JPS62114969A - 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-methionine 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-methionine and N-benzoyl-D- methionine 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 an intermediate for lysine and as a raw material for pharmaceuticals such as antihypertensive agents, and can be easily obtained industrially from synthetic raw materials such as nylon. is synthesized into However, the α-amino-ε-caprolactam thus synthesized was D
It is an L-form, and in order to obtain an optically active form, it is necessary to optically resolve it. Regarding the optical resolution of α-amino-ε-caprolactam, a method using a diastereomer with N-p-nitrobenzoylglutamic acid (Japanese Patent Publication No. 3635/1983) is known.

[Problem that the invention seeks to solve]

However, these methods have the drawback of low optical purity.

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-benzoylmethionine 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-benzoylmethionine, and its D-form and L-form, that is, N-benzoyl-D-methionine (hereinafter abbreviated as N-Bz-D-Met) and N- Benzoyl-methionine (hereinafter N
-Bz -L-Met) 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 2
．． 0 mol, preferably 0.5 to 10 mol amount cy)N-B
Contact with z-D-Met or N-Bz-L-Met. 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-D-Met @L-A CL salt or N-B
z-L-Met-D-A CL salt) crystallizes out. The temperature at which the poorly soluble diastereomer salt is precipitated from the splitting solvent may 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 between 0°C and 8°C.
A temperature range of 0°C is sufficient.

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 salt has been separated is used as it is or by concentrating and/or cooling to obtain the easily soluble diastereomeric salt (N-Bz-L-Met @
L-ACL salt or N-Bz-D-Met-D-A
CL 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-ACL or L
,4(,B can be separated and collected.

The method for decomposing diastereomeric salts is arbitrary; for example,
A method such as contacting with a cation exchange resin in an aqueous solvent can be applied. That is, when a diastereomeric salt is brought into contact with a cation exchange resin, only D-ACL or L-Al:L is adsorbed, and first, the resolving agent is quantitatively separated with high purity. Next, the cation exchange resin is eluted with ammonia etc. and D-
AQL or L-, ACL can be obtained.

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

〔Example〕

Hereinafter, the effects of the present invention will be illustrated with examples.

Example I N-Bz-D-Met 25.31 and DL-ACL
12.8y was heated and dissolved in 83 ml of water at 45°C.
After inoculation, the mixture was cooled to 20°C for 3 hours.

The precipitated crystals were collected and washed with 3 ml of water. Dry this and add TeN-Bz -D-Met @L-ACL salt 6
．． Obtained 3F. The yield from DL-ACL was 16.5%.

The crystals were dissolved in 100 ml of water and passed through a column filled with 50 ml of strongly acidic cation exchange resin (ammonium type). N-Bz-D-MetaNH.

After draining the aqueous salt solution, add 1 part of 5% ammonia solution to the resin.
Elute with 50 ml, concentrate the eluate to dryness, and add L-AC
Lz, 1y were obtained. Specific optical rotation [a] = -30,5°
(C=3.9, H2O).

Example 2 N-Bz-D-Met 12.7 f and DL-ACL
12.8f was heated and dissolved in 26 ml of water. After inoculating N-Bz-D-Met-L-ACL salt 0.01F at 42°C, it was cooled to 15°C over 3 hours.

The precipitated crystals were crushed and washed with 2 ml of water. This was dried to obtain 3.5 r of N-Bz-D-Met-L-ACL salt. The yield from DL-ACL was 9.2%.

After treatment with a strongly acidic cation exchange resin in the same manner as in Example 1, L-ACLL2F was obtained. Specific optical rotation [α] pi = -2
7,2° (C=4.5, H2O).

Comparative Example 1 N-7 cetyl monomethionine 9.6f and DL-ACL
6.4F was heated and dissolved in 34F methanol. 30℃
N-acetyl-L-methionine, L-ACL salt 0.0
After inoculating 1 F, the cells were cooled to 16° C. in 2 hours.

The precipitated crystals were collected and dried to give N-acetyl-L-
Methionine/DL-A CL salt 12F was obtained. DL-A
The yield from CL was 7.596.

After treatment with a strongly acidic cation exchange resin in the same manner as in Example 1, DL-A CL O, 47f was obtained. Specific optical rotation [jiji=-L12(C-4, H2O).

〔Effect of the invention〕

Thus, according to the present invention, DL-ACL can be optically resolved with high optical purity by an extremely simple method.

Claims (1)

[Claims] A method for producing optically active α-amino-ε-caprolactam, which comprises using optically active N-benzoylmethionine as an optical resolving agent in optically resolving DL-α-amino-ε-caprolactam.