JPH0226624B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to novel N-(diphenylmethylene)propylamine derivatives. The compound of the present invention is a compound useful as an intermediate for producing an amino acid. Various materials have been proposed as raw materials for producing amino acids, but most of them require passing through various intermediates. Although it is recognized that these compounds are suitable as raw materials for producing amino acids, endless improvements are desired in the following respects. That is, (a) the steps for synthesizing the intermediate or target product should be simplified; (b) the yield should be improved;
Improvements such as (c) stabilizing the reaction by relaxing the reaction conditions, and (d) simplifying the operation are desired. Therefore, the present inventors conducted extensive research on amino acids, particularly glutamine and glutamic acid, and intermediates for their production with the aim of making the above improvements, and as a result, discovered a very unique new intermediate and arrived at the present invention. That is, the present invention is based on the general formula () (In the formula, R ¹ and R ² are

[Formula]-CN,

[Formula] R ³ represents an alkyl group having 1 to 4 carbon atoms, and R ¹ and R ² may be the same or different. ) It is an N-(diphenylmethylene)propylamine derivative represented by: The compound of the present invention has the general formula () (In the formula, R ² is the same as in the above formula ()) and the general formula () R ¹ −CH=CH ₂ () (In the formula, R ¹ is the same as in the above formula ()) It can be obtained by reacting with the vinyl compound shown. As the Schiff base represented by the above formula (),
N-(diphenylmethylene)glycine methyl ester, N-(diphenylmethylene)glycine ethyl ester, N-(diphenylmethylene)glycine propyl ester, N-(diphenylmethylene)
Examples include N-(diphenylmethylene)glycine esters such as glycine butyl ester, N-(diphenylmethylene)aminoacetonitrile, and the like. N-(diphenylmethylene)glycine ester can be obtained in high yield by the dehydration reaction of glycine ester with benzophenone (Tetrahedron Lett., 2641 (1978)). It can be obtained by the dehydration reaction between aminoacetonitrile and benzophenone (Tetrahedron Lett., 4625 (1978)). In addition, the compound represented by the above formula () includes acrylic acid methyl ester, acrylic acid ethyl ester, acrylic acid ethyl ester, Acrylic esters such as acid propyl ester and butyl acrylate; examples include acrylonitrile and acrylamide. These vinyl compounds can be obtained by well-known methods. The compound of the present invention is represented by the above formula (). Schiff's base and the vinyl compound represented by the above formula () are mixed in an organic solvent such as dichloromethane in the presence of an aqueous base solution such as sodium hydroxide and, if necessary, a phase transfer catalyst such as tetrabutylammonium hydrogen sulfate. ℃, preferably by stirring at room temperature and normal pressure.In addition, among the compounds of the present invention, R ¹ and/or R ² in the above formula () are

[Formula] A compound in which R ¹ and/or R ² in the above formula () is

[Formula] The compound that is the group is ammonia By reacting in the presence of

[Formula] Group

It can also be produced by amidation of the group [Formula]. The compound of the present invention can be purified by column chromatography. The compound of the present invention can be efficiently purified by adsorbing the compound on the silica gel using a column filled with silica gel and then eluting the compound with a mixed solvent of ethyl acetate and cyclohexane, for example. The compounds of the present invention can be derived into glutamine, glutamic acid, and derivatives thereof by appropriately undergoing hydrolysis with acids, hydrolysis with bases, and amidation with hydrogen peroxide/sodium hydroxide. Hereinafter, the present invention will be specifically explained with reference to Examples. Example 1 N-(diphenylmethylene)glycine ethyl ester 5.3g (0.02mol), ethyl acrylate 2.0g
(0.02 mol), 0.7 g (0.002 mol) of tetrabutylammonium hydrogen sulfate, 50 ml of dichloromethane, and 5 ml of 4N aqueous sodium hydroxide solution were placed in an Erlenmeyer flask and stirred at room temperature for 1 hour. After the reaction, the reaction solution was separated, and the dichloromethane layer was washed with water and then dried. After removing the solvent, liquid crude N-
6.6 g of (diphenylmethylene)-1,3-bis(ethoxycarbonyl)propylamine was obtained. The yield is
It was 89.2%. This crude product was purified by high performance liquid chromatography using silica gel as a filler and a mixed solvent of ethyl acetate and cyclohexane as an eluent, and the solvent was removed from the resulting eluate under reduced pressure.
5.7g of purified compound was obtained. The analysis results of this purified compound are shown in Table 1. Examples 2 to 5 A Schiff base in which R ² in the above formula () is each shown in Table 1 and a Schiff base in the above formula ()
Using a vinyl compound in which R ¹ is as shown in Table ¹ as a raw material, in the same manner as in Example ¹ , N-( Diphenylmethylene)propylamine derivatives were obtained. Each compound was purified by the same method as in Example 1. Table 1 shows the yield of the crude product and the analytical results of the purified compound for each compound. Example 6 In a flask equipped with a stirrer, add 2.7 g (0.01 g) of N-(diphenylmethylene)glycine ethyl ester.
mol) dichloromethane 20ml, acrylonitrile
0.5 g (0.01 mol), 0.3 g (0.001 mol) of tetrabutylammonium hydrogen sulfate, and 1.1 g of a 35% aqueous sodium hydroxide solution were charged, and the mixture was reacted at room temperature for 30 minutes. The reaction solution was separated into layers, the organic layer was washed once with water, and then the solvent was removed. The concentrated solution was separated using a silica gel column to obtain liquid crude N-(diphenylmethylene)-
2.9 g of 1-ethoxycarbonyl-3-cyanopropylamine was obtained. The yield was 90.5%. Purification was performed in the same manner as in Example 1. The analysis results of this purified compound are shown in Table 1. Example 7 A Schiff base in which R ² in the above formula () is shown in Table 1 and R ¹ in the above formula ()
Using a vinyl compound as shown in Table ¹ as a raw material, in the same manner as in Example ⁶ , N-(diphenylmethylene ) A propylamine derivative was obtained. This compound was purified by the same method as in Example 1. Table 1 shows the yield of the crude product and the analysis results of the purified compound. Example 8 (diphenylmethylene)aminoacetonitrile
4.4g (0.02mol), ethyl acrylate 2.0g (0.02mol), tetrabutylammonium hydrogen sulfate 0.3g
(0.001 mol), 50 ml of dichloromethane, and 3.0 g of a 35% aqueous sodium hydroxide solution were placed in an Erlenmeyer flask and stirred at room temperature for 1 hour. After the reaction, the reaction solution was separated, and the cyclomethane layer was washed with water and then dried. The solvent was removed to obtain 6.1 g of crude N-(diphenylmethylene)-1-cyano-3-ethoxycarbonylpropylamine. Yield is 95.3
It was %. Purification was performed in the same manner as in Example 1. The analysis results of this compound are shown in Table 1. Examples 9-10 A Schiff base in which R ² in the above formula () is each shown in Table 1 and a Schiff base in the above formula ()
Using a vinyl compound in which R ¹ is as shown in Table ¹ as a raw material, in the same manner as in Example ⁸ , N-( Diphenylmethylene)propylamine derivatives were obtained. Each compound was purified by the same method as in Example 1. Table 1 shows the yield of the crude product and the analytical results of the purified compound for each compound. Example 11 (diphenylmethylene)aminoacetonitrile
4.4 g (0.02 mol), 1.1 g (0.02 mol) of acrylonitrile, 50 ml of dichloromethane, and 3.0 g of a 35% aqueous sodium hydroxide solution were placed in an Erlenmeyer flask and stirred at room temperature for 1 hour. The reaction solution and the reaction solution were separated, and the dichloromethane layer was washed with water and then dried. The solvent was removed to obtain 4.8 g of crude N-(diphenylmethylene)-1,3-dicyanopropylamine. The yield was 87.9%. After purification in the same manner as in Example 1, 3.9 g of white crystals were obtained from a mixed solvent of ethyl acetate and cyclohexane. The analysis results of this compound are shown in Table 1. Example 12 (diphenylmethylene)aminoacetonitrile
4.4g (0.02mol), acrylic acid amide 1.4g (0.02mol), tetrabutylammonium hydrogen sulfate 0.3g
(0.01 mol), 50 ml of dichloromethane, and 5.0 g of a 35% aqueous sodium hydroxide solution were placed in an Erlenmeyer flask and stirred at room temperature for 1 hour. After the reaction, the reaction solution was separated, and the dichloromethane layer was washed with water and dried. The solvent was removed to obtain 5.3 g of crude N-(diphenylmethylene)-1-cyano-3-aminocarbonylpropylamine. The yield was 91.4%. After purification in the same manner as in Example 1, white crystals were obtained from a mixed solvent of ethyl acetate and cyclohexane. The analysis results of this compound are shown in Table 1. Example 13 3.7 g (0.01 mol) of N-(diphenylmethylene)-1,3-bis(ethoxycarbonyl)propylamine was dissolved in 10 ml of methanol. 20 ml of concentrated ammonia water was added to this, and the mixture was stirred for 10 hours. The reaction solution was concentrated to 10 ml under reduced pressure and cooled, and the precipitated crystals were filtered and dried. Crude N-(diphenylmethylene)-
2.4 g of 1,3-bis(aminocarbonyl)propylamine was obtained. The yield was 77.4%. After purification in the same manner as in Example 1, white crystals were obtained from a mixed solvent of ethyl acetate and cyclohexane. The analysis results of this compound are shown in Table 1. Example 14 Crude N-(diphenylmethylene)-3-cyanopropylamide was obtained in the same manner as in Example 13 using N-(diphenylmethylene)-1-ethoxycarbonyl-3-cyanopropylamine as a raw material. It was purified by the same method as 1. Table 1 shows the yield of the crude product and the analytical results of the purified compound for this compound.

【table】

【table】

Claims (1)

[Claims] 1 General formula () (In the formula, R ¹ and R ² represent a group selected from [Formula] -CN [Formula], R ³ represents an alkyl group having 1 to 4 carbon atoms, and R ¹ and R ² are the same N-(diphenylmethylene)propylamine derivatives represented by: