A method for chiral resolution of fenobucarb enantiomers

Abstract

This invention belongs to the field of chemical synthesis technology, specifically relating to a method for chiral separation of sec-butylcarb enantiomers. The invention employs high-performance liquid chromatography-mass spectrometry (HPLC-MS / MS) to separate sec-butylcarb enantiomers. The chromatographic column is a chiral column based on polysaccharide derivatives. Mobile phase A is an organic solvent, and mobile phase B is pure water. The volume ratio of mobile phase A:B is 20:80–50:50. The column temperature is 30–35 °C, gradient elution is used, and the flow rate is 0.3–0.6 mL / min. This invention provides a method for effectively separating chiral sec-butylcarb enantiomers, which has the advantages of high sensitivity, simple operation, and fast separation speed.

Description

Technical Field

[0001] This invention belongs to the field of chemical synthesis technology, specifically relating to a method for chiral resolution of enantiomers of sec-butylcarbamate. Background Technology

[0002] The overuse of pesticides has led to residues in agricultural products and the environment, harming not only non-target organisms but also threatening human health and ecological security. Currently, chiral pesticides account for approximately 40% of all pesticides used in China, the majority of which are racemic mixtures of enantiomers, with herbicides forming the largest portion. Although enantiomers of chiral pesticides share similar physical and chemical properties, they typically exhibit different physicochemical and biochemical properties, displaying stereoselectivity differences in biological activity, ecotoxicity, and environmental behavior. Therefore, studying chiral pesticides at the enantiomer level is crucial for developing environmentally friendly, highly efficient, low-toxicity, optically pure monomeric pesticides.

[0003] Fenobucarb, chemical formula C 12 H 17 NO2, CAS No. 3766-81-2, is a low-toxicity carbamate insecticide that primarily kills pests by inhibiting acetylcholinesterase. It is mainly used to control leafhoppers, planthoppers, thrips, and weevils on rice, tea, sugarcane, wheat, cucurbitaceous plants, eggplant, and peppers, as well as to control bollworms and aphids on cotton. It is highly effective against planthoppers and spider mites, killing them rapidly, but its residual effect is short-lived, lasting only 4-5 days. It can be mixed with commonly used insecticides and fungicides. At normal dosages, it does not cause phytotoxicity to crops and has a transdermal effect on plants. Currently, there are no reports on the toxicity risks of the R and S enantiomers of sec-butylcarbate; therefore, establishing a chiral resolution method for the enantiomers of sec-butylcarbate for further research is particularly important.

[0004]

[0005] Zhong Dingwei Summary of the Invention

[0006] This invention provides a method for chiral separation of enantiomers of sec-butylcarbamate, using high performance liquid chromatography-mass spectrometry to achieve the separation of the R and S configurations of sec-butylcarbamate.

[0007] The technical solution adopted in this invention is:

[0008] A method for chiral separation of enantiomers of sec-butylcarbamate includes the following steps:

[0009] 1) Preparation of test solution: Weigh sec-butylcarbide, dissolve and dilute to volume with organic solvent to prepare sec-butylcarbide test solution;

[0010] 2) The enantiomers of sec-butylcarbamate in the test solution were separated by high performance liquid chromatography-mass spectrometry. The stationary phase was a chiral column of polysaccharide derivative, the mobile phase A was an organic solvent, and the mobile phase B was pure water, with gradient elution.

[0011] 3) Measured using an ultraviolet detector or a mass spectrometer.

[0012] Furthermore, in the above-mentioned method for chiral resolution of enantiomers of sec-butylcarbamate, in step 1), the organic solvent is one of methanol and acetonitrile.

[0013] Furthermore, in the above-mentioned method for chiral resolution of enantiomers of sec-butylcarbamate, in step 1), the concentration of the sec-butylcarbamate test solution is 10-500 ng / mL.

[0014] Preferably, the concentration of the sec-butylcarbate test solution is 100 ng / mL.

[0015] Furthermore, in the above-mentioned method for chiral separation of enantiomers of sec-butylcarbamate, in step 2), the polysaccharide derivative chiral chromatographic column is a polysaccharide derivative chiral chromatographic column with covalently bonded linear starch-tris(3-chloro-5-methylphenylcarbamate) on a silica gel surface.

[0016] Furthermore, in the above-mentioned method for chiral resolution of enantiomers of sec-butylcarbamate, in step 2), the mobile phase A is methanol or acetonitrile, and the mobile phase ratio A:B is 20:80-50:50 by volume. The column temperature is 30-35 ℃, the flow rate is 0.3-0.6 mL / min, and gradient elution is used.

[0017] Preferably, mobile phase A is acetonitrile and mobile phase B is pure water. The volume ratio of mobile phase A:B is 20:80-50:50. Gradient elution is used, the column temperature is 35 ℃, and the flow rate is 0.6 mL / min.

[0018] Furthermore, in step 3) of the above-mentioned method for chiral separation of enantiomers of sec-butylcarbamate, a mass spectrometer is used for determination.

[0019] The beneficial effects of this invention are: This invention uses high performance liquid chromatography-mass spectrometry to directly chirally separate sec-butylcarbamate, and its mobile phase consists of methanol and pure water. This method has the advantages of simple operation, high sensitivity, mild conditions, and short separation time. Attached Figure Description

[0020] Figure 1 This is the chromatographic separation chromatogram of Example 1.

[0021] Figure 2 This is the chromatographic separation chromatogram of Example 2.

[0022] Figure 3 This is the chromatographic separation chromatogram of Example 3.

[0023] Figure 4 This is the chromatographic separation chromatogram of Example 4. Detailed Implementation

[0024] The advantages of the present invention will be further illustrated below with reference to the accompanying drawings and specific embodiments.

[0025] Exemplary embodiments will now be described in detail, examples of which are illustrated in the accompanying drawings. When the following description relates to the drawings, unless otherwise indicated, the same numerals in different drawings denote the same or similar elements. The embodiments described in the following exemplary embodiments do not represent all embodiments consistent with the disclosure of this invention. Rather, they are merely examples of apparatuses and methods consistent with some aspects of the invention disclosed as detailed in the appended claims.

[0026] The terminology used in this disclosure is for the purpose of describing particular embodiments only and is not intended to be limiting of this disclosure. The singular forms “a,” “the,” and “the” as used in this disclosure and the appended claims are also intended to include the plural forms unless the context clearly indicates otherwise. It should also be understood that the term “and / or” as used herein refers to and includes any and all possible combinations of one or more of the associated listed items.

[0027] Example 1

[0028] A method for chiral separation of enantiomers of sec-butylcarbamate includes the following steps:

[0029] 1) Weigh a certain amount of sec-butylcarbide, dissolve it in methanol and make up to volume to prepare a sec-butylcarbide test solution with a concentration of 100 ng / mL.

[0030] 2) Chiral separation was performed using high performance liquid chromatography-mass spectrometry.

[0031] The high-performance liquid chromatography-mass spectrometry (HPLC-MS / MS) system used was an Agilent system, with a chiral column of polysaccharide derivatives as the stationary phase, and a CHIRALPAK column was used. ® The IG chiral column is a chiral column of polysaccharide derivatives of amylose-tris(3-chloro-5-methylphenylcarbamate) covalently bonded to the surface of silica gel. It has a size of 250 mm × 4.6 mm and a particle size of 5 μm.

[0032] Mobile phase A was methanol, and mobile phase B was pure water, calculated by volume ratio. Elution time was 0-5 min, with an A:B ratio of 20:80-75:25, using gradient elution. The chiral column for polysaccharide derivatives was set at 35 ℃; the flow rate was 0.6 mL / min; and the injection volume was 10 μL.

[0033] 3) Determination was performed using a mass spectrometer detector.

[0034] The results are as follows Figure 1 .Depend on Figure 1 It can be seen that the enantiomers of sec-butylcarbamate were not effectively separated.

[0035] Example 2

[0036] A method for chiral separation of enantiomers of sec-butylcarbamate includes the following steps:

[0037] 1) Weigh a certain amount of sec-butylcarbamate, dissolve it in acetonitrile and dilute to volume to prepare a sec-butylcarbamate test solution with a concentration of 100 ng / mL.

[0038] 2) Chiral separation was performed using high performance liquid chromatography-mass spectrometry.

[0039] The high-performance liquid chromatography-mass spectrometry (HPLC-MS / MS) system used was an Agilent system, with a chiral column of polysaccharide derivatives as the stationary phase, and a CHIRALPAK column was used. ® The IG chiral column is a chiral column of polysaccharide derivatives of amylose-tris(3-chloro-5-methylphenylcarbamate) covalently bonded to the surface of silica gel. It has a size of 250 mm × 4.6 mm and a particle size of 5 μm.

[0040] Mobile phase A was acetonitrile, and mobile phase B was pure water, calculated by volume ratio. Elution time was 0-5 min, with an A:B ratio of 40:60-80:20, using gradient elution. The chiral column for polysaccharide derivatives was set at 35 ℃; the flow rate was 0.6 mL / min; and the injection volume was 10 μL.

[0041] 3) Determination was performed using a mass spectrometer detector.

[0042] The results are as follows Figure 2 .Depend on Figure 2 It can be seen that the enantiomers of sec-butylcarbamate were not effectively separated.

[0043] Example 3

[0044] A method for chiral separation of enantiomers of sec-butylcarbamate includes the following steps:

[0045] 1) Weigh a certain amount of sec-butylcarbamate, dissolve it in acetonitrile and dilute to volume to prepare a sec-butylcarbamate test solution with a concentration of 100 ng / mL.

[0046] 2) Chiral separation was performed using high performance liquid chromatography-mass spectrometry.

[0047] The high-performance liquid chromatography-mass spectrometry (HPLC-MS / MS) system used was an Agilent system, with a chiral column of polysaccharide derivatives as the stationary phase, and a CHIRALPAK column was used. ® The IG chiral column is a chiral column of polysaccharide derivatives of amylose-tris(3-chloro-5-methylphenylcarbamate) covalently bonded to the surface of silica gel. It has a size of 250 mm × 4.6 mm and a particle size of 5 μm.

[0048] Mobile phase A was acetonitrile, and mobile phase B was pure water, calculated by volume ratio. Elution time was 0-10 min, with an A:B ratio of 20:80-45:55, using gradient elution. The column temperature for the chiral column containing polysaccharide derivatives was 35 ℃; the flow rate was 0.6 mL / min; and the injection volume was 10 μL.

[0049] 3) Determination was performed using a mass spectrometer detector.

[0050] The results are as follows Figure 3 .according to Figure 3 It can be seen that the enantiomers of sec-butylcarbamate are effectively separated, with a separation degree R=2.20.

[0051] Example 4

[0052] A method for chiral separation of enantiomers of sec-butylcarbamate includes the following steps:

[0053] 1) Weigh a certain amount of sec-butylcarbide, dissolve it in methanol and make up to volume to prepare a sec-butylcarbide test solution with a concentration of 100 ng / mL.

[0054] 2) Chiral separation was performed using high performance liquid chromatography-mass spectrometry.

[0055] The high-performance liquid chromatography-mass spectrometry (HPLC-MS / MS) system used was an Agilent system, with a chiral column of polysaccharide derivatives as the stationary phase, and a CHIRALPAK column was used. ® The IG chiral column is a chiral column of polysaccharide derivatives of amylose-tris(3-chloro-5-methylphenylcarbamate) covalently bonded to the surface of silica gel. It has a size of 250 mm × 4.6 mm and a particle size of 5 μm.

[0056] Mobile phase A was acetonitrile, and mobile phase B was pure water, calculated by volume ratio. Elution time was 0-10 min, with A:B ratios ranging from 20:80 to 50:50, using gradient elution. The column temperature for the chiral column containing polysaccharide derivatives was 35 ℃; the flow rate was 0.6 mL / min; and the injection volume was 10 μL.

[0057] 3) Determination was performed using a mass spectrometer detector.

[0058] The results are as follows Figure 4 .Depend on Figure 4 It can be seen that the enantiomers of sec-butylcarbamate are effectively separated, with a separation degree R=1.99.

[0059] In summary, this application employs ultra-high performance liquid chromatography (UHPLC), which, under specific chromatographic conditions—namely, mobile phase A being acetonitrile, mobile phase B being pure water, a mobile phase volume percentage of A:B of 20:80-50:50, a column temperature of 35 ℃, and a flow rate of 0.3-0.6 mL / min—can effectively achieve chiral separation of sec-butylcarbamate, with calculated resolutions exceeding 1.5, thus achieving effective baseline separation.

[0060] The separated methylbenzene can be used in subsequent practical industrial applications. It should be noted that the embodiments of the present invention have good implementability and are not intended to limit the present invention in any way. Any person skilled in the art may use the above-disclosed technical content to modify or alter equivalent effective embodiments. However, any modifications or equivalent changes and alterations made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention's technical solution shall still fall within the scope of the present invention's technical solution.

Claims

1. A method for chiral separation of enantiomers of sec-butylcarbamate, characterized in that, Includes the following steps: 1) Preparation of test solution: Weigh sec-butylcarbide, dissolve and dilute to volume with organic solvent to prepare sec-butylcarbide test solution; 2) The enantiomers of sec-butylcarbamate in the test solution were separated by high performance liquid chromatography-mass spectrometry. The stationary phase was a chiral column of polysaccharide derivative, the mobile phase A was an organic solvent, and the mobile phase B was pure water, with gradient elution. 3) Measured using an ultraviolet detector or a mass spectrometer.

2. The method for chiral resolution of enantiomers of sec-butylcarbamate as described in claim 1, characterized in that, In step 1), the organic solvent is one of methanol and acetonitrile.

3. The method for chiral resolution of enantiomers of sec-butylcarbamate as described in claim 1, characterized in that, In step 1), the concentration of the sec-butylcarbide test solution is 10-500 ng / mL.

4. The method for chiral resolution of enantiomers of sec-butylcarbamate as described in claim 3, characterized in that, In step 1), the concentration of the sec-butylcarbide test solution is 100 ng / mL.

5. The method for chiral resolution of enantiomers of sec-butylcarbamate as described in claim 1, characterized in that, In step 2), the polysaccharide derivative chiral chromatographic column is a polysaccharide derivative chiral chromatographic column with linear starch-tris(3-chloro-5-methylphenylcarbamate) covalently bonded to the surface of silica gel.

6. The method for chiral resolution of enantiomers of sec-butylcarbamate as described in claim 1, characterized in that, In step 2), the mobile phase A is methanol or acetonitrile, and the mobile phase ratio A:B is 20:80-50:50 by volume. The column temperature is 30-35 ℃, the flow rate is 0.3-0.6 mL / min, and gradient elution is used.

7. The method for chiral resolution of enantiomers of sec-butylcarbamate as described in claim 6, characterized in that, In step 2), the mobile phase A is acetonitrile, and the mobile phase ratio A:B is 20:80-50:50 by volume. Gradient elution is used, the column temperature is 35 ℃, and the flow rate is 0.6 mL / min.

8. The method for chiral resolution of enantiomers of sec-butylcarbamate as described in claim 1, characterized in that, In step 3), a mass spectrometer detector is used for determination.

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