JPH023636A - Production of aminobutenedicarboxylic acid derivative - Google Patents

Abstract

PURPOSE:To obtain the subject substance by adding chlorine to a maleic acid diester in a halogenated hydrocarbon solution to give a dichlorosuccinic acid derivative, reacting the acid derivative with a base to give a chlorobutenedicarboxylic acid derivative and treating the derivative with ammonia. CONSTITUTION:A maleic acid diester is reacted with chlorine in a halogenated hydrocarbon solution in the presence of an alcohol (e.g., methanol) at-10 to 35 deg.C to give a compound shown by formula I (R<1> and R<2> are 1-4C alkyl), which is reacted with a base (preferably ammonia) at 10-50 deg.C to give a compound shown by formula II. This compound is further reacted with ammonia to give a compound shown by formula III. When ammonia is used as the base, the compound shown by formula III is obtained from the compound shown by formula I by one stage. According to the above-mentioned method, the title substance useful as an intermediate for herbicides, etc., can be readily obtained from inexpensively obtainable raw materials in high yield.

Description

DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to a novel method for producing aminobutene dicarboxylic acid derivatives, which are useful intermediates for producing herbicides and the like.

(Prior art and problems to be solved by the invention) In recent years, various promising herbicides have been developed using pyridine-2,3-dicarboxylic acid derivatives as raw materials.
No. 39.607. The present inventor has recently developed a new method for easily synthesizing this pyridine-2,3-dicarboxylic conductor from an aminobutene dicarboxylic acid derivative (I) and enones (Japanese Patent Application No. 171730/1982).

However, known methods for synthesizing aminobutene dicarboxylic acid derivatives are not necessarily industrially advantageous.

For example, one known synthesis method involves reacting oxalacetate with ammonia gas under refluxing toluene [G,
Domschke, Chem, Ber, 98
．． 2920 (1965)], however, when synthesizing oxalacetic acid ester, metal sodium, which requires careful handling, or relatively expensive sodium alcoholade must be used while sufficiently removing moisture, and the reaction with ammonia gas is difficult. progresses only at a yield of around 50%.

Another known synthesis method is acetylene dicarboxylic! Method of adding ammonia to X conductor [R, HU isge
n et a 1. , Chem, Ber, ,
99.2526 (1966); s.

S., Washburne et al., J. Hete.
rocyclic Chem,, 12°369 (197
5); H, G, Voronkov, Zeitschri
ft der Chem.

, 21, 324 (1981)], but the acetylene dicarbobone derivative has the disadvantage that it must be synthesized from malein M and the like through several steps.

Yet another known synthesis method involves reacting a dibromosuccinic acid derivative with ammonia in the presence of triethylamine in acetonitrile [V, 1. Harkovet
al,,Zh,Org,Khim,,17.1180
(1981), cf c, ^, 95°168492x
] However, this method has drawbacks such as the use of relatively expensive bromine and the constant production of aziridine dicarbonate derivatives as by-products.

As described above, the known methods for synthesizing aminobutene dicarboxylic acid derivatives are not necessarily industrially advantageous.

(Object of the invention) The present invention aims to improve the above-mentioned drawbacks, and provides a method for producing aminobutene dicarboxylic acid derivatives in short steps and in good yields from inexpensive and easily available starting materials. The purpose is to

(Structure of the Invention) The present invention is directed to the following general formula (II) when producing an aminobutene dicarbon M derivative represented by the following general formula (I).
) This is a method for producing an aminobutene dicarboxylic acid derivative characterized by reacting a conductor with ammonia.

R1OOCCH=C(NH2)COOR2(1)R10
0CCI-! =C(C1) COOR2(I) (However, in the above general formulas (I>, (II), R1゜R2 each represents a linear or branched alkyl group having 1 to 4 carbon atoms, and may be the same as each other. In the present invention, the chlorine of the chlorobutene dicarboxylic acid derivative (hereinafter referred to as chlorobutene dicarboxylic acid derivative (II)) represented by the general formula (II) is the vinylo gas (vi
nylogous) and Rolo carbonized ester,
The ester is substituted with ammonia faster than it reacts with ammonia, and the aminobutene dicarbonate [conductor (hereinafter referred to as aminobutene dicarbon!!J\H) represented by the general formula (I) is replaced with ammonia.
It is called water (I>).

)give.

The characteristics of the present invention are that the raw material is a chlorobutene dicarboxylic acid derivative (II) obtained in high yield by a known method from a dichlorosuccinic acid derivative obtained almost quantitatively from inexpensive maleic acid diesters and chlorine; Since the reaction with ammonia occurs from the chlorobutene dicarboxylic 7p conductor <n>, no aziridine compound is produced as a by-product, and the aminobutene dicarboxylic acid derivative can be obtained in good yield and purity.

Furthermore, the present invention involves reacting a dichlorosuccinic acid derivative (III) synthesized from a chlorination reaction of maleic acid diesters with a base to produce a chlorobutene dicarboxylic acid derivative (II), and reacting this with ammonia to produce an aminobutene dicarboxylic acid derivative (II). It is possible to carry out the series of reactions to form the dicarboxylic acid derivative (I) using the same halogenated hydrocarbon solvent. In particular, when ammonia is used as a base, the aminobutenedicarboxylic acid derivative (1) can be obtained from the dichlorosuccinic acid derivative (III) in one step. In this way, the halogenated hydrocarbon solution of the crude product obtained at each step is directly subjected to the next step of reaction without purifying the product at each step of the reaction from maleic acid diesters to the final product. is possible, and the aminobutene dicarboxylic acid derivative (I>) can be obtained in good yield.

Chlorobutene dicarboxylic acid derivative used in the present invention (
II) is one in which R1 and R2 of general formula (II) may be the same or different and each is a straight or branched alkyl group having 1 to 4 carbon atoms.

R1 in the general formula ([) of the above chlorobutene dicarboxylic acid derivative (II). Examples of the alkyl group for R2 are:
Methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 5ec-butyl and tert-
Mention may be made of the butyl group.

Preferred specific examples of the chlorobutene dicarboxylic acid derivative (I) include chlorobutene dicarboxylic acid dimethyl ester ethyl ester sopropyl ester, chlorobutene dicarboxylic acid di-n
-butyl esters and the like.

General formula (I
In I), R1 and R2 are alkyl groups other than those mentioned above. For those with phenyl group, pencil group, etc., the price per mole of the corresponding alcohol (or phenol) is 01 to C above.
being relatively more expensive than 4-alkyl alcohols;
It is not industrially advantageous because it produces many side reactants during chlorination.

As the reagent for introducing an amine group in the present invention, commercially available aqueous ammonia and ammonia gas are desirable. The ammonia water used has a concentration of 5 to 30% by weight, and the ammonia gas used has a pressure of 0.1 to 10 atm.

The amount of ammonia used is chlorobutene dicarboxylic acid derivative (
The molar ratio to II) is usually 1:0.1 to 10,
The ratio is preferably 1:1 to 5, more preferably 1:2 to 4.

In carrying out the present invention, chlorobutene dicarboxylic acid derivatives (
II) without a solvent or dissolved in a reaction solvent, and reacted while adding a predetermined amount of ammonia water or introducing ammonia gas at a predetermined pressure.

The reaction solvent of the present invention is preferably ethers such as ether, tetrahydrofuran, and dioxane, halogenated hydrocarbons such as methylene chloride, carbon tetrachloride, and dichloroethane, or hydrocarbons such as benzene, toluene, and hexane, and these may be used alone. Or it can be used as a mixture of two or more types. Alcohols such as methanol and isopropanol, acetone, methyl ethyl ketone, etc.
- or esters such as ethyl acetate are not preferred because they cause side reactions.

The reaction temperature of the present invention is from 20 to 100°C, preferably from 20 to 70'C. A reaction temperature of 100° C. or higher is not preferred because side reactions become noticeable. Further, in order to prevent volatilization of ammonia, it is preferable to carry out the reaction under pressure.

After the reaction, the aminobutene dicarboxylic acid derivative (I) can be easily obtained in high purity by conventional purification means such as solvent extraction, distillation, and chromatography. In addition, the crude product after removing excess ammonia without going through these purification methods is used as it is in the applicant's patent application No. 17173/1986.
It is also possible to react with an enone, preferably in the presence of an acid catalyst, to give a pyridine-23-dicarboxylic acid derivative according to the method described in No. 0.

The chlorobutene dicarboxylic acid derivative (II) of the present invention is
General formula % Formula % (R1 and R2 each represent a linear or branched alkyl group having 1 to 4 carbon atoms, and may be the same or different from each other. It can be obtained in high yield by reacting a dichlorosuccinic acid derivative (hereinafter referred to as dichlorosuccinic acid derivative (III)) represented by (may be referred to as dichlorosuccinic acid derivative (III)) with a base by a known method.

That is, first, the general formula % represents a linear or branched alkyl group having 1 to 4 carbon atoms. ) in the presence of an alcohol in a halogenated hydrocarbon solvent at a temperature of -10 to +35° according to the method of Japanese Patent Publication No. 46-21564.
A dichlorosuccinic acid derivative (III>) can be obtained almost quantitatively by reacting with chlorine at C. Examples of halogenated hydrocarbons used in this case include carbon tetrachloride, dichloroethane, chloroform, and chlorobenpine. The alcohol is preferably a linear or branched alcohol with 1 to 5 carbon atoms, such as methanol, ethanol, isoamyl alcohol, etc., and the amount of alcohol used is usually 0.1 to 5 carbon atoms per maleic acid diester. On the other hand, the amount of chlorine used is usually 1 to 2 moles per mole of maleic acid diester.

Examples of the alkyl group represented by R1R2 in the general formula of the above maleic acid diesters include methyl and ethyl.

Mention may be made of the n-propyl, isopropyl, n-butyl, isobutyl, 5ec-butyl and tert-butyl groups. Preferred specific examples of maleic diesters having R1 and R2 groups include dimethyl maleate, diethyl maleate, diisopropyl maleate, di-n-butyl maleate, and the like. Dichlorosuccinic acid obtained from maleic acid diesters and chlorine! i
Corresponding examples of derivatives (III) are dichlorosuccinic acid dimethyl ester and dichlorosuccinic acid diethyl ester.

Examples include diisopropyl dichlorosuccinate, di-n-butyl dichlorosuccinate, and the like.

These dichlorosuccinic acid derivatives (III) are then reacted with a base in an organic solvent by a known method to obtain chlorobutene dicarboxylic acid derivatives (II) in high yield. The organic solvents used in this case are esters such as ethyl acetate, and ether.

Ethers such as dioxane, benzene, toluene.

Examples include hydrocarbons such as hexane, and halogenated hydrocarbons such as carbon tetrachloride and dichloroethane. Among these, halogenated hydrocarbons, which are also used in the synthesis of dichlorosuccinic acid derivative (III), are advantageous in that they are subsequently used. In addition, JAW is an aqueous solution with a concentration of 1% by weight to a saturated concentration of an alkali metal hydroxide such as this pickled sodium or an alkali metal charcoal salt such as potassium carbonate, and a concentration of 5%.
-30% by weight ammonia water, ammonia gas at a pressure of 0.1 to 10 atm, triethylamine, amines such as D8U, and one or more of these can also be used in combination. In particular, if ammonia is used, one aminobutene dicarboxylic acid derivative (I>) can be obtained from the dichlorosuccinic acid derivative (■) in one step.The amount of base used is usually 1 mole of the dichlorosuccinic acid derivative (■). ~
5 moles is sufficient. The reaction temperature ranges from 10 to 50'C.

In this case, dichlorosuccinic acid is reacted with a base! The halogenated hydrocarbon solution obtained from the reaction of maleic acid diesters and chlorine in the first stage can be directly used for the reaction without isolation and purification, and the chlorobutenedicarboxylic acid derivative (II) can be obtained in high yield. ) is obtained. Furthermore, this chlorobutene dicarbon r! The halogenated hydrocarbon solution of i derivative (II>) can be subjected to the next reaction with ammonia without being isolated and purified.

The present invention will be explained in more detail with reference to Examples below.

The reaction rate in the examples is indicated by the production rate or disappearance rate of chlorobutene dicarboxylic acid derivative (II) in gas chromatography analysis.

Example 1 5 (7! Dichlorosuccinic acid diethyl ester 5 in a sealed tube
．． Oq and 18.57 ml of carbon tetrachloride were taken and reacted at 40° C. while introducing ammonia gas at 3 atm. When the reaction rate of 97.8% was reached from the analysis of chlorobutene dicarboxylic acid diethyl ester in 3 hours, the reaction rate was then heated at 65°C.
The reaction was carried out while introducing ammonia gas at 3 atm.

The reaction was terminated when a reaction rate of 95% was reached in 18 hours, the precipitate was filtered and washed, and the liquid was concentrated.

The residue was subjected to column chromatography using silica gel (
Elution with an ether-hexane mixture) gave 2.67 l of aminobutene dicarboxylic acid diethyl ester (
yield 70.1%).

Example 2 Maleic acid di-n-butyl ester5. The solution was dissolved in a mixture of 20 Inl of carbon tetrachloride and 0.2 liters of 95% ethanol, and 1.9 g of chlorine gas was introduced at 15 to 20°C, followed by stirring at the same temperature until a reaction rate of 95% was achieved. .

After blowing nitrogen gas into the reaction solution to drive out excess chlorine, the reaction solution was transferred to a 50ml sealed tube and poured with 6 ml of concentrated ammonia water.
, Oml was added, the mixture was sealed, and the mixture was heated to 35°C.

After 3.5 hours, a reaction rate of 96.8% was reached based on analysis of chlorobutene dicarboxylic acid di-n-butyl ester. Subsequently, the reaction was carried out at 65°C, and when a reaction rate of 94% was reached, the mixture was cooled, the layers were separated, and the organic liquid layer was concentrated. The residue was subjected to column chromatography using silica gel (ether-
3.96 g of aminobutene dicarboxylic acid di-n-butyl ester was obtained (yield: 71.5%).

Example 3 Chlorobutene dicarboxylic acid dimethyl ester s, og and 257 carbon tetrachloride were placed in a 50d sealed tube, and reacted at 50° C. while introducing ammonia gas at 2 atm. 95%
The reaction was terminated when the reaction rate of 2. was reached, and purified by silica gel column chromatography in the same manner as in Example 1 to obtain aminobutene dicarboxylic acid dimethyl ester 2. OL;J
@obtained (yield 45.2%).

Example 4 In the same manner as in Example 2, maleic acid di-n-butyl ester was chlorinated in tetracarbon carbon and concentrated to obtain a crude product of dichlorosuccinic acid di-n-butyl ester.

Dissolve this in 20ml of toluene, and 6. Concentrate ammonia water in a 50d sealed tube. It was reacted with Oml at 40°C. After 4 hours, analysis of chlorobutene dicarboxylic acid di-n-butyl ester showed a reaction rate of 98.9%. 65 consecutively
The reaction was terminated when a reaction rate of 96.4% was reached after 25 hours at °C, and purified by the same post-treatment and silica gel column chromatography as in Example 2. Ester 3.520
was obtained (yield 63.6%).

Example 5 Chlorobutene dicarboxylic acid di-n-butyl ester 10
．． 0(J) was added with 28% ammonia water iom1 and stirred at 35° C. in a sealed tube. A reaction rate of 96.9% was reached in 12 hours, so extraction was performed with carbon tetrachloride and the extract was dried.

The residue obtained by distilling off the solvent was subjected to column chromatography using silica gel (eluted with an ether-hexane mixture).
6.34 g of aminobutene dicarboxylic acid di-n-butyl ester was obtained (yield: 68.6%).

(Effects of the Invention) According to the method of the present invention, amino acids can be produced industrially advantageously and with high purity in a -step reaction using easily available robutenedicarboxylic acid derivatives and ammonia as raw materials. Butenedicarboxylic acid derivatives can be synthesized. Also dichlorosuccinic acid derivatives from maleic acid diesters.

When an aminobutene dicarboxylic acid derivative is synthesized via a chlorobutene dicarboxylic acid derivative, the synthesis can be carried out in the same organic solvent solution without purifying each product, which is extremely advantageous industrially.

In this case, in particular, if ammonia is used in the reaction to produce chlorobutene dicarboxylic acid derivatives rather than dichlorosuccinic acid derivatives, it can be continued as is and used in the subsequent reaction to produce aminobutene dicarboxylic acid derivatives, streamlining the process. .

Claims (1)

[Scope of Claims] (1) When producing an aminobutenedicarboxylic acid derivative represented by the following general formula (I), the following general formula (II) is used.
A method for producing an aminobutene dicarboxylic acid derivative, which comprises reacting a chlorobutene dicarboxylic acid derivative represented by the formula with ammonia. R^1OOCCH=C(NH_2)COOR^2( I
)R^1OOCCH=C(Cl)COOR^2(II)(
However, in the above general formulas (I) and (II), R^1, R
^2 each represents a linear or branched alkyl group having 1 to 4 carbon atoms, and may be the same or different from each other. ) (2) The production method according to claim 1, wherein the chlorobutene dicarboxylic acid derivative represented by the general formula (II) is obtained by reacting a dichlorosuccinic acid derivative represented by the following general formula (III) with a base. . ▲There are mathematical formulas, chemical formulas, tables, etc.▼(III) (However, in the above general formula (III), R^1 and R^2 each represent a linear or branched alkyl group having 1 to 4 carbon atoms. , may be the same or different from each other.) (3) The production method according to claim 2, wherein ammonia is used as the base. (4) The production according to claim 2, wherein the dichlorosuccinic acid derivative represented by general formula (III) is obtained by adding chlorine to the corresponding maleic acid diester in the presence of alcohol in a halogenated hydrocarbon solution. Law. (5) Dichlorobutene dicarboxylic acid derivative represented by general formula (III), which is produced by adding chlorine to the corresponding maleic acid diester in the presence of alcohol in a halogenated hydrocarbon solution. 2. The method according to claim 1, wherein the succinic acid derivative is directly reacted with a base in the same halogenated hydrocarbon solution. (6) When producing an aminobutenedicarboxylic acid derivative represented by the following general formula (I), the following general formula ( III)
The dichlorosuccinic acid derivative represented by is directly reacted with ammonia in the same halogenated hydrocarbon solution, and the resulting chlorobutenedicarboxylic acid derivative represented by the following general formula (II) is reacted as it is with ammonia in the same halogenated hydrocarbon solution. A method for producing an aminobutene dicarboxylic acid derivative, which comprises reacting it. R^1OOCCH=C
(NH_2)COOR^2(I)R^1OOCCH=
C(Cl)COOR^2(II)▲There are mathematical formulas, chemical formulas, tables, etc.▼(III) (However, in the above general formula, R^1 and R^2 are linear or branched, each having 1 to 4 carbon atoms. represents a chain alkyl group,
They may be the same or different. )