ⁿ [Co(CO) ₄ ] _o (M ⁿ is an n-valent metal), [Co ₂ (Co) ₅ CH ₃ OH], [Co(CO)I ₂ ] _o , [Co ₂ (CO) ₆ Un], etc. are used. These cobalt compounds substantially form an anion of cobalt carbonyl, such as an alkali metal salt of cobalt carbonyl, in the reaction system due to the action of the coexisting basic agent.

In the process of the invention, for example, an alkali metal salt of tetracarbonyl cobalt is formed very easily in the presence of the alcohol and base used in each case without any separate prior synthesis.

The molar ratio of cobalt carbonyl catalyst to aromatic methyl halide compound ranges from 1:1 to 1:1000, preferably from 1:10 to 1:500.

The cobalt carbonyl catalyst can be used by dissolving it in a suitable solvent. In this case, preference is given to using the alcohols which take part in the respective reaction.

The reaction is carried out at a temperature range of 10-150°C, preferably 30-90°C.

The reaction time varies depending on the temperature and pressure selected, but is generally 1 to 20 hours.

The partial pressure of carbon monoxide is between 0.1 and 150 atm, preferably
Perform at 0.1 to 5 atm. At this time, an inert gas for the reaction, such as N ₂ , Ar, He, CO ₂ , etc. or
May contain _H2 .

Further, the reaction proceeds smoothly in the presence of an alcohol and a basic reagent while the cobalt carbonyl solution is well mixed with the aromatic halogenated methyl compound and carbon monoxide.

The reaction product can be easily removed by distillation after filtering out the solid components.

Phenyl acetate obtained according to the reaction production method is used as a base material for fragrances, but is also an important intermediate product for agricultural chemicals, medicines, etc.

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

All products were identified and quantified by gas chromatography.

The conversion rate, yield, and selectivity of each reaction product are based on the following formulas.

Conversion rate = Number of moles of reacted aromatic halogenated methyl compound/Number of moles of introduced aromatic halogenated methyl compound x 100 (%) Yield = Number of moles of arylacetate produced/Introduced aromatic methyl halide Number of moles of compound ×
100 (%) Selectivity = Number of moles of produced arylacetic acid alkyl ester / Number of moles of reacted aromatic halogenated methyl compound x 100 (%) Example 1 50 c.c. equipped with a stirrer, thermometer and water cooling device 20c.c. of methanol in a flask under a carbon monoxide atmosphere,
1.1g of Na ₂ CO ₃ and 0.034g of CO ₂ (CO) ₈ were introduced.
Stirred at 30°C for 15 minutes.

Benzyl chloride while keeping the temperature between 55-60℃.
1.25 g (10 mmol) was added and reacted for 1.5 hours under a CO head.

After cooling the reaction solution, analysis showed that the conversion rate of benzyl chloride was 91.2% and the yield of methyl phenyl acetate was
The response rate was 90.3% (selection rate 99.0%).

Example 2 In a reactor similar to Example 1, under a carbon monoxide atmosphere,
Methanol 20 c.c., Na ₂ CO ₃ 1.1 g and Co ₂
0.034 g of (CO) ₈ was introduced and stirred at 30° C. for 15 minutes.

While maintaining the temperature at 55 to 60°C, 1.4 g (10 mmol) of p-methylbenzyl chloride was added and reacted for 4 hours under a CO head.

After cooling the reaction solution, analysis revealed that the conversion rate of p-methylbenzyl chloride was 98.7%, while the yield of methyl p-methylphenylacetate was 94.4% (selectivity
95.6%).

Example 3 In a reactor similar to Example 1, 20 c.c. of ethanol, 1.1 g of NaOC ₃ and Co ₂ were placed in a carbon monoxide atmosphere.
0.068 g of (CO) ₈ was added and stirred at 0°C for 30 minutes.

While maintaining the temperature at 55 to 60°C, 1.4 g (10 mmol) of p-methylbenzyl chloride was added and reacted for 6 hours under a CO head.

As a result of analysis after cooling the reaction solution, the conversion rate of p-methylbenzyl chloride was 95.4%, while the yield of ethyl p-methylphenylacetate was 90.0% (selectivity 94.3).
%).

Example 4 In a reactor similar to Example 1, 20 c.c. of methanol, 4.0 g of K ₂ CO ₃ and Co ₂ were added under a carbon monoxide atmosphere.
0.22 g of (CO) ₈ was added and stirred at 30°C for 15 minutes. Add 3.37 g (24 mmol) of p-methylbenzyl chloride while maintaining the temperature at 55-60°C, and add 3.37 g (24 mmol) of p-methylbenzyl chloride,
Allowed time to react.

After cooling the reaction solution, analysis showed that the conversion rate of p-methylbenzylchloride was 99.1%, while the yield of methyl p-methylphenylacetate was 88.3% (selectivity 89.1).
%), and p-methylbenzyl methyl ether was obtained as a by-product in a yield of 77.4%.

Example 5 500c.c. equipped with stirrer, thermometer and water cooler.
200 methanol in a flask under carbon monoxide atmosphere
cc, 18 g of Na ₂ CO ₃ and 0.31 g of Co ₂ (CO) ₈ were added, and the mixture was stirred at 30° C. for 30 minutes.

While maintaining the temperature at 55-60° C., 20 g of p-methylbenzyl chloride was fed over 3 hours, and the reaction was then continued for an additional 2 hours.

The reaction solution was cooled and analyzed, and the conversion rate of p-methylbenzyl chloride was 99.0%, while the yield of methyl p-methylphenylacetate was 92.8% (selectivity 93.6).
%).

After removing solid components from the reaction solution, p-
Methyl phenylacetate 18.8g (purity 99.1%)
was gotten.

Example 6 In a reactor similar to Example 1, 20 c.c. of methanol, 1.0 g of NaHCO ₃ and Co ₂ were added under a carbon monoxide atmosphere.
0.034 g of (CO) ₈ was added and stirred at 30°C for 15 minutes.

While maintaining the temperature at 55 to 60°C, 1.4 g (10 mmol) of p-methylbenzyl chloride was added and reacted for 6 hours under a CO head.

After cooling the reaction solution, analysis revealed that the conversion rate of p-methylbenzyl chloride was 75.4%, while the yield of methyl p-methylphenylacetate was 62.9% (selectivity
83.4%), and the yield of p-methylbenzyl methyl ether was 10.4%.

Example 7 In a reactor similar to Example 1, 20 c.c. of methanol, 1.1 g of Na ₂ CO ₃ and Co ₂ were added under a carbon monoxide atmosphere.
0.034 g of (CO) ₈ was introduced and stirred at 30°C for 15 minutes. 1.69 g of benzyl bromide while maintaining the temperature between 55 and 60°C.
(10 mmol) was added and reacted for 2 hours.

After cooling the reaction solution, analysis showed that the conversion rate of benzyl bromide was 85.3% and the yield of methyl phenyl acetate was 75.0.
% (selectivity rate was 87.9%).

Comparative Example 1 In a reactor similar to Example 1, 20 c.c. of methanol, 0.54 g of NaOCH ₃ and Co ₂ were placed in a carbon monoxide atmosphere.
0.058 g of (CO) ₈ was added and stirred at 30°C for 15 minutes.

The temperature was maintained at 55-60°C, 1.4 g (10 mmol) of p-methylbenzyl chloride was added, and the mixture was reacted for 6 hours under a CO head.

After cooling the reaction solution, analysis revealed that the conversion rate of p-methylbenzyl chloride was 88.6%, while the yield of methyl p-methylphenylacetate was 33.8% (selectivity
38.1%), and the yield of p-methylbenzyl methyl ether was 28.2%.

Comparative Example 2 In a reactor similar to Example 1, 20 c.c. of methanol, 1.0 g of (C ₂ H ₅ ) ₃ N and Co ₂ were added in a carbon monoxide atmosphere.
0.034 g of (CO) ₈ was added and stirred at 30°C for 15 minutes.

While maintaining the temperature at 55 to 60°C, 1.4 g (10 mmol) of p-methylbenzyl chloride was added, and the mixture was reacted for 2 hours under a CO head.

After cooling the reaction solution, analysis revealed that the conversion rate of p-methylbenzyl chloride was 68.0%, while the yield of methyl p-methylphenylacetate was 40.1% (selectivity
59.0%).

Claims (1)

[Claims] 1. A method for producing an arylacetic acid alkyl ester by reacting an aromatic halogenated methyl compound, carbon monoxide, and alcohol in the presence of a cobalt carbonyl catalyst and a basic reagent, in which an alkali metal salt of an inorganic weak acid is used as the basic reagent. 1. A method for producing an arylacetic acid alkyl ester, characterized in that the basic reagent is introduced all at once before the start of the reaction.