Synthesis method of metribuzin isomer

Abstract

The invention discloses a synthesis method of a metribuzin isomer. Triazinone is used as a raw material, dimethyl carbonate is used as a methylation reagent, and the metribuzin isomer is prepared under base catalysis. The synthesis method is simple and convenient to operate, the used dimethyl carbonate replaces a traditional virulent methylation reagent, virulent by-products are eliminated, the method has the characteristics of low cost and environmental protection, a standard substance is provided for qualitative and quantitative analysis of impurities in metribuzin production, an optimized technical scheme is provided for production of triazinone herbicides, and the method is suitable for industrial production. The method is suitable for industrial application.

Description

Technical Field

[0001] The invention belongs to the technical field of pesticide chemical synthesis, and particularly relates to a method for synthesizing metribuzin isomers. Background Art

[0002] Metribuzin, also known as cyclazin, is a widely used herbicide in agriculture. It boasts low toxicity, low residue, and strong selectivity. It is suitable for use in a variety of crops, including soybeans, potatoes, tomatoes, peas, and sugarcane, effectively controlling a wide range of broadleaf and grass weeds. During the industrial production of metribuzin, various impurities are inevitably generated due to factors such as the reaction mechanism and process conditions. Some of these impurities have significant negative impacts on metribuzin's product quality, efficacy, and environmental safety. Some impurities may reduce metribuzin's herbicidal activity against target weeds, leading to increased pesticide usage, increasing agricultural production costs and potentially increasing the burden on the ecological environment due to excessive pesticide use. Other impurities may enhance metribuzin's toxicity to non-target organisms, posing a potential threat to ecological balance. According to relevant Chinese regulations, impurities present at levels above 0.1% require rigorous qualitative and quantitative analysis. During this analysis, reference standards must be used as a reference for structure confirmation and content calibration.

[0003] At present, the research on the synthesis process of metribuzin mainly focuses on the screening and optimization of methylating agents. For example, patent CN 1071181169 discloses a technical solution for synthesizing metribuzin using methyl bromide, methyl iodide, etc. as methylating agents. Patent CN 109320470A reports the use of dimethyl sulfate as a methylating agent, but this agent is a highly toxic substance and has serious safety and environmental risks. At the same time, the process has the problems of low yield of metribuzin and low product purity, which directly leads to increased raw material unit consumption and high process comprehensive cost. Patent CN 112010814 A proposes a methanol-sulfuric acid synthesis route using sulfuric acid as a solvent and methanol as a methylating agent. However, this method has the defects of long reaction cycle, low production efficiency, and high impurity content of the product. In addition, the wastewater generated during the reaction has a significant sulfur odor, and subsequent wastewater treatment is difficult and costly, limiting its industrial application.

[0004] In view of the shortcomings of the existing process in terms of safety, economy, environmental protection and product quality, there is an urgent need to develop a simple and efficient method for synthesizing metribuzin isomers to provide accurate reference standards for impurity control in metribuzin products. Summary of the Invention

[0005] The present invention aims to provide a simple and efficient method for preparing metribuzin isomers, which has significant advantages such as simple operation, low cost, and environmental friendliness. Specifically, triazone is reacted with dimethyl carbonate in the presence of a basic catalyst, and the reaction parameters are controlled to achieve a highly selective methylation reaction of triazone, thereby producing metribuzin isomers. The reaction equation is as follows:

[0006]

[0007] Preferably, the reaction is carried out in the presence of a solvent, wherein the solvent is one or a mixed solvent of methanol, acetonitrile, tetrahydrofuran, N,N-dimethylformamide, n-propanol, and isobutanol.

[0008] Preferably, the feed ratio of triazone to dimethyl carbonate is 1:1-5.

[0009] Preferably, the base is one of sodium hydroxide, potassium hydroxide, potassium carbonate, triethylamine, pyridine, and 1,8-diazabicycloundec-7-ene (DBU).

[0010] Preferably, the reaction temperature is 60-90°C.

[0011] Preferably, the reaction time is 2-8 hours.

[0012] This method uses triazone as a raw material and dimethyl carbonate as a methylating agent to produce metribuzin isomers in a single step under base catalysis. Compared to the traditional dimethyl sulfate process, this synthetic route eliminates highly toxic byproducts, is simple to operate, and is environmentally friendly, making it suitable for industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Figure 1 This is the infrared spectrum of metribuzin isomers.

[0014] Figure 2 This is the H NMR spectrum of metribuzin isomers.

[0015] Figure 3 This is the C-NMR spectrum of metribuzin isomers.

[0016] Figure 4 This is the mass spectrum of metribuzin isomers. Specific implementation plan

[0017] In order to facilitate understanding of the present invention, the present invention is further described in detail below in conjunction with preferred embodiments. It should be noted that the following embodiments are only used to illustrate the present invention and are not intended to limit the scope of protection of the present invention.

[0018] Example 1

[0019] 0.1 g of triazone was weighed and placed in a 50 mL round-bottom flask, dissolved in methanol, and 1 mL of dimethyl carbonate was slowly added dropwise to the flask. Subsequently, 0.5 mL of 30% NaOH aqueous solution was added. The reaction mixture was placed in a 60°C oil bath and reacted for 2 hours under continuous stirring. The reaction progress was monitored by thin-layer chromatography using n-hexane / ethyl acetate (volume ratio 9:1) as the developing solvent until the raw material spot basically disappeared or the target product spot became the main spot. After the reaction was completed, the reaction mixture was transferred and 10 mL of water was slowly added to quench the reaction. The resulting mixture was extracted three times with n-hexane. The organic phases were combined and dried over anhydrous sodium sulfate. The dried organic solution was evaporated under reduced pressure at 40°C to remove the solvent to obtain the target product as a solid with a yield of 88%.

[0020] Example 2

[0021] 0.1 g of triazone was weighed and placed in a 50 mL round-bottom flask, dissolved in acetonitrile, and 2 mL of dimethyl carbonate was slowly added dropwise to the flask. Subsequently, potassium carbonate was added. The reaction mixture was placed in a 70 ° C oil bath and reacted for 3 hours under continuous stirring. The reaction progress was monitored by thin layer chromatography using n-hexane / ethyl acetate (volume ratio 9:1) as the developing solvent until the raw material point basically disappeared or the target product point became the main spot. After the reaction was completed, the reaction mixture was transferred and 10 mL of water was slowly added to quench the reaction. The resulting mixture was extracted three times with dichloromethane. The organic phases were combined and dried over anhydrous sodium sulfate. The dried organic solution was evaporated under reduced pressure at 40 ° C to remove the solvent to obtain the target product solid with a yield of 85%.

[0022] Example 3

[0023] 0.1 g of triazone was weighed and placed in a 50 mL round-bottom flask, dissolved in tetrahydrofuran, and 3 mL of dimethyl carbonate was slowly added dropwise to the flask. Subsequently, triethylamine was added. The reaction mixture was placed in an 80 ° C oil bath and reacted for 4 hours under continuous stirring. The reaction progress was monitored by thin layer chromatography using n-hexane / ethyl acetate (volume ratio 9:1) as the developing solvent until the raw material point basically disappeared or the target product point became the main spot. After the reaction was completed, the reaction mixture was transferred and 10 mL of water was slowly added to quench the reaction. The resulting mixture was extracted three times with ethyl acetate. The organic phases were combined and dried over anhydrous sodium sulfate. The dried organic solution was evaporated under reduced pressure at 40 ° C to remove the solvent to obtain the target product solid with a yield of 86%.

[0024] Example 4

[0025] 0.1 g of triazone was weighed and placed in a 50 mL round-bottom flask. It was dissolved in N,N-dimethylformamide. 4 mL of dimethyl carbonate was slowly added dropwise to the flask, followed by pyridine. The reaction mixture was placed in a 90°C oil bath and stirred for 5 hours. The reaction progress was monitored by thin-layer chromatography using n-hexane / ethyl acetate (9:1 by volume) as the developing solvent until the starting material spot essentially disappeared or the target product spot became the main spot. After the reaction was completed, the reaction mixture was transferred and quenched by the slow addition of 10 mL of water. The resulting mixture was extracted three times with petroleum ether. The organic phases were combined and dried over anhydrous sodium sulfate. The dried organic solution was evaporated under reduced pressure at 40°C to remove the solvent, affording the target product as a solid in an 80% yield.

[0026] Example 5

[0027] 0.1 g of triazone was weighed and placed in a 50 mL round-bottom flask, dissolved in n-propanol, and 5 mL of dimethyl carbonate was slowly added dropwise to the flask. Subsequently, potassium hydroxide was added. The reaction mixture was placed in a 90 ° C oil bath and reacted for 6 hours under continuous stirring. The reaction progress was monitored by thin layer chromatography using n-hexane / ethyl acetate (volume ratio 9:1) as the developing solvent until the raw material point basically disappeared or the target product point became the main spot. After the reaction was completed, the reaction mixture was transferred and 10 mL of water was slowly added to quench the reaction. The resulting mixture was extracted three times with dichloromethane. The organic phases were combined and dried over anhydrous sodium sulfate. The dried organic solution was evaporated under reduced pressure at 40 ° C to remove the solvent to obtain the target product solid with a yield of 89%.

[0028] Example 6

[0029] 0.1 g of triazone was weighed and placed in a 50 mL round-bottom flask. Dissolved in isobutanol, 6 mL of dimethyl carbonate was slowly added dropwise to the flask. Subsequently, 1,8-diazabicycloundec-7-ene (DBU) was added. The reaction mixture was placed in a 90°C oil bath and reacted for 8 hours with constant stirring. Reaction progress was monitored by thin-layer chromatography using n-hexane / ethyl acetate (9:1 by volume) as the developing solvent until the starting material spot essentially disappeared or the target product spot became the main spot. After the reaction was completed, the reaction mixture was transferred and quenched by the slow addition of 10 mL of water. The resulting mixture was extracted three times with n-hexane. The organic phases were combined and dried over anhydrous sodium sulfate. The dried organic solution was evaporated under reduced pressure at 40°C to remove the solvent, affording the target product as a solid in a 98% yield.

Claims

1. A method for synthesizing metribuzin isomers, characterized in that: Using triazone as raw material and dimethyl carbonate as methylating agent, metribuzin isomers are prepared under base catalysis. The reaction equation is as follows:

2. The method for synthesizing metribuzin isomers according to claim 1, wherein: The base is one of sodium hydroxide, potassium hydroxide, potassium carbonate, triethylamine, pyridine and 1,8-diazabicycloundec-7-ene (DBU).

3. The method for synthesizing metribuzin isomers according to claim 1, wherein: The reaction is carried out in the presence of a solvent, wherein the solvent is one of methanol, acetonitrile, tetrahydrofuran, N,N-dimethylformamide, n-propanol, and isobutanol.

4. The method for synthesizing metribuzin isomers according to claim 1, wherein: The feeding ratio of triazone to dimethyl carbonate is 1:1-5.

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