JP2561500B2 - Process for producing pyridine-2,3-dicarboxylic acid derivative - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION <Field of Industrial Application> The present invention relates to a method for producing a pyridine-2,3-dicarboxylic acid derivative, more specifically, an intermediate useful for producing agrochemicals, pharmaceuticals, etc. It relates to a method for producing a pyridine-2,3-dicarboxylic acid derivative.

<Prior Art and Problems to be Solved by the Invention> Pyridine-2,3-dicarboxylic acid derivatives have, for example, 2- (2-imidazoline-) having a herbicidal action as disclosed in European Patent Application Publication No. 0041623. It is a compound useful as an intermediate of a 2-yl) pyridine-3-carboxylic acid derivative.

Conventionally, as a method for producing a pyridine-2,3-dicarboxylic acid derivative, quinolines and quinolinols are synthesized by a sclaup reaction of treating aniline and glycerin with concentrated sulfuric acid and nitrobenzene, and then quinoline,
Method for nitric acid oxidation of quinolinols (J. Chem. Soc. No. 443
1-substituted amino-1,4 by reacting an α, β-unsaturated hydrazone compound with a maleic acid compound in an inert solvent.
-After obtaining a dihydropyridine-2,3-dicarboxylic acid derivative, the obtained derivative is heated to remove the substituted amino group at the 1-position (JP-A-60-246369); 1-substituted amino A method of converting a 1,2,3,4-tetrahydropyridine-2,3-dicarboxylic acid derivative into an 1,4-dihydropyridine-2,3-dicarboxylic acid derivative by acid treatment and / or heat treatment, and then oxidizing the derivative ( JP-A-61-47482); Method for oxidizing quinoline with excess hypochlorite in the presence of ruthenium oxide (JP-A-61-212563)
Etc. are known.

Further, as a method for synthesizing a pyridine monocarboxylic acid derivative, 2-methyl-1,4-produced by condensation and cyclization reaction of α, β-unsaturated aldehyde such as acrolein and crotonaldehyde with ethyl β-aminocrotonate. Method for nitric acid oxidation of ethyl dihydronicotinates in mixed acid (J.
Org. Chem. Soc. Vol. 21, p. 800, 1956) is known.

However, according to the method of the above,
Not only is there a large number of reaction steps, but nitric acid oxidation, which is a radical reaction condition, is required, which is dangerous. Further, since pyridine-2,3-dicarboxylic acids are likely to undergo a decarboxylation reaction by heating under acidic conditions, the yield is low according to the above-mentioned nitric acid oxidation method, and a large amount of acidic waste liquid is produced. It is not suitable as an industrial production method for 1,3-dicarboxylic acids.

In the above production methods (1) and (2), since the number of reaction steps is large, the total yield is low and expensive starting materials must be used. Further, since a step of eliminating the substituted amino group of the intermediate is required, the yield is reduced, and there is a problem in terms of resource saving. Therefore, it is difficult to industrially produce the pyridine-2,3-dicarboxylic acid derivative by the above-mentioned production methods.

In the above-mentioned manufacturing method, there is a problem that it is necessary to use the oxidizing agent in a large excess and a large amount of waste liquid is generated, so that the waste liquid treatment is expensive.

<Purpose> The present invention has been made in view of the above problems, using inexpensive and easily available starting materials, the reaction is completed in one step and a high yield of pyridine-2,3-dicarboxylic acid derivative Another object of the present invention is to provide a method for producing a pyridine-2,3-dicarboxylic acid derivative capable of obtaining

<Means for Solving the Problems> The method for producing the pyridine-2,3-dicarboxylic acid derivative of the present invention, which has been made to solve the above problems, includes a pyridine-2,3 represented by the following general formula (1). -In the method for producing a dicarboxylic acid derivative, (In the formula, R ¹ and R ³ are the same or different and each represents a hydrogen atom or a lower alkyl group, and R ² has a hydrogen atom, a lower alkyl group, or a halogen atom or a lower alkyl group on the phenyl ring. A compound represented by the following general formula (2), wherein R ⁴ and R ⁵ are the same or different and each independently represent a hydroxy group or a lower alkoxy group. (In the formula, R ¹ , R ² and R ³ are the same as above.) A compound represented by the following general formula (3), (In the formula, R ⁴ and R ⁵ are the same as above. X represents a halogen atom.) And ammonia.

It is widely known by those skilled in the art that the compound of the general formula (3) can have ketoenol tautomerism. In the present specification, such tautomers are represented by the structural formula of the above general formula (3) for convenience.

In each of the above formulas, the lower alkyl group for R ¹ , R ² and R ³ includes methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tertiary butyl, pentyl,
Examples thereof include linear or branched alkyl groups having 1 to 8 carbon atoms such as hexyl, heptyl, and octyl groups.

Examples of the phenyl (lower) alkyl group which may have a halogen atom or a lower alkyl group on the phenyl ring of R ² include benzyl, 2-phenylethyl, 1-
Phenylethyl, 3-phenylpropyl, 4-phenylbutyl, 5-phenylpentyl, 6-phenylhexyl, 2-methyl-3-phenylpropyl, 4-chlorobenzyl, 3-fluorobenzyl, 2-bromobenzyl,
4-iodobenzyl, 2,4-dichlorobenzyl, 2-
(2-Fluorophenyl) ethyl, 1- (3-bromophenyl) ethyl, 3- (4-chlorophenyl) propyl, 4- (2-chlorophenyl) butyl, 5- (4-chlorophenyl) pentyl, 6- (4- Bromophenyl)
Hexyl, 4-methylbenzyl, 3-methylbenzyl,
4-ethylbenzyl, 4-isopropylbenzyl, 4-
Hexylbenzyl, 2- (4-methylphenyl) ethyl, 2- (4-propylphenyl) ethyl, 3- (4-
Methylphenyl) propyl, 3- (3-ethylphenyl) propyl, 4- (4-methylphenyl) butyl, 4
A halogen atom or a straight chain having 1 to 6 carbon atoms as a substituent on the phenyl ring, such as-(4-butylphenyl) butyl, 5- (2-methylphenyl) pentyl, 6- (4-hexylphenyl) hexyl group. Another example is a phenylalkyl group which may have a branched chain alkyl group and is a linear or branched chain alkyl group having 1 to 6 carbon atoms in the alkyl moiety.

Examples of the lower alkoxy group for R ⁴ and R ⁵ include methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, tertiary butoxy, pentyloxy,
A linear or branched alkoxy group having 1 to 6 carbon atoms such as a hexyloxy group can be exemplified.

Examples of the halogen atom for X include a chlorine atom and a bromine atom.

Specific examples of the compound represented by the general formula (2) include acrolein, crotonaldehyde, 2-pentenal,
4-methyl-2-pentenal, 2-hexenal, 5
-Methyl-2-hexenal, 2-heptenal, 2-
Octenal, 2-nonenal, 2-decenal, 2-
Undecenal, 2-methyl-2-propenal, 2-
Ethyl-2-propenal, 2-propyl-2-propenal, 2-isopropyl-2-propenal, 2-butyl-2-propenal, 2-pentyl-2-propenal, 2-hexyl-2-propenal, 2-heptyl- 2-propenal, 2-octyl-2-propenal, 2-benzyl-2-propenal, 2-β-phenethyl-2-propenal, 2- (3-phenylpropyl) -2-propenal, 2- (4-chlorobenzyl )
-2-propenal, 2- (4-bromobenzyl) -2
-Propenal, 2- (4-methylbenzyl) -2-propenal, 2- (3-methylbenzyl) -2-propenal, 2- (4-ethylbenzyl) -2-propenal, 2- (4-isopropylbenzyl) -2-propenal, 2-methyl-2-butenal, 2-ethyl-2-
Butenal, 2-benzyl-2-butenal, 2-methyl-2-pentenal, 2-ethyl-2-pentenal, 2-methyl-2-hexenal, 2-ethyl-2-
Hexenal, 2-methyl-2-heptenal, 2-ethyl-2-heptenal, 2-methyl-2-octenal, 2-ethyl-2-octenal, 2-methyl-2-
Nonenal, 2-ethyl-2-nonenal, 2-methyl-2-decenal, 2-ethyl-2-decenal, 2-
Methyl-2-undecenal, 2-ethyl-2-undecenal, 2-hexyl-2-undecenal, 3-buten-2-one, 3-benzyl-3-buten-2-one, 3- (4-chlorobenzyl) -3-buten-2-one, 3- (4-methylbenzyl) -3-buten-2-one, 1-penten-3-one, 3-penten-2-one, 4-hexen-3-one, 3-hexen-2-one, 3-hepten-2-one, 4-hepten-3-one, 2-hepten-4-one, 3-methyl-3-buten-2-one, 3-ethyl-3-one. Butene-2-on, 2-
Examples include methyl-1-penten-3-one, 2-ethyl-1-penten-3-one, 4-ethyl-4-hexen-3-one and the like.

Specific examples of the compound of the general formula (3) include, for example, α
-Chlorooxalacetic acid, α-bromooxalacetic acid, α-
Dimethyl chlorooxalacetate, Diethyl α-chlorooxalacetate, Dipropyl α-chlorooxalacetate, Diisopropyl α-chlorooxalacetate, Dibutyl α-chlorooxalacetate, Dipentyl α-chlorooxalacetate, α
-Dihexyl chlorooxalacetate, methyl ethyl α-chlorooxalacetate, dimethyl α-bromooxalacetate,
Examples include diethyl α-bromooxalacetate, dipropyl α-bromooxalacetate, diisopropyl α-bromooxalacetate, dibutyl α-bromooxalacetate, dipentyl α-bromooxalacetate, dihexyl α-bromooxalacetate.

The production method of the present invention can be shown by the following reaction process formula.

(In the formula, R ¹ , R ² , R ³ , R ⁴ , R ⁵ and X are the same as above.) In the above reaction scheme, the compound of the general formula (2),
The reaction of the compound of general formula (3) and ammonia is carried out without solvent or in an organic solvent. As the organic solvent used in this reaction, polar, nonpolar solvents, protic, aprotic solvents can be used regardless of the solvent that does not affect the reaction, for example, methanol, ethanol,
Alcohols such as isopropanol and butanol; halogenated hydrocarbons such as chloroform, 1,2-dichloroethane and carbon tetrachloride; aromatic hydrocarbons such as benzene, toluene, xylene, chlorobenzene, o-dichlorobenzene and nitrobenzene; dimethyl ether Ethers such as diethyl ether, dibutyl ether, tetrahydrofuran, dioxane, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether and dibenzyl ether; esters such as methyl acetate and ethyl acetate; sulfoxides such as dimethyl sulfoxy; N Carboxamides such as N-dimethylformamide, sulfonic acids such as dimethyl sulfone and sulfolane, and non-prototypes such as hexamethylphosphoric triamide. Sex polar solvents like.
You may use the said organic solvent in mixture of 2 or more types. Of the above organic solvents, aprotic organic solvents are preferred.

In addition, this reaction can be carried out without a solvent. According to the solvent-free method, the cost of the solvent, the cost of recovering the solvent, the cost of refining, and the like are unnecessary, so that the cost can be reduced.

The reaction temperature with the compound of the general formula (2), the compound of the general formula (3) and ammonia is not particularly limited and can be carried out at various temperatures, for example, in a temperature range of 20 to 200 ° C,
In particular, it is preferably carried out in the temperature range of 35 to 130 ° C. Further, the reaction is carried out under atmospheric pressure or under pressure, and the ammonia pressure is 0-3 kg / c in order to particularly favorably proceed the reaction.
It is preferable to carry out under a pressure condition of m ² , preferably 0.3 to 2.5 kg / cm ² . The reaction time is 30 minutes to 24 hours, usually about 1 to 10 hours. The compound of the general formula (2) and the compound of the general formula (3) can be used at an appropriate molar ratio. For example, for the compound of the general formula (3),
The compound of the general formula (2) is 0.8 to 1.5 times the molar amount, particularly 1.0
It is preferable to use a molar amount of up to 1.2 times. Ammonia is usually used in excess with respect to the compounds of general formula (2) and general formula (3).

In addition, in order to improve the yield of the compound of the general formula (1) which is the target compound in the above reaction, the above reaction is carried out, for example, by dimethylamine, trimethylamine, diethylamine, triethylamine, pyridine, 4- (N, N).
-Dimethylamino) pyridine, morpholine, N-methylmorpholine, 1,5-diazabicyclo [4.3.0] nonene-5
(DBN), 1,4-diazabicyclo [5.4.0] undecene-7
(DBU), 1,8-diazabicyclo [2.2.2] octane (DAB
It is preferably carried out in the presence of a secondary or tertiary amine such as CO).

In addition, the above reaction is preferably carried out in the presence of an ammonium salt, for example, ammonium carbonate, ammonium chloride, ammonium sulfate, ammonium nitrate, ammonium phosphate, ammonium acetate, etc., in order to efficiently produce the target compound.

The secondary, tertiary amine and ammonium salts are
Although it can be used in an appropriate amount, it is preferably used in an amount of 0.05 to 1.0 times the molar amount of the compound of the general formula (3).

In a preferred embodiment of this reaction, the compound of the general formula (2) and the compound of the general formula (3) are mixed at an ammonia pressure of 0.3
Under the conditions of ~2.5kg / cm ^2, without solvent or aprotic organic solvent is preferably carried out at a temperature of 70 to 130 ° C., more preferably, in addition to the above conditions, the secondary amine or It is advisable to add a tertiary amine and / or ammonium salt to react.

The compounds of the general formulas (2) and (3) are known or can be synthesized by a known method,
For example, the compound of the general formula (3) is J. of American Chemic
It can be produced by the method described in al Society, Vol. 72, 5221, (1950).

Among the compounds of the general formula (1), the carboxylic acid compound in which R ⁴ and / or R ⁵ is a hydroxy group is an ester compound in which R ⁴ and / or R ⁵ is an alkoxy group in the compound of the general formula (1). It can also be obtained by hydrolyzing. The above hydrolysis reaction can be carried out, for example, by a conventional method using an alkali metal hydroxide such as sodium hydroxide or potassium hydroxide. However, the carboxylic acid compound is easily soluble in water and the separation and purification step is complicated. Therefore, using a water-insoluble organic solvent such as benzene, toluene, xylene, and chlorobenzene together with water as a solvent, the hydrolysis reaction is carried out in the presence of the above basic compound, and the carboxylic acid in the aqueous layer formed by the hydrolysis reaction is used. 20 to 20
A method of precipitating the above carboxylic acids by acid precipitation treatment with a mineral acid such as hydrochloric acid, sulfuric acid, nitric acid or phosphoric acid at a temperature of 60 ° C. is preferable. The above hydrolysis reaction is carried out at room temperature to 150 ° C, preferably 40 to 100 ° C, and is usually completed in about 1 to 24 hours.

The pyridine-2,3-dicarboxylic acid derivative obtained by the method of the present invention is an intermediate for synthesizing various compounds such as agricultural chemicals and pharmaceuticals, for example, European Patent Application Publication 00
Known as herbicides as disclosed in 41623-
It is useful as an intermediate of (2-imidazolin-2-yl) pyridine-3-carboxylic acid derivative.

<Examples> Hereinafter, the present invention will be described in more detail based on Reference Examples and Examples, but the present invention is not limited to these Examples.

Reference Example 1 In a mixture of 21.9 g (0.20 mol) of triethylamine hydrochloride and 16.3 g (0.201 mol) of 37% formalin, 25 g (0.183 mol) of β-phenylpropionaldehyde at 20 to 35 ° C.
Was dripped. After the completion of dropping, the reaction was carried out at 110 to 115 ° C for 4 hours. After completion of the reaction, cool to 20 ° C and use diethyl ether 10
It was extracted with 0 ml. After the extract was dried over anhydrous sodium sulfate, the solvent was distilled off and the residue was distilled to give 2-
Benzyl-2-propenal (bp ₁₀ : 99-101 ° C) was obtained.

IR (liquid film): 3050 to 2800,1680 cm ^-1 NMR (CDCl ₃ ) ppm: 3.60 (2H, s), 6.1 (2H, d), 7,2 (5H, m) Example 1 equipped with reflux condenser Chlorobenzene 350ml and 2-ethyl-2-propenal 21.0g in the 1-necked 4-neck flask.
(0.25 mol) was added and the temperature was raised in an oil bath. When the internal temperature reached 88 ° C, a mixed solution of 44.5 g (0.20 mol) of diethyl α-chlorooxalacetate and 250 ml of chlorobenzene was added dropwise while bubbling dry ammonia gas into the reaction system. The internal temperature of 88-
It took 40 minutes in the range of 94 ° C. After the dropping was completed, the internal temperature was raised to 115 ° C., and ammonia gas was blown in for 4 hours. After cooling the reaction solution to room temperature, the insoluble material was filtered off, the filtrate was concentrated, and the residue was distilled to give 5-ethyl-2,3-diethoxycarbonylpyridine (bp ₂ : 151) in a yield of 76.5%. ˜152 ° C.) was obtained.

The above reaction was carried out using various solvents. Table 1 shows the type of solvent and the reaction conditions, and the yield of the target compound quantified by the gas chromatography method.

The 5-ethyl-2,3-diethoxycarbonylpyridine obtained above was hydrolyzed by the following method to give 5-
Ethylpyridine-2,3-dicarboxylic acid was obtained.

In a 200 ml four-necked flask equipped with a reflux condenser,
50 ml of toluene, 10.3 g (0.041 mol) of 5-ethyl-2,3-diethoxycarbonylpyridine and 29 ml of water were mixed,
21.9 g of 48% sodium hydroxide solution was added with vigorous stirring under a nitrogen atmosphere, and then the mixture was refluxed for 3.5 hours. The reaction solution was cooled to room temperature and allowed to stand, and separated into a water layer and a toluene layer. The aqueous layer was acidified with 28.3 g of 50% sulfuric acid at a temperature of 45 ° C. to 55 ° C., gradually cooled to 20 ° C., and the precipitated white crystals were filtered and washed with 10 ml of cold water. Dry under reduced pressure at 50 ℃ ~ 60 ℃,
5.9 g of 5-ethylpyridine-2,3-dicarboxylic acid was obtained.
The melting point of this 5-ethylpyridine-2,3-dicarboxylic acid was 154 ° C to 156 ° C (decomposition). Also obtained 5
-Ethylpyridine-2,3-dicarboxylic acid was added to acetone-n
The melting point of the product recrystallized from a mixed solvent of -hexane is 156.5.
The temperature was from ℃ to 157.5 ℃ (decomposition).

Example 2 Toluene 120 ml, α-in a glass autoclave
Mix 9.4 g (0.042 mol) of diethyl chlorooxalacetate and 4.2 g (0.05 mol) of 2-ethyl-2-propenal and keep the ammonia pressure at 0.5 kg / cm ² while keeping the internal temperature from 20 ° C over 30 minutes. Raised to 100 ° C. Further 100 ℃
After reacting for 4 hours at room temperature, the contents were cooled to room temperature, insoluble materials were filtered off, and the filtrate was analyzed by gas chromatography to find that it was 5-ethyl-2,3-diethoxycarbonylpyridine in a yield of 66.6%. Got

The above reaction was carried out using various solvents. Table 2 shows the kinds of solvents and the reaction conditions, and the yield of the target compound.

Example 3 Toluene 120 ml, α-in a glass autoclave
Diethyl chlorooxalacetate 9.4 g (0.042 mol), 2-
Ethyl-2-propenal (4.2 g (0.05 mol)) and triethylamine (0.9 g (0.009 mol)) were mixed, and the internal temperature was adjusted to 20 kg while maintaining the ammonia pressure at 0.5 kg / cm ^2.
The temperature was raised from ℃ to 100 ℃, and after reacting at 100 ℃ for 4 hours, the contents were cooled to room temperature, the insoluble materials were filtered off, and the filtrate was analyzed by gas chromatography. The yield was 71%. -Ethyl-2,3-diethoxycarbonylpyridine was obtained.

When dimethylamine, diphenylamine, ammonium acetate and ammonium carbonate were used in place of the above triethylamine and the same reaction as above was carried out, as shown in Table 3, the same yield as above was obtained with the desired yield. The compound is obtained.

Example 4 Toluene 360 ml, α-in a glass autoclave
After mixing 78.2 g (0.351 mol) of diethyl chlorooxalacetate and 24.6 g (0.351 mol) of 2-methyl-2-propenal and sealing the reaction vessel, the internal temperature was raised to 90 ° C. Then, the internal temperature was raised to 110 ° C. while maintaining the ammonia pressure at 1.5 kg / cm ^2, and the reaction was performed for 4.5 hours. The content was cooled to room temperature and the insoluble material was filtered off. The filtrate was concentrated and the residue was subjected to distillation using a Widmer column to give 5-methyl-2,3-diethoxycarbonylpyridine (bp _3.5 : 160-
48 g (yield 57.6%) was obtained.

Instead of the above-mentioned diethyl α-chlorooxalacetate, α-
When diethyl bromooxalacetate was used and the reaction was carried out in the same manner as above, the target compound was obtained in a good yield as above.

Example 5 69 g (0.31 mol) of diethyl .alpha.-chlorooxalacetate, 33 g (0.39 mol) of 2-ethyl-2-propenal and 4.8 g of ammonium acetate in a glass autoclave.
(0.06 mol) was mixed, the internal temperature was raised to 110 ° C, and the ammonium pressure was 0.5 kg / cm ² for 1.5 hours, 1.5 kg / cm ²
For 1.5 hours and 2.5 kg / cm ² for 2 hours. After completion of the reaction, cool to room temperature, remove insoluble materials, and then distill
5-Ethyl-2,3-diethoxycarbonylpyridine was obtained with a yield of 67%.

Example 6 A mixed solution of 37.6 g (0.168 mol) of diethyl α-chlorooxalacetate, 19.6 g (0.20 mol) of 2-ethyl-2-butenal and 480 ml of chlorobenzene was charged into an autoclave made of glass, and the ammonia pressure was set to 0.5 kg / cm. While maintaining at ² , the internal temperature was raised from 35 ° C to 105 ° C over about 1 hour. Furthermore, after reacting at 105 ° C. for 3.5 hours, the content was cooled to room temperature and the insoluble matter was filtered off. The filtrate was concentrated and the residue was subjected to distillation using a Widmer column to give 5-ethyl-4-methyl-2,3-diethoxycarbonylpyridine (b
p _2: 158~161 ℃) to give 6.6g.

Example 7 In an autoclave made of glass, 25 g (0.094 mol) of diethyl α-bromooxalacetate, 16.4 g (0.112 mol) of 2-benzyl-2-propenal, 1.5 g of ammonium acetate and 200 ml of toluene were mixed, and the internal temperature was 110 ° C. Then, the reaction was performed at an ammonia pressure of 0.5 kg / cm ² for 12.5 hours. After cooling to room temperature, 40 g of anhydrous sodium sulfate was added, the mixture was stirred overnight, and the solid matter was filtered off. The filtrate was concentrated and the residue was distilled to obtain 8 g of 5-benzyl-2,3-diethoxycarbonylpyridine (bp ₃ : 191-194 ° C).

IR (liquid film): 3000 to 2800,1700 cm ^-1 Examples 8 to 22 In the same manner as in Example 6, using a suitable starting material, a pyridine-2,3-dicarboxylic acid derivative represented by the following general formula was obtained. The obtained examples are shown in Table 4.

<Effects of the Invention> As described above, according to the method for producing a pyridine-2,3-dicarboxylic acid derivative of the present invention, the reaction is completed in one step without passing through an intermediate, and the target product is obtained in high yield. Obtainable. In addition, since it is possible to use inexpensive and easily available starting materials, it is safe because the reaction proceeds under mild conditions, and it is also easy to treat waste liquids, etc., and therefore the pyridine-2,3-dicarboxylic acid derivative Has the effect of being able to be manufactured on an industrial scale.

Claims (14)

(57) [Claims] 1. Pyridine-2 represented by the following general formula (1):
In the method for producing a 3-dicarboxylic acid derivative, (In the formula, R ¹ and R ³ are the same or different and each represents a hydrogen atom or a lower alkyl group, and R ² has a hydrogen atom, a lower alkyl group, or a halogen atom or a lower alkyl group on the phenyl ring. A compound represented by the following general formula (2), wherein R ⁴ and R ⁵ are the same or different and each independently represent a hydroxy group or a lower alkoxy group. (In the formula, R ¹ , R ² and R ³ are the same as above.) A compound represented by the following general formula (3), (In the formula, R ⁴ and R ⁵ are the same as above. X represents a halogen atom.) And ammonia are reacted with each other to prepare a pyridine-2,3-dicarboxylic acid derivative. 2. The method for producing a pyridine-2,3-dicarboxylic acid derivative according to claim 1, wherein the reaction temperature is 20 to 200 ° C. 3. The method for producing a pyridine-2,3-dicarboxylic acid derivative according to claim 2, wherein the reaction is carried out under pressure. 4. The method for producing a pyridine-2,3-dicarboxylic acid derivative according to claim 2, wherein the reaction is carried out under atmospheric pressure conditions. 5. The method for producing a pyridine-2,3-dicarboxylic acid derivative according to claim 3, wherein the reaction is carried out without a solvent. 6. The method for producing a pyridine-2,3-dicarboxylic acid derivative according to claim 5, wherein the reaction is carried out in the presence of a secondary amine or a tertiary amine and / or an ammonium salt. 7. The method for producing a pyridine-2,3-dicarboxylic acid compound according to claim 3, wherein the reaction is carried out in an organic solvent. 8. The method for producing a pyridine-2,3-dicarboxylic acid derivative according to claim 7, wherein the organic solvent is an aprotic solvent. 9. The method for producing a pyridine-2,3-dicarboxylic acid derivative according to claim 8, wherein the reaction is carried out in the presence of a secondary amine or a tertiary amine and / or an ammonium salt. 10. The method for producing a pyridine-2,3-dicarboxylic acid derivative according to claim 4, wherein the reaction is carried out without a solvent. 11. The method for producing a pyridine-2,3-dicarboxylic acid derivative according to claim 4, wherein the reaction is carried out in an organic solvent. 12. The method for producing a pyridine-2,3-dicarboxylic acid derivative according to claim 11, wherein the reaction is carried out in a non-ptonic organic solvent in the presence of a secondary amine or a tertiary amine and / or an ammonium salt. Method. 13. R ¹ and R ³ of the compound represented by the general formula (1) are hydrogen atoms, and R ^{2 of the} compound represented by the general formula (1) is a lower alkyl group or a phenyl ring. A phenyl (lower) alkyl group which may have a halogen atom or a lower alkyl group,
7. A method for producing a pyridine-2,3-dicarboxylic acid derivative according to 7, 8 or 9. 14. R ¹ and R ³ of the compound represented by the general formula (1) are hydrogen atoms, and R ^{2 of the} compound represented by the general formula (1) is a lower alkyl group or a phenyl ring. The method for producing a pyridine-2,3-dicarboxylic acid derivative according to claim 4, 10, 11 or 12, which is a phenyl (lower) alkyl group which may have a halogen atom or a lower alkyl group.