CN114685375A - Preparation method of [2- (6-chloropyrimidine-4-oxygen) phenyl ] -3, 3-dimethoxyacrylic acid methyl ester - Google Patents
Preparation method of [2- (6-chloropyrimidine-4-oxygen) phenyl ] -3, 3-dimethoxyacrylic acid methyl ester Download PDFInfo
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- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
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Abstract
The invention relates to the field of pesticides, and discloses a preparation method of [2- (6-chloropyrimidine-4-oxy) phenyl ] -3, 3-dimethoxy methyl acrylate, which comprises the following steps: 1) in the presence of a solvent, carrying out a first contact reaction on 3- (alpha-methoxy) -methylene benzofuran-2 (3H) -ketone and alkali to obtain a mixed solution; 2) and carrying out a second contact reaction on the mixed solution and 4, 6-dichloropyrimidine in the presence of a catalyst and a carbonate, wherein the alkali is one or more of alkali metal hydroxide, alkali metal alcoholate and alkali metal salt. According to the method, in the reaction process, the impurities are less, the selectivity and the conversion rate are high, the yield is high, the recovered solvent can be reused, no wastewater is generated, and the method is suitable for industrial production.
Description
Technical Field
The invention relates to the field of pesticides, and in particular relates to a preparation method of [2- (6-chloropyrimidine-4-oxy) phenyl ] -3, 3-dimethoxy methyl acrylate.
Background
The methyl [2- (6-chloropyrimidine-4-oxy) phenyl ] -3, 3-dimethoxyacrylate is an important intermediate of the novel efficient broad-spectrum systemic fungicide azoxystrobin, and the structure of the methyl [2- (6-chloropyrimidine-4-oxy) phenyl ] -3, 3-dimethoxyacrylate is shown in the specification.
At present, the synthesis of the methyl [2- (6-chloropyrimidine-4-oxygen) phenyl ] -3, 3-dimethoxyacrylate mainly comprises the following two synthesis methods. The first one is that 3- (alpha-methoxy) -methylene benzofuran-2 (3H) -ketone and 4, 6-dichloropyrimidine are etherified by adding strong base under the action of a catalyst in a one-pot method to prepare [2- (6-chloropyrimidine-4-oxygen) phenyl ] -3, 3-dimethoxy methyl acrylate. The second method is that 3- (alpha-methoxy) -methylene benzofuran-2 (3H) -ketone and sodium alkoxide are firstly subjected to ester exchange and addition, then are acidified to obtain 3, 3-dimethoxy-2- (2-hydroxyphenyl) methyl acrylate, and then are washed, extracted by dichloromethane and dried to remove the dichloromethane; and then the obtained 3, 3-dimethoxy-2- (2-hydroxyphenyl) methyl acrylate and 4, 6-dichloropyrimidine are used for obtaining [2- (6-chloropyrimidine-4-oxygen) phenyl ] -3, 3-dimethoxy methyl acrylate under the action of a catalyst.
Disclosure of Invention
The inventors of the present invention have intensively studied and found that, in the first synthesis method, three processes of ester exchange, addition and etherification are required in the preparation process, and since 3- (alpha-methoxy) -methylenebenzofuran-2 (3H) -one and 4, 6-dichloropyrimidine exist in the same system and are in competitive reaction with strong base, more 4-methoxy-6-chloropyrimidine impurities are generated in the reaction, and higher bis-impurity 2,2'- ((pyrimidine-4, 6-diylbis (oxy)) bis (2, 1-phenylene)) (2E,2' E) -bis (3-methoxyacrylate) is generated, which finally results in low yield, high DCP consumption and high cost.
In the second synthesis method, the selectivity is not high, and the synthesis method needs to be carried out at-20 ℃ when the 3, 3-dimethoxy-2- (2-hydroxyphenyl) methyl acrylate is synthesized by acidification, the yield of the 3, 3-dimethoxy-2- (2-hydroxyphenyl) methyl acrylate obtained after acidification is not high, and a large amount of waste water is generated, which is very unfavorable for industrial production.
The invention aims to overcome the problems in the prior art, and provides a method for preparing [2- (6-chloropyrimidine-4-oxy) phenyl ] -3, 3-dimethoxymethyl acrylate by using 3- (alpha-methoxy) -methylenebenzofuran-2 (3H) -ketone (a compound with a structure shown in a formula (1)) as a raw material.
In order to achieve the above objects, the present invention provides a method for preparing methyl [2- (6-chloropyrimidin-4-oxy) phenyl ] -3, 3-dimethoxyacrylate, wherein the method comprises the steps of,
1) carrying out a first contact reaction on a compound with a structure shown in a formula (1) and alkali in the presence of a solvent to obtain a mixed solution containing the compound with the structure shown in the formula (2);
2) in the presence of a catalyst and carbonate, carrying out a second contact reaction on a mixed solution containing a compound with a structure shown as a formula (2) and 4, 6-dichloropyrimidine
Wherein the base is one or more of an alkali metal hydroxide, an alkali metal alkoxide, and an alkali metal salt; in the formula (2), X is an alkali metal.
Preferably, in step 1), the molar ratio of the compound having the structure represented by formula (1) to the base is 1: 0.8 to 3; more preferably, the molar ratio of the compound of the structure represented by formula (1) to the base is 1: 0.9-1.5.
Preferably, in step 1), X is sodium and/or potassium.
Preferably, the base is one or more of sodium tert-butoxide, potassium tert-butoxide, sodium methoxide, potassium methoxide, sodium hydroxide, potassium carbonate and sodium carbonate; more preferably, the base is one or more of sodium tert-butoxide, sodium methoxide and sodium hydroxide.
Preferably, in the step 1), the molar ratio of the compound having the structure represented by the formula (1) to the solvent is 1: 2-50.
Preferably, the solvent is one or more of methanol, toluene and dimethylformamide; more preferably, the solvent is methanol.
Preferably, in step 1), the conditions of the first contact reaction include: the temperature of the contact reaction is-30 to 30 ℃, and the time of the contact reaction is 0.5 to 10 hours.
Preferably, in the step 2), the mixed solution containing the compound having the structure represented by the formula (2) is added to a mixture containing 4, 6-dichloropyrimidine, a catalyst, a carbonate and an organic solvent to perform the second contact reaction; more preferably, the second contact reaction is carried out by dropping a mixture containing the compound having the structure represented by the formula (2) into a mixture containing 4, 6-dichloropyrimidine, a catalyst, a carbonate and an organic solvent.
Preferably, the organic solvent is one or more of toluene, dimethylformamide, dimethylacetamide, ethylene glycol dimethyl ether, dimethyl sulfoxide, 4-methyl-2-pentanone, dimethyl carbonate and methyl benzoate.
Preferably, the organic solvent is used in an amount of 2 to 30mol with respect to 1mol of 4, 6-dichloropyrimidine.
Preferably, the carbonate is used in an amount of 0.05 to 1mol based on 1mol of the compound of the structure represented by formula (1) in step 1).
Preferably, the carbonate is one or more of potassium carbonate, sodium carbonate and cesium carbonate.
Preferably, 4, 6-dichloropyrimidine is used in an amount of 0.9 to 1.4mol based on 1mol of the compound of the structure represented by formula (1) in step 1).
Preferably, the catalyst is used in an amount of 0.001 to 1mol based on 1mol of the compound of the structure represented by formula (1) in step 1).
Preferably, the catalyst is one or more of 1, 4-diazabicyclo [2.2.2] octane, 2-methyl-1, 4-diazabicyclo [2.2.2] octane, and trimethylamine hydrochloride.
Preferably, the method further comprises the step of removing the solvent during said second contact reaction.
Preferably, the removed solvent is used as the solvent in step 1).
Preferably, the conditions of the second contact reaction include: the temperature of the contact reaction is 10-100 ℃, the pressure of the contact reaction is-0.04 to-0.1 MPa, and the time of the contact reaction is 0.5-10 hours.
According to the technical scheme, the invention provides the method for preparing the [2- (6-chloropyrimidine-4-oxygen) phenyl ] -3, 3-dimethoxy methyl acrylate by using the 3- (alpha-methoxy) -methylene benzofuran-2 (3H) -ketone as the raw material, the method has the advantages of less impurities, high selectivity and conversion rate and high yield in the reaction process, the recovered solvent can be used indiscriminately, no wastewater is generated, and the method is suitable for industrial production.
Detailed Description
The endpoints of the ranges and any values disclosed herein are not limited to the precise range or value, and such ranges or values should be understood to encompass values close to those ranges or values. For ranges of values, between the endpoints of each of the ranges and the individual points, and between the individual points may be combined with each other to give one or more new ranges of values, and these ranges of values should be considered as specifically disclosed herein.
The invention provides a preparation method of [2- (6-chloropyrimidine-4-oxygen) phenyl ] -3, 3-dimethoxy methyl acrylate, which comprises the following steps,
1) carrying out a first contact reaction on a compound with a structure shown in a formula (1) and alkali in the presence of a solvent to obtain a mixed solution containing the compound with the structure shown in the formula (2);
2) in the presence of a catalyst and carbonate, carrying out a second contact reaction on a mixed solution containing a compound with a structure shown in a formula (2) and 4, 6-dichloropyrimidine,
wherein the base is one or more of an alkali metal hydroxide, an alkali metal alkoxide, and an alkali metal salt; in the formula (2), X is an alkali metal.
According to the present invention, sodium and/or potassium is preferable as the alkali metal. The alkali metal salt is preferably a carbonate.
According to the present invention, preferably, in step 1), the base is one or more of sodium tert-butoxide, potassium tert-butoxide, sodium methoxide, potassium methoxide, sodium hydroxide, potassium carbonate and sodium carbonate; more preferably, the base is one or more of sodium tert-butoxide, sodium methoxide and sodium hydroxide.
According to the invention, in step 1), the amount of the base used can be selected according to the amount of the compound having the structure shown in formula (1), specifically, the molar ratio of the compound having the structure shown in formula (1) to the base is 1: 0.8 to 3; preferably, the molar ratio of the compound having the structure represented by formula (1) to the base is 1: 0.9-1.5; more preferably, the molar ratio of the compound of the structure represented by formula (1) to the base is 1: 0.95 to 1.3; further preferably, the molar ratio of the compound having the structure represented by formula (1) to the base is 1: 1-1.2.
According to the present invention, the first contact reaction is carried out in the presence of a solvent which is capable of dissolving the reaction raw material and is inert to the reaction raw material, preferably one or more of methanol, toluene and dimethylformamide, and more preferably methanol.
According to the present invention, the amount of the solvent used is not particularly limited as long as the first contact reaction can be sufficiently performed, and preferably, in step 1), the molar ratio of the compound having the structure represented by formula (1) to the solvent is 1: 2-50; more preferably, the molar ratio of the compound of the structure represented by formula (1) to the solvent is 1: 3-20.
According to the present invention, preferably, in step 1), the conditions of the first contact reaction include: the temperature of the contact reaction is below 30 ℃, and the time of the contact reaction is above 0.5 hour; more preferably, the conditions of the first contact reaction include: the temperature of the contact reaction is-30 to 30 ℃, and the time of the contact reaction is 0.5 to 10 hours; further preferably, the conditions of the first contact reaction include: the temperature of the contact reaction is-10 to 20 ℃, and the time of the contact reaction is 1 to 8 hours; still further preferably, the conditions of the first contact reaction include: the temperature of the contact reaction is-5 to 20 ℃, and the time of the contact reaction is 2 to 5 hours.
According to the present invention, the mode of the first contact reaction is not particularly limited, and may be any one that satisfies the above contact conditions, and may be any one of various contact modes generally used in the art, and preferably, the first contact reaction is carried out by dropping a solution of the base into a solution of the compound having the structure represented by formula (1).
According to the invention, after the first contact reaction is finished, the first contact reaction can be directly used for the second contact reaction without treatment.
According to the present invention, a mixed solution containing a compound having a structure represented by formula (2) and 4, 6-dichloropyrimidine are subjected to a second contact reaction in the presence of a catalyst and a carbonate. Preferably, in the step 2), the mixed solution containing the compound having the structure represented by the formula (2) is added to a mixture containing 4, 6-dichloropyrimidine, a catalyst, a carbonate and an organic solvent to perform the second contact reaction; more preferably, the second contact reaction is carried out by dropping a mixture containing the compound having the structure represented by the formula (2) into a mixture containing 4, 6-dichloropyrimidine, a catalyst, a carbonate and an organic solvent.
The organic solvent can be one or more of toluene, dimethylformamide, dimethylacetamide, ethylene glycol dimethyl ether, dimethyl sulfoxide, 4-methyl-2-pentanone, dimethyl carbonate and methyl benzoate; preferably, the organic solvent is one or more of toluene, dimethyl sulfoxide, dimethylformamide and dimethylacetamide.
According to the present invention, the amount of the above organic solvent may be selected according to the amount of 4, 6-dichloropyrimidine, and preferably, the amount of the organic solvent is 2 to 30mol with respect to 1mol of 4, 6-dichloropyrimidine; more preferably, the organic solvent is used in an amount of 5 to 15mol with respect to 1mol of 4, 6-dichloropyrimidine.
According to the present invention, preferably, the catalyst is one or more of 1, 4-diazabicyclo [2.2.2] octane (DABCO), 2-methyl-1, 4-diazabicyclo [2.2.2] octane, and trimethylamine hydrochloride; more preferably, the catalyst is 1, 4-diazabicyclo [2.2.2] octane.
According to the invention, since the reaction product is directly used for the next second contact reaction after the first contact reaction in step 1) is finished, the amount of 4, 6-dichloropyrimidine used can be selected according to the compound having the structure shown in formula (1), and preferably, the amount of 4, 6-dichloropyrimidine used is 0.9 to 1.3mol based on 1mol of the compound having the structure shown in formula (1) in step 1); more preferably, 4, 6-dichloropyrimidine is used in an amount of 0.95 to 1.1mol based on 1mol of the compound having the structure represented by formula (1) in step 1); further preferably, the amount of 4, 6-dichloropyrimidine used is 1 to 1.05mol based on 1mol of the compound having a structure represented by the formula (1) in the step 1).
Also, since the reaction product is directly used for the next second contact reaction after the first contact reaction of step 1) is finished, the amount of the catalyst to be used may be selected according to the compound having the structure represented by formula (1), and preferably, the amount of the catalyst to be used is 0.001 to 1mol based on 1mol of the compound having the structure represented by formula (1) in step 1); more preferably, the catalyst is used in an amount of 0.001 to 0.5mol based on 1mol of the compound having the structure represented by formula (1) in step 1); further preferably, the catalyst is used in an amount of 0.01 to 0.1mol based on 1mol of the compound having the structure represented by the formula (1) in the step 1); still more preferably, the catalyst is used in an amount of 0.01 to 0.05mol based on 1mol of the compound having the structure represented by formula (1) in step 1).
Also, since the reaction product is directly used for the next second contact reaction after the first contact reaction of step 1) is finished, the amount of the carbonate may be selected according to the compound having the structure represented by formula (1), and preferably, the amount of the carbonate is 0.1 to 1mol based on 1mol of the compound having the structure represented by formula (1) in step 1); more preferably, the carbonate is used in an amount of 0.2 to 0.5mol based on 1mol of the compound having the structure represented by formula (1) in step 1).
The carbonate may be, for example, one or more of potassium carbonate, sodium carbonate and cesium carbonate, and is preferably potassium carbonate and/or sodium carbonate.
According to the present invention, preferably, the method further comprises a step of removing the solvent during the second contact reaction. As a method for removing the solvent in the second contact reaction process, for example, the second contact reaction may be carried out while removing the solvent by distillation in the second contact reaction process.
In the present invention, the removed solvent is preferably used as the solvent in step 1).
According to the present invention, preferably, the conditions of the second contact reaction include: the temperature of the contact reaction is 10-100 ℃, the pressure of the contact reaction is-0.04 to-0.1 MPa, and the time of the contact reaction is 0.5-10 hours; more preferably, the conditions of the second contact reaction include: the temperature of the contact reaction is 15-95 ℃, the pressure of the contact reaction is-0.05 to-0.1 MPa, and the time of the contact reaction is 6-9 hours. Here, the time of the contact reaction includes a feeding time.
According to the present invention, after the completion of the second contact reaction, a filtrate having a low impurity content can be obtained by solid-liquid separation (e.g., filtration) of the reaction product, and when azoxystrobin is prepared, the filtrate can be used by removing the solvent (e.g., removing the solvent by distillation) without further purification treatment, but the filtrate can be purified by various purification methods in the art, and for example, the filtrate can be recrystallized using a solvent (e.g., methanol) after removing the solvent to obtain high-purity methyl [2- (6-chloropyrimidin-4-oxy) phenyl ] -3, 3-dimethoxyacrylate.
Specifically, the [2- (6-chloropyrimidine-4-oxygen) phenyl ] -3, 3-dimethoxy methyl acrylate is prepared by taking 3- (alpha-methoxy) -methylene benzofuran-2 (3H) -one as a raw material, the method has fewer impurities in the reaction process, high selectivity and conversion rate, the solvent can be directly used, and no waste water is generated. And after the first contact reaction, the reaction product can be directly used for the second contact reaction, and after the second contact reaction, the obtained reaction product has low impurity content and high yield of the target product, and can be used for preparing the azoxystrobin only by removing the solvent, so that the process is greatly simplified.
The present invention will be described in detail below by way of examples, but the present invention is not limited to the following examples.
In the following examples, the HPLC assay conditions were as follows:
the instrument comprises the following steps: agilent 1260 liquid chromatograph of Agilent
A detector: ultraviolet detector
Detection wavelength: 215nm
Column: RX-C18(250mm X4.6 mm,5um)
And (3) eluting: acetonitrile/PH 2-3 phosphoric acid water
Flow rate: 1ml/min
Sample introduction amount: 1.0. mu.l
Example 1
1) Opening the ring: in a 500ml four-necked flask, 35.9g (0.2mol, content 98 wt%) of the compound having the structure represented by formula (1) (3- (. alpha. -methoxy) -methylenebenzofuran-2 (3H) -one) was charged, and dissolved in 100ml of methanol, and 43.1g (0.24mol, content 30 wt%) of a sodium methoxide methanol solution was added dropwise at 20 ℃ or lower, and after dropping for 1 hour, the mixture was stirred at an elevated temperature for 2 hours to obtain a methanol solution containing the compound having the structure represented by formula (2) (LCMS: M/Z ═ 262(M + Na)+)；
2) Condensation: adding 31.7g (0.21mol, 98 wt%) of 4, 6-dichloropyrimidine, 14.1g (0.1mol, 98 wt%) of potassium carbonate, 0.4g of catalyst DABCO and 200ml of toluene into another 500ml four-neck flask, heating to 60 ℃, preserving heat at 60-65 ℃, and carrying out vacuum-0.05 MPa, dropwise adding the prepared methanol solution, distilling while dropwise adding methanol out of the reaction system, carrying out dropwise addition, preserving heat at 60-70 ℃ for 3H, filtering to remove inorganic salts, sampling filtrate, carrying out HPLC quantification, obtaining the yield of 92% (calculated by 3- (alpha-methoxy) -methylene benzofuran-2 (3H) -ketone), evaporating the solvent, and then recrystallizing by using methanol to obtain [2- (6-chloropyrimidine-4-oxygen) phenyl group]-3, 3-Dimethoxyacrylate methyl ester (LCMS: M/Z353 (M + H)+) The purity was 97% by weight.
Nuclear magnetic data of the product: HNMR (CDCl3): delta 8.6(1 H.s); 7.7-7.1(4 H.m); 6.9(1 H.s); 5.0(1 H.d); 4.2(1 H.d); 3.55(3 H.s); 3.4(3 H.s); 3.2(3H.s) ppm.
Example 2
1) Opening the ring: putting 35.9g (0.2mol, content 98 wt%) of 3- (alpha-methoxy) -methylene benzofuran-2 (3H) -ketone into a 500ml four-neck flask, adding 100ml of methanol, cooling to-5 ℃, keeping the temperature at-5 ℃, dropwise adding 41.1g (0.22mol, content 30 wt%) of a methanol solution of potassium hydroxide, dripping for 2H, keeping the temperature at 0 ℃ and stirring for 2H to obtain a methanol solution containing the compound with the structure shown in the formula (2);
2) condensation: adding 31.7g (0.21mol, 98 wt%) of 4, 6-dichloropyrimidine, 4.4g (0.04mol, 98 wt%) of sodium carbonate, 0.8g of DABCO and 200ml of DMSO into another 500ml four-neck flask, heating to 80 ℃, keeping the temperature at 80-90 ℃, and carrying out vacuum-0.095 MPa, dropwise adding the prepared methanol solution, distilling while dropwise adding methanol out of the reaction system, and finishing dropwise adding, after 4H incubation at 80-90 ℃ and removal of inorganic salts by filtration, the filtrate was sampled and quantified by HPLC to give a yield of 89% (calculated as 3- (. alpha. -methoxy) -methylenebenzofuran-2 (3H) -one), the solvent was evaporated off and recrystallized from methanol to give methyl [2- (6-chloropyrimidine-4-oxy) phenyl ] -3, 3-dimethoxyacrylate with a purity of 96% by weight.
Example 3
1) Opening the ring: putting 35.9g (0.2mol, content 98 wt%) of the compound with the structure shown in formula (1) into a 500ml four-mouth bottle, adding 100ml of methanol for dissolving, cooling to 20 ℃, dropwise adding 34.2g (0.19mol, content 30 wt%) of sodium methoxide methanol solution below 20 ℃, dropwise adding after 1 hour, preserving heat and stirring for 3 hours after dropwise adding to obtain methanol solution containing the compound with the structure shown in formula (2);
2) condensation: adding 31.7g (0.21mol, 98 wt%) of 4, 6-dichloropyrimidine, 11.26g (0.08mol, 98 wt%) of potassium carbonate, 1.14g of catalyst DABCO and 200ml of toluene into another 500ml four-neck flask, heating to 20 ℃, preserving the temperature at 20-30 ℃, and carrying out vacuum-0.085 MPa, dropwise adding the prepared methanol solution, distilling the methanol out of the reaction system while dropwise adding, preserving the temperature at 25-30 ℃ for 2H after 4H dropwise adding, filtering to remove inorganic salts, sampling the filtrate, carrying out HPLC quantification, obtaining the yield of 90% (calculated by 3- (alpha-methoxy) -methylene benzofuran-2 (3H) -ketone), evaporating the solvent, recrystallizing by using the methanol to obtain [2- (6-chloropyrimidine-4-oxy) phenyl ] -3, 3-dimethoxy methyl acrylate, the purity was 95% by weight.
Example 4
The procedure of example 1 was repeated, except that methanol was not distilled off during the dropwise addition of the methanol solution, to obtain methyl [2- (6-chloropyrimidine-4-yloxy) phenyl ] -3, 3-dimethoxyacrylate in a yield of 50% and a purity of 55% by weight in the same manner as in example 1.
The preferred embodiments of the present invention have been described above in detail, but the present invention is not limited thereto. Within the scope of the technical idea of the invention, many simple modifications can be made to the technical solution of the invention, including combinations of various technical features in any other suitable way, and these simple modifications and combinations should also be regarded as the disclosure of the invention, and all fall within the scope of the invention.
Claims (10)
1. A preparation method of [2- (6-chloropyrimidine-4-oxygen) phenyl ] -3, 3-dimethoxyacrylic acid methyl ester is characterized by comprising the following steps of,
1) carrying out a first contact reaction on a compound with a structure shown in a formula (1) and alkali in the presence of a solvent to obtain a mixed solution containing the compound with the structure shown in the formula (2);
2) in the presence of a catalyst and carbonate, carrying out a second contact reaction on a mixed solution containing a compound with a structure shown in a formula (2) and 4, 6-dichloropyrimidine,
wherein the base is one or more of an alkali metal hydroxide, an alkali metal alkoxide, and an alkali metal salt; in the formula (2), X is an alkali metal.
2. The method according to claim 1, wherein in step 1), the molar ratio of the compound having the structure represented by formula (1) to the base is 1: 0.8 to 3;
preferably, the molar ratio of the compound of the structure represented by formula (1) to the base is 1: 0.9-1.5.
3. The method according to claim 1, wherein in step 1), X is sodium and/or potassium;
preferably, the base is one or more of sodium tert-butoxide, potassium tert-butoxide, sodium methoxide, potassium methoxide, sodium hydroxide, potassium carbonate and sodium carbonate;
preferably, the base is one or more of sodium tert-butoxide, sodium methoxide and sodium hydroxide.
4. The method according to any one of claims 1 to 3, wherein in step 1), the molar ratio of the compound having the structure represented by formula (1) to the solvent is 1: 2-50;
preferably, the solvent is one or more of methanol, toluene and dimethylformamide;
preferably, the solvent is methanol.
5. The method according to any one of claims 1 to 3, wherein in step 1), the conditions of the first contact reaction comprise: the temperature of the contact reaction is-30 to 30 ℃, and the time of the contact reaction is 0.5 to 10 hours.
6. The method according to any one of claims 1 to 3, wherein in the step 2), the second contact reaction is carried out by adding a mixture containing the compound having the structure represented by the formula (2) to a mixture containing 4, 6-dichloropyrimidine, a catalyst, a carbonate, and an organic solvent;
preferably, the second contact reaction is carried out by dropwise adding a mixture containing a compound having a structure represented by formula (2) to a mixture containing 4, 6-dichloropyrimidine, a catalyst, a carbonate and an organic solvent;
preferably, the organic solvent is one or more of toluene, dimethylformamide, dimethylacetamide, ethylene glycol dimethyl ether, dimethyl sulfoxide, 4-methyl-2-pentanone, dimethyl carbonate and methyl benzoate;
preferably, the organic solvent is used in an amount of 2 to 30mol with respect to 1mol of 4, 6-dichloropyrimidine.
7. The method according to any one of claims 1 to 3, wherein the carbonate is used in an amount of 0.05 to 1mol based on 1mol of the compound having the structure represented by formula (1) in step 1);
preferably, the carbonate is one or more of potassium carbonate, sodium carbonate and cesium carbonate.
8. The method according to any one of claims 1 to 3, wherein 4, 6-dichloropyrimidine is used in an amount of 0.9 to 1.4mol based on 1mol of the compound having the structure represented by formula (1) in step 1);
preferably, the catalyst is used in an amount of 0.001 to 1mol based on 1mol of the compound having the structure represented by formula (1) in step 1);
preferably, the catalyst is one or more of 1, 4-diazabicyclo [2.2.2] octane, 2-methyl-1, 4-diazabicyclo [2.2.2] octane, and trimethylamine hydrochloride.
9. The process of any one of claims 1 to 3, further comprising the step of removing the solvent during the second contact reaction;
preferably, the removed solvent is used as the solvent in step 1).
10. The method of any one of claims 1-3, wherein the conditions of the second contact reaction comprise: the temperature of the contact reaction is 10-100 ℃, the pressure of the contact reaction is-0.04 to-0.1 MPa, and the time of the contact reaction is 0.5-10 hours.
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| CN202011580210.4A CN114685375A (en) | 2020-12-28 | 2020-12-28 | Preparation method of [2- (6-chloropyrimidine-4-oxygen) phenyl ] -3, 3-dimethoxyacrylic acid methyl ester |
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| CN116120241A (en) * | 2023-02-27 | 2023-05-16 | 江苏快达农化股份有限公司 | Method for synthesizing azoxystrobin intermediate by using composite catalyst |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102311392A (en) * | 2011-08-24 | 2012-01-11 | 重庆紫光化工股份有限公司 | Synthetic method of azoxystrobin and special intermediate for synthesis |
| CN104926736A (en) * | 2015-05-29 | 2015-09-23 | 重庆紫光化工股份有限公司 | Synthesis methods for azoxystrobin and intermediate thereof |
| CN104974097A (en) * | 2015-05-29 | 2015-10-14 | 重庆紫光化工股份有限公司 | Azoxystrobin synthesis method |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102311392A (en) * | 2011-08-24 | 2012-01-11 | 重庆紫光化工股份有限公司 | Synthetic method of azoxystrobin and special intermediate for synthesis |
| WO2013026391A1 (en) * | 2011-08-24 | 2013-02-28 | 重庆紫光化工股份有限公司 | Synthesis method of azoxystrobin and exclusive intermediate in the synthesis thereof |
| CN104926736A (en) * | 2015-05-29 | 2015-09-23 | 重庆紫光化工股份有限公司 | Synthesis methods for azoxystrobin and intermediate thereof |
| CN104974097A (en) * | 2015-05-29 | 2015-10-14 | 重庆紫光化工股份有限公司 | Azoxystrobin synthesis method |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN116120241A (en) * | 2023-02-27 | 2023-05-16 | 江苏快达农化股份有限公司 | Method for synthesizing azoxystrobin intermediate by using composite catalyst |
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