Resolution method of enantiomer of chiral herbicide clethodim

Abstract

The invention belongs to the technical field of chemical synthesis, and particularly provides a resolution method of enantiomers of chiral herbicide clethodim. A test solution is prepared, clethodim enantiomers in the clethodim test solution are separated by adopting ultrahigh liquid chromatography, a stationary phase is a # imgabs0 # IA chiral chromatographic column, a mobile phase A is an organic solvent, and a mobile phase B is an ammonium acetate aqueous solution; a detector is adopted for determination, and clethodim chiral monomer fractions are collected in a fraction collector at the same time. And then, concentrating the monomer fraction, and confirming the absolute configuration of the monomer fraction through calculation electron circular dichroism and actual measurement electron circular dichroism. The invention provides the clethodim chiral enantiomer which can be effectively separated and can be used for preparing a certain scale, and the method has the characteristics of mild and simple operation conditions, high sensitivity, high separation speed, high purity of the separated monomer and the like.

Description

Technical Field

[0001] The invention belongs to the technical field of chemical synthesis, and particularly relates to a method for separating enantiomers of a chiral herbicide clethodim. Background Art

[0002] Pesticides are essential for protecting crops and increasing food production. In recent years, the selectivity of chiral pesticides has received extensive attention, such as selective biological activity, toxicity and toxicology, environmental behavior, asymmetric synthesis, etc. Chiral pesticide enantiomers usually have different biological activities, and there are high-efficiency, low-efficiency or ineffective enantiomers. Chiral pesticides often have only one configuration that is effective, and their enantiomers are not only ineffective, but sometimes even harmful to the environment. Therefore, the development of single-configuration chiral pesticides is becoming more and more common. The use of single-configuration chiral pesticides not only protects plants and increases food production, but also saves resources and reduces the harm of ineffective isomers to the environment. This forces pesticide companies to produce efficient single enantiomers in the production of chiral pesticides. Therefore, pesticide companies at home and abroad are currently promoting single enantiomer chiral pesticides. This undoubtedly plays a positive role in promoting environmental protection and sustainable development.

[0003] Clethodim, (±)-2-[(E)-1-[(E)-3-chloroallyloxyimino]propyl]-5-[2-(ethylthio)propyl]-3-hydroxycyclohex-2-enone ( Figure 1 ) is a highly effective, safe and selective cyclohexenone herbicide introduced on the market, which is widely used to control annual and perennial herbs in various broadleaf crops. Sethodim competitively binds to acetyl-CoA carboxylase, the enzyme responsible for lipid biosynthesis, causing weeds to stop growing and eventually die. Currently, sethodim is still used in the form of a racemate, and due to the limitations of analytical separation methods, there are no reports on its enantiomeric differences. Therefore, an analytical separation method for the chiral pesticide sethodim is established to provide a theoretical basis for further studies on its selective environmental behavior and the development and application of chiral pesticides as efficient, environmentally friendly optically pure monomer pesticides.

[0004] Summary of the invention

[0005] The purpose of the invention is to provide a method for preparing the chiral herbicide clethodim.

[0006] The technical solution adopted by the present invention is: a method for separating the enantiomers of a chiral herbicide clethodim, comprising the following steps:

[0007] 1) Preparing a test solution: weighing a certain amount of clethodim and dissolving it in an organic solvent to prepare a clethodim test solution;

[0008] 2) Using ultra high performance liquid chromatography to separate the enantiomers of clethodim in the clethodim test solution, the stationary phase is IA chiral chromatographic column, mobile phase A is an organic solvent, mobile phase B is an aqueous solution of ammonium acetate with a concentration of 1-10 mmol / L, in the mobile phase, mobile phase B accounts for 10-40% by volume, column temperature is 20-35°C, column pressure is a constant pressure of 12-15 MPa, and flow rate is 0.4-0.7 mL / min;

[0009] 3) The detector is used for measurement, and the chiral monomer fraction of clethodim is collected in a fraction collector.

[0010] Furthermore, in the above-mentioned method for resolving enantiomers of a chiral herbicide clethodim, in step 1), the organic solvent is selected from one of methanol, ethanol, acetonitrile and isopropanol.

[0011] Furthermore, in the above-mentioned method for resolving enantiomers of a chiral herbicide clethodim, in step 1), the concentration of the clethodim test solution is 50 μg / mL-200 μg / mL.

[0012] Furthermore, in the above-mentioned method for resolving enantiomers of a chiral herbicide clethodim, in step 1), the concentration of the clethodim test solution is 100 μg / mL.

[0013] Furthermore, in the above-mentioned method for resolving enantiomers of a chiral herbicide clethodim, in step 2), the IA chiral chromatography column is a silica gel column with amylose-tris (3,5-dimethylphenylcarbamate) covalently bonded to the surface.

[0014] Further, in the above-mentioned method for resolving enantiomers of a chiral herbicide clethodim, in step 2), the mobile phase A is methanol, the mobile phase B is an aqueous solution of ammonium acetate with a concentration of 5 mmol / L, in the mobile phase, the mobile phase B accounts for 20% by volume, the column temperature is 30° C., the column pressure is a constant pressure of 15 MPa, and the flow rate is 0.6 mL / min;

[0015] Furthermore, in the above-mentioned method for resolving enantiomers of a chiral herbicide clethodim, in step 3), the detector is an ultraviolet detector or a mass spectrometer detector.

[0016] Compared with the prior art, the technical solution of the present application has the following beneficial effects: the present invention adopts ultra-high performance liquid chromatography to directly chirally separate sethoxydim, and its mobile phase is composed of an organic reagent and ultrapure water containing a certain amount of ammonium acetate. This method overcomes the shortcomings of the prior art and has the characteristics of mild and simple operating conditions, high sensitivity, fast separation speed, and high purity of separated monomers. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 It is the chromatographic separation pattern of Example 1.

[0018] Figure 2 It is the chromatographic separation pattern of Example 2.

[0019] Figure 3 It is the chromatographic separation pattern of Example 3.

[0020] Figure 4 It is the chromatographic separation pattern of Example 4.

[0021] Figure 5 It is the chromatographic separation spectrum of comparative example. DETAILED DESCRIPTION

[0022] The advantages of the present invention are further described below in conjunction with the accompanying drawings and specific embodiments.

[0023] Exemplary embodiments will be described in detail herein, examples of which are shown in the accompanying drawings. When the following description refers to the drawings, the same numbers in different drawings represent the same or similar elements unless otherwise indicated. The embodiments described in the following exemplary embodiments do not represent all embodiments consistent with the present disclosure. Instead, they are merely examples of devices and methods consistent with some aspects of the present disclosure as detailed in the appended claims.

[0024] The terms used in this disclosure are for the purpose of describing specific embodiments only and are not intended to limit the disclosure. The singular forms of "a", "said" and "the" used in this disclosure and the appended claims are also intended to include plural forms unless the context clearly indicates otherwise. It should also be understood that the term "and / or" used herein refers to and includes any or all possible combinations of one or more associated listed items.

[0025] Example 1

[0026] A method for chiral separation of clethodim enantiomers comprises the following steps:

[0027] (1) Weigh a certain amount of clethodim, dissolve it in methanol and make up to volume to prepare a clethodim test solution with a concentration of 100 μg / ml.

[0028] (2) Chiral separation using ultra-high performance liquid chromatography

[0029] The ultra-high performance liquid chromatography (UHPLC) system used was an Agilent system, and the stationary phase was a polysaccharide derivative chiral chromatographic column. IA chiral chromatographic column is a polysaccharide derivative chiral chromatographic column with amylose-tris(3,5-dimethylphenylcarbamate) covalently bonded to the silica gel surface. The specification is 250mm×4.6mm and the particle size is 5μm.

[0030] The mobile phase A is methanol, the mobile phase B is an aqueous solution of ammonium acetate with a concentration of 5 mM, and the mobile phase B accounts for 25% by volume. The column temperature of the polysaccharide derivative chiral chromatographic column is 35°C, the column pressure is 10 MPa, the flow rate is 0.4 mL / min, and the injection volume is 20 μL.

[0031] (3) HP-UV2040 was used for determination. At the same time, the chiral monomer fraction of clethodim was collected in a fraction collector. The monomer fraction was concentrated and its absolute configuration was confirmed by calculated and measured electron circular dichroism spectra.

[0032] The results are as follows Figure 1 .according to Figure 1 It can be seen that the chromatographic peaks of clethodim enantiomers have a separation trend, and the calculated separation degree is 1.32.

[0033] Example 2

[0034] A method for chiral separation of clethodim enantiomers comprises the following steps:

[0035] (1) Weigh a certain amount of clethodim, dissolve it in methanol and make up to volume to prepare a clethodim test solution with a concentration of 100 μg / mL.

[0036] (2) Chiral separation using ultra-high performance liquid chromatography

[0037] The ultra-high performance liquid chromatography (UHPLC) system used was an Agilent system, and the stationary phase was a polysaccharide derivative chiral chromatographic column. IA chiral chromatographic column is a polysaccharide derivative chiral chromatographic column with amylose-tris(3,5-dimethylphenylcarbamate) covalently bonded to the silica gel surface. The specification is 250mm×4.6mm and the particle size is 5μm.

[0038] Mobile phase A is methanol, mobile phase B is 5 mM ammonium acetate aqueous solution, and in the mobile phase, phase B accounts for 15% by volume. The column temperature of the polysaccharide derivative chiral chromatographic column is 35°C, the column pressure is 10 MPa, the flow rate is 0.4 mL / min, and the injection volume is 20 μL.

[0039] (3) HP-UV2040 was used to measure, and the chiral monomer fraction of clethodim was collected in a fraction collector. The monomer fraction was concentrated and its absolute configuration was confirmed by calculated and measured electronic circular dichroism spectra.

[0040] The results are as follows Figure 2 .according to Figure 2 It can be seen that the chromatographic peaks of clethodim enantiomers have a separation trend, and the calculated separation degree is 1.48.

[0041] Example 3

[0042] A method for chiral separation of clethodim enantiomers comprises the following steps:

[0043] (1) Weigh a certain amount of clethodim, dissolve it in methanol and make up to volume to prepare a clethodim test solution with a concentration of 100 μg / ml.

[0044] (2) Chiral separation using ultra-high performance liquid chromatography

[0045] The ultra-high performance liquid chromatography (UHPLC) system used was an Agilent system, and the stationary phase was a polysaccharide derivative chiral chromatographic column. IA chiral chromatographic column is a polysaccharide derivative chiral chromatographic column with amylose-tris(3,5-dimethylphenylcarbamate) covalently bonded to the silica gel surface. The specification is 250mm×4.6mm and the particle size is 5μm.

[0046] The mobile phase A is acetonitrile, the mobile phase B is an aqueous solution of ammonium acetate with a concentration of 5 mM, and the mobile phase B accounts for 30% by volume. The column temperature of the polysaccharide derivative chiral chromatographic column is 35°C, the column pressure is 10 MPa, the flow rate is 0.4 mL / min, and the injection volume is 20 μL.

[0047] (3) HP-UV2040 was used to measure, and the chiral monomer fraction of clethodim was collected in a fraction collector. The monomer fraction was concentrated and its absolute configuration was confirmed by calculated and measured electronic circular dichroism spectra.

[0048] The results are as follows Figure 3 .according to Figure 3 It can be seen that the enantiomers of clethodim are effectively separated, and the calculated separation degree is 1.85.

[0049] Example 4

[0050] A method for chiral separation of clethodim enantiomers comprises the following steps:

[0051] (1) Weigh a certain amount of clethodim, dissolve it in acetonitrile and make up to volume to prepare a clethodim test solution with a concentration of 100 μg / mL.

[0052] (2) Chiral separation using ultra-high performance liquid chromatography

[0053] The ultra-high performance liquid chromatography (UHPLC) system used was an Agilent system, and the stationary phase was a polysaccharide derivative chiral chromatographic column. IA chiral chromatographic column is a polysaccharide derivative chiral chromatographic column with straight-chain starch-tris(3,5-dimethylphenylcarbamate) covalently bonded to the surface of silica gel. The specification is 250mm×4.6mm and the particle size is 5μm.

[0054] The mobile phase A is acetonitrile, the mobile phase B is an aqueous solution of ammonium acetate with a concentration of 5 mM, and the mobile phase B accounts for 20% by volume. The column temperature of the polysaccharide derivative chiral chromatographic column is 35°C, the column pressure is 10 MPa, the flow rate is 0.6 mL / min, and the injection volume is 20 μL.

[0055] (3) HP-UV2040 was used for determination, and the chiral monomer fraction of clethodim was collected in the fraction collector. The monomer fraction was concentrated and its absolute configuration was confirmed by calculating the electronic circular dichroism spectrum and measuring the electronic circular dichroism spectrum. The results are as follows Figure 4 .according to Figure 4 It can be seen that the enantiomers of clethodim are effectively separated, and the calculated separation degree is 2.01.

[0056] Comparative Example

[0057] (1) Weigh a certain amount of clethodim, dissolve it in acetonitrile and make up to volume to prepare a clethodim test solution with a concentration of 100 μg / mL.

[0058] (2) Chiral separation using ultra-high performance liquid chromatography

[0059] The ultra-high performance liquid chromatography (UHPLC) system used was an Agilent system, and the stationary phase was a polysaccharide derivative chiral chromatographic column. IB chiral chromatographic column is a polysaccharide derivative chiral chromatographic column with cellulose-tris(3,5-dimethylphenylcarbamate) covalently bonded to the silica gel surface, with specifications of 250mm×4.6mm and a particle size of 5μm.

[0060] The mobile phase A is acetonitrile, the mobile phase B is an aqueous solution of ammonium acetate with a concentration of 5 mM, and the mobile phase B accounts for 20% by volume. The column temperature of the polysaccharide derivative chiral chromatographic column is 35°C, the column pressure is 10 MPa, the flow rate is 0.4 mL / min, and the injection volume is 20 μL.

[0061] (3) HP-UV2040 was used to measure, and the chiral monomer fraction of clethodim was collected in a fraction collector. The monomer fraction was concentrated and its absolute configuration was confirmed by calculated and measured electronic circular dichroism spectra.

[0062] The results are as follows Figure 5 .according to Figure 5 It can be seen that the chromatographic peaks of the enantiomers of sethoxydim were not effectively separated.

[0063] In summary, the present application adopts ultra-high liquid chromatography, and only under specific chromatographic conditions, that is, mobile phase A is an organic reagent (methanol, acetonitrile), mobile phase B is an aqueous solution of ammonium acetate with a concentration of 5mM, mobile phase B accounts for 15% by volume, column temperature is 35°C, column pressure is 12-15MPa constant pressure, and flow rate is 0.3-0.6mL / min, can effectively achieve chiral separation of clethodim, the calculated separation degree reaches more than 1.5, and effective baseline separation is achieved. Mobile phase A is acetonitrile, mobile phase B is an aqueous solution of ammonium acetate with a concentration of 5mM, mobile phase B accounts for 10% by volume, column temperature is 35°C, column pressure is 15MPa constant pressure, and flow rate is 0.6mL / min, rapid separation can be achieved.

[0064] The separated clethodim can be used for subsequent practical industrial applications. It should be noted that the embodiments of the present invention have better practicability and are not intended to limit the present invention in any form. Any technician familiar with the field may use the above disclosed technical content to change or modify it into an equivalent effective embodiment. However, any modification or equivalent changes and modifications made to the above embodiments based on the technical essence of the present invention without departing from the content of the technical solution of the present invention are still within the scope of the technical solution of the present invention.

Claims

1. A method for resolving the enantiomers of the chiral herbicide clethodim, It is characterized in that The following steps are involved: 1) Preparing a test solution: weighing a certain amount of clethodim and dissolving it in an organic solvent to prepare a clethodim test solution; 2) Using ultra high performance liquid chromatography to separate the enantiomers of clethodim in the clethodim test solution, the stationary phase is IA chiral chromatographic column, mobile phase A is an organic solvent, mobile phase B is an aqueous solution of ammonium acetate with a concentration of 1-10 mmol / L, in the mobile phase, mobile phase B accounts for 10-40% by volume, column temperature is 20-35°C, column pressure is a constant pressure of 12-15 MPa, and flow rate is 0.4-0.7 mL / min; 3) The detector is used for measurement, and the chiral monomer fraction of clethodim is collected in a fraction collector.

2. A method for resolving enantiomers of a chiral herbicide clethodim according to claim 1, It is characterized in that In step 1), the organic solvent is selected from one of methanol, ethanol, acetonitrile and isopropanol.

3. A method for resolving enantiomers of a chiral herbicide clethodim according to claim 1, It is characterized in that In step 1), the concentration of the clethodim test solution is 50 μg / mL-200 μg / mL.

4. A method for resolving enantiomers of a chiral herbicide clethodim according to claim 3, It is characterized in that In step 1), the concentration of the clethodim test solution is 100 μg / mL.

5. A method for resolving enantiomers of a chiral herbicide clethodim according to any one of claims 1 to 4, It is characterized in that In step 2), the IA chiral chromatography column is a silica gel column with amylose-tris (3,5-dimethylphenylcarbamate) covalently bonded to the surface.

6. A method for resolving enantiomers of a chiral herbicide clethodim according to claim 5, It is characterized in that Mobile phase A is methanol, mobile phase B is an aqueous solution of ammonium acetate with a concentration of 5 mmol / L, in which mobile phase B accounts for 20% by volume, the column temperature is 30°C, the column pressure is a constant pressure of 15 MPa, and the flow rate is 0.6 mL / min.

7. A method for resolving enantiomers of a chiral herbicide clethodim according to claim 1, It is characterized in that In step 3), the detector is an ultraviolet detector or a mass spectrometer detector.

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