CN101088986A - Metalaxyl synthesizing process - Google Patents
Metalaxyl synthesizing process Download PDFInfo
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- CN101088986A CN101088986A CN 200710112703 CN200710112703A CN101088986A CN 101088986 A CN101088986 A CN 101088986A CN 200710112703 CN200710112703 CN 200710112703 CN 200710112703 A CN200710112703 A CN 200710112703A CN 101088986 A CN101088986 A CN 101088986A
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- metalaxyl
- dimethylphenyl
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- methyl esters
- alanine methyl
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Abstract
The metalaxyl synthesizing process includes the following steps: the reaction of 2-(2, 6-dimethyl phenyl) methyl alanine, alkali and catalyst 4-dimethylin pyridine in the molar ratio of 1 to 1-2 to 0.01-0.1 and dissolved in proper solvent; dropping methoxyl acetyl chloride to react for 1-4 hr, with the molar ratio between 2-(2, 6-dimethyl phenyl) methyl alanine and methoxyl acetyl chloride being 1 to 1-1.5; water washing the resultant, ether extraction and concentrating to obtain metalaxyl. The process has the features of mild reaction condition, high yield, less side reactions and short reaction period.
Description
Technical field:
The present invention relates to a kind of synthetic method of Fungicidal active compound, the method for Metalaxyl synthesizing under especially a kind of room temperature condition.
Background technology:
Metaxanin is the sterilant that present big area is used, its synthetic method has lactic acid method, high-pressure hydrogenation method and halopropanoic acid ester method, wherein halopropanoic acid ester method is with 2, the 6-xylidine is a starting raw material, with alpha-chloro or bromo propionic acid A ester reaction, Synthetic 2-(2, the 6-3,5-dimethylphenyl) alanine methyl esters, 2-(2, the 6-3,5-dimethylphenyl) alanine methyl esters and methoxyacetyl chloride are in the presence of sodium bicarbonate then, and 110 ℃ are reacted 6 hours Metalaxyl synthesizings.In the end reaction compares difficulty in the one-step synthesis, needs comparatively high temps and long time, and side reaction is more.
Summary of the invention:
In order to overcome disadvantages of background technology, the invention provides a kind of method of Metalaxyl synthesizing, this method has mild condition, yield height, side reaction and reaches short characteristics of reaction times less.
Technical scheme of the present invention is: the method for this Metalaxyl synthesizing comprises the following steps: to add respectively 2-(2 in reaction flask, the 6-3,5-dimethylphenyl) alanine methyl esters, alkali and catalyzer 4-Dimethylamino pyridine, 2-(2, the 6-3,5-dimethylphenyl) mol ratio of alanine methyl esters and alkali is 1: 1～2,2-(2, the 6-3,5-dimethylphenyl) mol ratio of alanine methyl esters and 4-Dimethylamino pyridine is 1: 0.01～0.1, add an amount of dissolution with solvents again, agitation and dropping methoxyacetyl chloride under the room temperature, 2-(2, the 6-3,5-dimethylphenyl) mol ratio of alanine methyl esters and methoxyacetyl chloride is 1: 1～1.5, stopped reaction after 1～4 hour, washing, extracted with diethyl ether concentrate metaxanin.
Above-mentioned alkali is yellow soda ash, salt of wormwood, triethylamine or pyridine; Range of reaction temperature is 0 ℃～140 ℃; Range of reaction temperature is 25 ℃～45 ℃; The solvent of described reaction is toluene, benzene, ethylene dichloride or methylene dichloride.
Compare with existing method, the present invention has the following advantages: the present invention is with 2, the 6-xylidine is a starting raw material, with alpha-chloro or bromo propionic acid A ester reaction, Synthetic 2-(2, the 6-3,5-dimethylphenyl) alanine methyl esters, 2-(2, the 6-3,5-dimethylphenyl) alanine methyl esters and methoxyacetyl chloride react Metalaxyl synthesizing in the presence of the 4-of acid binding agent and catalytic amount Dimethylamino pyridine.This method temperature of reaction is low, and room temperature can react, and transformation efficiency increases substantially.Liquid chromatographic detection purity, product purity are 85%～90%, productive rate 80%～83%.Present method is specially adapted to the synthetic of chirality metaxanin, can overcome because the racemization role that pyroreaction causes.
Description of drawings:
Accompanying drawing 1 is a reaction equation of the present invention.
Embodiment:
Under embodiment 1, the nitrogen protection, add 24.2 gram (0.2 moles) 2 in the reaction flask respectively, 6-xylidine, 25.2 gram (0.3 mole) sodium bicarbonates and 50 gram (0.3 mole) 2 bromopropionic acid methyl esters.Stir down, in one hour, slowly be warmed up to 120～125 ℃, maintain 18 hours postcooling of this temperature.Reaction mixture is poured in 300 milliliters of frozen water, uses ethyl acetate extraction, the extract anhydrous sodium sulfate drying.Under 40 ℃, rotary evaporation concentrates, and obtains the crude product ester, and distillation purifying gets 2-(2, the 6-3,5-dimethylphenyl) alanine methyl esters 26 grams, yield 63%.
In reaction flask, add 20.7 gram (0.1 mole) 2-(2 respectively, the 6-3,5-dimethylphenyl) alanine methyl esters, 0.61 gram (0.005 mole) 4-Dimethylamino pyridine (DMAP), 50 milliliters of toluene, triethylamine 10.1 grams (0.1 mole), agitation and dropping 11.9 gram (0.11 mole) methoxyacetyl chlorides under the room temperature, control reaction temperature is lower than 45 ℃, stopped reaction after 2 hours, washing, extracted with diethyl ether concentrate to such an extent that metaxanin 26.2 restrains liquid chromatography purity 89%, yield 80% (with 2-(2, the 6-3,5-dimethylphenyl) alanine methyl esters meter).The liquid-phase chromatographic analysis condition: the C18 post (250mm * 4mm), moving phase: methyl alcohol+water=70+30 (v/v), flow 1.0mL/min detects wavelength 220nm, and the metaxanin retention time is 5.8min, and area normalization is quantitative.
Embodiment 2, in reaction flask, add 207 gram (1 mole) 2-(2 respectively, the 6-3,5-dimethylphenyl) alanine methyl esters, 6.1 gram (0.05 mole) 4-Dimethylamino pyridine, pyridine 79 grams (1 mole), 600 milliliters of methylene dichloride, agitation and dropping 108.5 gram (1 mole) methoxyacetyl chlorides under the room temperature, temperature of reaction is raised to 40 ℃, dropwises, temperature of reaction is reduced to room temperature gradually, stopped reaction after 4 hours, washing, 100 milliliters of extractions of methylene dichloride, concentrate to such an extent that metaxanin 255 restrains, liquid chromatography purity 90%, yield 82% (with 2-(2, the 6-3,5-dimethylphenyl) alanine methyl esters meter).The liquid-phase chromatographic analysis condition: the C18 post (250mm * 4mm), moving phase: methyl alcohol+water=70+30 (v/v), flow 1.0mL/min detects wavelength 220nm, and the metaxanin retention time is 5.8min, and area normalization is quantitative.
Embodiment 3, in reaction flask, add respectively 207 the gram (1 mole) 2-(2, the 6-3,5-dimethylphenyl) alanine methyl esters, 0.12 gram (0.01 mole) 4-Dimethylamino pyridine, Anhydrous potassium carbonate 276 grams (2 moles), 600 milliliters of ethylene dichloride, agitation and dropping 119 gram (1.1 moles) methoxyacetyl chlorides under the room temperature, temperature of reaction maintains 120～140 ℃, stopped reaction after 1 hour, washing, 100 milliliters of extractions of methylene dichloride, concentrate to such an extent that metaxanin 255 restrains, liquid chromatography purity 90%, yield 82% (with 2-(2, the 6-3,5-dimethylphenyl) alanine methyl esters meter).The liquid-phase chromatographic analysis condition: the C18 post (250mm * 4mm), moving phase: methyl alcohol+water=70+30 (v/v), flow 1.0 mL/min detect wavelength 220nm, and the metaxanin retention time is 5.8min, and area normalization is quantitative.
Embodiment 4, in reaction flask, add respectively 20.7 the gram (0.1 mole) 2-(2, the 6-3,5-dimethylphenyl) alanine methyl esters, 0.61 gram (0.005 mole) 4-Dimethylamino pyridine (DMAP), 50 milliliters of benzene, yellow soda ash 21.2 grams (0.2 mole), agitation and dropping 11.9 gram (0.11 mole) methoxyacetyl chlorides under the room temperature, 0～25 ℃ of control reaction temperature, stopped reaction after 4 hours, washing, extracted with diethyl ether concentrate to such an extent that metaxanin 26.2 restrains liquid chromatography purity 89%, yield 80% (with 2-(2, the 6-3,5-dimethylphenyl) alanine methyl esters meter).The liquid-phase chromatographic analysis condition: the C18 post (250mm * 4mm), moving phase: methyl alcohol+water=70+30 (v/v), flow 1.0mL/min detects wavelength 220nm, and the metaxanin retention time is 5.8min, and area normalization is quantitative.
Embodiment 5, in reaction flask, add respectively 20.7 the gram (0.1 mole) 2-(2, the 6-3,5-dimethylphenyl) alanine methyl esters, 1.22 gram (0.01 mole) 4-Dimethylamino pyridine (DMAP), 50 milliliters of toluene, triethylamine 10.1 grams (0.1 mole), agitation and dropping 16.3 gram (0.15 mole) methoxyacetyl chlorides under the room temperature, control reaction temperature is lower than 45 ℃, stopped reaction after 2 hours, washing, extracted with diethyl ether concentrate to such an extent that metaxanin 26.2 restrains purity 89%, yield 80% (with 2-(2, the 6-3,5-dimethylphenyl) alanine methyl esters meter).The liquid-phase chromatographic analysis condition: the C18 post (250mm * 4mm), moving phase: methyl alcohol+water=70+30 (v/v), flow 1.0mL/min detects wavelength 220nm, and the metaxanin retention time is 5.8min, and area normalization is quantitative.
Claims (6)
1, a kind of method of Metalaxyl synthesizing, it is characterized in that: comprise the following steps: in reaction flask, to add respectively 2-(2, the 6-3,5-dimethylphenyl) alanine methyl esters, alkali and catalyzer 4-Dimethylamino pyridine, 2-(2, the 6-3,5-dimethylphenyl) mol ratio of alanine methyl esters and alkali is 1: 1～2,2-(2, the 6-3,5-dimethylphenyl) mol ratio of alanine methyl esters and 4-Dimethylamino pyridine is 1: 0.01～0.1, add an amount of dissolution with solvents again, agitation and dropping methoxyacetyl chloride under the room temperature, 2-(2, the 6-3,5-dimethylphenyl) mol ratio of alanine methyl esters and methoxyacetyl chloride is 1: 1～1.5, stopped reaction after 1～4 hour, washing, extracted with diethyl ether concentrate metaxanin.
2, the method for Metalaxyl synthesizing according to claim 1 is characterized in that: the mol ratio of 2-(2, the 6-3,5-dimethylphenyl) alanine methyl esters, alkali and methoxyacetyl chloride is 1: 1: 1.
3, the method for Metalaxyl synthesizing according to claim 1 is characterized in that: described alkali is yellow soda ash, salt of wormwood, triethylamine or pyridine.
4, the method for Metalaxyl synthesizing according to claim 1 is characterized in that: described range of reaction temperature is 0 ℃～140 ℃.
5, the method for Metalaxyl synthesizing according to claim 4 is characterized in that: described range of reaction temperature is 25 ℃～45 ℃.
6, the method for Metalaxyl synthesizing according to claim 1 is characterized in that: the solvent of described reaction is toluene, benzene, ethylene dichloride or methylene dichloride.
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| CN2007101127033A CN101088986B (en) | 2007-06-09 | 2007-06-09 | Metalaxyl synthesizing process |
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| CN2007101127033A CN101088986B (en) | 2007-06-09 | 2007-06-09 | Metalaxyl synthesizing process |
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| CN101088986B CN101088986B (en) | 2010-06-23 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110078636A (en) * | 2019-05-23 | 2019-08-02 | 浙江海洲制药有限公司 | A method of preparing Iopromide intermediate |
| CN114031512A (en) * | 2021-11-30 | 2022-02-11 | 浙江禾本科技股份有限公司 | Synthetic method of metalaxyl key intermediate N- (2, 6-xylyl) methyl aminopropionate |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE397191B (en) * | 1972-10-13 | 1977-10-24 | Ciba Geigy Ag | N- (1'-ALCOXICARBONYL-ETHYL) -N-HALOACETYL-2,6-DIALKYLANILINES FOR USE AS FUNGICIDE |
| CN85106327B (en) * | 1985-08-10 | 1987-10-14 | 化学工业部沈阳化工研究院 | Synthesis of metalaxyl from n-(2,6 dimethylphenyl) amino-meth-acrylate |
| CN1051906A (en) * | 1989-11-21 | 1991-06-05 | 化学工业部沈阳化工研究院 | The preparation method of metaxanin |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110078636A (en) * | 2019-05-23 | 2019-08-02 | 浙江海洲制药有限公司 | A method of preparing Iopromide intermediate |
| CN110078636B (en) * | 2019-05-23 | 2022-05-17 | 浙江海洲制药有限公司 | Method for preparing iopromide intermediate |
| CN114031512A (en) * | 2021-11-30 | 2022-02-11 | 浙江禾本科技股份有限公司 | Synthetic method of metalaxyl key intermediate N- (2, 6-xylyl) methyl aminopropionate |
| CN114031512B (en) * | 2021-11-30 | 2023-08-15 | 浙江禾本科技股份有限公司 | Synthetic method of metalaxyl key intermediate N- (2, 6-xylyl) methyl amino propionate |
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