JPS588045A - Preparation of alpha-phenylpropionic ester - Google Patents

Abstract

PURPOSE:To obtain the titled compound useful as an intermediate for medicines, etc. under mild conditions in high yield and purity in a short step, by reacting an inexpensive and easily available raw material benzene with an alpha-chlorosulfonyloxypropionic ester. CONSTITUTION:Benzene is reacted with an alpha-chlorosulfonyloxypropionic ester of formulaI(R is alkyl) to give a compound of formula II. The reaction is preferably carried out in the presence of a Lewis acid, e.g. aluminum chloride, and the product obtained by reacting a lactic ester with sulfuryl chloride can be used as the compound of formulaIwithout isolation. The use of benzene in a little excess as a reaction solvent permits the advantageous progress of the reaction. The method is industrially advantageous from the following reasons: The reaction can be carried out at ordinary temperature, and the separation and purification of the aimed substance are easily carried. No by-product is formed, and the waste water is simply treated.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to analogs of α-phenylpro and onic acid esters useful as intermediates for pharmaceuticals, agricultural chemicals, and dyes, and α-phenylpropion obtained by subjecting them to hydrolysis as necessary. This invention relates to a method for producing acid.

Conventionally, various methods have been proposed for producing a-phenylpropionic acid and its esters. these are,
All of these methods have the drawbacks of requiring multiple steps and expensive raw materials, and cannot be said to be economical methods. For example, Tokuko Sho 40-”7
No. 491 discloses that alkyl phenylacetic acid esters are reacted with alkyl carbonates and metal alcoholades to form malonic esters, and then the active methylene group is methidiformed with methyl iodide, followed by hydrolysis and removal of leg acid. A method of manufacturing has been proposed. This method requires multiple steps.
No. 111 [51-95035] proposes a method in which reduction is carried out after decomposition of acetophenol.

This method has drawbacks such as requiring multiple steps and using sodium cyanide or potassium cyanide, which are often dangerous to handle.

Further, JP-A No. 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,
Although this method is considered to be an economical method, it still has the drawbacks that P-toluenesulfonyl chloride is relatively expensive, it is easily available, and it generates completely unnecessary P-toluenesulfone.

In order to solve the various drawbacks of the conventional methods, the present inventors discovered that when a Cv+ oxyprobionic acid ester is reacted with a Lewis acid, an α-phenylpropionate ester is produced, and the present invention has been achieved. Here, R in formula (1) represents a full radical.

The object of the present invention is to provide a simple and inexpensive method, the gist of which is characterized by reacting pen with a dipropionic acid ester in α-chlorus llephonyl. This is a method for producing α-) engineered diluprobionic acid esters.

Furthermore, specifically, it provides a method for obtaining d-phenylpropionic acid esters with good yield and dullness in a simple process using inexpensive and easily available raw materials. Propionate ester can be isolated by steaming or other methods, but in carrying out the present invention, it is not necessarily necessary to use a single purified lorsulunyl oxybrobion ester, but rather to use lactic acid ester and chloride ester. sulf9rv
The reaction product with □ can be used as is. For example, the reaction mixture obtained by adding sulfuryl chloride to lactic acid ester at room temperature, or if an excess of sulfuryl chloride is added, the residual liquid obtained by subjecting the excess sulfuryl chloride to reduced pressure F can be used as is. The present invention can be used.As the lactic acid ester, in addition to lower alkyl esters such as methyl, ethyl, and propyl, higher alkyl esters can also be used.

The reactions of the invention are preferably carried out in the presence of a Lewis acid. As Lewis acids, for example, aluminum chloride, zinc chloride, iron chloride, tin chloride, trifluoride WJ, etc. are used, but in particular, aluminum chloride main reaction fleas do not necessarily require a solvent, 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 a method in which benzene, which is a reaction reagent, is used in some excess and garlic is used as a solvent.

In order to carry out the process of the present invention smoothly, for example, aluminum chloride is suspended in benzene, and then the paddle-chlorosulfonyl dipropionate is added to the mixture under stirring at a temperature of -10 to 0°C, preferably θ to 30"C. After each addition, this temperature is maintained for 5 to 3 hours.

Further, the molar ratio of Lewis acid to α-chlorosulfonyl dipropionate is suitably in the range of 0.2 to 10, but more preferably hydrochloric acid, sulfuric acid, or aluminum chloride is included to neutralize It can be made harmless only by sanctioning.

The conventional method using beneyne and lactic acid ester (P-)sylate described in JP-A No. 54-27533 uses lysine as a catalyst and solvent, making post-treatment difficult and requiring a long reaction time. It has disadvantages such as the synthesis of the raw material α-tosyloxypropionate ester is a solid phase, the reaction time is long and the reaction temperature is high, and the treatment of the by-product P-)luenesulfone powder is difficult. However, the raw material used in the present invention is lactic acid ester.

It is a safe 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. In addition, for α-talolus~honyloxybrobionic acid ester, the reaction between lactic acid and benzene can be carried out using benzene itself as a solvent, and in addition, no special reaction conditions are required. The temperature is room temperature, the reaction time is short, the separation and purification of the target product is easy, and in terms of pollution such as wastewater treatment, treatment is easy as there are no unnecessary substances such as P-toluenesulfonic acid. The present invention can be said to be an industrially advantageous method having numerous advantages such as.

The present invention will be specifically explained by referring to a numbered example. −
However, the present invention is not limited thereby.

Example 1 Preparation of methyl a-phenicibropionate Sulfuryl chloride A/1 equipped with stirrer, thermometer and dropping funnel
01.2 g (0.75 mol) were added over the course of 1 hour. Stir egg at 1-0 to 20℃ for 2 hours Boiling point 70 to 71
Methidi α-chlorosulfonyloxypropionate of °C/2 am HK was obtained. Yield: 66.1 g Yield: 59.
It was 4% (relative to lactate methyl IV).

Next, in the same frass as above, 93.7 f (1
, 2 mol) and anhydrous aluminum chloride -Og (0,
6 mol) and stir, among which 4: 1 methyl α-thalolsulfonyloxybrobionic acid manufactured by Ell 40.
5 g (0.2 mol) was added at a liquid temperature of 10 to 15°C (using a trowel for 1 hour).

The reaction was then terminated by stirring at 10-25° C. for 2 hours.

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 drying with the addition of non-bobo salt, it was steamed, firstly excess benzene was recovered, and then (1) was obtained with a boiling point of 55-56°C. 1-Methidi was obtained.
Example 2 8.1 g of iZ, yield 85.6% In the same manner as in Example 1, 52.1 g of methyl lactate (0,
5mo1v) and sulfur chloride IJ 7shi7+, 2g (0,
A reaction product 10 containing about 80% of methyl α-chlorol lephonyl dipropionate
1.0 g was obtained.

Next, instead of using 40.5 g (0.2 mol) of methyl dipropionate in Example 1, the above-mentioned methyl dipropionate was used. Reaction products containing 40.
Four reactions and treatments were carried out in the same manner as in Example 1, except that 6 g was used.

The yield was 19.81% and the yield was 60.1% (based on methyl lactate).

This was carried out to obtain ethyl dipropionate in α-chloride having a boiling point of 90-92°C/2ausHg.

) Yield: 82.3 g, yield: 57.5% (based on ethyl lactate).

Next, in Example 3, 40.5 g of methyl dipropionate in a-chlorosulfonyl was used (instead of a
-Chlorsulfonyloxypropionate ethyl 43.3
The reaction and post-treatment were carried out in the same manner as in Example 2, except that g (0.2 mol) was used, and the boiling point was 69-70°C/2.
Ethyl α-phenylpropionate with axis Hg was obtained.

The yield was 30.7 g, and the yield was 86.0% (based on a-chlorosulfonyloxypropiontyl).

Applicant: Steel Chemical Industry Co., Ltd. Representative Hiroshi Sasamoto

Claims (1)

[Scope of Claims]
- A method for producing phenylpropionate ester. (2) α-Chlorsulfonyloxypropionic acid
A method according to Patent Claims (1) in which a reaction product of a lactic acid ester and sulfuryl chloride is used as a ster without isolating it.