Novel compound containing pyridine-2, 3-dicarboxylic acid dimethyl ester group and preparation method thereof
A novel synthetic route for 5-R-alkyl pyridine-2,3-dicarboxylic acid dimethyl esters addresses inefficiencies and safety concerns in existing methods, achieving cost-effective and safer production for use in agricultural chemicals and pharmaceuticals.
Patent Information
- Application Number
- CN202510422799.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-04-07
- Publication Date
- 2025-07-08
AI Technical Summary
It is difficult to efficiently synthesize dimethyl 5-R pyridine-2,3-dicarboxylic acid dimethyl ester in the prior art, resulting in high production costs, serious environmental pollution and high safety risks.
2-R acrolein and dimethyl 2-chloro-3-oxosuccinate were used to react in the presence of ammonia to form dimethyl 5-R pyridine-2,3-dicarboxylate. By controlling the reaction conditions and selecting suitable solvents, the synthesis route was optimized to improve yield.
The efficient synthesis of dimethyl 5-R pyridine-2,3-dicarboxylate was achieved, reducing production costs, reducing environmental pollution and safety risks, and providing raw materials for pesticides, medicines and new materials.
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Abstract
Description
Technical Field
[0001] The present invention belongs to the fine chemical industry and the field of organic synthesis technology, and relates to the structural formulas and preparation methods of a group of novel compounds including dimethyl 5-methoxypyridine-2,3-dicarboxylate, dimethyl 5-ethylpyridine-2,3-dicarboxylate, dimethyl 5-propylpyridine-2,3-dicarboxylate, dimethyl 5-isopropylpyridine-2,3-dicarboxylate, and dimethyl 5-allylpyridine-2,3-dicarboxylate. Background Art
[0002] Pyridine and its derivatives have good biological activities and can be widely applied in the fields of pesticides, pharmaceuticals, new materials, feed additives, dyes, surfactants, catalysts, etc. Dimethyl 5-R-pyridine-2,3-dicarboxylate is a type of novel pyridine and its derivative compound, which can effectively replace diethyl 5-R-pyridine-2,3-dicarboxylate to achieve the purposes of reducing production costs, reducing environmental pollution, and reducing the risks of safe production. At the same time, it can be used as a supplement to pyridine and its derivative compounds and applied in the synthesis of pesticide technicals, the synthesis of pharmaceutical raw materials, and new materials. Summary of the Invention
[0003] The main content of the present invention is to create a group of novel compounds and the synthetic routes and methods selected for achieving the creation purpose. There are mainly the following novel compounds: dimethyl 5-methoxypyridine-2,3-dicarboxylate, dimethyl 5-ethylpyridine-2,3-dicarboxylate, dimethyl 5-propylpyridine-2,3-dicarboxylate, dimethyl 5-isopropylpyridine-2,3-dicarboxylate, and dimethyl 5-allylpyridine-2,3-dicarboxylate. The preparation method is as follows: 2-R-acrolein reacts with dimethyl 2-chloro-3-oxosuccinate, ammonia water, and a solvent under heating to generate dimethyl 5-R-pyridine-2,3-dicarboxylate. At the same time, the synthesis method of 2-R-acrolein is involved. Detailed Embodiments
[0004] The following detailed embodiments elaborate on the specific implementation schemes of the present invention. These detailed embodiments are only for description and are not used to limit the scope or implementation principles of the present invention. The protection scope of the present invention is subject to the claims, including obvious changes or variations made on this basis, etc.
[0005] Example 1
[0006] Into a 500-ml four-necked flask, 136.5 g of liquid sodium ethoxide was charged, 180 g of xylene was added, and 75.3 g of dimethyl oxalate was slowly added to the flask. During the addition process, attention was paid to cooling. Then, 53.1 g of methyl chloroacetate was added dropwise into the flask. During the dropping process, the temperature was controlled at about 40 °C. After the dropping was completed, it was kept warm for about two hours to generate the intermediate dimethyl 2-chloro-3-oxosuccinate for standby. Another 1000-ml four-necked flask was charged with 193.8 g of formaldehyde solution, 240 g of solvent, 153.4 g of propionaldehyde, 5 g of glacial acetic acid and 8 g of ethylenediamine, and the temperature was raised for reaction. The temperature was raised to reflux for reaction for two hours to generate the intermediate I 2-methylacrolein. Another 1000-ml four-necked flask was added with 112.2 g of sulfamic acid and dissolved completely with water, and then the intermediate dimethyl 2-chloro-3-oxosuccinate was added. The temperature was raised to reflux, and 150 g of the intermediate 2-methylacrolein was added dropwise during reflux. After the dropping was completed, water and xylene were distilled out, and then trimethylbenzene was added to extract dimethyl 5-methylpyridine-2,3-dicarboxylate. After the extraction was completed, trimethylbenzene was distilled out to obtain 84.3 g of the product dimethyl 5-methylpyridine-2,3-dicarboxylate, and the yield of the first three steps was 83%. Another 500-ml four-necked flask was added with 84.3 g of dimethyl 5-methylpyridine-2,3-dicarboxylate, 220 g of toluene was added, sodium bromate and sodium bisulfite were charged, and the acid-binding agent trimethylamine was added. The reaction was refluxed for two hours, and the trimethylamine sodium salt was filtered out. Then the liquid material was washed with water, the toluene layer was taken, and toluene was distilled out to obtain 75.5 g of the target product dimethyl 5-methoxypyridine-2,3-dicarboxylate, and the total yield was 69%.
[0007]
[0008]
[0009] Example 2
[0010] In a 500 ml four-necked flask, 136.5 g of liquid sodium ethoxide was added, 180 g of mesitylene solution was added, 75.3 g of dimethyl oxalate was slowly added to the flask, and the temperature was lowered during the addition process. Then, 53.1 g of methyl chloroacetate was added dropwise into the flask. The temperature was controlled at about 50 °C during the addition process. After the addition was completed, it was kept warm for about two hours to produce the intermediate dimethyl 2-chloro-3-oxosuccinate for standby. Another 1000 ml four-necked flask was charged with 193.8 g of formaldehyde solution, 240 g of ethanol solvent, 190.4 g of n-butanal, 5 g of glacial acetic acid and 8 g of ethylenediamine, and the temperature was raised for reaction. The temperature was raised to reflux for reaction for two hours to produce the intermediate 2-ethylacrolein. Another 1000 ml four-necked flask was added with 112.2 g of sulfamic acid and dissolved completely with water, then the intermediate dimethyl 2-chloro-3-oxosuccinate was added, and the temperature was raised to reflux. 159.3 g of the intermediate 2-ethylacrolein was added dropwise during reflux. After the addition was completed, water and mesitylene solvent were distilled out, and then mesitylene was added to extract dimethyl 5-ethylpyridine-2,3-dicarboxylate. After the extraction was completed, mesitylene was distilled out to obtain 86 g of the target product dimethyl 5-ethylpyridine-2,3-dicarboxylate, with a total yield of 80.3%.
[0011]
[0012] Example 3
[0013] In a 500 ml four-necked flask, 136.5 g of liquid sodium methoxide was added, 180 g of pure benzene solvent was added, 75.3 g of dimethyl oxalate was slowly added to the flask, and the temperature was lowered during the addition process. Then, 53.1 g of methyl chloroacetate was added dropwise into the flask. The temperature was controlled at about 55 °C during the addition process. After the addition was completed, it was kept warm for about two hours to produce the intermediate dimethyl 2-chloro-3-oxosuccinate for standby. Another 1000 ml four-necked flask was charged with 193.8 g of formaldehyde solution, 240 g of water, 227.4 g of n-pentanal, 5 g of butyric acid and 8 g of ethylenediamine, and the temperature was raised for reaction. The temperature was raised to reflux for reaction for two hours to produce the intermediate 2-propylacrolein. Another 1000 ml four-necked flask was added with 112.2 g of sulfamic acid and dissolved completely with water, then the intermediate dimethyl 2-chloro-3-oxosuccinate was added, and the temperature was raised to reflux. 168.5 g of the intermediate 2-propylacrolein was added dropwise during reflux. After the addition was completed, water and the solvent were distilled out, and then mesitylene was added to extract dimethyl 5-propylpyridine-2,3-dicarboxylate. After the extraction was completed, mesitylene was distilled out to obtain 93.3 g of the target product dimethyl 5-propylpyridine-2,3-dicarboxylate, with a total yield of 81.0%.
[0014]
[0015] Example 4
[0016] 136.5 g of liquid sodium ethoxide was charged into a 500-ml four-necked flask, 180 g of acetonitrile solvent was added, 75.3 g of dimethyl oxalate was slowly added to the flask, and the temperature was lowered during the addition process. Then, 53.1 g of methyl chloroacetate was added dropwise to the flask, and the temperature was controlled at about 45 °C during the addition process. After the addition was completed, the mixture was kept warm for about 2.5 hours to produce the intermediate dimethyl 2-chloro-3-oxosuccinate for standby. Another 1000-ml four-necked flask was charged with 77.5 g of paraformaldehyde, 240 g of water, 227.4 g of 3-methylbutyraldehyde, 5 g of glacial acetic acid and 8 g of ethylenediamine, and the temperature was raised for reaction. The temperature was raised to reflux for reaction for two hours to produce the intermediate II 2-isopropylacrolein. Another 1000-ml four-necked flask was added with 112.2 g of sulfamic acid and dissolved completely with water, and then the intermediate dimethyl 2-chloro-3-oxosuccinate was added. The temperature was raised to reflux, and 168.5.3 g of the intermediate 2-isopropylacrolein was added dropwise during reflux. After the addition was completed, water and the solvent were distilled out, and then trimethylbenzene was added to extract dimethyl 5-isopropylpyridine-2,3-dicarboxylate. After the extraction was completed, trimethylbenzene was distilled out to obtain 91.0 g of the target product dimethyl 5-isopropylpyridine-2,3-dicarboxylate, with an overall yield of 79.1%.
[0017]
[0018] Example 5
[0019] 136.5 g of liquid sodium ethoxide was charged into a 500-ml four-necked flask, 180 g of methanol solvent was added, 75.3 g of dimethyl oxalate was slowly added to the flask, and the temperature was lowered during the addition process. Then, 53.1 g of methyl chloroacetate was added dropwise to the flask, and the temperature was controlled at about 40 °C during the addition process. After the addition was completed, the mixture was kept warm for about two hours to produce the intermediate dimethyl 2-chloro-3-oxosuccinate for standby. Another 1000-ml four-necked flask was charged with 193.8 g of formaldehyde solution, 240 g of water, 222.1 g of 4-pentenal, 5 g of butyric acid and 8 g of ethylenediamine, and the temperature was raised for reaction. The temperature was raised to reflux for reaction for 2.5 hours to produce the intermediate 2-ene-4-pentenal. Another 1000-ml four-necked flask was added with 70.2 g of 28% ammonia water and dissolved completely with water, and then the intermediate dimethyl 2-chloro-3-oxosuccinate was added. The temperature was raised to reflux, and 167.2 g of the intermediate 2-ene-4-pentenal was added dropwise during reflux. After the addition was completed, water and the solvent were distilled out, and then trimethylbenzene was added to extract dimethyl 5-allylpyridine-2,3-dicarboxylate. After the extraction was completed, trimethylbenzene was distilled out to obtain 88.5 g of the target product dimethyl 5-allylpyridine-2,3-dicarboxylate, with an overall yield of 77.5%.
[0020]
[0021] Example 6
[0022] 136.5 g of liquid sodium ethoxide was put into a 500 ml four-necked flask, 180 g of petroleum ether solvent was added, 75.3 g of dimethyl oxalate was slowly added to the flask, and the temperature was lowered during the addition process. Then, 53.1 g of methyl chloroacetate was added dropwise into the flask. The temperature was controlled at about 50 °C during the addition process. After the addition was completed, the mixture was kept warm for about two hours to obtain the intermediate dimethyl 2-chloro-3-oxosuccinate for standby. Another 1000 ml four-necked flask was charged with 193.8 g of formaldehyde solution, 240 g of water, 222.1 g of 3-pentenal, 5 g of glacial acetic acid and 8 g of ethylenediamine, and the temperature was raised for reaction. The temperature was raised to reflux for two hours to obtain the intermediate 2-en-3-pentenal. Another 1000 ml four-necked flask was added with 112.2 g of sulfamic acid and dissolved completely with water. Then, the intermediate dimethyl 2-chloro-3-oxosuccinate was added, and the temperature was raised to reflux. 167.2 g of the intermediate 2-en-3-pentenal was added dropwise during reflux. After the addition was completed, water and the solvent were distilled out. Then, dichloromethane was added for extraction of dimethyl 5-allylpyridine-2,3-dicarboxylate. After the extraction was completed, dichloromethane was distilled out to obtain 89.2 g of the target product dimethyl 5-allylpyridine-2,3-dicarboxylate, with a total yield of 78.1%.
[0023]
[0024] The above embodiments describe the basic principles, main features and advantages of the present invention. For those skilled in the art, it is obvious that the present invention is not limited to the details of the above exemplary embodiments, and can be implemented in other specific forms without departing from the spirit or basic features of the present invention. The embodiments are exemplary and non-limiting. The scope of the present invention is defined by the claims rather than the above description.
Claims
1. A novel compound containing a dimethyl pyridine-2,3-dicarboxylate group (Formula I) and its preparation method. Wherein: - R is a group selected from the following: ⑴ - O - CH3 (methoxy), ⑵ - CH2CH3 (ethyl), ⑶ - CH2CH2CH3 (propyl), ⑷ ⑸ - CHCHCH3, - CH2CHCH2 (allyl).
2. The selective synthesis method of any of the compounds according to claim 1, characterized in that propionaldehyde, butyraldehyde, 3-methylbutyraldehyde, valeraldehyde, 3-pentenal, 4-pentenal are respectively reacted with formaldehyde and / or paraformaldehyde, glacial acetic acid, butyric acid, ethylenediamine to generate 2-R-group acrolein (Formula II). Wherein: - R is a group selected from the following (the same as R in claim 1): ⑴ - O - CH3 (methoxy), ⑵ - CH2CH3 (ethyl), ⑶ - CH2CH2CH3 (propyl), ⑷ ⑸ - CHCHCH3, - CH2CHCH2 (allyl).
3. The selective synthesis method of any of the compounds according to claims 1 to 2, characterized in that 2-R-group acrolein (Formula II) is reacted with dimethyl 2-chloro-3-oxosuccinate (Formula III), ammonia water / and or sulfamic acid, and a solvent under heating conditions to generate dimethyl 5-R-pyridine-2,3-dicarboxylate (Formula I).
4. The selective synthesis method of any of the compounds according to claims 1 to 3, characterized in that the solvents used are pure benzene, toluene, xylene, mesitylene, methanol, ethanol, dichloromethane, acetonitrile, petroleum ether.
5. The selective synthesis method of any of the compounds according to claim 3, characterized in that the optimal heating temperature is 65 - 125 °C.
6. The selective synthesis method of any of the compounds according to claim 2, characterized in that sodium bromate (NaBrO3), sodium bisulfite (NaHSO3), trimethylamine, dimethylamine, sodium ethoxide / and or sodium methoxide are also used.
7. The use of any of the compounds according to claim 1 is for synthesizing pesticide technical materials and / or pharmaceutical raw materials and / or new materials.