CN108409616B - Preparation method of 3-bromomethyl-2-halo-4-alkylsulfonylbenzoate - Google Patents
Preparation method of 3-bromomethyl-2-halo-4-alkylsulfonylbenzoate Download PDFInfo
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Abstract
The invention relates to the field of pesticides, and discloses a preparation method of 3-bromomethyl-2-halo-4-alkylsulfonylbenzoate, which comprises the following steps: in the presence of acid and initiator, the substrate compound is contacted and reacted with bromate and bromide. According to the method, bromate and sodium bromide are used as brominating agents, and a target product is obtained under the action of acid. Wherein, bromate and bromide are cheap, meanwhile, when 3-bromomethyl-2-halo-4-alkylsulfonylbenzoate is used as an intermediate to further prepare the tembotrione herbicide, bromide salt can be generated, and the bromide salt can be reused in the invention, so that the bromide salt can be recycled and reused; moreover, the method has high yield; therefore, the method is suitable for large-scale industrial production.
Description
Technical Field
The invention relates to the field of pesticides, and in particular relates to a preparation method of 3-bromomethyl-2-halo-4-alkylsulfonylbenzoate.
Background
3-bromomethyl-2-halo-4-alkylsulfonylbenzoate, an intermediate in the preparation of the pesticide herbicide tembotrione.
WO2000021924 discloses a preparation method of 3-bromomethyl-2-chloro-4-methylsulfonyl methyl benzoate, which is to react 3-methyl-2-chloro-4-methylsulfonyl methyl benzoate with a brominating agent NBS (N-bromosuccinimide) to obtain 3-bromomethyl-2-chloro-4-methylsulfonyl methyl benzoate. In addition, CN02817704 discloses a preparation method of 3-bromomethyl-2-chloro-4-methylsulfonylbenzoic acid, which comprises reacting 3-methyl-2-chloro-4-methylsulfonylbenzoic acid with a brominating agent NBS to obtain 3-bromomethyl-2-chloro-4-methylsulfonylbenzoic acid. In these bromination methods, although the yields are high, up to 87-90%, the cost of preparation is high due to the high price of NBS.
Disclosure of Invention
The invention aims to overcome the defect of high cost of preparing 3-bromomethyl-2-halo-4-alkylsulfonylbenzoate by adopting the prior art, and provides a preparation method of 3-bromomethyl-2-halo-4-alkylsulfonylbenzoate.
In order to achieve the above object, the present invention provides a method for producing 3-bromomethyl-2-halo-4-alkylsulfonylbenzoate represented by the formula (1), characterized by comprising: in the presence of acid and an initiator, carrying out contact reaction on the compound shown in the formula (2), the compound shown in the formula (3) and the compound shown in the formula (4);
wherein R is1Is C1-C7A straight or branched hydrocarbon group of (1); r2And R5Each independently is Li, Na or K; r3F, Cl or Br; r4Is C1-C5Alkyl group of (1).
In the invention, bromate and bromide are used as brominating agents, and a target product is obtained under the action of acid. Wherein, the bromate and the bromide are cheap; meanwhile, when 3-bromomethyl-2-halo-4-alkylsulfonylbenzoate is used as an intermediate to further prepare the tembotrione herbicide, bromide salt is generated, and can be reused in the invention, so that the bromide salt is recycled and reused; moreover, the method has high yield; therefore, the method is suitable for large-scale industrial production.
Additional features and advantages of the invention will be set forth in the detailed description which follows.
Detailed Description
The following describes in detail specific embodiments of the present invention. It should be understood that the detailed description and specific examples, while indicating the present invention, are given by way of illustration and explanation only, not limitation.
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 3-bromomethyl-2-halo-4-alkylsulfonylbenzoate shown in formula (1), which is characterized by comprising the following steps: in the presence of acid and an initiator, carrying out contact reaction on the compound shown in the formula (2), the compound shown in the formula (3) and the compound shown in the formula (4);
wherein R is1Is C1-C7A straight or branched hydrocarbon group of (1); r2And R5Each independently is Li, Na or K; r3F, Cl or Br; r4Is C1-C5Alkyl group of (1).
In the formula (2), R1Is C1-C7The straight-chain or branched hydrocarbon group of (b) may be, for example, a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a tert-butyl group, a n-pentyl group or a n-hexyl group. Preferably, R1Is C1-C3The straight-chain or branched hydrocarbon group of (2) may be, for example, a methyl group, an ethyl group or an isopropyl group.
In the formula (2), R3F, Cl or Br; preferably, R3Is Cl or Br; more preferably, R3Is Cl.
In the formula (2), R4Is C1-C5The alkyl group of (b) may be, for example, a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a tert-butyl group, a n-pentyl group, an isopentyl group, a neopentyl group or a tert-pentyl group; preferably, R4Is C1-C3The alkyl group of (b) may be, for example, a methyl group, an ethyl group, a n-propyl group or an isopropyl group; more preferably, R4Is methyl.
In the present invention, the compound represented by the formula (3)The compound is a bromate, which acts as a brominating agent required for the reaction. The bromate salt may be obtained commercially; the compound represented by formula (4) is a bromide salt, which also serves as a brominating agent required for the reaction. The bromates and bromides are commercially available and the bromides are also recovered. In the formulae (3) and (4), R2And R5Each independently is Li, Na or K; preferably, R2And R5Each independently is Na or K.
In the present invention, the amount of the compound represented by formula (3) is not particularly limited, but in order to make full use of the compound represented by formula (3) and the compound represented by formula (2) to improve reaction efficiency and reduce production cost, it is preferable that the molar ratio of the amount of the compound represented by formula (3) to the amount of the compound represented by formula (2) is 0.3 to 3: 1, preferably 0.35-0.5: 1.
in the present invention, the amount of the compound represented by formula (4) is not particularly limited, but in order to make full use of the compound represented by formula (4) and the compound represented by formula (2) to improve reaction efficiency and reduce production cost, it is preferable that the molar ratio of the amount of the compound represented by formula (4) to the amount of the compound represented by formula (2) is 0.5 to 3: 1, preferably 0.65 to 1: 1.
in the invention, the reaction principle of the contact reaction is that the compound shown in the formula (3) and the compound shown in the formula (4) generate active elemental bromine under the action of acid; under the action of an initiator, carrying out bromination reaction on the elemental bromine and a compound shown as a formula (2).
In the present invention, the acid may be an acid conventionally used in the art, and preferably, the acid is at least one of sulfuric acid, hydrochloric acid and phosphoric acid; more preferably, the acid is sulfuric acid and/or phosphoric acid; most preferably, the acid is sulfuric acid. The amount of the acid used in the present invention is not particularly limited as long as the acid is used in an amount that allows the compound represented by formula (3) and the compound represented by formula (4) to react completely, and preferably, the molar ratio of the amount of the acid used in terms of H to the amount of the compound represented by formula (2) is 0.8 to 4: 1, more preferably 1.2 to 2: 1.
in the present invention, the initiator is not particularly limited and may be an initiator conventionally used in the art, and preferably, the initiator is azobisisobutyronitrile and/or benzoyl peroxide. The amount of the initiator used in the present invention is not particularly limited as long as the amount of the initiator used is such that the contact reaction can be completely carried out, and preferably, the weight ratio of the amount of the initiator used to the amount of the compound represented by formula (2) is from 0.005 to 0.5: 1, preferably 0.01 to 0.2: 1, more preferably 0.03 to 0.1: 1.
in the present invention, the contact reaction is preferably carried out in a solvent. Preferably, the solvent is 1, 2-dichloroethane and/or chlorobenzene. In the present invention, the amount of the solvent is not particularly limited, but in order to completely dissolve the compound represented by the formula (2) in the solvent, the weight ratio of the amount of the solvent to the amount of the compound represented by the formula (2) is preferably 0.5 to 10: 1, preferably 2 to 6: 1, more preferably 3 to 5: 1.
when the solvent is a mixture of 1, 2-dichloroethane and chlorobenzene, the weight ratio of the 1, 2-dichloroethane to the chlorobenzene is preferably 0.2-5: 1.
in the present invention, the process of contact-reacting the compound represented by the formula (2) with the compound represented by the formula (3) preferably comprises the steps of:
(1) dissolving a compound represented by formula (2) in the solvent to obtain a solution, and adding a compound represented by formula (3) and a compound represented by formula (4) to the solution to obtain a mixture;
(2) and (2) reacting the mixture obtained in the step (1) under the action of acid and an initiator.
In the step (1), the compound represented by the formula (3) and the compound represented by the formula (4) are added in the form of an aqueous solution, preferably, the concentration of the aqueous solution of the compound represented by the formula (3) is 5 to 50% by weight, more preferably 20 to 40% by weight, further preferably 20 to 35% by weight; the concentration of the aqueous solution of the compound represented by the formula (4) is 5 to 50% by weight, more preferably 20 to 40% by weight, and still more preferably 20 to 35% by weight.
In step (2), the acid is added in the form of an aqueous solution, preferably, an aqueous solution of an acid is added dropwise to the mixture; more preferably, the concentration of the aqueous acid solution is 5 to 60% by weight, and still more preferably 20 to 40% by weight.
In the invention, after the acid is dripped, the heat preservation stirring reaction is continuously carried out at the temperature of dripping the aqueous solution of the reducing agent. The temperature of the dropwise addition of the aqueous acid solution and the reaction temperature in the step (2) are 30-130 ℃, preferably 60-100 ℃, and more preferably 70-90 ℃; the dropping time of the aqueous acid solution is 1 to 20 hours, preferably 2 to 15 hours, and more preferably 3 to 8 hours. After the addition of the aqueous acid solution is completed, the reaction is continued at the temperature for 0.5 to 3 hours, preferably 1 to 2 hours, with stirring, in order to complete the reaction.
In the invention, after the contact reaction is finished, the water phase and the organic phase are separated by standing and layering, the separated organic phase is leached once by using sodium sulfite aqueous solution, the organic solvent is recovered, and the compound shown in the formula (1) is obtained, and can be recrystallized and purified by using ethanol according to the requirement.
When 3-bromomethyl-2-halo-4-alkylsulfonylbenzoate is used as an intermediate to further prepare a cyclazone herbicide (for example, example 3b of WO 2000021924), a byproduct bromide salt is generated, and is recovered, and the recovered bromide salt can be reused in the invention, so that the recovery and the reuse of the bromide salt are realized. The method for recovering the bromide salt may be conventional in the art, for example, as exemplified in example 3b of WO2000021924, the bromide salt may be recovered by: and (3) carrying out negative pressure solvent removal on the reaction mixture obtained in the example 3b of WO2000021924, mixing the solution subjected to solvent removal with toluene and water, stirring, standing and layering to obtain a water layer, namely the bromide aqueous solution.
The present invention will be described in detail below by way of examples.
In the following examples, the target product was determined by liquid chromatography;
the yield was calculated by the following formula:
in the following examples, potassium bromate, sodium bromate, potassium bromide and sodium bromide were purchased from Beijing Chemicals, Inc.;
chlorobenzene, 1, 2-dichloroethane, azobisisobutyronitrile, benzoyl peroxide, sodium bisulfite, all from Beijing Chemicals;
2, 6-dichlorotoluene, 2, 6-dibromotoluene and sodium methyl mercaptide are all purchased from Beijing coupling technology Co., Ltd;
the preparation method comprises the following steps of self-making 2-chloro-3-methyl-4-methylsulfonyl methyl benzoate, 2-chloro-3-methyl-4-methylsulfonyl ethyl benzoate, 2-chloro-3-methyl-4-methylsulfonyl isopropyl benzoate and 2-bromo-3-methyl-4-ethylsulfonyl methyl benzoate:
compounds III, IV, V, VI were prepared according to the method of WO 2000021924: reacting a compound I with an anhydrous compound II by using hexamethylphosphoramide as a solvent to obtain a compound III; reacting the compound III with anhydrous aluminum trichloride and acetyl chloride to obtain a compound IV, and reacting with hydrogen peroxide to obtain a compound V; reacting the compound V with sodium hypochlorite to obtain a compound VI;
preparation of compound VII: adding 50g of compound VI and dichloroethane of 4 times of weight into a reaction bottle, heating to 60 ℃, dropwise adding thionyl chloride of 1.5 molar times of the compound VI, reacting at 70 ℃ for 3 hours after dropwise adding, removing excessive thionyl chloride and dichloroethane under negative pressure, and obtaining a residue in the bottle, namely a compound VII;
preparation of a compound represented by the formula (2): adding new dichloroethane, 2 times of the compound VIII in molar amount and 1.5 times of triethylamine in molar amount at 20-30 ℃ into the compound VII obtained in the previous step. After the triethylamine is dripped, stirring and reacting for 3 hours at 40 ℃, adding water, adjusting the pH to 2 by using HCl, standing, separating a water layer, washing an organic layer once to obtain a plurality of layers of compounds shown in the formula (2) after negative pressure desolventization;
in the preparation of methyl 2-chloro-3-methyl-4-methylsulfonylbenzoate, R1Is methyl, R3Is Cl, R4Is methyl;
in the preparation of ethyl 2-chloro-3-methyl-4-methylsulfonylbenzoate, R1Is ethyl, R3Is Cl, R4Is methyl;
preparation of isopropyl 2-chloro-3-methyl-4-methylsulfonylbenzoate, R1Is isopropyl, R3Is Cl, R4Is methyl;
in the preparation of methyl 2-bromo-3-methyl-4-ethylsulfonylbenzoate, R1Is methyl, R3Is Br, R4Is ethyl.
Example 1
30g (0.112mol) of methyl 2-chloro-3-methyl-4-methylsulfonylbenzoate and 120g of chlorobenzene were added to a 500mL four-necked reaction flask; dissolving 6.8g (0.045mol) of sodium bromate in 60g of water to obtain a sodium bromate aqueous solution, dissolving 11.6g (0.112mol) of sodium bromide in 60g of water to obtain a sodium bromate aqueous solution, and adding the obtained sodium bromate aqueous solution and the sodium bromate aqueous solution into the 500mL four-mouth reaction bottle; heating to 80 ℃ under stirring, and adding 0.93g (0.006mol) of azobisisobutyronitrile into a 500mL four-mouth reaction bottle; 19.2g (0.078mol) of 40% sulfuric acid aqueous solution is dropwise added under stirring at 80 ℃ for 3 hours; after the dripping is finished, stirring and reacting for 1 hour at 80 ℃, then standing and layering the mixture while the mixture is hot, and separating out a water phase; adding a small amount of sodium bisulfite aqueous solution into the organic phase for washing once, separating a water layer, recovering the solvent from the organic phase under negative pressure, adding ethanol into the obtained solid for recrystallization, and obtaining 35.9g of 3-bromomethyl-2-chloro-4-methylsulfonylbenzoic acid methyl ester with the purity of 98.1 percent and the yield of 92.1 percent.
Example 2
31.57g (0.112mol) of ethyl 2-chloro-3-methyl-4-methylsulfonylbenzoate and 94.71g of chlorobenzene were added to a 500mL four-necked reaction flask; 5.61g (0.034mol) of potassium bromate is dissolved in 20g of water to obtain a potassium bromate aqueous solution; adding 7.5g (0.0728mol) of sodium bromide into 30g of water to obtain an aqueous solution of the sodium bromide, and adding an aqueous solution of potassium bromate and an aqueous solution of the sodium bromide into a 500mL four-mouth reaction bottle; heating to 90 ℃ under stirring, and adding 3.16g (0.019mol) of azobisisobutyronitrile into a 500mL four-mouth reaction bottle; 41.16g (0.084mol) of 20% sulfuric acid aqueous solution is added dropwise at 90 ℃ while stirring, and the dropwise addition is completed within 4 hours; after the dripping is finished, stirring and reacting for 0.5 hour at 90 ℃, then standing and layering the mixture while the mixture is hot, and separating out a water phase; adding a small amount of sodium bisulfite aqueous solution into the organic phase for washing once, separating a water layer, recovering the solvent from the organic phase under negative pressure, adding ethanol into the obtained solid for recrystallization, and obtaining 37.32g (0.103mol) of 3-bromomethyl-2-chloro-4-methylsulfonylbenzoic acid ethyl ester, wherein the purity is 98.4 percent, and the yield is 92.2 percent.
Example 3
33.2g (0.112mol) of isopropyl 2-chloro-3-methyl-4-methylsulfonylbenzoate and 165.7g of 1, 2-dichloroethane were charged into a 500mL four-necked reaction flask; dissolving 8.46g (0.056mol) of sodium bromate in 30g of water to obtain a sodium bromate aqueous solution; dissolving 10.77g (0.090mol) of potassium bromide in 60g of water to obtain a potassium bromide aqueous solution, and adding a sodium bromate aqueous solution and a potassium bromide aqueous solution into the 500mL four-mouth reaction bottle; heating to 75 ℃ under stirring, and adding 2.32g (0.01mol) of benzoyl peroxide into a 500mL four-mouth reaction bottle; at 75 ℃, dropwise adding 27.5g (0.056mol) of 20% phosphoric acid aqueous solution while stirring, and finishing dropwise adding within 5 hours; after the dripping is finished, stirring and reacting for 2 hours at 75 ℃, then standing and layering the mixture while the mixture is hot, and separating out a water phase; adding a small amount of sodium bisulfite aqueous solution into the organic phase for washing once, separating a water layer, recovering the solvent from the organic phase under negative pressure, adding ethanol into the obtained solid for recrystallization, and obtaining 39.56g of 3-bromomethyl-2-chloro-4-methylsulfonylbenzoic acid isopropyl ester with the purity of 96.8 percent and the yield of 92.5 percent.
Example 4
The procedure is as in example 1, except that the reaction substrate is methyl 2-bromo-3-methyl-4-ethylsulfonylbenzoate. The product, methyl 3-bromomethyl-2-bromo-4-ethylsulfonylbenzoate, had a purity of 96.5% and a yield of 91.8%.
Example 5
The procedure is as in example 1, except that the solvent is a mixture of 1, 2-dichloroethane and chlorobenzene in a weight ratio 1, 2-dichloroethane to chlorobenzene of 0.5: 1. the purity of the product was 98.4% and the yield was 93.5%.
Comparative example 1
This comparative example illustrates the yield of 3-bromomethyl-2-chloro-4-methylsulfonylbenzoic acid methyl ester using NBS as the brominating agent.
The procedure is as in example 1, except that the brominating agent is NBS. The purity of the product was 94.8% and the yield was 87.9%.
Comparative example 2
This comparative example illustrates the yield of 3-bromomethyl-2-chloro-4-methylsulfonylbenzoic acid methyl ester from liquid bromine as the brominating agent.
30g (0.112mol) of methyl 2-chloro-3-methyl-4-methylsulfonylbenzoate and 120g of chlorobenzene were added to a 500mL four-necked reaction flask; dissolving 27.4g (0.17mol) of liquid bromine in 107g of water to obtain a bromine aqueous solution, and adding the obtained bromine aqueous solution into a 500mL four-mouth reaction bottle; heating to 80 ℃ under stirring, and adding 0.93g (0.006mol) of azobisisobutyronitrile into a 500mL four-mouth reaction bottle; 19.2g (0.078mol) of 40% sulfuric acid aqueous solution is dropwise added under stirring at 80 ℃ for 3 hours; after the dripping is finished, stirring and reacting for 1 hour at 80 ℃, then standing and layering the mixture while the mixture is hot, and separating out a water phase; adding a small amount of sodium bisulfite aqueous solution into the organic phase for washing once, separating out a water layer, recovering the solvent from the organic phase under negative pressure, adding ethanol into the obtained solid for recrystallization, and obtaining the product with the purity of 82.5 percent and the yield of 49.7 percent.
Comparative example 3
This comparative example serves to illustrate the preparation of methyl 3-bromomethyl-2-chloro-4-methylsulfonylbenzoate using sodium bromate and sodium bisulfite.
30g (0.112mol) of methyl 2-chloro-3-methyl-4-methylsulfonylbenzoate and 120g of chlorobenzene were added to a 500mL four-necked reaction flask; dissolving 25.6g (0.168mol) of sodium bromate in 100g of water to obtain a sodium bromate aqueous solution, and adding the obtained sodium bromate aqueous solution into a 500mL four-mouth reaction bottle; heating to 85 ℃ under stirring, and adding 0.93g (0.006mol) of azobisisobutyronitrile into a 500mL four-mouth reaction bottle; 59g (0.224mol) of 40% sodium bisulfite aqueous solution is dropwise added under stirring at 85 ℃ for 3 hours; after the dripping is finished, stirring and reacting for 1 hour at 85 ℃, then standing and layering the mixture while the mixture is hot, and separating out a water phase; adding a small amount of sodium bisulfite aqueous solution into the organic phase for washing once, separating a water layer, recovering the solvent from the organic phase under negative pressure, adding ethanol into the obtained solid for recrystallization, and obtaining 35.6g of 3-bromomethyl-2-chloro-4-methylsulfonylbenzoic acid methyl ester with the purity of 97.4 percent and the yield of 90.7 percent.
As can be seen from the comparison between example 1 and comparative example 1, the method of the present invention has higher yield and significantly lower cost than the method of brominating 3-bromomethyl-2-halo-4-alkylsulfonylbenzoate by using NBS as a brominating agent; as can be seen from the comparison of example 1 with comparative examples 2 and 3, the yield of 3-bromomethyl-2-halo-4-alkylsulfonylbenzoate prepared by the process of the present invention is higher.
The embodiment shows that the preparation method of the 3-bromomethyl-2-halo-4-alkylsulfonylbenzoate provided by the invention has the advantages of simple steps, mild conditions, low cost, high product yield, environmental protection and the like, and is suitable for large-scale industrial production.
The preferred embodiments of the present invention have been described in detail, however, the present invention is not limited to the specific details of the above embodiments, and various simple modifications may be made to the technical solution of the present invention within the technical idea of the present invention, and these simple modifications are within the protective scope of the present invention.
It should be noted that the various technical features described in the above embodiments can be combined in any suitable manner without contradiction, and the invention is not described in any way for the possible combinations in order to avoid unnecessary repetition.
In addition, any combination of the various embodiments of the present invention is also possible, and the same should be considered as the disclosure of the present invention as long as it does not depart from the spirit of the present invention.
Claims (2)
1. A preparation method of 3-bromomethyl-2-chloro-4-methylsulfonyl ethyl benzoate is characterized by comprising the following steps: adding 31.57g of ethyl 2-chloro-3-methyl-4-methylsulfonylbenzoate and 94.71g of chlorobenzene into a 500mL four-mouth reaction bottle; dissolving 5.61g of potassium bromate in 20g of water to obtain a potassium bromate aqueous solution; adding 7.5g of sodium bromide into 30g of water to obtain an aqueous solution of the sodium bromide, and adding an aqueous solution of potassium bromate and an aqueous solution of the sodium bromide into a 500mL four-mouth reaction bottle; heating to 90 ℃ under stirring, and adding 3.16g of azobisisobutyronitrile into a 500mL four-mouth reaction bottle; at 90 ℃, 41.16g of 20% sulfuric acid aqueous solution is dropwise added under stirring, and the dropwise addition is completed within 4 hours; after the dripping is finished, stirring and reacting for 0.5 hour at 90 ℃, then standing and layering the mixture while the mixture is hot, and separating out a water phase; and adding a small amount of sodium bisulfite aqueous solution into the organic phase for washing once, separating a water layer, recovering the solvent from the organic phase under negative pressure, and adding ethanol into the obtained solid for recrystallization to obtain 37.32g of 3-bromomethyl-2-chloro-4-methylsulfonylbenzoic acid ethyl ester.
2. A preparation method of 3-bromomethyl-2-chloro-4-methylsulfonyl methyl benzoate is characterized by comprising the following steps: 30g of methyl 2-chloro-3-methyl-4-methylsulfonylbenzoate and 120g of a mixture of 1, 2-dichloroethane and chlorobenzene were added to a 500mL four-necked reaction flask, wherein the weight ratio of the amount of 1, 2-dichloroethane to the amount of chlorobenzene was 0.5: 1; dissolving 6.8g of sodium bromate in 60g of water to obtain a sodium bromate aqueous solution, dissolving 11.6g of sodium bromide in 60g of water to obtain a sodium bromide aqueous solution, and adding the obtained sodium bromate aqueous solution and the sodium bromide aqueous solution into the 500mL four-mouth reaction bottle; heating to 80 ℃ under stirring, and adding 0.93g of azobisisobutyronitrile into a 500mL four-mouth reaction bottle; 19.2g of 40% sulfuric acid aqueous solution is dropwise added under stirring at the temperature of 80 ℃, and the dropwise addition is completed within 3 hours; after the dripping is finished, stirring and reacting for 1 hour at 80 ℃, then standing and layering the mixture while the mixture is hot, and separating out a water phase; adding a small amount of sodium bisulfite aqueous solution into the organic phase for washing once, separating out a water layer, recovering the solvent from the organic phase under negative pressure, and adding ethanol into the obtained solid for recrystallization to obtain the 3-bromomethyl-2-chloro-4-methylsulfonyl methyl benzoate.
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| CN111233721B (en) * | 2018-11-28 | 2022-12-13 | 沈阳科创化学品有限公司 | Synthesis method of 2-alkylthio-6-halogenated alkylbenzene |
| CN109369577A (en) * | 2018-12-28 | 2019-02-22 | 安徽工大化工科技有限公司 | A kind of furans sulphur humulone intermediate and preparation method thereof |
| CN112194603B (en) * | 2019-07-08 | 2022-11-18 | 长沙嘉桥生物科技有限公司 | Preparation method of 2-chloro-3-methyl-4-methylsulfonylbenzoic acid |
| CN112778171A (en) * | 2019-11-07 | 2021-05-11 | 帕潘纳(北京)科技有限公司 | Preparation method of 3-bromomethyl-2-chloro-4-methylsulfonylbenzoic acid |
| CN112851549A (en) * | 2021-03-11 | 2021-05-28 | 安徽云帆药业有限公司 | Experiment method for sodium bromide application |
| CN115232039B (en) * | 2022-09-21 | 2023-01-13 | 启农生物科技(北京)有限公司 | Preparation method of 3-methyl-2-chloro-4-methylsulfonyl methyl benzoate |
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| CN106083668A (en) * | 2016-06-20 | 2016-11-09 | 北京颖泰嘉和生物科技股份有限公司 | A kind of preparation method of 3 bromomethyl 2 halo 4 alkyl sulphonyl benzoate |
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