Resolution method of chiral herbicide pyriftalid enantiomer
Through ultra-high performance liquid chromatography and mass spectrometry combined technology, chiral resolution of enantiomers of cycloester ether was achieved, solving the problem of lack of enantiomer resolution methods in the prior art, and achieving efficient and high purity separation effect.
Patent Information
- Application Number
- CN202510040057.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-01-10
- Publication Date
- 2025-04-15
AI Technical Summary
The lack of the resolution method of the R and S configuration enantiomers of cycloester ethers and the study of biological activity, toxicity and environmental risks of enantiomers in the prior art has limited the full understanding of enantiomer stereoselectivity and the development of highly active pesticides.
The chiral resolution of the enantiomer of cycloester ether is achieved by using ultra-high performance liquid chromatography and mass spectrometry combined technology through ID chiral chromatography column and specific mobile phase combinations (such as the mixture of acetonitrile and pure water).
The effective separation of the enantiomer of cyclic ester ether is achieved, with gentle and simple operating conditions, high sensitivity, fast separation speed and high purity of separation monomers.
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Figure CN119823108A_ABST
Abstract
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 pyrifos-butyl. Background Art
[0002] Cyclohexyl, commonly known as pyriftalid, IUPAC chemical name (RS)-7-(4,6-dimethoxypyrimidin-2-ylthio)-3-methyl-2-benzofuran-1(3H)-one, CAS registration number 135186-78-6, relative molecular mass 318.4, molecular formula C 15 H 14 N2O4S, cypermethrin belongs to the branched-chain amino acid synthesis (ASL or AHAS) inhibitor, is a pyrimidine oxygen (sulfur) benzoate herbicide, the structure is similar to pyrimidine hydroxybenzoic acid, and its activity seems to come from the conversion to the open-ring salicylic acid form. Cypermethrin is used in rice fields to control annual grass weeds.
[0003] Chiral pesticide enantiomers differ in biological activity, toxicity, environmental behavior, etc. Fully understanding the stereoselectivity of enantiomers is of great significance for the development of highly active pesticides and reduced use. At present, there are no reports in the literature on the separation method of the R and S configuration enantiomers of cypermethrin, as well as the biological activity, toxicity and environmental risks of the R and S configuration enantiomers. Therefore, it is particularly important to establish a chiral separation method for cypermethrin enantiomers for further research.
[0004]
[0005] Cyclopentasil structure (*chiral center) Summary of the invention
[0006] The purpose of the invention is to provide a method for preparing the chiral herbicide cypermethrin. The technical solution adopted by the present invention is:
[0007] A chiral separation method of a chiral herbicide pyrifos-butyl, comprising the following steps:
[0008] 1) Preparation of test solution: Weigh a certain amount of cypermethrin and dissolve it in an organic solvent to prepare a cypermethrin test solution.
[0009] 2) using ultra-high performance liquid chromatography-mass spectrometry to separate the enantiomers of cypermethrin in the cypermethrin test solution; the stationary phase is ID chiral chromatographic column, mobile phase A is an organic solvent, mobile phase B is pure water, the mobile phase is calculated by volume ratio, mobile phase A: mobile phase B is 20:80-100:0, the column temperature is 30-35°C, the column pressure is a constant pressure of 12-15MPa, and the flow rate is 0.6mL / min.
[0010] 3) Measured using a detector.
[0011] In the above-mentioned method for resolving enantiomers of a chiral herbicide pyrifos-butyl, in step 1), the organic solvent is selected from one of methanol and acetonitrile.
[0012] In the above-mentioned method for resolving enantiomers of a chiral herbicide cypermethrin, in step 1), the concentration of the cypermethrin test solution is 100 ng / mL.
[0013] The above-mentioned method for separating enantiomers of a chiral herbicide pyrifos-butyl, in step 2), the ID chiral chromatography columns have amylose-tris(3-chlorophenylcarbamate) covalently bonded to the surface of silica gel.
[0014] In the above-mentioned method for separating the enantiomers of a chiral herbicide cypermethrin, mobile phase A is acetonitrile, mobile phase B is pure water, mobile phase B accounts for 30% by volume of the mobile phase, 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] In the above-mentioned method for separating the enantiomers of a chiral herbicide cypermethrin, mobile phase A is acetonitrile, mobile phase B is pure water, in the mobile phase, phase B accounts for 80%-0% by volume, column temperature is 35° C., column pressure is 10 MPa, and flow rate is 0.6 mL / min.
[0016] In the above-mentioned method for separating the enantiomers of a chiral herbicide cypermethrin, mobile phase A is acetonitrile, mobile phase B is pure water, in the mobile phase, phase B accounts for 30% by volume, the column temperature is 35° C., the column pressure is 10 MPa, and the flow rate is 0.6 mL / min.
[0017] In the above-mentioned method for separating the enantiomers of a chiral herbicide cypermethrin, mobile phase A is acetonitrile, mobile phase B is pure water, in the mobile phase, phase B accounts for 20% by volume, the column temperature is 35° C., the column pressure is 10 MPa, and the flow rate is 0.6 mL / min.
[0018] In the above-mentioned method for resolving enantiomers of a chiral herbicide pyrifos-butyl, in step 3), the detector is an ultraviolet detector or a mass spectrometer detector.
[0019] 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 cyclohexyl, and its mobile phase is composed of organic reagents and ultrapure water. 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
[0020] Figure 1 It is the chromatographic separation pattern of Example 1.
[0021] Figure 2 It is the chromatographic separation pattern of Example 2.
[0022] Figure 3 It is the chromatographic separation pattern of Example 3.
[0023] Figure 4 It is the chromatographic separation spectrum of comparative example. DETAILED DESCRIPTION
[0024] The advantages of the present invention are further described below in conjunction with the accompanying drawings and specific embodiments.
[0025] 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.
[0026] 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 "a", "the" 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 terms "and, or" used herein refer to and include any or all possible combinations of one or more associated listed items.
[0027] Example 1
[0028] A method for chiral separation of fenpropimorph enantiomers comprises the following steps:
[0029] (1) Weigh a certain amount of cypermethrin, dissolve it in acetonitrile and make up to volume to prepare a cypermethrin test solution with a concentration of 100 ng / mL.
[0030] (2) Chiral separation using ultra high performance liquid chromatography.
[0031] The ultra-high performance liquid chromatography (UHPLC) system used was an Agilent system, and the stationary phase was a polysaccharide derivative chiral chromatographic column. ID chiral chromatographic column is a polysaccharide derivative chiral chromatographic column with amylose-tris (3-chlorophenyl carbamate) covalently bonded to the silica gel surface, with specifications of 250mm×4.6mm and a particle size of 5μm.
[0032] The mobile phase A is acetonitrile, and the mobile phase B is pure water, and in the mobile phase, the B phase accounts for 80%-0% by volume. The column temperature of the polysaccharide derivative chiral chromatographic column is 35°C; the column pressure is 10MPa; the flow rate is 0.6mL / min; and the injection volume is 20μL.
[0033] (3) Determination by mass spectrometry.
[0034] The results are as follows Figure 1 .according to Figure 1 It can be seen that the chromatographic peaks of cypermethrin enantiomers have a separation trend, and the calculated separation degree is 2.96.
[0035] Example 2
[0036] A method for chiral separation of fenpropimorph enantiomers comprises the following steps:
[0037] (1) Weigh a certain amount of cypermethrin, dissolve it in acetonitrile and make up to volume to prepare a cypermethrin test solution with a concentration of 100 ng / mL.
[0038] (2) Chiral separation using ultra high performance liquid chromatography.
[0039] The ultra-high performance liquid chromatography (UHPLC) system used was an Agilent system, and the stationary phase was a polysaccharide derivative chiral chromatographic column. ID chiral chromatographic column is a polysaccharide derivative chiral chromatographic column with amylose-tris (3-chlorophenyl carbamate) covalently bonded to the silica gel surface, with specifications of 250mm×4.6mm and a particle size of 5μm.
[0040] The mobile phase A is acetonitrile, the mobile phase B is pure water, 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 0.6 mL / min, and the injection volume is 20 μL.
[0041] (3) Determination by mass spectrometry.
[0042] The results are as follows Figure 2 .according to Figure 2 It can be seen that the chromatographic peaks of cypermethrin enantiomers have a separation trend, and the calculated separation degree is 3.029.
[0043] Example 3
[0044] A method for chiral separation of fenpropimorph enantiomers comprises the following steps:
[0045] (1) Weigh a certain amount of cypermethrin, dissolve it in acetonitrile and make up to volume to prepare a cypermethrin test solution with a concentration of 100 ng / mL.
[0046] (2) Chiral separation using ultra high performance liquid chromatography.
[0047] The ultra-high performance liquid chromatography (UHPLC) system used was an Agilent system, and the stationary phase was a polysaccharide derivative chiral chromatographic column. ID chiral chromatographic column is a polysaccharide derivative chiral chromatographic column with amylose-tris (3-chlorophenyl carbamate) covalently bonded to the silica gel surface, with specifications of 250mm×4.6mm and a particle size of 5μm.
[0048] The mobile phase A is acetonitrile, the mobile phase B is pure water, 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.
[0049] (3) Determination by mass spectrometry.
[0050] The results are as follows Figure 3 .according to Figure 3 It can be seen that the chromatographic peaks of cypermethrin enantiomers have a separation trend, and the calculated separation degree is 1.898.
[0051] Comparative Example
[0052] A method for chiral separation of fenpropimorph enantiomers comprises the following steps:
[0053] (1) Weigh a certain amount of cypermethrin, dissolve it in acetonitrile and make up to volume to prepare a cypermethrin test solution with a concentration of 100 ng / mL.
[0054] (2) Chiral separation using ultra-high performance liquid chromatography
[0055] 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.
[0056] The mobile phase A is acetonitrile, and the mobile phase B is pure water. In the mobile phase, the mobile phase is calculated by volume ratio, A: B is 70:30-100:0. The column temperature of the polysaccharide derivative chiral chromatographic column is 35°C; the column pressure is 10MPa; the flow rate is 0.6mL / min; and the injection volume is 20μL.
[0057] (4) Determined using a mass spectrometer.
[0058] The results are as follows Figure 4 .according to Figure 4It can be seen that the chromatographic peaks of cypermethrin enantiomers were not effectively separated.
[0059] In summary, the present application adopts high performance liquid chromatography-mass spectrometry technology. Only under specific chromatographic conditions, that is, mobile phase A is acetonitrile, mobile phase B is pure water, the mobile phase is calculated by volume ratio, A:B is 70:30, isocratic elution, column temperature is 35°C, flow rate is 0.6mL / min, can effective chiral separation of cyclohexyl be achieved, the chromatographic peaks of cyclohexyl enantiomers are effectively separated, the calculated separation degree reaches more than 1.5, and effective baseline separation is achieved.
[0060] The separated cypermethrin 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 chiral resolution method for the chiral herbicide pyraclostrobin, characterized in that: The following steps are involved: 1) Preparation of test solution: Weigh a certain amount of cypermethrin and dissolve it in an organic solvent to prepare a cypermethrin test solution. 2) using ultra-high performance liquid chromatography-mass spectrometry to separate the enantiomers of cypermethrin in the cypermethrin test solution; the stationary phase is ID chiral chromatographic column, mobile phase A is an organic solvent, mobile phase B is pure water, the mobile phase is calculated by volume ratio, mobile phase A: mobile phase B is 20:80-100:0, the column temperature is 30-35°C, the column pressure is a constant pressure of 12-15MPa, and the flow rate is 0.6mL / min. 3) Measured using a detector.
2. The method for resolving enantiomers of a chiral herbicide pyrifos-butyl as claimed in claim 1, characterized in that: In step 1), the organic solvent is selected from methanol and acetonitrile.
3. The method for resolving enantiomers of a chiral herbicide pyraclostrobin as claimed in claim 1, characterized in that: In step 1), the concentration of the cypermethrin test solution is 100 ng / mL.
4. A method for resolving enantiomers of a chiral herbicide pyraclostrobin according to any one of claims 1 to 3, characterized in that: In step 2), the ID chiral chromatography columns have amylose-tris(3-chlorophenylcarbamate) covalently bonded to the surface of silica gel.
5. The method for resolving enantiomers of a chiral herbicide pyrifos-butyl as claimed in claim 4, characterized in that: Mobile phase A is acetonitrile, mobile phase B is pure water, in the mobile phase, mobile phase B accounts for 30% 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.
6. The method for resolving enantiomers of a chiral herbicide pyrifos-butyl as claimed in claim 4, characterized in that: Mobile phase A is acetonitrile, mobile phase B is pure water, in the mobile phase, phase B accounts for 80%-0% by volume, column temperature is 35°C, column pressure is 10MPa, and flow rate is 0.6mL / min.
7. The method for resolving enantiomers of a chiral herbicide pyrifos-butyl as claimed in claim 4, characterized in that: Mobile phase A is acetonitrile, mobile phase B is pure water, in the mobile phase, phase B accounts for 30% by volume, column temperature is 35°C, column pressure is 10 MPa, and flow rate is 0.6 mL / min.
8. The method for resolving enantiomers of a chiral herbicide pyrifos-butyl as claimed in claim 4, characterized in that: Mobile phase A is acetonitrile, mobile phase B is pure water, in the mobile phase, phase B accounts for 20% by volume, column temperature is 35°C, column pressure is 10 MPa, and flow rate is 0.6 mL / min.
9. The method for resolving enantiomers of a chiral herbicide pyrifos-butyl as claimed in claim 1, characterized in that: In step 3), the detector is an ultraviolet detector or a mass spectrometer detector.