Sulfonation-chlorination two-step continuous preparation process of bentazone intermediate

Abstract

The invention discloses a bentazone intermediate sulfonation-chlorination two-step continuous preparation process which comprises the following steps: continuously metering and adding a solvent, chlorosulfonic acid, triethylamine, isopropylamine and a catalyst into a first-section tubular reactor, and carrying out sulfonation reaction to obtain a reaction material isopropylaminosulfonic acid; continuously introducing the reaction material isopropylamine sulfonic acid into a second section of tubular reactor, and simultaneously continuously metering and adding methyl anthranilate and phosphorus oxychloride for chlorination reaction; after the reaction is finished, quenching the reaction liquid with water, and carrying out layering and distillation treatment to obtain an intermediate o-isopropylamine sulfonamide methyl benzoate solid; and carrying out ring-closure reaction on the intermediate o-isopropylamino sulfonamido methyl benzoate solid and sodium methoxide in a methanol solution to prepare the bentazone active compound. According to the method, the defects of low bentazone product content and poor yield caused by high temperature of intermittent sulfonation and chlorination are effectively overcome, the operation time is shortened, and the productivity is improved.

Description

Technical Field

[0001] This invention relates to a two-step continuous preparation process of metribuzin intermediate by sulfonation and chlorination, belonging to the field of pesticide synthesis. Background Technology

[0002] Benzoate (also known as bentazon) is a highly effective herbicide of the benzothiadiazinone class developed by BASF. It is widely used in rice, soybean, fruit, vegetable, corn, lawn, peanut and various cereal crops. It has excellent control efficacy against broadleaf weeds and sedges, especially showing significant inhibition of perennial noxious weeds and resistant weeds. It is also highly safe for crops and has important application value in agricultural production.

[0003] The mainstream synthetic route for bentazon in China is as follows: using dichloroethane as an organic solvent, chlorosulfonic acid is first added, followed by the dropwise addition of triethylamine under low-temperature conditions (-5 to 10°C) to generate sulfur trioxide / triethylamine double salt. Isopropylamine is then added to react and synthesize the intermediate isopropylaminosulfonic acid. This intermediate further reacts with methyl anthranilate and phosphorus oxychloride to generate the key intermediate methyl anthranilate (M272). After distillation and water washing to obtain solid M272, it undergoes a ring-closing reaction with sodium methoxide in methanol solution to finally obtain bentazon technical grade. The synthetic route for bentazon is as follows:

[0004] .

[0005] In the above synthetic route, the sulfonation reaction of chlorosulfonic acid and the chlorination reaction of phosphorus oxychloride are the core steps that determine the product yield and purity. In the existing process, these two reactions are mostly carried out in batch operation using a batch reactor, but there are significant technical defects: First, the batch process of batch reactor is cumbersome, with a large equipment footprint and high material holding capacity. Moreover, sulfonation and chlorination are both strongly exothermic reactions, and uneven mixing of materials in the batch reactor can easily lead to local overheating, which not only increases safety risks but also triggers side reactions and reduces product selectivity. Second, due to the limitations of reaction conditions, the yield of bentazon technical grade by the existing batch process is only 82-84% (calculated as methyl anthranilate), and the product content is only 95-96%, which is difficult to meet the requirements of high-quality production.

[0006] To address the aforementioned issues, continuous process research has been conducted in related fields. Existing patents disclose a continuous preparation process for the sulfonation reaction of bentazon (CN117619328A), which achieves continuous sulfonation through a two-section tubular reactor. However, this technology only optimizes the single-step sulfonation reaction and does not address the continuous design of the chlorination reaction, which plays a crucial role in product yield and purity, thus failing to fundamentally improve product quality. Another patent discloses a continuous production process for bentazon (CN111704592B), employing a multi-reactor series overflow method to achieve continuous condensation and cyclization processes. Although it covers both sulfonation and chlorination, the multi-reactor series structure makes it difficult to quickly remove the large amount of heat generated by the sulfonation and chlorination reactions, still posing a risk of localized overheating leading to increased side reactions. Another patent describes a continuous method for preparing bentazon (CN111269198A), which uses a continuous tubular reactor to prepare bentazon. The reactor is continuously fed by a pump to carry out sulfonation, chlorination-sulfonation and cyclization reactions. Solid phosgene (BTC) is used as the chlorine source for the chlorination-sulfonation reaction. The reaction temperature and residence time are controlled, and finally, acidification is carried out under low temperature conditions.

[0007] In summary, existing processes either only achieve continuous single-step reactions or suffer from insufficient heat transfer efficiency, failing to simultaneously address the core requirements of reaction safety, product quality, and production efficiency. Summary of the Invention

[0008] To address the problems existing in the prior art, this invention provides a two-step continuous preparation process for bentazon intermediates, namely sulfonation and chlorination. This process solves the problem that intermittent sulfonation and chlorination can easily lead to excessively high temperatures, resulting in low bentazon product content and poor yield. Furthermore, it reduces operation time and increases production capacity.

[0009] To achieve the above objectives, the present invention employs a two-step continuous preparation process for metribuzin intermediates via sulfonation and chlorination, comprising the following steps:

[0010] S1. Solvent, chlorosulfonic acid, triethylamine, isopropylamine and catalyst are continuously metered into the first tubular reactor to carry out sulfonation reaction to obtain the reactant isopropylamine sulfonic acid; the catalyst is Pd(PPh3)4 or Pd(PPh3)2Cl2.

[0011] S2. The reactant isopropylamine sulfonic acid is directly and continuously introduced into the second tubular reactor. At the same time, methyl o-aminobenzoate and phosphorus oxychloride are continuously metered into the second tubular reactor to carry out the chlorination reaction. After the reaction is completed, the reaction solution is quenched with water, and after layering and distillation, the intermediate methyl o-isopropylamine sulfonamide benzoate solid is obtained.

[0012] S3. The intermediate methyl o-isopropylamine sulfonamide benzoate solid was subjected to a ring-closure reaction with sodium methoxide in methanol solution to obtain bentazon technical grade.

[0013] As an improvement, the first section of the tubular reactor is provided with a solvent and catalyst mixing inlet, a triethylamine inlet, an isopropylamine inlet, and a chlorosulfonic acid inlet in sequence along the material flow direction;

[0014] The second tubular reactor is provided with an isopropylamine sulfonic acid inlet, an o-aminobenzoate methyl ester inlet, and a phosphorus oxychloride inlet in sequence along the material flow direction; wherein the isopropylamine sulfonic acid inlet is directly connected to the product outlet of the first tubular reactor.

[0015] As an improvement, both the first and second tubular reactors are equipped with a jacketed heating and cooling circulation system for real-time temperature control.

[0016] As an improvement, the molar ratio of methyl anthranilate, chlorosulfonic acid, isopropylamine, triethylamine, and phosphorus oxychloride is 1:(1.2-3.0):(1.15-4):(4-5):(1.05-6).

[0017] As an improvement, the catalyst is used in a weight ratio of (1-5):100 to methyl anthranilate.

[0018] As an improvement, the solvent may be any one of dichloroethane, toluene, xylene, or n-hexane.

[0019] As an improvement, the sulfonation reaction temperature in step S1 is 0℃-50℃; and / or the residence time in the first tubular reactor is 1-30 min; and / or the rotation speed of the first tubular reactor is 200 r / min-1200 r / min.

[0020] As an improvement, the chlorination reaction temperature in step S2 is 10℃-70℃; and / or the residence time in the second tubular reactor is 1-30 min; and / or the rotation speed of the second tubular reactor is 200 r / min-1200 r / min.

[0021] As an improvement, the continuous feeding of solvent, chlorosulfonic acid, triethylamine, isopropylamine and catalyst in step S1, and the continuous feeding of methyl anthranilate and phosphorus oxychloride in step S2, are all metered by precision metering pumps; and by adjusting the flow rate of the precision flow pump to match the preset residence time of the tubular reactor in steps S1 and S2, continuous and stable feeding of materials is achieved.

[0022] As an improvement, the obtained bentazon technical grade has a content of ≥99% and a yield of ≥97% based on methyl anthranilate.

[0023] Compared with the prior art, the beneficial effects of the present invention are:

[0024] (1) This invention employs two dynamic tubular reactors to respectively carry the core reactions of sulfonation and chlorination, coupled with a jacketed heating and cooling circulation system. This system can remove the large amount of reaction heat generated during the sulfonation-chlorination process in real time and uniformly, fundamentally solving the problem of local overheating caused by uneven material mixing in traditional batch reactor processes, and significantly reducing the safety risks caused by system overheating. At the same time, the closed structure of the dynamic tubular reactor can effectively reduce the volatilization loss of the low-boiling-point raw material isopropylamine, improve the raw material utilization rate, and the equipment is made of Hastelloy, which can withstand the corrosion of phosphorus oxychloride and chlorosulfonic acid, extending the service life of the equipment and further ensuring the continuity and stability of production. In addition, precise temperature control and a closed environment work together to reduce side reactions such as over-sulfonation and chlorination impurities caused by high temperature, laying the foundation for improving product quality.

[0025] (2) This invention introduces a catalyst (Pd(PPh3)4 or Pd(PPh3)2Cl2), which can precisely activate the reaction system, significantly improve the selectivity of the subsequent chlorination reaction, and effectively inhibit the generation of impurities. Combined with the stable temperature control and precise material ratio of the two-step continuous process (achieved through a precision metering pump), the final content of the metribuzin technical material is stable at over 99%, and the yield based on methyl anthranilate is over 97%, which is a qualitative leap compared to the traditional batch process (content 95-96%, yield 82-84%). Compared with existing continuous technologies, this invention adopts a dynamic tubular reactor design, which has better stirring effect and higher reaction efficiency. Compared with the static tubular reactor process (such as CN111269198A, the yield is only about 90%), the yield is significantly improved, and the impurity content is lower, significantly enhancing the product competitiveness.

[0026] (3) The present invention achieves continuous feeding of raw materials through a precision metering pump, and the sulfonation product isopropylamine sulfonic acid is directly and continuously introduced into the chlorination reaction without the need for additional metering and transfer steps, which simplifies the operation process, reduces manual intervention, and significantly shortens the production cycle. At the same time, the tubular reactor has a smaller footprint and lower material holding capacity compared with the traditional batch reactor, and the unit time capacity is significantly improved. It can be flexibly adapted to industrial production lines of different scales, effectively solving the pain points of insufficient capacity and long production cycle of intermittent processes, and providing technical support for large-scale mass production.

[0027] (4) The solvents (dichloroethane, toluene, etc.), chlorosulfonic acid, methyl anthranilate, and other raw materials used in this invention are all readily available industrial products, requiring no special customization and making procurement costs controllable. In addition, the continuous process reduces losses during material transfer, and the increased utilization rate of isopropylamine and reduced side reactions also lower waste disposal costs, thereby improving the economic benefits of enterprises while reducing environmental pressure.

[0028] (5) The process of this invention is adaptable to different regional climates, solving the industry problem that ordinary methods cannot stably produce high-quality products due to climate influences: Chlorosulfonic acid and phosphorus oxychloride are extremely prone to water absorption and deterioration. Ordinary batch processes, due to the open feeding system and long reaction cycle, make the raw materials easily come into contact with moisture in the air and undergo hydrolysis. At the same time, the long reaction time leads to excess chlorosulfonic acid and phosphorus oxychloride causing excessive sulfonation and chlorination side reactions, resulting in a final product yield of only 82-84% (calculated as methyl anthranilate) and a content of 95-96%, and a significant increase in raw material consumption. In this invention, the raw materials do not come into contact with air from the storage container to the reactor, thus avoiding water absorption and hydrolysis at the source; with the precise metering pump, the feed amount is accurately controlled, there is no excess raw material residue, and the reaction residence time is short, greatly reducing the occurrence of side reactions. At the same time, the reaction equipment is equipped with a reaction over-temperature alarm system, combined with a jacketed heating and cooling circulation system for precise temperature control, unaffected by high ambient temperatures, and the final product content is stable at over 99% and the yield is over 97%. In addition, the present invention autonomously regulates the reaction temperature through a jacketed heating and cooling cycle system, which is not affected by low ambient temperature. It can precisely maintain the optimal reaction range of 0-50℃ for sulfonation and 10-70℃ for chlorination according to the catalyst activity requirements. If the ambient temperature is too low, the system can be heated or the residence time can be appropriately extended to ensure that the catalytic reaction is fully carried out, thus completely eliminating the constraint of ambient temperature on the reaction.

[0029] Furthermore, isopropylamine has a boiling point of only 33°C, and the open system of conventional batch processes easily leads to its significant volatilization during the reaction, increasing raw material consumption and reducing reaction efficiency. The closed tubular reactor and continuous feeding system of this invention effectively reduce isopropylamine volatilization losses, further ensuring stable raw material ratios and helping to maintain high and stable product yield and purity. In summary, this invention breaks the dependence of conventional methods on dry climates, enabling stable production of high-content (over 99%) and high-yield (over 97%) metribuzin technical grade under different regional climate conditions, significantly reducing geographical production limitations and adapting to the industrialization needs of different climate regions worldwide. Attached Figure Description

[0030] The following description uses some of the characterization results in the embodiments of the present invention as examples for illustrative demonstration and explanation. The experimental results of other embodiments are obtained by using the same characterization method and the characterization results are similar. Due to space limitations and the fact that the experimental results data of each embodiment have been recorded in detail and the characterization results do not affect the understanding and reproduction of the innovative content of the present invention, they are not all listed.

[0031] Figure 1 This is the liquid chromatogram of intermediate M272 obtained after the chlorination reaction in Example 1;

[0032] Figure 2 This is the liquid chromatogram of the bentazon dry powder obtained in Example 1;

[0033] Figure 3 This is a schematic diagram of the apparatus of the present invention; in the figure, 1# is the chlorosulfonic acid inlet, 2# is the isopropylamine inlet, 3# is the triethylamine inlet, 4# is the solvent and catalyst inlet, 5# is the phosphorus oxychloride inlet, and 6# is the methyl anthranilate inlet. Detailed Implementation

[0034] The following embodiments are further illustrations of the present invention and serve as explanations of the technical content of the present invention. However, the essence of the present invention is not limited to the embodiments described below. Those skilled in the art can and should know that any simple changes or substitutions based on the spirit of the present invention should fall within the protection scope claimed by the present invention.

[0035] Example 1

[0036] Combination Figure 3 As shown, a two-step continuous preparation process for bentazon intermediate by sulfonation-chlorination includes the following steps:

[0037] S1. Sulfonation reaction: Start the jacket heating and cooling circulation system of the first tubular reactor, set the initial temperature control target to 0℃, the reaction residence time to 5min, set the flow rate of the precision flow pump according to the residence time, and adjust the reactor speed to 800r / min at the same time.

[0038] The reactor is continuously fed into it using precision metering pumps.

[0039] Material A: 65g (1.09mol) of isopropylamine (inlet #2), 1.15g of Pd(PPh3)4 and 1000g of dichloroethane (inlet #4);

[0040] Material B: 125g (1.06mol) of chlorosulfonic acid (inlet #1);

[0041] Material C: Triethylamine 325g (3.18mol) (inlet #3);

[0042] During the reaction, two reaction zones were observed to form inside the reactor: the first reaction zone (sulfonation zone) had an actual temperature of 30-40℃, and the second reaction zone (maturation zone) had an actual temperature of 20-25℃. After the reaction was completed, the intermediate isopropylamine sulfonic acid was obtained.

[0043] S2, Chlorination reaction: The above isopropylamine sulfonic acid is introduced into the second section of the chlorination tubular reactor. The initial temperature control target is set to 0℃, the residence time is 5min, the flow rate of the precision flow pump is set according to the residence time, and the reactor speed is adjusted to 800r / min.

[0044] Continuous feeding via a precision metering pump:

[0045] Material D: 114.5g (0.75mol) of methyl anthranilate (inlet #6);

[0046] Material E: Phosphorus oxychloride 127.5g (0.825mol) (5# inlet);

[0047] The actual temperature of the first reaction zone (chlorination zone) inside the reactor was monitored to be 40-50℃, and the actual temperature of the second reaction zone (aging zone) was 35-40℃.

[0048] S3. The chlorination reaction solution was directly quenched with water. After standing and separating into layers, the organic phase was distilled to obtain the intermediate methyl o-isopropylaminosulfonamide benzoate (M272) solid, weighing 203.2 g, with a purity of 98.8% and a yield of 98.41% (based on methyl o-aminobenzoate). M272 was dissolved in methanol solution, and sodium methoxide was added to carry out a ring-closing reaction to obtain 175.8 g of metribuzin technical grade, with a purity of 99.34% and a yield of 97.02% (based on methyl o-aminobenzoate).

[0049] Figure 1 is a liquid chromatogram of methyl o-isopropylamine sulfonamide benzoate (M272), the intermediate obtained by chlorination reaction using the process of the present invention, followed by layering and distillation; Figure 2 is a liquid chromatogram of bentazon dry powder (i.e. bentazon technical) obtained by ring-closing reaction of intermediate M272 with sodium methoxide.

[0050] Analysis of the liquid chromatography data in Figures 1 and 2 shows that the target peak in the chromatogram of intermediate M272 is symmetrical and has no obvious impurity peaks. The target peak in the chromatogram of metribuzin powder has a high purity integral ratio and very low impurity peak content, indicating that the intermediate M272 and the finished metribuzin technical product prepared by the process of this invention have high purity.

[0051] Example 2

[0052] A two-step continuous preparation process for bentazon intermediates via sulfonation and chlorination includes the following steps:

[0053] S1. Sulfonation reaction: Start the jacket heating and cooling circulation system of the first tubular reactor, set the initial temperature control target to 0℃, the reaction residence time to 5min, set the flow rate of the precision flow pump according to the residence time, and adjust the reactor speed to 800r / min at the same time.

[0054] The reactor is continuously fed into it using precision metering pumps.

[0055] Material A: 65g (1.09mol) of isopropylamine, 41.15g of Pd(PPh3), and 1000g of dichloroethane;

[0056] Material B: 132.5g (1.126mol) of chlorosulfonic acid;

[0057] Material C: 345g (3.38mol) of triethylamine;

[0058] During the reaction, two reaction zones were observed to form inside the reactor: the first reaction zone (sulfonation zone) had an actual temperature of 30-40℃, and the second reaction zone (maturation zone) had an actual temperature of 20-25℃. After the reaction was completed, the intermediate isopropylamine sulfonic acid was obtained.

[0059] S2, Chlorination reaction: The above isopropylamine sulfonic acid is introduced into the second section of the chlorination tubular reactor. The initial temperature control target is set to 0℃, the residence time is 5min, the flow rate of the precision flow pump is set according to the residence time, and the reactor speed is adjusted to 800r / min.

[0060] Continuous feeding via a precision metering pump:

[0061] Material D: 114.5 g (0.75 mol) of methyl anthranilate.

[0062] Material E: 127.5g (0.825mol) of phosphorus oxychloride;

[0063] The actual temperature of the first reaction zone (chlorination zone) inside the reactor was monitored to be 40-50℃, and the actual temperature of the second reaction zone (aging zone) was 35-40℃.

[0064] S3. The chlorination reaction solution was directly quenched with water. After standing and separating into layers, the organic phase was distilled to obtain the intermediate methyl o-isopropylaminosulfonamide benzoate (M272) solid, weighing 204.4 g, with a purity of 98.5% and a yield of 98.69% (based on methyl o-aminobenzoate). M272 was dissolved in methanol solution, and sodium methoxide was added to carry out a ring-closing reaction to obtain 175.9 g of bentazon technical grade, with a purity of 99.4% and a yield of 97.14% (based on methyl o-aminobenzoate).

[0065] Example 3

[0066] A two-step continuous preparation process for bentazon intermediates via sulfonation and chlorination includes the following steps:

[0067] S1. Sulfonation reaction: Start the jacket heating and cooling circulation system of the first tubular reactor, set the initial temperature control target to 0℃, the reaction residence time to 5min, set the flow rate of the precision flow pump according to the residence time, and adjust the reactor speed to 800r / min at the same time.

[0068] The reactor is continuously fed into it using precision metering pumps.

[0069] Material A: 67.5g (1.13mol) of isopropylamine, 41.15g of Pd(PPh3), and 1000g of dichloroethane;

[0070] Material B: 132.5g (1.126mol) of chlorosulfonic acid;

[0071] Material C: 345g (3.38mol) of triethylamine;

[0072] During the reaction, two reaction zones were observed to form inside the reactor: the first reaction zone (sulfonation zone) had an actual temperature of 30-40℃, and the second reaction zone (maturation zone) had an actual temperature of 20-25℃. After the reaction was completed, the intermediate isopropylamine sulfonic acid was obtained.

[0073] S2, Chlorination reaction: The above isopropylamine sulfonic acid is introduced into the second section of the chlorination tubular reactor. The initial temperature control target is set to 10℃ and the residence time is 5min. The flow rate of the precision flow pump is set according to the residence time, and the reactor speed is adjusted to 800r / min.

[0074] Continuous feeding via a precision metering pump:

[0075] Material D: 114.5 g (0.75 mol) of methyl anthranilate.

[0076] Material E: 127.5g (0.825mol) of phosphorus oxychloride;

[0077] The actual temperature of the first reaction zone (chlorination zone) inside the reactor was monitored to be 45-50℃, and the actual temperature of the second reaction zone (aging zone) was 35-45℃.

[0078] S3. The chlorination reaction solution was directly quenched with water. After standing and separating into layers, the organic phase was distilled to obtain the intermediate methyl o-isopropylaminosulfonamide benzoate (M272) solid, weighing 203.6 g, with a purity of 98.4% and a yield of 98.2% (based on methyl o-aminobenzoate). M272 was dissolved in methanol solution, and sodium methoxide was added to carry out a ring-closing reaction to obtain 176.5 g of metribuzin technical grade, with a purity of 99.2% and a yield of 97.27% (based on methyl o-aminobenzoate).

[0079] Example 4

[0080] A two-step continuous preparation process for bentazon intermediates via sulfonation and chlorination includes the following steps:

[0081] S1. Sulfonation reaction: Start the jacket heating and cooling circulation system of the first tubular reactor, set the initial temperature control target to 5℃, the reaction residence time to 5min, set the flow rate of the precision flow pump according to the residence time, and adjust the reactor speed to 800r / min at the same time.

[0082] The reactor is continuously fed into it using precision metering pumps.

[0083] Material A: 67.5g (1.13mol) of isopropylamine, 4.5g of Pd(PPh3)2Cl2, and 1000g of dichloroethane;

[0084] Material B: 132.5g (1.126mol) of chlorosulfonic acid;

[0085] Material C: 345g (3.38mol) of triethylamine;

[0086] During the reaction, two reaction zones were observed to form inside the reactor: the first reaction zone (sulfonation zone) had an actual temperature of 35-45℃, and the second reaction zone (maturation zone) had an actual temperature of 25-30℃. After the reaction was completed, the intermediate isopropylamine sulfonic acid was obtained.

[0087] S2, Chlorination reaction: The above isopropylamine sulfonic acid is introduced into the second section of the chlorination tubular reactor. The initial temperature control target is set to 10℃ and the residence time is 5min. The flow rate of the precision flow pump is set according to the residence time, and the reactor speed is adjusted to 800r / min.

[0088] Continuous feeding via a precision metering pump:

[0089] Material D: 114.5 g (0.75 mol) of methyl anthranilate.

[0090] Material E: 127.5g (0.825mol) of phosphorus oxychloride;

[0091] The actual temperature of the first reaction zone (chlorination zone) inside the reactor was monitored to be 45-50℃, and the actual temperature of the second reaction zone (aging zone) was 35-45℃.

[0092] S3. The chlorination reaction solution was directly quenched with water. After standing and separating into layers, the organic phase was distilled to obtain the intermediate methyl o-isopropylaminosulfonamide benzoate (M272) solid, weighing 203.6 g, with a purity of 98.6% and a yield of 98.41% (based on methyl o-aminobenzoate). M272 was dissolved in methanol solution, and sodium methoxide was added to carry out a ring-closing reaction to obtain 176.2 g of bentazon technical grade, with a purity of 99.4% and a yield of 97.3% (based on methyl o-aminobenzoate).

[0093] Example 5

[0094] A two-step continuous preparation process for bentazon intermediates via sulfonation and chlorination includes the following steps:

[0095] S1. Sulfonation reaction: Start the jacket heating and cooling circulation system of the first tubular reactor, set the initial temperature control target to 0℃, the reaction residence time to 5min, set the flow rate of the precision flow pump according to the residence time, and adjust the reactor speed to 400r / min at the same time.

[0096] The reactor is continuously fed into it using precision metering pumps.

[0097] Material A: 72g (1.21mol) of isopropylamine, 1.15g of Pd(PPh3)2Cl2, and 1000g of dichloroethane;

[0098] Material B: 132.5g (1.126mol) of chlorosulfonic acid;

[0099] Material C: 345g (3.38mol) of triethylamine;

[0100] During the reaction, two reaction zones were observed to form inside the reactor: the first reaction zone (sulfonation zone) had an actual temperature of 30-40℃, and the second reaction zone (maturation zone) had an actual temperature of 20-25℃. After the reaction was completed, the intermediate isopropylamine sulfonic acid was obtained.

[0101] S2, Chlorination reaction: The above isopropylamine sulfonic acid is introduced into the second section of the chlorination tubular reactor. The initial temperature control target is set to 0℃, the residence time is 5min, the flow rate of the precision flow pump is set according to the residence time, and the reactor speed is adjusted to 1000r / min.

[0102] Continuous feeding via a precision metering pump:

[0103] Material D: 114.5 g (0.75 mol) of methyl anthranilate.

[0104] Material E: 127.5g (0.825mol) of phosphorus oxychloride;

[0105] The actual temperature of the first reaction zone (chlorination zone) inside the reactor was monitored to be 40-50℃, and the actual temperature of the second reaction zone (aging zone) was 35-40℃.

[0106] S3. The chlorination reaction solution was directly quenched with water. After standing and separating into layers, the organic phase was distilled to obtain the intermediate methyl o-isopropylaminosulfonamide benzoate (M272) solid, weighing 203.5 g, with a purity of 98.3% and a yield of 98.06% (based on methyl o-aminobenzoate). M272 was dissolved in methanol solution, and sodium methoxide was added to carry out a ring-closing reaction to obtain 176.3 g of metribuzin technical grade, with a purity of 99.5% and a yield of 97.45% (based on methyl o-aminobenzoate).

[0107] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions or improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A two-step continuous preparation process for bentazon intermediates via sulfonation and chlorination, characterized in that, Includes the following steps: S1. Solvent, chlorosulfonic acid, triethylamine, isopropylamine and catalyst are continuously metered into the first tubular reactor to carry out sulfonation reaction to obtain the reactant isopropylamine sulfonic acid; the catalyst is Pd(PPh3)4 or Pd(PPh3)2Cl2. S2. The reactant isopropylamine sulfonic acid is directly and continuously introduced into the second tubular reactor. At the same time, methyl o-aminobenzoate and phosphorus oxychloride are continuously metered into the second tubular reactor to carry out the chlorination reaction. After the reaction is completed, the reaction solution is quenched with water, and after layering and distillation, the intermediate methyl o-isopropylamine sulfonamide benzoate solid is obtained. S3. The intermediate methyl o-isopropylamine sulfonamide benzoate solid was subjected to a ring-closing reaction with sodium methoxide in methanol solution to obtain bentazon technical grade.

2. The two-step continuous preparation process of bentazon intermediate by sulfonation-chlorination according to claim 1, characterized in that, The first tubular reactor is provided with a solvent and catalyst mixing inlet, a triethylamine inlet, an isopropylamine inlet, and a chlorosulfonic acid inlet in sequence along the material flow direction; The second tubular reactor is provided with an isopropylamine sulfonic acid inlet, an o-aminobenzoate methyl ester inlet, and a phosphorus oxychloride inlet in sequence along the material flow direction; wherein, the isopropylamine sulfonic acid inlet is directly connected to the product outlet of the first tubular reactor.

3. The two-step continuous preparation process of bentazon intermediate by sulfonation-chlorination according to claim 1, characterized in that, Both the first and second tubular reactors are equipped with jacketed heating and cooling circulation systems for real-time temperature control.

4. The two-step continuous preparation process of bentazon intermediate by sulfonation-chlorination according to claim 1, characterized in that, The molar ratio of methyl anthranilate, chlorosulfonic acid, isopropylamine, triethylamine, and phosphorus oxychloride is 1:(1.2-3.0):(1.15-4):(4-5):(1.05-6).

5. The two-step continuous preparation process of bentazon intermediate by sulfonation-chlorination according to claim 1, characterized in that, The weight ratio of the catalyst to methyl anthranilate is (1-5):

100.

6. The two-step continuous preparation process of bentazon intermediate by sulfonation-chlorination according to claim 1, characterized in that, The solvent is any one of dichloroethane, toluene, xylene, and n-hexane.

7. The two-step continuous preparation process of bentazon intermediate by sulfonation-chlorination according to claim 1, characterized in that, In step S1, the sulfonation reaction temperature is 0℃-50℃; and / or, the residence time in the first tubular reactor is 1-30 min; and / or, the rotation speed of the first tubular reactor is 200 r / min-1200 r / min.

8. The two-step continuous preparation process of bentazon intermediate by sulfonation-chlorination according to claim 1, characterized in that, In step S2, the chlorination reaction temperature is 10℃-70℃; and / or, the residence time in the second tubular reactor is 1-30 min; and / or, the rotation speed of the second tubular reactor is 200 r / min-1200 r / min.

9. The two-step continuous preparation process of bentazon intermediate by sulfonation-chlorination according to claim 1, characterized in that, In step S1, the continuous feeding of solvent, chlorosulfonic acid, triethylamine, isopropylamine, and catalyst, and in step S2, the continuous feeding of methyl anthranilate and phosphorus oxychloride, are all performed using precision metering pumps. Furthermore, by adjusting the flow rate of the precision flow pump to match the preset residence time of the tubular reactor in steps S1 and S2, continuous and stable material feeding is achieved.

10. The two-step continuous preparation process of bentazon intermediate by sulfonation-chlorination according to claim 1, characterized in that, The obtained bentazon technical grade has a content of ≥99% and a yield of ≥97% based on methyl anthranilate.

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