CN112479995A - Preparation method of 2-chloro-N, N-dimethylnicotinamide - Google Patents
Preparation method of 2-chloro-N, N-dimethylnicotinamide Download PDFInfo
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- CN112479995A CN112479995A CN202011508593.4A CN202011508593A CN112479995A CN 112479995 A CN112479995 A CN 112479995A CN 202011508593 A CN202011508593 A CN 202011508593A CN 112479995 A CN112479995 A CN 112479995A
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- dimethylnicotinamide
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
- B01J31/0235—Nitrogen containing compounds
- B01J31/0245—Nitrogen containing compounds being derivatives of carboxylic or carbonic acids
- B01J31/0247—Imides, amides or imidates (R-C=NR(OR))
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
- B01J2231/42—Catalytic cross-coupling, i.e. connection of previously not connected C-atoms or C- and X-atoms without rearrangement
- B01J2231/4277—C-X Cross-coupling, e.g. nucleophilic aromatic amination, alkoxylation or analogues
- B01J2231/4283—C-X Cross-coupling, e.g. nucleophilic aromatic amination, alkoxylation or analogues using N nucleophiles, e.g. Buchwald-Hartwig amination
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
Abstract
The invention belongs to the technical field of pesticides, and particularly relates to a preparation method of 2-chloro-N, N-dimethylnicotinamide. The preparation method of the 2-chloro-N, N-dimethyl nicotinamide adopts 2-chloro nicotinic acid as a raw material to carry out esterification reaction with methanol to obtain 2-chloro methyl nicotinate; then carrying out aminolysis reaction with dimethylamine in the presence of a catalyst N, N-dimethylnicotinamide to obtain the 2-chloro-N, N-dimethylnicotinamide. The preparation method has the advantages of mild and controllable reaction, simple process equipment, low dimethylamine consumption, greatly reduced waste water amount, easy treatment, low production cost and good product quality.
Description
Technical Field
The invention belongs to the technical field of pesticides, and particularly relates to a preparation method of 2-chloro-N, N-dimethylnicotinamide.
Background
2-chloro-N, N-dimethyl nicotinamide is an important intermediate of medicine and pesticide, and is mainly used for producing high-efficiency green herbicide nicosulfuron technical. The main synthesis methods comprise the following steps: oxidizing nicotinic acid with hydrogen peroxide to obtain nicotinic acid N-oxide, and performing chlorination and aminolysis reaction to obtain 2-chloro-N, N-dimethylnicotinamide; propiolic alcohol and di-N-propylamine are used as initial raw materials, firstly, 3-di-N-propylamine acrolein is generated through catalytic oxidation, and then, the reaction product and 2-cyano-N, N-dimethylacetamide are subjected to Knoevenagel reaction, and then, the reaction product and HCl are cyclized to obtain a target product; chinese patent CN101693687A discloses a method for preparing 2-chloro-N, N-dimethylnicotinamide, which uses 2-chloro-3-trichloromethyl pyridine as raw material to react with dimethylamine in water to obtain 2-chloro-N, N-dimethylnicotinamide.
At present, 2-chloronicotinic acid is mostly adopted by production enterprises as a raw material, and is subjected to acyl chlorination reaction with thionyl chloride to obtain 2-chloronicotinoyl chloride, and then is subjected to aminolysis reaction with dimethylamine to obtain 2-chloro-N, N-dimethylnicotinamide.
The chemical reaction formula is as follows:
the above methods exist: the production process is complex, the production amount of waste water is large, the production cost is high, and some defects of poor process safety controllability and the like exist.
Disclosure of Invention
Aiming at the defects of the prior art, the invention aims to provide the preparation method of the 2-chloro-N, N-dimethylnicotinamide, which has the advantages of mild and controllable reaction, simple process equipment, low dimethylamine consumption, greatly reduced wastewater amount, easy treatment, low production cost and good product quality.
The preparation method of 2-chloro-N, N-dimethylnicotinamide adopts 2-chloronicotinic acid as a raw material to perform esterification reaction with methanol to obtain 2-chloronicotinic acid methyl ester; then carrying out aminolysis reaction with dimethylamine in the presence of a catalyst N, N-dimethylnicotinamide to obtain the 2-chloro-N, N-dimethylnicotinamide.
The reaction equation of the present invention is as follows:
preferably, the preparation method of 2-chloro-N, N-dimethylnicotinamide specifically comprises the following steps:
1) firstly, adding 2-chloronicotinic acid and methanol into a reactor, then adding a catalyst, stirring and carrying out reflux reaction, and after the reaction is finished, evaporating partial methanol to obtain a 2-chloronicotinic acid methyl ester methanol solution;
2) under stirring, adding a catalyst N, N-dimethyl nicotinamide into the methyl 2-chloronicotinate methanol solution, introducing dimethylamine for ammonolysis reaction, and distilling out methanol to obtain the 2-chloro-N, N-dimethyl nicotinamide.
Wherein:
in the step 1), the catalyst is cationic resin or concentrated sulfuric acid.
In the step 2), the adding amount of the catalyst N, N-dimethyl nicotinamide is 1.0-1.5% of the mass of the 2-chloronicotinic acid.
In step 2), the temperature of introducing dimethylamine is not more than 20 ℃.
In the step 2), after the dimethylamine is introduced, the temperature is raised to 30-40 ℃, the reaction is carried out for 6-7 hours by heat preservation and stirring, and the reaction product is placed for 10-12 hours at room temperature.
The methanol recovered in the step 1) and the step 2) is returned to the esterification process for recycling.
Compared with the prior art, the invention has the following beneficial effects:
1. the method adopts 2-chloronicotinic acid as a raw material, and performs esterification reaction with methanol to obtain 2-chloronicotinic acid methyl ester, then performs aminolysis reaction on the 2-chloronicotinic acid methyl ester and dimethylamine to obtain 2-chloro-N, N-dimethylnicotinamide, and the recovered methanol is returned to the esterification process for recycling. Mild and controllable reaction, simple process equipment, low dimethylamine consumption, great reduction of wastewater amount, easy treatment, low production cost and good product quality.
2. The invention adopts N, N-dimethyl nicotinamide as the catalyst to prevent the ammonolysis reaction of the substituted chlorine, obtains the product with ideal high purity (the purity is more than 98.7 percent), and meets the production requirement of the pesticide.
Detailed Description
The present invention will be further described with reference to the following embodiments.
The raw materials used in the examples were all commercially available materials except for those specifically mentioned.
Example 1
Adding 15.8 g (0.1mol) of 2-chloronicotinic acid into a reaction bottle provided with a thermometer, a stirring and reflux condenser, adding 60 g of methanol, adding 1 g of 001 x 7 type cationic resin, stirring, heating, refluxing, reacting for 5 hours, detecting the end point, distilling 20 g of methanol after the reaction is finished, and performing the next esterification reaction for use, wherein the remainder is 2-chloronicotinic acid methyl ester methanol solution.
Adding 0.2 g of catalyst N, N-dimethylformamide into the methyl 2-chloronicotinate methanol solution under stirring, introducing 4.8 g of dimethylamine to carry out aminolysis reaction, controlling the reaction temperature to be not more than 20 ℃, heating to 30 ℃ after the dimethylamine is added, carrying out heat preservation stirring reaction for 6 hours, standing at room temperature for 10 hours, detecting the residual 1% or less of methyl 2-chloronicotinate in the reaction solution by gas chromatography, and finishing the reaction. Heating to distill out methanol for reuse, and vacuum distilling for 40 min to eliminate solvent to obtain 2-chloro-N, N-dimethyl nicotinamide with content of 98.8% and yield of 97.3%.
Example 2
Adding 15.8 g (0.1mol) of 2-chloronicotinic acid into a reaction bottle provided with a thermometer, a stirring and reflux condenser, adding 60 g of methanol, adding 1 g of 001 x 7 type cationic resin, stirring, heating, refluxing, reacting for 5 hours, detecting the end point, distilling 20 g of methanol after the reaction is finished, and performing the next esterification reaction for use, wherein the remainder is 2-chloronicotinic acid methyl ester methanol solution.
Adding 0.2 g of catalyst N, N-dimethylformamide into the methyl 2-chloronicotinate methanol solution under stirring, introducing 4.8 g of dimethylamine to carry out aminolysis reaction, controlling the reaction temperature to be not more than 20 ℃, heating to 35 ℃ after the dimethylamine is added, carrying out heat preservation stirring reaction for 6 hours, standing at room temperature for 10 hours, detecting the residual 1% or less of methyl 2-chloronicotinate in the reaction solution by gas chromatography, and finishing the reaction. Heating to distill out methanol for reuse, and vacuum distilling for 40 min to eliminate solvent to obtain 2-chloro-N, N-dimethyl nicotinamide with content of 98.7% and yield of 95.6%.
Example 3
Adding 15.8 g (0.1mol) of 2-chloronicotinic acid into a reaction bottle provided with a thermometer, a stirring and reflux condenser, adding 60 g of methanol, adding 1 g of concentrated sulfuric acid, stirring, heating, refluxing for reaction, detecting the end point after 5 hours, distilling 20 g of methanol after the reaction is finished, and performing the next esterification reaction for reuse, wherein the residue is 2-chloronicotinic acid methyl ester methanol solution.
Adding 0.2 g of catalyst N, N-dimethylformamide into the methyl 2-chloronicotinate methanol solution under stirring, introducing 4.8 g of dimethylamine to carry out aminolysis reaction, controlling the reaction temperature to be not more than 20 ℃, heating to 40 ℃ after the dimethylamine is added, carrying out heat preservation stirring reaction for 6 hours, standing at room temperature for 10 hours, detecting the residual 1% or less of methyl 2-chloronicotinate in the reaction solution by gas chromatography, and finishing the reaction. Heating to distill out methanol for reuse, and vacuum distilling for 40 min to eliminate solvent to obtain 2-chloro-N, N-dimethyl nicotinamide with content of 98.9% and yield of 96.3%.
The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.
Claims (6)
1. A preparation method of 2-chloro-N, N-dimethylnicotinamide is characterized in that: 2-chloronicotinic acid is adopted as a raw material and is subjected to esterification reaction with methanol to obtain 2-chloronicotinic acid methyl ester; then carrying out aminolysis reaction with dimethylamine in the presence of a catalyst N, N-dimethylnicotinamide to obtain the 2-chloro-N, N-dimethylnicotinamide.
2. The process of claim 1 for the preparation of 2-chloro-N, N-dimethylnicotinamide, characterized in that: the method comprises the following steps:
1) firstly, adding 2-chloronicotinic acid and methanol into a reactor, then adding a catalyst, stirring and carrying out reflux reaction, and after the reaction is finished, evaporating partial methanol to obtain a 2-chloronicotinic acid methyl ester methanol solution;
2) under stirring, adding a catalyst N, N-dimethyl nicotinamide into the methyl 2-chloronicotinate methanol solution, introducing dimethylamine for ammonolysis reaction, and distilling out methanol to obtain the 2-chloro-N, N-dimethyl nicotinamide.
3. The process of claim 1 for the preparation of 2-chloro-N, N-dimethylnicotinamide, characterized in that: in the step 1), the catalyst is cationic resin or concentrated sulfuric acid.
4. The process of claim 1 for the preparation of 2-chloro-N, N-dimethylnicotinamide, characterized in that: in the step 2), the adding amount of the catalyst N, N-dimethyl nicotinamide is 1.0-1.5% of the mass of the 2-chloronicotinic acid.
5. The process of claim 1 for the preparation of 2-chloro-N, N-dimethylnicotinamide, characterized in that: in step 2), the temperature of introducing dimethylamine is not more than 20 ℃.
6. The process of claim 1 for the preparation of 2-chloro-N, N-dimethylnicotinamide, characterized in that: in the step 2), after the dimethylamine is introduced, the temperature is raised to 30-40 ℃, the reaction is carried out for 6-7 hours by heat preservation and stirring, and the reaction product is placed for 10-12 hours at room temperature.
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| CN202011508593.4A CN112479995B (en) | 2020-12-18 | 2020-12-18 | Preparation method of 2-chloro-N, N-dimethylnicotinamide |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040048866A1 (en) * | 2002-03-08 | 2004-03-11 | Teodozyj Kolasa | Indazole derivatives that are activators of soluble guanylate cyclase |
| CN109796402A (en) * | 2018-12-28 | 2019-05-24 | 京博农化科技有限公司 | A kind of chloro- N of nicosulfuron intermediate 2-, the preparation method of N- dimethyl nicotinamide |
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2020
- 2020-12-18 CN CN202011508593.4A patent/CN112479995B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040048866A1 (en) * | 2002-03-08 | 2004-03-11 | Teodozyj Kolasa | Indazole derivatives that are activators of soluble guanylate cyclase |
| CN109796402A (en) * | 2018-12-28 | 2019-05-24 | 京博农化科技有限公司 | A kind of chloro- N of nicosulfuron intermediate 2-, the preparation method of N- dimethyl nicotinamide |
Non-Patent Citations (1)
| Title |
|---|
| 王福海等: "《硬脂酸及脂肪酸衍生物生产工艺》", 31 July 1991, 轻工业出版社 * |
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