JPS5840937B2 - Method for producing 2-arylpropionic acid ester - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for producing 2-arylpropionic acid esters useful as organic fine chemical intermediates.

2-Arylpropionic esters are precursors of 2-arylpropionic acids.

There are many compounds in 2-arylpropionic acid that have physiological effects such as anti-inflammatory, analgesic and antipyretic properties, and various derivatives having such physiological effects have also been developed for use.

In addition, methods for synthesizing these derivatives have also attracted attention, and various methods have been developed (e.g., using end materials, weaving methods, chemical industry materials,
13.85 (1978)).

A typical method for synthesizing 2-arylfuropionic acid is, for example, by methylating arylacetonitrile and
There is a method (JP-A-52-111536) in which arylpropionitrile is produced and then hydrolyzed to produce 2-arylpropionic acid derivatives.

However, this method has the disadvantage of using a highly toxic alkali cyanide and has problems with methylation selectivity, making it difficult to implement industrially.

Furthermore, a method has been proposed in which substituted arylethylene is carbonylated with carbon monoxide in the presence of a palladium catalyst, alcohol, or water (Japanese Patent Laid-Open Nos. 52-51338 and 18533-1983).

In this method, the synthesis of the raw material arylethylene is often complicated, and it cannot be said to be suitable for industrial implementation.

Furthermore, a method using arylacetic acid or its ester, which is relatively easy to synthesize, as a raw material has also been developed.

For example, arylacetic acid is metallated with an alkali metal compound, then methylated with a methyl halide, and 2-
Method for synthesizing aryl furopionic acid (JP-A-52-5
3833) Alternatively, a method has been proposed in which aryl acetate is reacted with sodium hydride and ethyl formate to form 2-aryl-2-formylacetate, and then the enol ester is hydrogenated to form 2-arylpropionate. ing.

However, both of these methods have drawbacks such as the use of alkali metal compounds and low product yields, and are problematic in their industrial implementation.

As a result of intensive studies to overcome these drawbacks and develop a method for producing 2-arylpropionate suitable for industrial implementation, the present inventors discovered that aryl acetate, formaldehyde and carbon oxide were The inventors have discovered that diarylpropionic acid esters can be efficiently synthesized by reacting in the presence of a tertiary amine, a small amount of water, and a rhodium catalyst, leading to the completion of the present invention.

That is, the present invention combines an arylacetic acid ester represented by the general formula (in which Ar is an aromatic group and R is an alkyl group having 1 to 6 carbon atoms), formaldehyde, and carbon monoxide into a tertiary amine. The present invention provides a method for producing 2-dipropionate, which is characterized in that the reaction is carried out in the presence of a small amount of water and rhodium trichloride.

The reaction of the present invention proceeds according to the following formula.

In the method of the present invention, typical examples of the aryl group of the arylacetate starting material include phenyl,
Examples include tolyl, isobutylphenyl, tert-, 7" tylphenyl, cyclohexylphenyl, anisyl, m-phenoxyphenyl, naphthyl, 2-(6-methoxy)naphthyl, benzoylphenyl, diphenyl groups, and fluorine- and chlorine-substituted products thereof. .

In the method of the present invention, it is appropriate to use paraformaldehyde as the formaldehyde, and it is used in a molar amount of 1.2 to 6.0 times that of the arylacetic acid ester.

At this time, if the amount of formaldehyde used is small, the selectivity will improve, but the reaction rate will decrease.

One feature of the method of the present invention is that -carbon oxide is used.

The carbon monoxide pressure at this time is in the range of 10 to 200 k(i/ca), particularly preferably in the range of 50 to 100 kg/crA.

The reaction of the present invention proceeds smoothly due to the presence of a tertiary amine.

Examples of tertiary amines include triethylamine, tri-n-butylamine, N-methylpiperidine, N-methylpyrrolidine, and N-methylmorpholine.
-Methylmorpholine is suitable.

In addition, a small amount of water is required for the reaction of the present invention, and is usually used in a molar range of 0.5 to 1.0 times the amount of arylacetic acid ester, but if used in excess, the yield of the target compound will decrease.

The rhodium trichloride used in the process of the invention acts as a catalyst.

The amount used is 0.001 per aryl acetate.
-5% by weight, preferably 0.01-1% by weight.

The reaction of the present invention is usually carried out in the presence of a solvent.

Examples of the solvent include alcohols such as methanol and ethanol, ethers such as diethyl ether, tetrahydrofuran and dioxane, and aromatic hydrocarbons such as benzene and toluene.

In addition, the reaction temperature is 150 to 220°C, preferably 100 to 220°C.
It is determined within the range of 200℃.

As described above, according to the method of the present invention, 2-arylpropionic acid ester can be effectively produced with high selectivity, and the tertiary amine and the main rhodium chloride of the catalyst can be easily recovered and reused, making it suitable for industrial use. It is suitable for implementation.

Next, the present invention will be explained in more detail based on examples.

Note that the selectivity in the examples is the percentage of 2-arylpropionate to the 2-aryl acetate that disappeared.

Example 1 Rhodium trichloride 20μ, methyl phenylacetate 3.0P
(0.05 mol), paraformaldehyde 6.1' (
0.2 mol), water 0.5 ml, N-methylmorpholine 5
A 100 ml stainless steel autoclave was charged with 10 rrLl of methanol and -carbon oxide at room temperature until its pressure reached 100 kg/crA.

Next, the autoclave was heated to 180°C, and at the same temperature
I stirred for hours.

After the reaction was completed, the autoclave was cooled and the product was analyzed by gas chromatography.

The conversion rate of methyl phenylacetate was 79%, and the selectivity of methyl 2-phenylpropionate was 64%.

Examples 2 and 3 The reaction was carried out in the same manner as in Example 1 except that the amount of paraformaldehyde was changed to 3.01 or 1.81.

The results are shown in Table 1 together with Example 1.

Example 4 Reaction time is 20 hours The reaction was carried out in the following manner.

The conversion rate of methyl phenylacetate was 84% and the selectivity of methyl 2-phenylpropionate was 62%, which was the same as in Example 1 except that.

Examples 5 to 8 Reactions were carried out in the same manner as in Example 1, except that the same moles of various aryl methyl acetates shown in Table 2 were used instead of phenylacetate methyl.

The results are shown in the same table.

Claims (1)

[Scope of Claims] 1 An arylacetic acid ester represented by the general formula (in the formula, Ar is an aromatic group and R is an alkyl group having 1 to 6 carbon atoms);
A method for producing a 2-arylpropionic acid ester, which comprises reacting formaldehyde and carbon monoxide in the presence of a tertiary amine, a small amount of water, and rhodium trichloride. 2. The method according to claim 1, wherein the tertiary amine is N-methylmorpholine.