CN115232039A - Preparation method of 3-methyl-2-chloro-4-methylsulfonyl methyl benzoate - Google Patents
Preparation method of 3-methyl-2-chloro-4-methylsulfonyl methyl benzoate Download PDFInfo
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Abstract
The invention belongs to the field of chemical industry, and provides a preparation method of an intermediate 3-methyl-2-chloro-4-methylsulfonyl methyl benzoate for synthesizing benzoylcyclohexanediones, which comprises the following steps: (1) Selecting sulfuric acid as an acid catalytic reagent, and slowly dripping concentrated nitric acid into a raw material 3-methyl-2-chloro-4-methylthioacetophenone (compound 1) at the temperature of 40-80 ℃ to perform oxidation reaction so as to generate 3-methyl-2-chloro-4-methylsulfinylbenzoic acid (compound 2); (2) Adding absolute methanol to carry out esterification reaction to generate 3-methyl-2-chlorine-4-methylsulfinylbenzoic acid methyl ester (compound 3); (3) An oxidizing agent is added to carry out an oxidation reaction to produce methyl 3-methyl-2-chloro-4-methylsulfonylbenzoate (compound 4). In the inventionThe method is a continuous production method, has simple steps, does not need post-treatment operation among reaction steps, and is particularly suitable for industrial production.
Description
Technical Field
The invention belongs to the field of chemical industry, relates to a preparation method of 3-methyl-2-chloro-4-methylsulfonyl methyl benzoate, and particularly provides a preparation method of 3-methyl-2-chloro-4-methylsulfonyl methyl benzoate used as an intermediate for synthesizing benzoylcyclohexanediones.
Background
Methyl 3-methyl-2-chloro-4-methylsulfonylbenzoate is an important fine chemical intermediate for the synthesis of herbicides of the benzoylcyclohexanedione type, such as tembotrione, benzofuranone and triafamone.
Several conventional processes for preparing methyl 3-methyl-2-chloro-4-methylsulfonylbenzoate exist in the prior art. One preparation process is shown in the following route I, 2, 6-dichlorotoluene or 3-chloro-2-methylaniline is used as a raw material and reacts with a sodium methyl mercaptide solution to prepare 2-methyl-3-chlorobenzenethioether; reacting and acylating 2-methyl-3-chlorobenzenethioate and acetyl chloride, and oxidizing with hydrogen peroxide to obtain 3-methyl-2-chloro-4-methylsulfonyl acetophenone; oxidizing by sodium hypochlorite to obtain 3-methyl-2-chloro-4-methylsulfonylbenzoic acid; further, 3-methyl-2-chloro-4-methylsulfonylbenzoic acid was reacted with thionyl chloride and anhydrous methanol to obtain methyl 3-methyl-2-chloro-4-methylsulfonylbenzoate.
Route one
Both "research and development progress on application of herbicide tembotrione" (current pesticide "volume 16, stage 5, pages 40-44, 2017.10) of lingling et al and" synthesis of novel herbicide tembotrione and pesticide spirotetramat "of yuyu jade" disclose tembotrione synthesis routes, wherein the preparation of an intermediate methyl 2-substituted-3-methyl-4-methylsulfonylbenzoate shown in the first route is involved.
Furthermore, the existing preparation process also includes a method for preparing 2-substituted-3-methyl-4-methylsulfonyl methyl benzoate as disclosed in chinese patent application CN105601548A, specifically, glacial acetic acid is used as a solvent, sodium tungstate is used as a catalyst, 2-chloro-3-methyl-4-methylthioacetophenone is used as a raw material, sodium tungstate is used as a catalyst, hydrogen peroxide is added dropwise to perform an oxidation reaction, and after the reaction is completed, post-treatment is performed to obtain a solid 2-substituted-3-methyl-4-methylsulfonyl acetophenone; taking dioxane as a solvent and 2-substituted-3-methyl-4-methylsulfonyl acetophenone as a raw material, dropwise adding sodium hypochlorite, heating to 80 ℃, preserving heat for reaction to generate 2-substituted-3-methyl-4-methylsulfonyl benzoic acid, after complete reaction, evaporating the solvent under reduced pressure, then cooling to 40 ℃, dropwise adding hydrochloric acid to adjust the pH value to 2, filtering, and drying to obtain a white solid with the yield of 95%; adding methanol, 2-substituted-3-methyl-4-methylsulfonyl benzoic acid and thionyl chloride, controlling the reaction temperature not to exceed 25 ℃, heating to reflux reaction, carrying out esterification reaction to obtain 2-substituted-3-methyl-4-methylsulfonyl methyl benzoate, cooling to room temperature after the reaction is finished, carrying out suction filtration, and drying to obtain a solid with the yield of 93.4%. Likewise, german patent application DE19846792A and Chinese patent application CN1323292A also disclose in their chemical examples a similar process for the preparation of the intermediate methyl 2-substituted-3-methyl-4-methylsulfonylbenzoate, starting from 2-chloro-3-methyl-4-methylthioacetophenone, in which glacial acetic acid is used as solvent, sodium tungstate is used as catalyst, a solution of hydrogen peroxide is added dropwise and simultaneously cooled, the mixture is stirred at room temperature, diluted with water, the precipitated solid is filtered off with suction, washed and dried, in a yield of 48% of theory; dissolving 2-chloro-3-methyl-4-methylsulfonylacetophenone in dioxane, adding a sodium hypochlorite solution for treatment, heating the mixture at 80 ℃, cooling, separating a bottom phase, diluting with water, acidifying with HCl, sucking precipitated solids, washing with water, and drying to obtain 2-chloro-3-methyl-4-methylsulfonylbenzoic acid with a theoretical yield of 88%; 2-chloro-3-methyl-4-methylsulfonylbenzoic acid is dissolved in methanol, HCl is introduced at reflux temperature, and the mixture is then left to cool and concentrated on a rotary evaporator to give methyl 2-chloro-3-methyl-4-methylsulfonylbenzoate in a yield of 98% of theory. In these patent documents, the yield of the intermediate 2-chloro-3-methyl-4-methylsulfonylbenzoic acid methyl ester from the starting material to the intermediate 2-chloro-3-methyl-4-methylsulfonylbenzoic acid methyl ester is very limited because the intermediate obtained in each reaction requires post-treatment to obtain the reactant for the next reaction.
It can be easily found that the existing preparation process of the intermediate methyl 2-chloro-3-methyl-4-methylsulfonylbenzoate described above has the following disadvantages:
1. the 3-methyl-2-chloro-4-methylsulfonyl acetophenone is oxidized to generate 3-methyl-2-chloro-4-methylsulfonyl benzoic acid by using excessive sodium hypochlorite, and then excessive hydrochloric acid is needed to generate acid by acidification, the oxidation process generates a large amount of waste acid water, and the waste acid water treatment cost is high, so that the production cost is obviously increased; excess and residual sodium hypochlorite also produces toxic gases during the acidification process, which is harmful to the environment and operators.
2. The water content of the 3-methyl-2-chloro-4-methylsulfonylbenzoic acid obtained by sodium hypochlorite oxidation is between 30 and 50 percent, and the centrifugation is not easy. Before the reaction with thionyl chloride to prepare acyl chloride, reflux dehydration treatment is required, which requires a long time, and thus inevitably consumes production equipment, thereby increasing production cost.
3. The oxidation of sodium hypochlorite to 3-methyl-2-chloro-4-methylsulfonylbenzoic acid usually contains a large amount of sodium chloride, and in order to prevent sodium chloride from affecting the next reaction, a large amount of water is added for washing to remove sodium chloride as much as possible, and the post-treatment of the step generates a large amount of wastewater.
Aiming at the current production situation and the defects of 3-methyl-2-chloro-4-methyl sulfonyl methyl benzoate in the prior art, the inventor of the application aims to provide a new preparation process of an intermediate 3-methyl-2-chloro-4-methyl sulfonyl methyl benzoate more suitable for industrial production, the process has the advantages of low raw material cost, less steps, simple operation, no need of high-temperature and high-pressure reaction conditions, no need of a large amount of sodium hypochlorite solution and hydrochloric acid solution, and remarkably reduced amount of generated wastewater, thereby greatly reducing the treatment cost; after the raw material 3-methyl-2-chloro-4-methylthioacetophenone (compound 1) is oxidized to generate 3-methyl-2-chloro-4-methylsulfinylbenzoic acid (compound 2), methanol can be directly added for methyl esterification reaction without carrying out post-treatment operation, so that the process can really realize continuous production. In the production process, the waste sulfuric acid can be directly recycled after being subjected to dehydration treatment, so that the production cost is greatly reduced.
Disclosure of Invention
The invention aims to provide a novel, simpler, more environment-friendly and lower-cost preparation method of an intermediate 3-methyl-2-chloro-4-methylsulfonyl methyl benzoate, which comprises the following steps shown in a scheme:
(1) Selecting sulfuric acid as an acid catalytic reagent, using an organic solvent chlorinated C1-C2 alkane or olefin as a reaction solvent, and slowly dripping concentrated nitric acid into a raw material 3-methyl-2-chloro-4-methylthioacetophenone (compound 1) at the temperature of 40-80 ℃ to perform oxidation reaction so as to generate 3-methyl-2-chloro-4-methylsulfinylbenzoic acid (compound 2);
(2) Adding anhydrous methanol into 3-methyl-2-chloro-4-methylsulfinylbenzoic acid (compound 2) to perform esterification reaction to generate 3-methyl-2-chloro-4-methylsulfinylbenzoic acid methyl ester (compound 3); and
(3) An oxidizing agent is added to methyl 3-methyl-2-chloro-4-methylsulfinylbenzoate (Compound 3) to conduct an oxidation reaction to produce methyl 3-methyl-2-chloro-4-methylsulfonylbenzoate (Compound 4).
Further, the step (3) comprises: dropwise adding the product obtained in the step (2) into ice water for quenching and extracting to obtain dichloroethane solution containing 3-methyl-2-chloro-4-methylsulfinylbenzoic acid methyl ester; adding glacial acetic acid and concentrated sulfuric acid into dichloroethane solution containing 3-methyl-2-chloro-4-methylsulfinylmethyl benzoate, stirring, heating to 50-110 ℃, dropwise adding hydrogen peroxide, and after dropwise adding, keeping the temperature for reaction; cooling to 40-50 ℃, separating, spin-drying and drying the organic phase to obtain the product 3-methyl-2-chloro-4-methylsulfonyl methyl benzoate. Wherein, concentrated sulfuric acid is used as a catalyst, glacial acetic acid is firstly oxidized into peroxyacetic acid by hydrogen peroxide, and the peroxyacetic acid is oxidized into 3-methyl-2-chloro-4-methylsulfinylmethyl benzoate to generate 3-methyl-2-chloro-4-methylsulfonylbenzoic acid methyl ester and glacial acetic acid which can be recycled.
Further, the reaction temperature in the step (1) is 40-70 ℃, 50-70 ℃, 60-70 ℃ or 70-80 ℃. Preferably, 60 ℃ to 70 ℃.
Further, the molar ratio of 3-methyl-2-chloro-4-methylthioacetophenone to concentrated nitric acid fed in step (1) is 1.0-1, preferably, the molar ratio is 1.5-1.
Further, the organochlorinated C1-C2 alkane or alkene used in step (1) is selected from any one of dichloromethane, chloroform, dichloroethane and trichloroethylene, preferably, dichloroethane is used as the reaction solvent.
Further, the weight ratio of the chlorinated C1-C2 alkane or alkene to 3-methyl-2-chloro-4-methylthioacetophenone in step (1) is from 2 to 1, preferably, from 3.
Further, the acid catalyst in the step (1) is sulfuric acid with the mass fraction of 80% -98%, preferably 90% -95%.
Further, the feeding molar ratio of the 3-methyl-2-chloro-4-methylthioacetophenone to the 90% sulfuric acid in the step (1) is 1.
Further, in the step (2), the feeding amount of the 3-methyl-2-chloro-4-methylsulfinylbenzoic acid compound 2 to the anhydrous methanol is 1.
Further, in the step (3), the oxidant is hydrogen peroxide, and the molar ratio of the fed amount of the methyl 3-methyl-2-chloro-4-methylsulfinylbenzoate to the fed amount of the hydrogen peroxide is 1.0-1, preferably, the molar ratio is 1.
Further, in the step (3), the molar ratio of the fed amount of the methyl 3-methyl-2-chloro-4-methylsulfinylbenzoate to the fed amount of concentrated sulfuric acid is 1.
Further, in the step (3), the molar ratio of the fed amount of the methyl 3-methyl-2-chloro-4-methylsulfinylbenzoate to the fed amount of the glacial acetic acid is 1.
Further, in the step (3), preferably, the oxidation reaction is carried out at 70 ℃ to 80 ℃.
The preparation method of the 3-methyl-2-chloro-4-methyl sulfonyl methyl benzoate provided by the invention is a continuous production method, has low raw material cost, low operation condition severity, no need of high-temperature and high-pressure reaction conditions, simple steps, no need of post-treatment operation after the steps (1) and (2), no need of a large amount of sodium hypochlorite solution and hydrochloric acid solution, greatly reduced wastewater treatment cost, and is particularly suitable for industrial production.
In addition, the invention also provides an intermediate 3-methyl-2-chloro-4-methylsulfonyl methyl benzoate with higher yield and purity, which is prepared by the method, wherein the yield is 95.82% -97.24%, and the purity is more than or equal to 95%.
Advantageous effects
The invention aims to provide a preparation method of a continuous intermediate 3-methyl-2-chloro-4-methylsulfonyl methyl benzoate, so that the preparation method has industrial prospects and significance. Specifically, the method has simple steps, mild reaction conditions and no need of post-treatment among the steps, so that the whole reaction process is a continuous process; moreover, the method effectively reduces the waste water in the production process and greatly reduces the cost of raw materials. The method is favorable for simplifying the production method of the benzoyl cyclohexanediones and greatly reducing the production cost of the benzoyl cyclohexanediones; the product yield and purity are greatly improved. In the production process, the waste sulfuric acid can be directly recycled after being subjected to dehydration post-treatment, so that the generation of waste gas is reduced; the reactant glacial acetic acid can be recycled after being used, which is favorable for greatly reducing the production cost and ensures that the method is more environment-friendly.
Detailed Description
The technical solutions of the present invention are further explained below with reference to specific embodiments, but the present invention is not limited in any way, and any modifications, alterations, or equivalent replacement methods that can be implemented by those skilled in the art to which the present invention pertains will fall within the scope of the claims of the present invention without departing from the technical solutions of the present invention.
The experimental procedures used in the following examples are all conventional procedures unless otherwise specified.
Materials, reagents and the like used in the following examples are commercially available unless otherwise specified.
The continuous preparation method of the intermediate 3-methyl-2-chloro-4-methyl sulfonyl methyl benzoate described in the invention is a conventional method by selecting appropriate catalysts and reactants and controlling specific parameters such as the addition amount and the molar ratio of the reactants at a reduced reaction temperature, so as to improve the reaction rate of different steps, the generation amount of products and better yield and purity of intermediate products.
A process for the preparation of the intermediate methyl 3-methyl-2-chloro-4-methylsulfonylbenzoate, which comprises the steps shown in the following scheme:
(1) Selecting sulfuric acid as an acid catalytic reagent, using an organic solvent chlorinated C1-C2 alkane or olefin as a reaction solvent, and slowly dripping concentrated nitric acid into a raw material 3-methyl-2-chloro-4-methylthioacetophenone (compound 1) at the temperature of 40-80 ℃ to perform oxidation reaction so as to generate 3-methyl-2-chloro-4-methylsulfinylbenzoic acid (compound 2);
(2) Adding anhydrous methanol into 3-methyl-2-chloro-4-methylsulfinylbenzoic acid (compound 2) to perform esterification reaction to generate 3-methyl-2-chloro-4-methylsulfinylbenzoic acid methyl ester (compound 3); and
(3) An oxidizing agent is added to methyl 3-methyl-2-chloro-4-methylsulfinylbenzoate (Compound 3) to conduct an oxidation reaction to produce methyl 3-methyl-2-chloro-4-methylsulfonylbenzoate (Compound 4).
Further, the step (3) comprises: dropwise adding the product obtained in the step (2) into ice water for quenching and extracting to obtain dichloroethane solution containing 3-methyl-2-chloro-4-methylsulfinylbenzoic acid methyl ester; adding glacial acetic acid and concentrated sulfuric acid into dichloroethane solution containing 3-methyl-2-chloro-4-methylsulfinylmethyl benzoate, stirring, heating to 50-110 ℃, dropwise adding hydrogen peroxide, and after dropwise adding, keeping the temperature for reaction; cooling to 40-50 ℃, separating, spin-drying and drying an organic phase to obtain a product of 3-methyl-2-chloro-4-methylsulfonyl methyl benzoate, wherein concentrated sulfuric acid is used as a catalyst, glacial acetic acid is oxidized into peroxyacetic acid by hydrogen peroxide, the peroxyacetic acid is oxidized into 3-methyl-2-chloro-4-methylsulfinylmethyl benzoate to generate 3-methyl-2-chloro-4-methylsulfonyl methyl benzoate and glacial acetic acid, and the glacial acetic acid can be recycled.
Further, the reaction temperature in the step (1) is 40-70 ℃, 50-70 ℃, 60-70 ℃ or 70-80 ℃. Preferably, from 60 ℃ to 70 ℃.
Further, the feeding molar ratio of the 3-methyl-2-chloro-4-methylthioacetophenone to the concentrated nitric acid in the step (1) is 1.0-1, preferably, the molar ratio is 1.5-1.
Further, in the step (1), a chlorinated C1-C2 alkane or alkene selected from any one of dichloromethane, chloroform, dichloroethane and trichloroethylene is used, preferably, dichloroethane is used as a reaction solvent.
Further, the weight ratio of the chlorinated C1-C2 alkane or alkene to 3-methyl-2-chloro-4-methylthioacetophenone in step (1) is from 2 to 1, preferably, the weight ratio is from 3 to 1.
Further, the acid catalyst in the step (1) is sulfuric acid with the mass fraction of 80% -98%, preferably 90% -95%.
Further, the feeding molar ratio of the 3-methyl-2-chloro-4-methylthioacetophenone to the 90% sulfuric acid in the step (1) is 1.
Further, in the step (2), the molar ratio of the 3-methyl-2-chloro-4-methylsulfinylbenzoic acid compound 2 to the anhydrous methanol is 1.
Further, in the step (3), the oxidant is hydrogen peroxide, and the molar ratio of the fed amount of the methyl 3-methyl-2-chloro-4-methylsulfinylbenzoate to the fed amount of the hydrogen peroxide is 1.0-1, preferably, the molar ratio is 1.
Further, in the step (3), the molar ratio of the fed amount of the methyl 3-methyl-2-chloro-4-methylsulfinylbenzoate to the fed amount of concentrated sulfuric acid is 1.
Further, in the step (3), the molar ratio of the fed amount of the methyl 3-methyl-2-chloro-4-methylsulfinylbenzoate to the fed amount of the glacial acetic acid is 1.
Further, in the step (3), preferably, the oxidation reaction is carried out at 70 ℃ to 80 ℃.
In a specific embodiment, 3-methyl-2-chloro-4-methylthioacetophenone (compound 1), dichloroethane and a 90% sulfuric acid solution are added into a four-mouth reaction flask with a thermometer, a reflux condenser and a stirring paddle, the temperature is slowly raised to 60-70 ℃, a nitric acid solution is dropwise added between 1.5-2.0h, and after the dropwise addition is finished, the reaction is carried out for about 0.5h-1h under the condition of heat preservation to obtain 3-methyl-2-chloro-4-methylsulfinylbenzoic acid (compound 2). And (4) sampling and analyzing, further dropwise adding anhydrous methanol to perform esterification reaction if the reaction is finished, and after the dropwise adding is finished, keeping the temperature to perform reaction for about 2.0 hours to obtain the 3-methyl-2-chloro-4-methylsulfinylbenzoic acid methyl ester (compound 3). Sampling and analyzing, if the reaction is finished, adding the compound 3 into ice water, quenching, standing and layering; and extracting and layering by using dichloroethane, performing post-treatment on the aqueous phase sulfuric acid for recycling, adding concentrated sulfuric acid and glacial acetic acid into the organic phase, heating to 70-80 ℃, slowly dropwise adding 30% hydrogen peroxide for oxidation reaction, and after dropwise adding, keeping the temperature and reacting for about 0.5h. After sampling and analysis, if the reaction is finished, the temperature is reduced to 40-50 ℃, standing and layering are carried out, the organic phase is dried in a spinning mode, and the product 3-methyl-2-chloro-4-methyl sulfonyl methyl benzoate (compound 4) is quantitatively analyzed.
Example 1
107.35g (0.5 mol) of 3-methyl-2-chloro-4-methylthioacetophenone, 272.42g (2.5 mol) of 90% sulfuric acid and 429.4g (4 eq) of dichloroethane are added into a 500ml four-mouth reaction flask with a thermometer, a reflux condenser and a stirring paddle, stirred and heated to 60-70 ℃, 47.26g (0.75 mol) of concentrated nitric acid is added dropwise between 1.5-2.0h, and after the addition is finished, the reaction is kept warm for about 0.5h, and sampling analysis is carried out. If the reaction is finished, 80.11g (2.5 mol) of anhydrous methanol is slowly dripped between 1.5 and 2.0h, the reaction is kept for about 2.0h after the dripping is finished, and a sample is taken for analysis. After the reaction was completed, the solution was quenched by dropping into ice water, allowed to stand for delamination, the aqueous phase was extracted twice with an appropriate amount of dichloroethane, and the organic phases were combined to obtain a dichloroethane solution containing compound 3 of molecular weight MW 246. Adding 15.32g (0.25 mol) of glacial acetic acid and 10.01g (0.1 mol) of concentrated sulfuric acid into a dichloroethane solution containing the compound 3, stirring and heating to 70-80 ℃, dropwise adding 79.37g (0.7 mol) of 30% hydrogen peroxide within 1.5-2.0h, preserving heat for reacting for about 0.5h after dropwise adding, and sampling and analyzing. If the reaction is finished, cooling to 40-50 ℃, standing for layering, extracting the water phase twice by using a proper amount of dichloroethane, combining the organic phases, carrying out spin drying to obtain a solid, and drying to obtain a product of methyl 3-methyl-2-chloro-4-methylsulfonylbenzoate (compound 4), wherein the quantitative rate is 95.6 percent, and the yield is 97.24 percent.
Example 2
107.35g (0.5 mol) of 3-methyl-2-chloro-4-methylthioacetophenone, 272.42g (2.5 mol) of 90% sulfuric acid and 429.4g (4 eq) of dichloroethane are added into a 500ml four-mouth reaction flask with a thermometer, a reflux condenser and a stirring paddle, the temperature is raised to any temperature between 70 and 80 ℃ by stirring, 31.5g (0.5 mol) of concentrated nitric acid is dropwise added between 1.5 and 2.0 hours, the reaction is kept for about 0.5 hour after the dropwise addition is finished, and sampling analysis is carried out. If the reaction is finished, slowly dropwise adding 80.11g (4.0 mol) of anhydrous methanol between 1.5 and 2.0h, preserving the temperature after the dropwise adding is finished, reacting for about 2.0h, sampling and analyzing, dropwise adding into ice water after the reaction is finished, quenching, standing and layering, extracting the water phase twice by using a proper amount of dichloroethane, and combining the organic phases to obtain a dichloroethane solution containing a compound 3 with the molecular weight MW 246. Adding 15.32g (0.25 mol) of glacial acetic acid and 10.01g (0.1 mol) of concentrated sulfuric acid into a dichloroethane solution containing the compound 3, stirring and heating to any temperature between 70 and 80 ℃, dropwise adding 79.37g (0.7 mol) of 30% hydrogen peroxide within 1.5 to 2.0h, preserving heat for about 0.5h after the dropwise adding is finished, and sampling and analyzing. And if the reaction is finished and the temperature is reduced to 40-50 ℃, standing and layering are carried out, the water phase is extracted twice by using a proper amount of dichloroethane, the organic phases are combined, the solid is obtained by spin drying, 132.47g of the product 3-methyl-2-chloro-4-methylsulfonyl methyl benzoate (compound 4) is obtained by drying, the quantification is 95.01 percent, and the yield is 95.82 percent.
Example 3
107.35g (0.5 mol) of 3-methyl-2-chloro-4-methylthioacetophenone, 272.42g (2.5 mol) of 90% sulfuric acid and 429.4g (4 eq) of trichloroethylene are added into a 500ml four-mouth reaction flask with a thermometer, a reflux condenser and a stirring paddle, stirred and heated to any temperature between 60 ℃ and 70 ℃, 47.26g (0.75 mol) of concentrated nitric acid is dripped in 1.5-2.0h, after the dripping is finished, the mixture is kept warm for about 0.5h and sampled for analysis. If the reaction is finished, slowly dropwise adding 80.11g (2.5 mol) of anhydrous methanol between 1.5 and 2.0h, preserving the temperature after the dropwise adding is finished, reacting for about 2.0h, sampling and analyzing, dropwise adding into ice water after the reaction is finished, quenching, standing and layering, extracting the water phase twice by using a proper amount of dichloroethane, and combining the organic phases to obtain a dichloroethane solution containing a compound 3 with the molecular weight MW 246. Adding 15.32g (0.25 mol) of glacial acetic acid and 10.01g (0.1 mol) of concentrated sulfuric acid into the solution containing the compound 3, stirring and heating to any temperature between 70 and 80 ℃, dropwise adding 68.03g (0.6 mol) of 30 percent hydrogen peroxide into the solution for 1.5 to 2.0 hours, preserving the temperature and reacting for about 0.5 hour after the dropwise adding is finished, and sampling and analyzing. If the reaction is finished and the temperature is reduced to any temperature between 40 and 50 ℃, standing and layering are carried out, the water phase is extracted twice by using a proper amount of dichloroethane, the organic phases are combined and dried in a spinning way to obtain solid, 133.24g is obtained by drying, the quantification is 95.3%, and the yield is 96.74%.
Comparative example 1
Compound 4 was generated according to the prior art route shown below:
the method specifically comprises the following steps:
107.35g (0.5 mol) of 3-methyl-2-chloro-4-methylthioacetophenone, 429.4g (4 eq) dichloroethane, 15.32g (0.25 mol) glacial acetic acid and 10.01g (0.1 mol) concentrated sulfuric acid are sequentially added into a 1000ml four-mouth bottle with a mechanical stirrer, a thermometer and a condenser, stirred and heated to any temperature between 70 ℃ and 80 ℃, 141.73g (1.25 mol) of 30% hydrogen peroxide is dropwise added between 1.5 h and 2.0h, after the reaction is finished, the mixture is stood for layering, the organic phase is cooled to 40 ℃ to 50 ℃, 1400g (1.5 mol) of 8 NaClO solution is dropwise added within 3.0 h to 4.0h, after the reaction is finished, the lower organic phase is removed by standing for layering, 152.08g (1.5 mol) of concentrated hydrochloric acid is added into the aqueous phase for acidification, and viscous solid is obtained by suction filtration after the acidification is finished. The viscous solid was charged into a 1000ml four-necked flask, and 429.4g (4 eq) of dichloroethane was added for reflux dehydration, which took 15 hours. And after dehydration is finished, 72.10g (0.6 mol) of thionyl chloride is added dropwise within 1.5-2.0h, 160.21g (5 mol) of anhydrous methanol is added after reaction is finished, 372g (3 eq) of water is added, redundant salt is washed away, the mixture is kept stand for layering, the organic phase is dried by spinning to 101.08g, the content is 95.38%, and the yield is 77.16%.
From the procedures of comparative examples, it can be seen that the preparation method generates hazardous waste gases such as chlorine, hydrogen chloride and oxygen, has corrosion phenomena to the production equipment using sulfuric acid, acetic acid, and generates a large amount of waste acid water, and thus the method is significantly inferior to the above-described examples 1 to 3 of the present invention in terms of environmental friendliness.
Compared with a comparative example, the preparation method provided by the invention can obtain the compound 4 with higher purity and yield, in a preferred embodiment, the purity of the compound 4 obtained by the preparation method provided by the invention can reach about 95%, the yield can reach more than 95%, and the preparation method is simple to operate and suitable for one-pot continuous production.
As proved by the examples in the application, the technical concept and the technical scheme of the invention improve the existing preparation method of the intermediate 3-methyl-2-chloro-4-methyl sulfonyl methyl benzoate for synthesizing the benzoylcyclohexanediones, overcome the defects in the prior art and are more suitable for industrially producing the intermediate 3-methyl-2-chloro-4-methyl sulfonyl methyl benzoate. The method has the advantages of low raw material cost, few steps, simple operation, no need of high-temperature and high-pressure reaction conditions, no need of using a large amount of sodium hypochlorite solution and hydrochloric acid solution, and remarkably reduced waste water amount, so that the treatment cost is reduced; moreover, the intermediate step does not need to carry out post-treatment operation, and the method can really realize continuous production. In the production process, the waste sulfuric acid can be directly recycled after being subjected to dehydration treatment, and the generation of waste gas is reduced; the reactant glacial acetic acid can participate in the oxidation reaction and can be recycled, so that the method is favorable for greatly reducing the production cost and has better environmental friendliness.
Claims (10)
1. A preparation method of 3-methyl-2-chloro-4-methylsulfonyl methyl benzoate used as an intermediate for synthesizing benzoylcyclohexanediones is characterized by comprising the following steps:
(1) Selecting sulfuric acid as an acid catalytic reagent, using chlorinated C1-C2 alkane or olefin as a reaction solvent, and slowly dripping concentrated nitric acid into a raw material 3-methyl-2-chloro-4-methylthioacetophenone at the temperature of 40-80 ℃ to perform oxidation reaction so as to generate 3-methyl-2-chloro-4-methylsulfinylbenzoic acid;
wherein, in the step (1), the feeding molar ratio of the 3-methyl-2-chloro-4-methylthioacetophenone to the concentrated nitric acid is 1.0-1.2, and the weight ratio of the chlorinated C1-C2 alkane or alkene to the 3-methyl-2-chloro-4-methylthioacetophenone is 2;
(2) Adding anhydrous methanol into 3-methyl-2-chloro-4-methylsulfinylbenzoic acid to perform esterification reaction to generate methyl 3-methyl-2-chloro-4-methylsulfinylbenzoate;
wherein the feeding amount molar ratio of the 3-methyl-2-chloro-4-methylsulfinylbenzoic acid to the anhydrous methanol in the step (2) is 1; and
(3) Adding an oxidant into the 3-methyl-2-chlorine-4-methylsulfinylbenzoic acid methyl ester for oxidation reaction to generate 3-methyl-2-chlorine-4-methylsulfonylbenzoic acid methyl ester.
2. The method of claim 1, wherein the step (3) comprises:
after the reaction in the step (2) is finished, dropwise adding the product in the step (2) into ice water for quenching and extracting to obtain dichloroethane solution containing 3-methyl-2-chloro-4-methylsulfinylbenzoic acid methyl ester; and
adding glacial acetic acid and concentrated sulfuric acid into the dichloroethane solution containing the 3-methyl-2-chloro-4-methylsulfinylmethyl benzoate, stirring, heating to 50-110 ℃, dropwise adding hydrogen peroxide, carrying out heat preservation reaction, cooling to 40-50 ℃, separating, spin-drying and drying an organic phase to obtain a product of 3-methyl-2-chloro-4-methylsulfinylmethyl benzoate.
3. The method according to claim 1, wherein the reaction temperature in the step (1) is 60 ℃ to 70 ℃.
4. The preparation method according to claim 1, wherein the feeding molar ratio of the 3-methyl-2-chloro-4-methylthioacetophenone to the concentrated nitric acid in the step (1) is 1.5-1.8.
5. The method for preparing a compound according to claim 1, wherein the chlorinated C1-C2 alkane or alkene in the step (1) is any one selected from dichloromethane, chloroform, dichloroethane and trichloroethylene.
6. The process according to claim 1, wherein the weight ratio of the chlorinated C1-C2 alkane or alkene to 3-methyl-2-chloro-4-methylthioacetophenone in step (1) is 3.
7. The preparation method according to claim 1, wherein the acid catalyst in the step (1) is sulfuric acid with a mass fraction of 80% -98%.
8. The preparation method according to claim 1, wherein the oxidant in step (3) is hydrogen peroxide, and the molar ratio of the fed amount of the methyl 3-methyl-2-chloro-4-methylsulfinylbenzoate to the fed amount of the hydrogen peroxide is 1.0-1.
9. The preparation method according to claim 2, further comprising the step (3), wherein the feeding amount molar ratio of the methyl 3-methyl-2-chloro-4-methylsulfinylbenzoate to the concentrated sulfuric acid is 1.
10. The preparation method according to claim 2, further comprising the step (3), wherein the feeding amount molar ratio of the methyl 3-methyl-2-chloro-4-methylsulfinylbenzoate to the glacial acetic acid is 1.
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