S-metolachlor active compound as well as synthesis method and application thereof
By using a coated chiral catalyst, the problems of insufficient chiral selectivity and easy catalyst deactivation in the synthesis of S-metolachlor have been solved, realizing the synthesis of high-purity, low-cost, and environmentally friendly S-metolachlor technical material, which is suitable for the preparation of herbicides for crops such as corn, soybeans, and cotton.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-12-30
- Publication Date
- 2026-04-03
AI Technical Summary
Existing methods for synthesizing metolachlor suffer from insufficient chiral selectivity, easy catalyst deactivation, harsh reaction conditions, cumbersome processes, and environmental unfriendliness, resulting in low product purity, high costs, and significant environmental risks.
A coated chiral catalyst, comprising a chiral phosphine-phosphonamide ligand, an iridium metal complex, and a mesoporous silica coating layer, is used to synthesize metolachlor technical grade through a two-step reaction. This avoids catalyst aggregation, reduces reaction energy consumption, and simplifies the process.
It improves chiral selectivity and product purity, reduces drug dosage, lowers environmental residues, reduces production costs, achieves green synthesis, and meets environmental protection requirements.
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Abstract
Description
Technical Field
[0001] This invention relates to the field of pesticide chemical synthesis technology, and in particular to a metolachlor technical grade pesticide, its synthesis method, and its application. Background Technology
[0002] S-metolachlor is a highly effective, broad-spectrum selective pre-emergence herbicide widely used in fields of various crops such as corn, soybeans, cotton, and peanuts. It can effectively control annual grass weeds such as barnyard grass, foxtail grass, and some broadleaf weeds, and plays an important role in ensuring crop yield and reducing weed damage in modern agricultural production.
[0003] As a typical chiral pesticide, the herbicidal activity of S-metolachlor mainly depends on its specific chiral enantiomer (usually the S-enantiomer). Non-target enantiomers not only have extremely low herbicidal activity, but may also increase the dosage and aggravate the risk of environmental residues. Therefore, chiral selective synthesis is the core technical challenge in the preparation of S-metolachlor technical.
[0004] Existing methods for synthesizing S-metolachlor have many shortcomings, limiting its industrial application and environmental upgrades: 1) Insufficient chiral selectivity: Traditional synthesis often uses racemic resolution or ordinary chiral catalysts. The enantiomeric excess value (ee value) is usually less than 90%. Insufficient purity of the target enantiomeric substance leads to insufficient efficacy, requiring increased dosage to achieve the desired control effect, which increases both the cost of use and the environmental burden. 2) Defects in catalyst performance: Traditional chiral catalysts are mostly homogeneous catalysts, which have problems such as easy agglomeration and deactivation, difficulty in recycling and reuse, and easy residue of metal ions in the product. This not only increases production costs, but may also affect the purity of the active ingredient and environmental safety. 3) Harsh reaction conditions: Some synthesis processes need to be carried out in high temperature, high pressure or strong acid and alkali environment, which results in high energy consumption, high equipment requirements, and easy generation of side reactions, leading to reduced product yield and increased impurity content. 4) Low process efficiency: Traditional methods involve complicated steps, long reaction cycles, and require the use of highly toxic and volatile organic solvents, which puts great pressure on the environment and does not conform to the trend of green chemical development. 5) Poor stability of intermediates: During the synthesis process, chiral amine intermediates are prone to racemization or oxidation, which further reduces the purity and yield of the target product and increases the difficulty of subsequent separation and purification.
[0005] Therefore, it is of great significance to provide a method for synthesizing metolachlor technical with high chiral selectivity, stable and recyclable catalyst, mild reaction conditions, simple and environmentally friendly process, and high product purity. Summary of the Invention
[0006] To address the aforementioned technical problems, the present invention aims to provide a technical grade of metolachlor, its synthesis method, and its application.
[0007] To achieve the above-mentioned objectives, the present invention provides the following technical solution: This invention provides a method for synthesizing metolachlor technical grade, comprising the following steps: 1) N-(2-methyl-6-ethylphenyl)methoxypropylimine, a coated chiral catalyst, an iodine additive, and an acid are reacted in a hydrogen atmosphere to obtain a chiral amine intermediate; 2) An acylation reaction is carried out on a chiral amine intermediate, chloroacetyl chloride and an organic base in an organic solvent. After the reaction is completed, the technical grade of metolachlor is obtained.
[0008] Furthermore, the coated chiral catalyst includes a core and a coating layer, wherein the coating layer encapsulates the core within its pores; The core is a complex formed by a chiral phosphine-phosphine ligand and iridium metal; The coating layer is a porous inorganic oxide material.
[0009] Furthermore, the chiral phosphine-phosphamide ligand is a monophosphine-phosphamide ligand with a P-chiral center or a phosphine-phosphamide ligand with a rigid spirocyclic skeleton; The porous inorganic oxide material is mesoporous silicon dioxide, and the most probable pore size of the porous inorganic oxide material is 2~10nm.
[0010] Furthermore, the iodine additive includes one or more of potassium iodide, sodium iodide, and tetrabutylammonium iodide; The acid includes one or more of formic acid, acetic acid, and trifluoroacetic acid.
[0011] Furthermore, the organic solvent includes toluene and / or chlorobenzene; The organic base includes triethylamine and / or N,N-diisopropylethylamine.
[0012] Furthermore, the molar ratio of the N-(2-methyl-6-ethylphenyl)ethyleneamine, the coated chiral catalyst, the iodine additive, and the acid is 1:0.0001~0.001:0.0005~0.002:0.005~0.1; The molar ratio of the chiral amine intermediate, chloroacetyl chloride, and organic base is 1:1~1.2:1.1~2; The amount of organic solvent added is such that the molar concentration of the chiral amine intermediate is 50-200 mL / mmol.
[0013] Furthermore, in step 1), the reaction temperature is 20~40℃, the reaction time is 0.5~2h, and the hydrogen pressure is 1~3MPa.
[0014] Furthermore, in step 2), the acylation reaction temperature is 70~100℃, and the acylation reaction time is 3~4h.
[0015] This invention provides a synthetic method for preparing metolachlor technical grade.
[0016] This invention also provides the application of metolachlor technical in the preparation of herbicides.
[0017] The beneficial effects of this invention are: 1) This invention uses a complex formed by a phosphine-phosphine ligand with a P-chiral center or a rigid spirocyclic skeleton and iridium metal as the core catalytic unit, supplemented by a mesoporous silica coating layer, which can significantly improve the enantiomeric excess value (ee value) of the chiral amine intermediate, thereby improving the purity of the final product, metolachlor. The high-purity chiral structure can ensure the maximum herbicidal activity of the active ingredient. Compared with traditional processes, it can reduce the amount of pesticide used, thereby reducing the cost for farmers and reducing the environmental residues of pesticides in soil and water. 2) The catalyst used in this invention has stable performance and can be recycled: the mesoporous silica coating layer (most probable pore size 2~10nm) wraps the catalytic core inside the pores, which can effectively prevent catalyst particles from agglomerating and deactivating, and enhance the chemical stability of the metal complex. 3) The synthesis method of the present invention requires only two tandem reactions to obtain the target product. The process is short and simple to operate, and no additional protection / deprotection steps are required, which greatly improves production efficiency. At the same time, the reaction conditions are mild, energy consumption and side reactions are significantly reduced, and high-temperature and high-pressure equipment is not required. This not only reduces equipment investment and operating costs, but also avoids side reactions such as intermediate racemization and amide bond hydrolysis that are prone to occur under high temperature and high pressure. The quality standards of the original drug can be achieved without complex separation and purification, thus realizing the green synthesis goal of low toxicity, low consumption and low emission. 4) This invention effectively suppresses the formation of byproducts by precisely controlling the molar ratio of reactants, reaction temperature and time, and finally achieves high purity of metolachlor technical grade, which meets the national pesticide technical grade quality standards and international environmental protection requirements; when applied to the preparation of herbicides, it has high safety for crops and low toxicity to beneficial organisms, which helps to maintain the ecological balance of farmland. Detailed Implementation
[0018] This invention provides a method for synthesizing metolachlor technical grade, comprising the following steps: 1) N-(2-methyl-6-ethylphenyl)methoxypropylimine, a coated chiral catalyst, an iodine additive, and an acid are reacted in a hydrogen atmosphere to obtain a chiral amine intermediate; 2) An acylation reaction is carried out on a chiral amine intermediate, chloroacetyl chloride and an organic base in an organic solvent. After the reaction is completed, the technical grade of metolachlor is obtained.
[0019] In this invention, the coated chiral catalyst includes a core and a coating layer, wherein the coating layer encapsulates the core within its pores. The core is a complex formed by a chiral phosphine-phosphine ligand and iridium metal; The coating layer is a porous inorganic oxide material.
[0020] In this invention, the chiral phosphine-phosphamide ligand is a monophosphine-phosphamide ligand with a P-chiral center or a phosphine-phosphamide ligand with a rigid spirocyclic skeleton, preferably a phosphine-phosphamide ligand with a rigid spirocyclic skeleton; The porous inorganic oxide material is preferably mesoporous silica, and the most probable pore size of the porous inorganic oxide material is 2~10nm, preferably 2.5~8nm, and more preferably 3~5nm.
[0021] In this invention, the core component is a chiral phosphine-phosphine ligand, which provides an asymmetric reaction environment to ensure that the reduction reaction preferentially generates the target chiral configuration; iridium metal is the catalytic active center, which activates the reactivity of hydrogen and imine; the coating layer can fix the catalyst, prevent its agglomeration and deactivation, and improve the reusability of the catalyst.
[0022] In this invention, the iodine additive includes one or more of potassium iodide, sodium iodide and tetrabutylammonium iodide, preferably potassium iodide and / or tetrabutylammonium iodide, and more preferably tetrabutylammonium iodide. The acid includes one or more of formic acid, acetic acid and trifluoroacetic acid, preferably acetic acid and / or trifluoroacetic acid, and more preferably acetic acid.
[0023] In this invention, the organic solvent includes toluene and / or chlorobenzene, preferably toluene; The organic base includes triethylamine and / or N,N-diisopropylethylamine, preferably N,N-diisopropylethylamine.
[0024] In this invention, the molar ratio of N-(2-methyl-6-ethylphenyl)ethyleneamine, the coated chiral catalyst, the iodine additive, and the acid is 1:0.0001~0.001:0.0005~0.002:0.005~0.1, preferably 1:0.0003~0.0008:0.0008~0.0018:0.01~0.09, and more preferably 1:0.0005:0.001~0.0015:0.03~0.07; The molar ratio of the chiral amine intermediate, chloroacetyl chloride, and organic base is 1:1~1.2:1.1~2, preferably 1:1.05~1.15:1.3~1.8, and more preferably 1:1.1:1.5~1.6; The amount of organic solvent added is such that the molar concentration of the chiral amine intermediate is 50-200 mL / mmol, preferably 80-170 mL / mmol, and more preferably 100-150 mL / mmol.
[0025] In this invention, in step 1), the reaction temperature is 20~40℃, preferably 25~35℃, and more preferably 30℃; the reaction time is 0.5~2h, preferably 0.8~1.7h, and more preferably 1~1.5h; the hydrogen pressure is 1~3MPa, preferably 1.5~2.5MPa, and more preferably 2MPa.
[0026] In this invention, the reaction temperature can avoid the decomposition of chiral ligands or racemization of chiral centers, which would destroy selectivity, while ensuring the reaction rate; the hydrogen pressure ensures that hydrogen dissolves and participates in the reaction, avoiding incomplete reduction; the reaction time can balance reaction efficiency and energy consumption, ensuring that imine is completely reduced to amine, and that there are no excessive reaction byproducts.
[0027] In this invention, in step 2), the temperature of the acylation reaction is 70~100℃, preferably 75~95℃, and more preferably 80~90℃; the time of the acylation reaction is 3~4h, preferably 3.2~3.8h, and more preferably 3.5h.
[0028] In this invention, during the acylation reaction, the temperature range of this invention can not only activate the acylation activity of chloroacetyl chloride and ensure the acylation reaction rate, but also avoid the hydrolysis of amide bonds or racemization of chiral centers caused by high temperature; the acylation reaction time of this invention can ensure complete acylation of amine intermediates and avoid residual intermediates affecting the purity of the original drug.
[0029] This invention provides a synthetic method for preparing metolachlor technical grade.
[0030] This invention also provides the application of metolachlor technical in the preparation of herbicides.
[0031] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.
[0032] Example 1
[0033] A complex formed by a rigid spirocyclic framework of phosphine-phosphine ligand and iridium metal was used as the core and coated inside the pores of mesoporous silica with a most probable pore size of 3 nm to obtain a coated chiral catalyst. N-(2-methyl-6-ethylphenyl)methoxypropylimine, a coated chiral catalyst, tetrabutylammonium iodide, and acetic acid in a molar ratio of 1:0.0005:0.0012:0.05 were reacted in a hydrogen atmosphere at a temperature of 30°C for 1.2 h and a hydrogen pressure of 2 MPa. After the reaction was completed, a chiral amine intermediate was obtained. A mixture of a chiral amine intermediate, chloroacetyl chloride, and N,N-diisopropylethylamine in a molar ratio of 1:1.1:1.5 was placed in toluene (the amount of toluene added was such that the molar concentration of the chiral amine intermediate was 120 mL / mmol) and subjected to an acylation reaction at 80 °C. The reaction was completed after 3.5 h to obtain the technical grade of metolachlor.
[0034] Example 2
[0035] A complex formed by a P-chiral center monophosphine phosphoramide ligand and iridium metal was used as the core and coated inside the pores of mesoporous silica with a most probable pore size of 5 nm to obtain a coated chiral catalyst. N-(2-methyl-6-ethylphenyl)methoxypropylimine, a coated chiral catalyst, potassium iodide, and trifluoroacetic acid in a molar ratio of 1:0.0003:0.0009:0.03 were reacted in a hydrogen atmosphere at a temperature of 25°C for 1.5 h and a hydrogen pressure of 1.5 MPa. After the reaction was completed, a chiral amine intermediate was obtained. A mixture of a chiral amine intermediate, chloroacetyl chloride, and triethylamine in a molar ratio of 1:1.05:1.3 was placed in chlorobenzene (the amount of chlorobenzene added was such that the molar concentration of the chiral amine intermediate was 100 mL / mmol) and subjected to an acylation reaction at 80 °C. The reaction was completed after 3.8 h to obtain the technical grade of metolachlor.
[0036] Example 3
[0037] A complex formed by a rigid spirocyclic framework of phosphine-phosphamide ligand and iridium metal was used as the core and coated inside the pores of mesoporous silica with a most probable pore size of 4 nm to obtain a coated chiral catalyst. N-(2-methyl-6-ethylphenyl)methoxypropylimine, a coated chiral catalyst, tetrabutylammonium iodide, and acetic acid in a molar ratio of 1:0.0008:0.0016:0.07 were reacted in a hydrogen atmosphere at a temperature of 35°C for 1.0 h and a hydrogen pressure of 2.5 MPa. After the reaction was completed, a chiral amine intermediate was obtained. A mixture of a chiral amine intermediate, chloroacetyl chloride, and triethylamine in a molar ratio of 1:1.15:1.6 was placed in a mixed solution of toluene and chlorobenzene (volume ratio of toluene and chlorobenzene was 1:1, and the amount of toluene and chlorobenzene added was such that the molar concentration of the chiral amine intermediate was 1.50 mL / mmol). The reaction was carried out at 90 °C for 3.2 h to obtain the technical grade of metolachlor.
[0038] Comparative Example 1
[0039] Compared with Example 1, the difference is that the catalyst in Comparative Example 1 is a homogeneous iridium-triphenylphosphine complex without a coating layer.
[0040] Comparative Example 2
[0041] The difference between this example and Example 1 is that the reaction temperature in Comparative Example 2 is 50°C.
[0042] Comparative Example 3
[0043] Compared with Example 1, the difference is that in Comparative Example 3, the molar ratio of N-(2-methyl-6-ethylphenyl)methoxypropylimine, coated chiral catalyst, tetrabutylammonium iodide and acetic acid is 1:0.00005:0.0012:0.05.
[0044] Comparative Example 4
[0045] Compared with Example 1, the difference is that the molar ratio of chiral amine intermediate, chloroacetyl chloride and N,N-diisopropylethylamine in Comparative Example 4 is 1:0.9:1.0.
[0046] The technical grade metolachlor prepared in Examples 1-3 and Comparative Examples 1-4 were tested using the following methods: Enantiomeric excess value (ee value) of chiral amine intermediates: determined by high performance liquid chromatography (HPLC) using a chiral column (Chiralcel OD-H), with a mobile phase of n-hexane / isopropanol = 95 / 5 (v / v), a flow rate of 1.0 mL / min, and a column temperature of 30 °C. Yield of metolachlor technical grade: calculated as the ratio of the actual mass to the theoretical mass of the target product; Purity of the active ingredient: determined by gas chromatography (GC) using an HP-5 capillary column (30m×0.32mm×0.25μm). Column temperature program: initial temperature 80℃, held for 1 min, then increased to 280℃ at a rate of 10℃ / min, held for 5 min. Catalyst recovery activity: After the reaction, the catalyst was separated by filtration, washed, dried, and reused in the reaction. The catalytic activity retention rate after 5 recovery cycles was recorded (based on the ee value of the first reaction). The test results are shown in Table 1.
[0047] Table 1. Test results of Examples 1-3 and Comparative Examples 1-4
[0048] As can be seen from the above embodiments, the present invention provides a technical grade of metolachlor, its synthesis method, and its application. The synthesis method of the metolachlor technical grade includes the following steps: reacting N-(2-methyl-6-ethylphenyl)methoxypropylimine, a coated chiral catalyst, an iodine additive, and an acid in a hydrogen atmosphere to obtain a chiral amine intermediate; and performing an acylation reaction of the chiral amine intermediate, chloroacetyl chloride, and an organic base in an organic solvent. After the reaction is completed, the metolachlor technical grade is obtained. The catalyst used in this invention is stable and recyclable, exhibits high chiral selectivity, high product purity, mild reaction conditions, and a simple and environmentally friendly process.
[0049] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.
Claims
1. A method for synthesizing S-metolachlor technical grade, characterized in that, Includes the following steps: 1) N-(2-methyl-6-ethylphenyl)methoxypropylimine, a coated chiral catalyst, an iodine additive, and an acid are reacted in a hydrogen atmosphere to obtain a chiral amine intermediate; 2) An acylation reaction is carried out on a chiral amine intermediate, chloroacetyl chloride and an organic base in an organic solvent. After the reaction is completed, the technical grade of metolachlor is obtained.
2. The method for synthesizing metolachlor technical grade according to claim 1, characterized in that, The coated chiral catalyst includes a core and a coating layer, wherein the coating layer encapsulates the core within its pores. The core is a complex formed by a chiral phosphine-phosphine ligand and iridium metal; The coating layer is a porous inorganic oxide material.
3. The method for synthesizing metolachlor technical grade according to claim 2, characterized in that, The chiral phosphine-phosphamide ligand is a monophosphine-phosphamide ligand with a P-chiral center or a phosphine-phosphamide ligand with a rigid spirocyclic skeleton; The porous inorganic oxide material is mesoporous silicon dioxide, and the most probable pore size of the porous inorganic oxide material is 2~10nm.
4. The method for synthesizing metolachlor technical grade according to claim 3, characterized in that, The iodine additive includes one or more of potassium iodide, sodium iodide and tetrabutylammonium iodide; The acid includes one or more of formic acid, acetic acid, and trifluoroacetic acid.
5. The method for synthesizing metolachlor technical grade according to claim 4, characterized in that, The organic solvent includes toluene and / or chlorobenzene; The organic base includes triethylamine and / or N,N-diisopropylethylamine.
6. The method for synthesizing metolachlor technical grade according to claim 4 or 5, characterized in that, The molar ratio of N-(2-methyl-6-ethylphenyl)ethyleneamine, the coated chiral catalyst, the iodine additive, and the acid is 1:0.0001~0.001:0.0005~0.002:0.005~0.1; The molar ratio of the chiral amine intermediate, chloroacetyl chloride, and organic base is 1:1~1.2:1.1~2; The amount of organic solvent added is such that the molar concentration of the chiral amine intermediate is 50~200 mL / mmol.
7. The method for synthesizing metolachlor technical grade according to claim 6, characterized in that, In step 1), the reaction temperature is 20~40℃, the reaction time is 0.5~2h, and the hydrogen pressure is 1~3MPa.
8. The method for synthesizing metolachlor technical grade according to claim 7, characterized in that, In step 2), the acylation reaction temperature is 70~100℃ and the acylation reaction time is 3~4h.
9. A synthetic method for preparing metolachlor technical grade according to any one of claims 1 to 8.
10. The use of the metolachlor technical grade as described in claim 9 in the preparation of herbicides.