CN113968814A - Method for preparing 5-bromomethyl-2, 3-pyridine carboxylic acid dimethyl ester - Google Patents
Method for preparing 5-bromomethyl-2, 3-pyridine carboxylic acid dimethyl ester Download PDFInfo
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- CN113968814A CN113968814A CN202010710177.6A CN202010710177A CN113968814A CN 113968814 A CN113968814 A CN 113968814A CN 202010710177 A CN202010710177 A CN 202010710177A CN 113968814 A CN113968814 A CN 113968814A
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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
- C07D213/79—Acids; Esters
- C07D213/80—Acids; Esters in position 3
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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
- C07D213/79—Acids; Esters
- C07D213/803—Processes of preparation
Abstract
The invention relates to an imidazolinone herbicide technology, and discloses a method for preparing 5-bromomethyl-2, 3-pyridine carboxylic acid dimethyl ester, which comprises the following steps: the compound shown in the formula (II) is in contact reaction with hydrobromic acid in the presence of an organic solvent, an initiator and hydrogen peroxide. In the process for preparing the 5-bromomethyl-2, 3-pyridine carboxylic acid dimethyl ester (namely the compound shown in the formula (I)), the advantage of high product yield can be realized on the premise of avoiding using bromine, and meanwhile, the cost of raw materials can be effectively reduced, the three wastes generated in the process can be reduced, and the post-treatment steps of the product can be simplified.
Description
Technical Field
The invention relates to an imidazolinone herbicide technology, in particular to a method for preparing 5-bromomethyl-2, 3-pyridine carboxylic acid dimethyl ester.
Background
Imidazolinone herbicides are a large class of high-efficiency, low-toxicity, broad-spectrum herbicides developed by cyanamide company of America, and imidazolinone herbicides such as imazamox, imazaquin, imazapic, imazethapyr, and imazethapyr have been commercialized so far.
The action mechanism of the imidazolone herbicides is mainly to inhibit the biosynthesis of side chain amino acids by inhibiting ALS. The characteristics of high activity, low dosage, good weeding effect and the like enable the herbicide to be used in large quantities.
The 5-bromomethyl-2, 3-pyridine carboxylic acid dimethyl ester is an important fine chemical intermediate for synthesizing imazamox and imazapic, and the preparation method of the 5-bromomethyl-2, 3-pyridine carboxylic acid dimethyl ester in the prior art mainly comprises the following 2 methods:
1. EP0548532A1 discloses that the bromination reaction of 5-methyl-2, 3-pyridine carboxylic acid dimethyl ester and excessive NBS or dibromohydantoin is carried out, the price of the NBS and the dibromohydantoin in the method is high, the cost of the process route is high, the amplification reaction is not easy to control, and the generated solid waste is excessive; the CN109467531A uses bromine, the reaction conversion rate is low, the post treatment is complex, and the environment is greatly polluted due to improper use of the bromine.
2. CN107216286A relates to a method for preparing a brominated copolymer by carrying out bromination reaction on 5-methyl-2, 3-pyridinecarboxylic acid dimethyl ester serving as a raw material and hydrobromic acid in an organic solvent under the condition that sodium bromate and azobisisobutyronitrile are jointly used as an initiator, although the reaction rate of the synthesis route is high, the synthesis process route generates more by-products of multi-substituted bromine (di-substituted bromine and tri-substituted bromine) so as to reduce the product yield and generate more solid wastes such as sodium bromide, the reaction process is not easy to control, the production process steps and the production cost are increased, in addition, the wastewater amount is huge, the post-treatment is difficult, and the environmental pollution is serious.
Disclosure of Invention
The invention aims to overcome the defects of high product purity and yield caused by a plurality of byproducts in the process of producing 5-bromomethyl-2, 3-pyridine carboxylic acid dimethyl ester in the prior art.
In order to achieve the above object, the present invention provides, in a first aspect, a process for preparing a dimethyl 5-bromomethyl-2, 3-pyridinecarboxylate compound represented by formula (I), which comprises: in the presence of an organic solvent, an initiator and hydrogen peroxide, carrying out contact reaction on the compound shown in the formula (II) and hydrobromic acid;
wherein the conditions of the contact reaction satisfy: the temperature is 50-90 ℃;
the initiator is azobisisobutyronitrile and/or dibenzoyl peroxide.
The method for preparing the 5-bromomethyl-2, 3-pyridine carboxylic acid dimethyl ester compound shown in the formula (I) has the advantages of high yield and high purity.
More specifically, the method for preparing the 5-bromomethyl-2, 3-pyridine carboxylic acid dimethyl ester compound shown in the formula (I) can overcome the defects of difficulty in controlling the reaction process, complex production process steps, high production cost, serious environmental pollution and the like, and has the advantages of high yield, less solid waste, simple post-treatment process and the like.
Preferably, the method for preparing the 5-bromomethyl-2, 3-pyridine carboxylic acid dimethyl ester compound shown in the formula (I) can overcome the defects of difficult control of reaction process, complex post-treatment process and the like in the prior art for preparing the 5-bromomethyl-2, 3-pyridine carboxylic acid dimethyl ester compound shown in the formula (I).
Other features and advantages of the present invention will be described in more detail in the detailed description that follows.
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.
As described above, the present invention provides a process for producing a 5-bromomethyl-2, 3-pyridinecarboxylic acid dimethyl ester compound represented by the formula (I), which comprises: in the presence of an organic solvent, an initiator and hydrogen peroxide, carrying out contact reaction on the compound shown in the formula (II) and hydrobromic acid;
wherein the conditions of the contact reaction satisfy: the temperature is 50-90 ℃;
the initiator is azobisisobutyronitrile and/or dibenzoyl peroxide.
Preferably, the hydrogen peroxide is used in the form of a solution; the concentration of the hydrogen peroxide solution in the present invention is not particularly limited, and may be, for example, a hydrogen peroxide solution having a mass concentration of 15 to 45 wt%, and the mass concentration of hydrogen peroxide is, for example, 15 wt%, 20 wt%, 25 wt%, 30 wt%, 35 wt%, 40 wt%, 45 wt%, or any value in the range of any two of these values.
However, the hydrogen peroxide is metered in the present invention hereinafter in pure form, unless otherwise specified.
Preferably, the hydrobromic acid is used in the form of a solution; the concentration of the hydrobromic acid solution in the present invention is not particularly limited, and for example, the hydrobromic acid solution may have a mass concentration of 25 to 55 wt%, and the hydrobromic acid may be, for example, 25 wt%, 30 wt%, 35 wt%, 40 wt%, 45 wt%, 50 wt%, 55 wt%, or any value in the range defined by any two of these values.
However, the hydrobromic acid is metered in pure form in the present invention hereinafter, unless otherwise specified.
In the present invention, the temperature of the contact reaction is 50 to 90 ℃, and may be, for example, 50 ℃, 60 ℃, 70 ℃, 80 ℃, 90 ℃ or any value in the range of any two of these values.
In the present invention, the compound represented by formula (II) can be synthesized by a method known in the art, or can be commercially available.
In the present invention, in the contact reaction, the compound represented by the formula (II), the hydrogen peroxide, and the hydrobromic acid are used in a molar ratio of 1: 3.0-6.0: 2.0-4.0.
More preferably, in the contact reaction, the compound represented by the formula (II), the hydrogen peroxide and the hydrobromic acid are used in a molar ratio of 1: 4.0-5.0: 3.0-4.0.
In the contact reaction, the compound shown in the formula (II) and the initiator are used in a molar ratio of 1: 0.01-0.05; more preferably, in the contact reaction, the compound represented by the formula (II) and the initiator are used in a molar ratio of 1: 0.03-0.04. The inventors have found that in this preferred embodiment, the protocol of the invention has the advantage that the course of the reaction is more easily controlled.
Preferably, the initiator is azobisisobutyronitrile. The inventors have found that in this preferred embodiment, the scheme of the present invention has a higher reaction yield.
In the present invention, preferably, the conditions of the contact reaction include: the temperature is 70-80 ℃, the time is 2-20h, and can be any value in the range of 2h, 3h, 5h, 7h, 9h, 11h, 13h, 15h, 17h, 20h and any two of the values. The inventors have found that in this preferred embodiment, the scheme of the present invention has a higher reaction yield.
Preferably, the organic solvent is at least one selected from acetonitrile, chlorobenzene, dichloromethane, chloroform, dichloroethane, trichloroethylene and tetrachloroethylene. Preferably, the organic solvent is dichloroethane. The inventors have found that in this preferred embodiment, the compounds of formula (I) in the scheme of the present invention are more pure.
In the present invention, the amount of the organic solvent used is not particularly limited as long as it allows sufficient contact between the reactants, and illustratively, the weight ratio of the amount of the organic solvent used to the amount of the compound represented by formula (II) is 3.0 to 5.0: 1.0.
in the present invention, the contact reaction may be a reaction in which the organic solvent, the initiator, the hydrogen peroxide, the compound represented by the formula (II) and hydrobromic acid are mixed so that the compound represented by the formula (II) and the hydrobromic acid can be contacted to react.
Preferably, the process of the contact reaction comprises: (a) carrying out first mixing on the organic solvent and the compound shown in the formula (II) and heating to obtain a material I with the temperature of 70-80 ℃; (b) second mixing the material I with the hydrobromic acid and the hydrogen peroxide in the presence of the initiator to obtain a material II.
Preferably, in the step (b), the initiator participates in the second mixing by means of dropwise addition. The inventors have found that the compound of formula (I) can be obtained in high purity and high yield by using azobisisobutyronitrile alone as the initiator of the present invention.
Preferably, the process for preparing the compound of formula (I) further comprises: and thirdly mixing the material II obtained after the contact reaction with a sodium bisulfite aqueous solution to obtain a material III, and purifying the material III to obtain the compound shown in the formula (I) with the purity of more than 95 wt%.
Preferably, the purification treatment process comprises: and (3) sequentially carrying out standing, layering and reduced pressure distillation on the material III. The inventors have found that in this preferred embodiment, the compounds of formula (I) according to the scheme of the present invention are more pure.
Illustratively, the purification treatment process comprises standing the mixture III for layering to obtain an organic layer containing the compound represented by the formula (I) and an aqueous layer, and removing the organic solvent from the organic layer by distillation under reduced pressure to obtain a purified compound represented by the formula (I).
Through the technical scheme, the process for preparing the compound shown in the formula (I) avoids using sodium bromate and bromine, effectively reduces the cost of raw materials, reduces three wastes generated in the process, and has high product yield.
The present invention will be described in detail below by way of examples. In the following examples of the present invention,
the amounts of reactants and products were determined by liquid chromatography (Agilent HPLC 1260).
The yield of the reaction was calculated by the following formula:
yield ═ molar amount of reaction product formed/initial molar amount of key component × 100%.
In the case where no particular mention is made, the starting materials used are commercially available products, and the content of the compound represented by the formula (I) means the mass percentage of the compound represented by the formula (I) in the final product.
Example 1
(1) 88.08g of dichloroethane and the compound (0.1 mol of pure substance) with the concentration of 95.0 weight percent shown in the formula (II) are added into a 250ml four-mouth reaction bottle provided with a mechanical stirring, a thermometer and a condenser tube, the temperature is raised to 75 ℃, and the mixture is stirred and reacted for 3 hours to obtain a mixed material I;
(2) slowly dropwise adding a hydrobromic acid aqueous solution with the concentration of 40 wt% (0.3 mol of pure substance) and a dioxygen aqueous solution with the concentration of 30 wt% (0.5 mol of pure substance) into the material I obtained in the step (1), adding 4mmol of azobisisobutyronitrile into the material I every 1.0h, carrying out reflux reaction for 5 hours, and monitoring the completion of the reaction by using HPLC (high performance liquid chromatography) to obtain a reaction material II;
(3) the reaction material II was washed once with an aqueous sodium bisulfite solution, the washed solution was allowed to stand and layer-separate to obtain an organic layer containing the compound represented by formula (I), and dichloroethane was removed by depressurization to obtain a material III in which the content of the compound represented by formula (I) was 95.59% by weight and the yield was 96.0% (obtained based on the compound represented by formula (II)).
Example 2
(1) 88.08g of dichloroethane and the compound (0.1 mol of pure substance) with the concentration of 95.0 weight percent shown in the formula (II) are added into a 250ml four-mouth reaction flask provided with a mechanical stirring, a thermometer and a condenser tube, the temperature is raised to 75 ℃, and the mixture is stirred and reacted for 5 hours to obtain a mixed material I;
(2) slowly dropwise adding a hydrobromic acid aqueous solution with the concentration of 40 wt% (0.4 mol of pure substance) and a dioxygen aqueous solution with the concentration of 30 wt% (0.5 mol of pure substance) into the material I obtained in the step (1), adding 3mmol of azobisisobutyronitrile into the material I every 1.0h, carrying out reflux reaction for 10 hours, and monitoring the completion of the reaction by using HPLC (high performance liquid chromatography) to obtain a reaction material II;
(3) the reaction material II was washed once with an aqueous sodium bisulfite solution, the washed solution was allowed to stand and layer, an organic layer containing the compound represented by formula (I) was obtained, and dichloroethane was removed by depressurization, whereby a material III was obtained in which the content of the compound represented by formula (I) was 96.2% by weight and the yield was 96.87% (obtained based on the compound represented by formula (II)).
Example 3
(1) 88.08g of chloroform and a compound (0.1 mol of pure substance) with the concentration of 95.0 weight percent shown in the formula (II) are added into a 250ml four-mouth reaction bottle provided with a mechanical stirring device, a thermometer and a condenser, the temperature is raised to 75 ℃, and the mixture is stirred and reacted for 3 hours to obtain a mixed material I;
(2) slowly dropwise adding a hydrobromic acid aqueous solution with the concentration of 40 wt% (0.3 mol of pure substance) and a dioxygen aqueous solution with the concentration of 30 wt% (0.4 mol of pure substance) into the material I obtained in the step (1), adding 4mmol of azobisisobutyronitrile into the material I every 1.0h, carrying out reflux reaction for 12 hours, and monitoring the completion of the reaction by using HPLC (high performance liquid chromatography) to obtain a reaction material II;
(3) the reaction material II was washed once with an aqueous sodium bisulfite solution, the washed solution was allowed to stand and layer-separate to obtain an organic layer containing the compound represented by formula (I), and chloroform was removed from the organic layer under reduced pressure to obtain a material III having a content of the compound represented by formula (I) of 96.03% by weight and a yield of 95.26% (obtained based on the compound represented by formula (II)).
Example 4
This example was carried out in a similar manner to example 1, except that:
the initiator used in this example was dibenzoyl peroxide in the same molar amount as in example 1.
The content of the compound represented by the formula (I) in the obtained material III was 95.3% by weight, and the yield was 90.26% (obtained based on the compound represented by the formula (II)).
Example 5
(1) 63.54g of dichloroethane and the compound (0.1 mol of pure substance) with the concentration of 95.0 weight percent shown in the formula (II) are added into a 250ml four-mouth reaction bottle provided with a mechanical stirring device, a thermometer and a condenser tube, the temperature is raised to 80 ℃, and the mixture is stirred and reacted for 5 hours to obtain a mixed material I;
(2) slowly dropwise adding a hydrobromic acid aqueous solution with the concentration of 40 wt% (0.4 mol of pure substance) and a hydrogen peroxide aqueous solution with the concentration of 35 wt% (0.5 mol of pure substance) into the material I obtained in the step (1), adding 3.5mmol of azobisisobutyronitrile every 1.0h, carrying out reflux reaction for 10 hours, and monitoring the completion of the reaction by using HPLC (high performance liquid chromatography) to obtain a reaction material II;
(3) the reaction material II was washed once with an aqueous sodium bisulfite solution, the washed solution was allowed to stand and layer, an organic layer containing the compound represented by formula (I) was obtained, and dichloroethane was removed by depressurization, whereby a material III was obtained in which the content of the compound represented by formula (I) was 95.84% by weight and the yield was 95.69% (obtained based on the compound represented by formula (II)).
Example 6
(1) Adding 79.42g of acetonitrile and 95.0 weight percent of compound (0.1 mol of pure substance) shown in formula (II) into a 250ml four-mouth reaction bottle provided with a mechanical stirring device, a thermometer and a condenser, heating to 70 ℃, and stirring for reaction for 5 hours to obtain a mixed material I;
(2) slowly dropwise adding 35 wt% hydrobromic acid aqueous solution (pure substance weight is 0.3mol) and 30 wt% hydrogen peroxide aqueous solution (pure substance weight is 0.4mol) into the material I obtained in the step (1), adding 3mmol azobisisobutyronitrile into the material I every 1.0h, carrying out reflux reaction for 10 hours, and monitoring the completion of the reaction by using HPLC (high performance liquid chromatography) to obtain a reaction material II;
(3) the reaction material II was washed once with an aqueous sodium bisulfite solution, the washed solution was allowed to stand and layer, an organic layer containing the compound represented by formula (I) was obtained, and dichloroethane was removed by depressurization, whereby a material III was obtained in which the content of the compound represented by formula (I) was 96.15% by weight and the yield was 95.19% (based on the compound represented by formula (II)).
Comparative example 1
(1) 88.08g of dichloroethane and the compound (0.1 mol of pure substance) with the concentration of 95.0 weight percent shown in the formula (II) are added into a 250ml four-mouth reaction bottle provided with a mechanical stirring, a thermometer and a condenser tube, the temperature is raised to 75 ℃, and the mixture is stirred and reacted for 3 hours to obtain a mixed material I;
(2) slowly dropwise adding 32.0g of bromine into the material I obtained in the step (1), adding 4mmol of azobisisobutyronitrile into the material I every 1.0h, carrying out reflux reaction for 5 hours, and monitoring the completion of the reaction by using HPLC (high performance liquid chromatography) to obtain a reaction material II;
(3) the reaction material II was washed once with an aqueous sodium bisulfite solution, the washed solution was allowed to stand and layer-separate to obtain an organic layer containing the compound represented by formula (I), and dichloroethane was removed by depressurization to obtain a material III having a content of the compound represented by formula (I) of 95.69% by weight and a yield of 80.34% (based on the compound represented by formula (II)).
Comparative example 2
(1) 88.08g of dichloroethane and the compound (0.1 mol of pure substance) with the concentration of 95.0 weight percent shown in the formula (II) are added into a 250ml four-mouth reaction bottle provided with a mechanical stirring, a thermometer and a condenser tube, the temperature is raised to 75 ℃, and the mixture is stirred and reacted for 3 hours to obtain a mixed material I;
(2) slowly dropwise adding 40 wt% hydrobromic acid aqueous solution (pure substance weight is 0.3mol) into the material I obtained in the step (1), adding 2mmol azodiisobutyronitrile and 2mmol sodium bromate every 1.0h, carrying out reflux reaction for 5 hours, and monitoring the completion of the reaction by using HPLC (high performance liquid chromatography) to obtain a reaction material II;
(3) adding a sodium bisulfite aqueous solution into the reaction material II to wash the reaction material II once to obtain a material III, adjusting the pH value of the washed material III to 6.0 +/-0.2 by using a sodium hydroxide solution, stirring the mixture, standing the mixture for layering to obtain an organic layer containing the compound shown in the formula (I), decompressing the organic layer to remove dichloroethane, and obtaining a material IV, wherein the content of the compound shown in the formula (I) is 85.3 wt%, and the yield is 81.1% (calculated by taking the compound shown in the formula (II) as a reference).
The results of the above examples show that the process for preparing dimethyl 5-bromomethyl-2, 3-pyridinecarboxylate (i.e., the compound represented by formula (I)) of the present invention can achieve the advantage of high product yield without using bromine, and at the same time, can effectively reduce the cost of raw materials, reduce three wastes generated during the process, and simplify the product post-treatment steps.
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 process for producing a 5-bromomethyl-2, 3-pyridinecarboxylic acid dimethyl ester compound represented by the formula (I), which comprises: in the presence of an organic solvent, an initiator and hydrogen peroxide, carrying out contact reaction on the compound shown in the formula (II) and hydrobromic acid;
wherein the conditions of the contact reaction satisfy: the temperature is 50-90 ℃;
the initiator is azobisisobutyronitrile and/or dibenzoyl peroxide.
2. The method of claim 1, wherein the compound represented by formula (II), the hydrogen peroxide and the hydrobromic acid are used in a molar ratio of 1: 3.0-6.0: 2.0-4.0;
preferably, the compound shown in the formula (II), the hydrogen peroxide and the hydrobromic acid are used in a molar ratio of 1: 4.0-5.0: 3.0-4.0.
3. The process according to claim 1 or 2, wherein the compound of formula (II) and the initiator are used in a molar ratio of 1: 0.01-0.05;
preferably, the compound represented by the formula (II) and the initiator are used in a molar ratio of 1: 0.03-0.04.
4. The method of any one of claims 1-3, wherein the initiator is azobisisobutyronitrile.
5. The method of any one of claims 1-4, wherein the conditions of the contact reaction comprise: the temperature is 70-80 ℃ and the time is 2-20 h.
6. The process according to any one of claims 1 to 5, wherein the organic solvent is selected from at least one of acetonitrile, chlorobenzene, dichloromethane, chloroform, dichloroethane, trichloroethylene, tetrachloroethylene.
7. The method of any one of claims 1-6, wherein the organic solvent is dichloroethane.
8. The method of any one of claims 1-7, wherein the contacting comprises:
(a) carrying out first mixing on the organic solvent and the compound shown in the formula (II) and heating to obtain a material I with the temperature of 70-80 ℃;
(b) second mixing the material I with the hydrobromic acid and the hydrogen peroxide in the presence of the initiator to obtain a material II.
9. The method of any one of claims 1-8, wherein the method further comprises: and thirdly mixing the material II obtained after the contact reaction with a sodium bisulfite aqueous solution to obtain a material III, and purifying the material III to obtain the compound shown in the formula (I) with the purity of more than 95 wt%.
10. The method of claim 9, wherein the purifying process comprises: and (3) sequentially carrying out standing, layering and reduced pressure distillation on the material III.
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| CN114933561A (en) * | 2022-05-09 | 2022-08-23 | 沈阳万菱生物技术有限公司 | Preparation method of 5-substituted-2, 3-pyridine dicarboxylic ester compound and quaternary ammonium salt thereof |
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