JPS649306B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to α-phenylpropionate esters useful as intermediates for pharmaceuticals, agricultural chemicals, and dyes, and α-phenylpropionic acid esters obtained by subjecting the same to hydrolysis as necessary.
The present invention relates to a method for producing phenylpropionic acid.

Conventionally, various methods have been proposed for producing α-phenylpropionic acid and its esters. All of these methods have disadvantages of requiring multiple steps and expensive raw materials, and cannot be said to be economical methods. For example, in Japanese Patent Publication No. 40-7491, alkyl phenyl acetates are reacted with alkyl carbonates and metal alcoholates to form romanic acid esters, the active methylene group is then methylated with methyl iodide, and then hydrolyzed and decarboxylated. A manufacturing method has been proposed. This method requires multiple steps and has the disadvantage of using expensive alkyl carbonate and methyl iodide.

JP-A-51-95035 proposes a method in which alkyl acetophenone is treated with sodium cyanide or potassium cyanide and hydrochloric acid, then hydrolyzed with caustic alkali, and then reduced.
This method has drawbacks such as requiring multiple steps and using sodium cyanide or potassium cyanide, which are often dangerous to handle.

Furthermore, JP-A-54-27533 proposes a method for producing α-phenylpropionic acid and its ester by reacting benzene with tosylate of lactic acid or tosylate of lactic acid ester.
This method has relatively short steps among various methods and is considered to be an economical method, but still
-Toluenesulfonyl chloride is relatively expensive, difficult to obtain, and completely unnecessary P.
-It has the disadvantage of producing toluenesulfonic acid as a by-product.

The present inventors have conducted intensive research on an economical industrial production method for α-phenylpropionic acid and its ester in order to solve the various drawbacks of conventional methods. As a result, as shown in formula (1), benzene and The present invention was achieved by discovering that α-phenylpropionate is produced when sulfonyloxypropionate is reacted, preferably in the presence of a Lewis acid.

Here, R in formula (1) represents an alkyl group.

The purpose of the present invention is to provide a method for easily and inexpensively producing α-phenylpropionic acid ester, and the gist thereof is to provide a method for producing α-phenylpropionic acid ester easily and inexpensively. α-, which is characterized by reacting with
This is a method for producing phenylpropionate esters. More specifically, we use inexpensive and easily available raw materials to produce high-yield α-
A method for obtaining phenylpropionate esters is provided.

The α-chlorosulfonyloxypropionic ester of the present invention is generally synthesized from a lactic acid ester and sulfuryl chloride by a known method. This α-chlorosulfonyloxypropionate ester can be isolated by methods such as distillation, but in carrying out the present invention, it is not necessary to use isolated and purified α-chlorosulfonyloxypropionate.
-Chlorsulnyloxypropionate is not necessary, and the reaction product of lactic acid ester and sulfuryl chloride can be used as is. For example, a reaction mixture obtained by adding sulfuryl chloride to a lactic acid ester at room temperature, or when an excess of sulfuryl chloride is further added, the residual liquid obtained by distilling off the excess sulfuryl chloride under reduced pressure can be directly used in the present invention. It can be used for. As the lactic acid ester, in addition to lower alkyl esters such as methyl, ethyl, and propyl, higher alkyl esters are also used.

The reaction of the invention is preferably carried out in the presence of a Lewis acid. As the Lewis acid, aluminum chloride, zinc chloride, iron chloride, tin chloride, boron trifluoride, etc. are used, and aluminum chloride is especially used because it is easily available and relatively inexpensive. There are many.

Although a solvent is not necessarily required for this reaction, any solvent can be used as long as it is inert to this reaction. In particular, the present invention can be carried out advantageously by using benzene, which is a reaction reagent, in a slight excess and using this as a solvent.

In order to carry out the method of the present invention smoothly, for example, aluminum chloride is suspended in benzene,
Preferably, this is carried out by gradually adding α-chlorosulfonyloxypropionic acid ester at a temperature of 0 to 30° C. under stirring, and then maintaining this temperature for an additional 0.5 to 3 hours.

In addition, the molar ratio of Lewis acid to this α-chlorosulfonyloxypropionate is 0.2
A range of 10 to 10 is appropriate, but more preferably 1
Good results can be obtained when the value is in the range of 5 to 5.

After the reaction is complete, the reaction product is poured into an appropriate amount of ice water to separate the organic layer from the aqueous layer, which is then repeatedly washed with water. After distilling off benzene from the organic layer, it is rectified under reduced pressure to obtain high purity. α-phenylpropionate can be obtained with a yield of over 85%. The aqueous layer contains hydrochloric acid, sulfuric acid, and aluminum chloride, and can be rendered harmless only by neutralization.

The conventional method using benzene and lactic acid ester-P-tosylate described in JP-A-54-27533 uses pyridine as a catalyst and solvent, making post-treatment difficult and requiring a long reaction time. The synthesis of α-tosyloxypropionate is difficult, the reaction time is long,
However, the raw materials used in the present invention are lactic acid ester,
It is a cheap and easy-to-handle raw material such as sulfuryl chloride, aluminum chloride, and benzene. This is due to the fact that no solvent is required, no post-treatment is required, etc. Furthermore, as α-chlorosulfonyloxypropionate, a reaction mixture of lactic acid ester and sulfuryl chloride can be used as it is, and for the reaction between chlorosulfate and benzene, benzene itself can be used as a solvent; In addition, it does not require special reaction conditions, the reaction temperature is room temperature, the reaction time is short, the separation and purification of the target product is easy, and P-toluenesulfonic acid etc. The present invention can be said to be an industrially advantageous method, as it has many advantages such as simple processing since there are no unnecessary substances.

Next, the present invention will be specifically explained with reference to Examples. However, the present invention is not limited to this example.

Example 1 Production of methyl α-phenylpropionate 52.1 g (0.5 mol) of methyl lactate was placed in a flask equipped with a stirrer, a thermometer, and a dropping funnel, and the temperature was maintained at 0 to 5°C. 101.2 g (0.75 mol) of sulfuryl chloride was added over a period of 1 hour. After further stirring at 10 to 20°C for 2 hours, by-product hydrogen chloride and excess sulfuryl chloride were distilled off under reduced pressure.
Methyl α-chlorosulfonyloxypropionate was obtained at 71°C/2mmHg. Yield 60.1g Yield 59.4%
(vs. methyl lactate).

Then add 93.7g of benzene to the same flask as above.
(1.2 mol) and anhydrous aluminum chloride 80.0 g (0.6
mol), stir, and add the purified α-
Methyl chlorsulfonyloxypropionate
40.5 g (0.2 mol) was added over 1 hour at a liquid temperature of 10 to 15°C.

The reaction was further stirred at 10 to 25°C for 2 hours to complete the reaction.

The reaction product was discharged into 200 g of ice water, stirred well and allowed to stand. The organic layer was separated and thoroughly washed with water.
After adding anhydrous sulfur salt and drying, distillation is performed to first recover excess benzene, then reduce the boiling point to 55-56℃/
Methyl α-phenylpropionate was obtained as a fraction at 11.5 mmHg. The yield was 28.1g, and the yield was 85.6%. (vs. methyl α-chlorosulfonyloxypropionate).

Example 2 In the same manner as in Example 1, 52.1 g (0.5
mol) and 74.2 g (0.55 mol) of sulfuryl chloride were reacted to obtain 101.0 g of a reaction product containing about 80% of methyl α-chlorosulfonyloxypropionate.

Next, in Example 1, purified methyl α-chlorosulfonyloxypropionate 40.5 g (0.2 mol)
The reaction and treatment were carried out in the same manner as in Example 1, except that 40.6 g of the reaction product containing methyl α-chlorosulfonyloxypropionate was used instead of using methyl α-chlorosulfonyloxypropionate.

The yield was 19.8g, 60.1% (based on methyl lactate).

Example 3 Production of ethyl α-phenylpropionate The reaction and post-treatment were carried out in the same manner as in Example 2, except that 59.1 g (0.5 mol) of ethyl lactate was used instead of 52.1 g of methyl lactate in Example 1. , ethyl α-chlorosulfonyloxypropionate having a boiling point of 90-92°C/2 mmHg was obtained.

Yield 62.3g, yield 57.5% (based on ethyl lactate). Next, instead of using 40.5 g of methyl α-chlorosulfonyloxypropionate in Example 1, α
-Ethyl chlorsulfonyloxypropionate
The reaction and post-treatment were carried out in the same manner as in Example 2, except that 43.3 g (0.2 mol) was used, and the boiling point was 69-70.
℃/2mmHg ethyl α-phenylpropionate was obtained. The yield was 30.7 g, yield 86.0% (based on ethyl α-chlorosulfonyloxypropionate).

Claims (1)

[Scope of Claims] 1. A method for producing α-phenylpropionic esters, which comprises reacting benzene with α-chlorosulfonyloxypropionic esters. 2. The method according to claim 1, in which a reaction product of a lactic acid ester and sulfuryl chloride is used as the α-chlorosulfonyloxypropionate ester without isolation.