CN114031512B - Synthetic method of metalaxyl key intermediate N- (2, 6-xylyl) methyl amino propionate - Google Patents
Synthetic method of metalaxyl key intermediate N- (2, 6-xylyl) methyl amino propionate Download PDFInfo
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- CN114031512B CN114031512B CN202111447582.4A CN202111447582A CN114031512B CN 114031512 B CN114031512 B CN 114031512B CN 202111447582 A CN202111447582 A CN 202111447582A CN 114031512 B CN114031512 B CN 114031512B
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/04—Formation of amino groups in compounds containing carboxyl groups
- C07C227/06—Formation of amino groups in compounds containing carboxyl groups by addition or substitution reactions, without increasing the number of carbon atoms in the carbon skeleton of the acid
- C07C227/08—Formation of amino groups in compounds containing carboxyl groups by addition or substitution reactions, without increasing the number of carbon atoms in the carbon skeleton of the acid by reaction of ammonia or amines with acids containing functional groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/38—Separation; Purification; Stabilisation; Use of additives
- C07C227/40—Separation; Purification
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Abstract
The invention discloses a method for synthesizing a key intermediate N- (2, 6-xylyl) amino methyl propionate of metalaxyl, which comprises the steps of taking methyl chloropropionate and 2, 6-dimethylaniline as raw materials, taking sodium carbonate as an acid binding agent, taking potassium iodide as a catalyst, heating to 66 ℃ under ultrasonic waves, carrying out heat preservation reaction for 6h612h, washing with water, layering to obtain a crude product of N- (2, 6-xylyl) amino methyl propionate, and carrying out vacuum reduced pressure distillation to obtain the N- (2, 6-xylyl) amino methyl propionate. The content of the N- (2, 6-xylyl) amino methyl propionate finally prepared by the reaction is more than 96.2%, and the yield is more than 96.3%.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a method for synthesizing a key intermediate N- (2, 6-xylyl) methyl amino propionate of metalaxyl.
Background
Metalaxyl is a high-efficiency, low-toxicity systemic fungicide with protective and therapeutic effects, which acts mainly by inhibiting protein synthesis of oomycete fungi, and has the chemical name of N- (2, 6-xylyl) -N (2-methoxyacetyl-racemization-methyl aminopropionate). The synthesis method of N- (2, 6-xylyl) -N (2-methoxyacetyl-racemization-methyl amino propionate) mainly adopts the amidation reaction of N- (2, 6-xylyl) methyl amino propionate and methoxyacetyl chloride to prepare the N- (2, 6-xylyl) methyl amino propionate. Wherein, N- (2, 6-xylyl) amino methyl propionate is one of the most important reactants for synthesizing metalaxyl and is the most key intermediate of metalaxyl.
The synthesis of N- (2, 6-xylyl) amino methyl propionate is generally prepared by taking 2, 6-dimethylaniline and methyl chloropropionate as raw materials and sodium carbonate as an acid binding agent through catalysis and rectification separation. The old synthesis process of the N- (2, 6-xylyl) methyl amino propionate comprises the following steps: 2, 6-dimethylaniline and methyl chloropropionate are used as raw materials, sodium carbonate is used as an acid binding agent, the raw materials react for 35 to 48 hours at the temperature of 120 to 130 ℃ through catalysis to prepare a crude product, and then aniline and an intermediate are separated through rectification to obtain the N- (2, 6-xylyl) methyl aminopropionate, wherein the product content is generally more than 98 percent, and the yield is about 93 percent.
The method for synthesizing the N- (2, 6-xylyl) amino methyl propionate by adopting the old process has the problems of high synthesis reaction temperature, low crude product yield, long reaction time, complex operation steps, rectification treatment of the product, difficult recovery of intermediates and the like.
Disclosure of Invention
In view of the above, the invention provides a method for synthesizing N- (2, 6-xylyl) amino methyl propionate, a key intermediate of metalaxyl, so as to solve the technical problems.
The invention provides the following technical scheme:
a synthetic method of a metalaxyl key intermediate N- (2, 6-xylyl) methyl amino propionate takes methyl chloropropionate and 2, 6-dimethylaniline as raw materials, and comprises the following steps:
step 1, adding methyl chloropropionate, 2, 6-dimethylaniline, sodium carbonate and potassium iodide into a four-mouth bottle at room temperature, raising the temperature to 55-85 ℃ under ultrasonic waves, and carrying out heat preservation reaction for 7-14 h;
step 2, controlling the content of methyl chloropropionate to be less than 0.5% -1% in the heat preservation reaction process in step 1; adding deionized water into the reactant obtained in the step 1, washing and layering to obtain a crude product of N- (2, 6-xylyl) methyl amino propionate;
and 3, carrying out reduced pressure distillation on the crude product of the N- (2, 6-xylyl) amino methyl propionate obtained in the step 2 under vacuum, collecting the obtained front fraction, and continuing to carry out reduced pressure distillation to obtain the N- (2, 6-xylyl) amino methyl propionate.
In the present invention, the reaction equation is as follows:
preferably, in the step 1, the molar ratio of the methyl chloropropionate to the 2, 6-dimethylaniline is 1:1.03-1.07.
More preferably, the molar ratio of the methyl chloropropionate to the 2, 6-dimethylaniline is 1:1.04-1.06.
Preferably, the molar ratio of the methyl chloropropionate to the sodium carbonate is 1:0.5-0.6.
Preferably, the addition amount of the potassium iodide is 0.02 to 0.025 times the weight of the methyl chloropropionate.
Preferably, the temperature is increased to 60-80 ℃, and the reaction is kept for 8-12 hours.
Preferably, in the step 2, the deionized water is added in an amount of 1.01 to 1.02 times by weight of methyl chloropropionate.
Preferably, in step 3, 2, 6-dimethylaniline is included in the front cut; the 2, 6-dimethylaniline in the front cut is used for the next batch reaction.
Preferably, in the step 3, the content of the N- (2, 6-xylyl) amino methyl propionate is more than 98.2%, and the yield is more than 96.3%.
The invention also aims to provide a method for synthesizing the key intermediate N- (2, 6-xylyl) methyl amino propionate of metalaxyl, which is prepared according to the synthesis method.
From the technical scheme, the beneficial effects of the invention are as follows:
(1) According to the synthesis method, 2, 6-dimethylaniline and methyl chloropropionate are used as raw materials, sodium carbonate is used as an acid binding agent, and potassium iodide is used as a catalyst, so that the methyl chloropropionate is not hydrolyzed in the reaction process, and almost no side reaction exists, and the purity of the generated crude product is high.
(2) The synthesis method of the invention is to react under ultrasonic wave, the reaction temperature is reduced from the original 120 ℃ to 130 ℃ to 60 ℃ to 80 ℃, and the reaction temperature is reduced; the reaction time is shortened from 35h to 48h to 8h to 12h, the reaction is obviously shortened, the energy consumption in the reaction process is greatly saved, and the production efficiency of the reaction is obviously reduced.
(3) According to the synthesis method disclosed by the invention, after the reaction is finished, the N- (2, 6-xylyl) methyl amino propionate can be obtained by simply carrying out distillation treatment instead of a rectification treatment step, so that the reaction time is shortened, the energy consumption is greatly reduced, and the yield of a product is improved.
(4) According to the synthesis method disclosed by the invention, the reaction yield is greatly improved, the content of N- (2, 6-xylyl) amino methyl propionate obtained by the reaction is more than 98.2%, the yield is more than 96.3%, the content is pure, the yield is high, and the synthesis steps are simple.
Detailed Description
The present invention will be described in further detail with reference to the following embodiments, in order to make the objects, technical solutions and advantages of the present invention more apparent. The exemplary embodiments of the present invention and the descriptions thereof are used herein to explain the present invention, but are not intended to limit the invention.
Example 1
Synthetic method of metalaxyl key intermediate N- (2, 6-xylyl) methyl amino propionate
The key intermediate N- (2, 6-xylyl) amino methyl propionate of metalaxyl is prepared by the following synthesis method:
the reaction equation is as follows:
495g of methyl chloropropionate, 503g of 2, 6-dimethylaniline, 245g of sodium carbonate and 10g of potassium iodide are added into a four-necked flask, and the temperature is increased to 55 ℃ under ultrasonic waves for thermal insulation reaction for 10 hours; controlling the content of methyl chloropropionate to be less than 0.6% in the heat preservation reaction process, adding 500g of deionized water, washing and layering to obtain a crude product of N- (2, 6-xylyl) methyl aminopropionate; vacuum distillation, distillation of 24.8g of 2, 6-dimethylaniline (containing 6.3g of N- (2, 6-xylyl) amino methyl propionate) in the front fraction, application to the next batch reaction, distillation of 775.8g of N- (2, 6-xylyl) amino methyl propionate, content 98.3% and yield 96.3%.
Example 2
Synthetic method of metalaxyl key intermediate N- (2, 6-xylyl) methyl amino propionate
The key intermediate N- (2, 6-xylyl) amino methyl propionate of metalaxyl is prepared by the following synthesis method: 495g of methyl chloropropionate, 510g of 2, 6-dimethylaniline, 240g of sodium carbonate and 10g of potassium iodide are added into a four-necked flask, and the temperature is increased to 80 ℃ under ultrasonic waves for thermal insulation reaction for 8 hours; controlling the content of methyl chloropropionate to be less than 0.5% in the heat preservation reaction process, adding 500g of deionized water, washing and layering to obtain a crude product of N- (2, 6-xylyl) methyl aminopropionate; vacuum distillation, distillation of 25.5g of 2, 6-dimethylaniline (containing 5.5g of N- (2, 6-xylyl) amino methyl propionate) in the front fraction, application to the next batch reaction, distillation of 810g of N- (2, 6-xylyl) amino methyl propionate in the content of 99% and yield of 97.5%.
Example 3
Synthetic method of metalaxyl key intermediate N- (2, 6-xylyl) methyl amino propionate
The key intermediate N- (2, 6-xylyl) amino methyl propionate of metalaxyl is prepared by the following synthesis method: 495g of methyl chloropropionate, 518g of 2, 6-dimethylaniline, 225g of sodium carbonate and 11g of potassium iodide are added into a four-necked flask, and the temperature is increased to 80 ℃ under ultrasonic waves for thermal insulation reaction for 8 hours; controlling the content of methyl chloropropionate to be less than 0.5% in the heat preservation reaction process, adding 500g of deionized water, washing and layering to obtain a crude product of N- (2, 6-xylyl) methyl aminopropionate; vacuum distillation, distillation of front cut 2, 6-dimethyl aniline 41.2g (containing N- (2, 6-xylyl) amino methyl propionate 10.3 g), application to the next batch reaction, distillation of N- (2, 6-xylyl) amino methyl propionate 795g, 98.5% content, 96.5% yield.
Example 4
Synthetic method of metalaxyl key intermediate N- (2, 6-xylyl) methyl amino propionate
The key intermediate N- (2, 6-xylyl) amino methyl propionate of metalaxyl is prepared by the following synthesis method: 495g of methyl chloropropionate, 520g of 2, 6-dimethylaniline, 240g of sodium carbonate and 10g of potassium iodide are added into a four-necked flask, and the temperature is increased to 70 ℃ under ultrasonic waves, and the reaction is carried out for 12 hours under heat preservation; controlling the content of methyl chloropropionate to be less than 1% in the heat preservation reaction process, adding 500g of deionized water, washing and layering to obtain a crude product of N- (2, 6-xylyl) methyl aminopropionate; vacuum distillation, distillation of front cut 2, 6-dimethyl aniline 52g (containing N- (2, 6-xylyl) amino methyl propionate 19 g), using to the next batch reaction, and distillation of N- (2, 6-xylyl) amino methyl propionate 793.6g, content 98.8%, yield 96.7%.
Example 5
Synthetic method of metalaxyl key intermediate N- (2, 6-xylyl) methyl amino propionate
The key intermediate N- (2, 6-xylyl) amino methyl propionate of metalaxyl is prepared by the following synthesis method: 495g of methyl chloropropionate, 515g of 2, 6-dimethylaniline, 230g of sodium carbonate and 12g of potassium iodide are added into a four-necked flask, and the temperature is increased to 80 ℃ under ultrasonic waves for thermal insulation reaction for 8 hours; controlling the content of methyl chloropropionate to be less than 1% in the heat preservation reaction process, adding 500g of deionized water, washing and layering to obtain a crude product of N- (2, 6-xylyl) methyl aminopropionate; vacuum distillation, distillation of 50.5g of 2, 6-dimethylaniline (containing 15.3g of N- (2, 6-xylyl) amino methyl propionate) as a front fraction, application to the next batch reaction, and distillation of 810g of N- (2, 6-xylyl) amino methyl propionate as a back fraction, wherein the content is 99%, and the yield is 97.5%.
Example 6
Synthetic method of metalaxyl key intermediate N- (2, 6-xylyl) methyl amino propionate
The key intermediate N- (2, 6-xylyl) amino methyl propionate of metalaxyl is prepared by the following synthesis method: 495g of methyl chloropropionate, 523g of 2, 6-dimethylaniline, 251g of sodium carbonate and 12g of potassium iodide are added into a four-necked flask, and the temperature is increased to 85 ℃ under ultrasonic waves for thermal insulation reaction for 10 hours; controlling the content of methyl chloropropionate to be less than 1% in the heat preservation reaction process, adding 500g of deionized water, washing and layering to obtain a crude product of N- (2, 6-xylyl) methyl aminopropionate; vacuum distillation, distillation of 35.2g of 2, 6-dimethylaniline (containing 10.2g of N- (2, 6-xylyl) amino methyl propionate) as a front fraction, application to the next batch reaction, and distillation of 815g of N- (2, 6-xylyl) amino methyl propionate with the content of 98.7% and the yield of 98.2%.
The above description is only of the preferred embodiments of the present invention and is not intended to limit the present invention, and various modifications and variations can be made to the embodiments of the present invention by those skilled in the art. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (7)
1. A synthetic method of a metalaxyl key intermediate N- (2, 6-xylyl) methyl amino propionate is characterized by taking methyl chloropropionate and 2, 6-dimethylaniline as raw materials, and comprises the following steps:
step 1, adding methyl chloropropionate, 2, 6-dimethylaniline, sodium carbonate and potassium iodide into a four-mouth bottle at room temperature, raising the temperature to 55-85 ℃ under ultrasonic waves, and carrying out heat preservation reaction for 7-14 h;
step 2, controlling the content of methyl chloropropionate to be less than 0.5% -1% in the heat preservation reaction process in the step 1; adding deionized water into the reactant obtained in the step 1, washing and layering to obtain a crude product of N- (2, 6-xylyl) methyl amino propionate;
step 3, carrying out reduced pressure distillation on the crude product of the N- (2, 6-xylyl) amino methyl propionate obtained in the step 2 under vacuum, collecting a front fraction, and continuing the reduced pressure distillation to obtain the N- (2, 6-xylyl) amino methyl propionate;
in the step 1, the molar ratio of the methyl chloropropionate to the 2, 6-dimethylaniline is 1:1.03-1.07;
in the step 1, the molar ratio of the methyl chloropropionate to the sodium carbonate is 1:0.5-0.6.
2. The key intermediate of metalaxyl, namely N- (2, 6-xylyl) amino methyl propionate, according to claim 1, wherein in the step 1, the molar ratio of the methyl chloropropionate to the 2, 6-dimethylaniline is 1:1.04-1.06.
3. The key intermediate N- (2, 6-xylyl) amino methyl propionate of metalaxyl according to claim 1, wherein in the step 1, the addition amount of potassium iodide is 0.02-0.025 times of the weight of methyl chloropropionate.
4. The key intermediate N- (2, 6-xylyl) amino methyl propionate of metalaxyl according to claim 1, wherein in the step 1, the temperature is raised to 60-80 ℃, and the reaction is carried out for 8-12 h.
5. The key intermediate N- (2, 6-xylyl) amino methyl propionate of metalaxyl according to claim 1, wherein in the step 2, the addition amount of deionized water is 1.01-1.02 times of the weight of methyl chloropropionate.
6. The key intermediate of metalaxyl, methyl N- (2, 6-xylyl) amino propionate according to claim 1, wherein in step 3, the front-end fraction comprises 2, 6-dimethylaniline; the 2, 6-dimethylaniline in the front cut is used for the next batch reaction.
7. The key intermediate of metalaxyl, methyl N- (2, 6-xylyl) amino propionate according to claim 1, wherein in step 3, the content of the methyl N- (2, 6-xylyl) amino propionate is more than 98.2%, and the yield is more than 96.3%.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4267356A (en) * | 1980-06-09 | 1981-05-12 | Ciba-Geigy Corporation | Process for the preparation of N-(1'-alkoxycarbonylethyl)-2,6-dialkylanilines |
| CN101088986A (en) * | 2007-06-09 | 2007-12-19 | 大庆石油管理局 | Metalaxyl synthesizing process |
| CN110229076A (en) * | 2019-05-30 | 2019-09-13 | 浙江禾本科技有限公司 | A kind of technique using recyclable catalyst synthesis 2- (2,6- 3,5-dimethylphenyl) aminopropanoate |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4267356A (en) * | 1980-06-09 | 1981-05-12 | Ciba-Geigy Corporation | Process for the preparation of N-(1'-alkoxycarbonylethyl)-2,6-dialkylanilines |
| CN101088986A (en) * | 2007-06-09 | 2007-12-19 | 大庆石油管理局 | Metalaxyl synthesizing process |
| CN110229076A (en) * | 2019-05-30 | 2019-09-13 | 浙江禾本科技有限公司 | A kind of technique using recyclable catalyst synthesis 2- (2,6- 3,5-dimethylphenyl) aminopropanoate |
Non-Patent Citations (1)
| Title |
|---|
| 3-(4-chlorophenyl)-[1, 2, 3] oxadiazol-3-ium-5-olate and its 4-formyl analog-Ultrasound assisted synthesis and in-vitro anticancer evaluation against human tumor cell lines;Sachin K Bhosale等;Pak. J. Pharm. Sci.;第30卷(第2期);513-520 * |
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