JPS62114968A - Production of optically active alpha-amino-epsilon-caprolactam - Google Patents

Abstract

PURPOSE:To obtain the titled compound in high yield and optical purity with simple procedure, by carrying out the optical resolution of DL-alpha-amino-epsilon- caprolactam using an optically active N-benzoyl-alanine as an optical resolution agent. CONSTITUTION:1mol of DL-alpha-amino-epsilon-caprolactam (abbreviated as DL-ACL) is made to contact with 0.1-2.0mol of N-benzoyl-L-alanine and N-benzoyl-D- alanine used as an optical resolution agent at 0-80 deg.C preferably in water. A hardly soluble diastereomer salt is crystallized from the resultant solution e.g. by cooling the solution. The salt is separated by a solid-liquid separation process such as filtration, centrifugal separation, etc., and is subjected to optical resolution e.g. by contacting with a cation exchange resin in an aqueous solvent. The resolution agent is separated and the cation exchange resin is eluted with NH3, etc., to obtain D-ACL or L-ACL. USE:Intermediate for L-lysine or raw material of pharmaceuticals such as hypotensor.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a method for producing optically active α-amino-ε-caprolactam.

[Conventional technology]

Optically active α-amino-ε-caprolactam is one of the essential amino acids and is an important compound as a raw material for LIJ resin intermediates and medical products such as antihypertensive agents. Easily synthesized. However, the α-amino-ε-caprolactam thus synthesized is in the DL form, and in order to obtain the optically active form, it is necessary to optically resolve this. For the optical resolution of α-amino-ε-caprolactam, a method using diastereomers with N-p-nitrobenzoylglutamic acid (
Japanese Patent Publication No. 48-3635) is known.

[Problem that the invention seeks to solve]

However, these methods had the drawback that optical purity and yield were not always high at the same time.

Therefore, from this point of view, the present inventors investigated optically active α-
Various studies were conducted with the aim of establishing a new method for producing amino-ε-caprolactam.

[Means to solve the problem]

As a result, it was found that the above object can be achieved by using optically active N-benzoylalanine as an optical resolving agent in optically resolving DL-α-amino-ε-caprolactam.

Hereinafter, the configuration of the present invention will be explained in detail.

The resolving agent used in the present invention is an optically active form of N-benzoylalanine, and its L form and 0 form, that is, N-benzoyl-th-alanine (hereinafter abbreviated as N-Bz-L-Ala), N- Benzoyl-D-Ala (hereinafter N-Bz
-D-Ala) can be used.

DL-α-amino-ε-caprolactam (hereinafter referred to as DL-A
(abbreviated as CL) is carried out under the following procedure and conditions.

First, in a solvent, 0, 1 to 1 mole of DL-ACL
An amount of 2.0 mol, preferably 0.5 to 10 mol, of said resolving agent is contacted.

Water is preferred as the solvent used here.

The method of bringing the dividing agent into contact with DL-ACL is as follows:
DL-ACL and the resolving agent may be dissolved separately and mixed in the above-mentioned solvent, or they may be sequentially dissolved in the solvent. Furthermore, a salt prepared in advance from DL-ACL and a resolving agent may be added and dissolved in the solvent.

Next, the solution obtained by contacting is cooled and/or concentrated. Then, a poorly soluble diastereomeric salt (N-
Bz -L-Ala -D-ACL salt or N-Bz
-D-Ala-L-ACL salt) is crystallized.

The temperature at which the poorly soluble diastereomeric salt is precipitated from the splitting solvent may be within the range from the freezing point to the boiling point of the solvent used, and is determined as appropriate depending on the purpose, but is usually in the range of 0°C to 80°C. It is enough.

Crystals of poorly soluble diastereomeric salts can be easily separated by conventional solid-liquid separation methods such as filtration and centrifugation.

On the other hand, the remaining mother liquor from which the poorly soluble diastereomeric salts have been separated can be used as is or concentrated and/or cooled to obtain easily soluble diastereomeric salts (N-Bz -D-Ala
-D-ACL salt or N-Bz-L-Ala -L-
ACL salt) can also be precipitated and separated.

By decomposing each diastereomer salt obtained in this way by an appropriate method, the resolving agent and D-ΔqL or L-8(1,L) can be separated and collected.

Any method can be used to decompose the diastereomer salt, and for example, a method of contacting it with a cation exchange resin in an aqueous solvent can be applied. That is, when a diastereomer salt is brought into contact with a cation exchange resin, only D-8OL or L-8CL is adsorbed, and first, the resolving agent is quantitatively separated with high purity. Next, elute the cation exchange resin with ammonia etc. and perform D-ACL.
Or L-ACL can be obtained.

Note that the method of the present invention can also be applied when a DL mixture containing an excess of either L-α-amino-ε-caprolactam or D-α-amino-ε-caprolactam is used as a raw material.

〔Example〕

The present invention will be specifically explained below with reference to Examples.

Example 1 N-Bz-D-Ala 19.3 f and DL-AC
L12.81 was heated and dissolved in 96xl of water. After inoculating 0.0 IF of N-Bz-D-Ala-L-ACL salt at 48°C, it was cooled to 20°C over 2 hours. 2 more
After stirring at 0°C for 1 hour, the precipitated crystals were counted and 7
Washed with ml cold water. Dry this and make N-Bz-D
-Altt-L-ACL salt 10.9N was obtained. DL-
The yield from ACL was 33.8%.

The crystals were dissolved in 150++/water and passed through a column packed with a strongly acidic cation exchange resin (ammonium form >50xl.
After draining the aqueous solution of H3 salt, the resin was eluted with 150 ml of 5% ammonia water, the eluate was concentrated to dryness, and L-A
CL 4.3F was obtained. , specific optical rotation [α)20=-3
6,2° (C=6.4, f(20) [Effects of the Invention] Thus, according to the present invention, it is possible to optically resolve DL-ACL in a very simple manner with good yield and high optical purity. can.

Patent application Daitoshi Co., Ltd.

Claims (1)

[Claims] Optically active α-amino-caprolactam is characterized in that optically active N-benzoylalanine is used as an optical resolving agent in optically resolving DL-α-amino-ε-caprolactam.
Method for producing ε-caprolactam.