A method for analyzing the content of flufenacet intermediates

Abstract

The present invention relates to the field of chemical analysis technology, and in particular to an analytical method for the content of flufenacet intermediate 2-(acetoxy)-N-(4-fluorophenyl)-N-(1-methylethyl) acetamide. The method comprises the following steps: (1) preparing a standard solution and a sample solution to be tested; (2) setting the detection wavelength to within the range of 200-250nm, sample injection analysis, a chromatographic column being an ODS-C18 reverse phase chromatographic column, a chromatographic column temperature of 30-50°C, and a mobile phase being a mixed system of acetonitrile and glacial acetic acid aqueous solution; (3) calculating the mass fraction of 2-(acetoxy)-N-(4-fluorophenyl)-N-(1-methylethyl) acetamide in the sample to be tested according to an external standard method formula. The present invention fills a technical gap, has strong specificity, good precision, high recovery rate, good repeatability, and is particularly suitable for quality control of pesticide original intermediate products.

Description

Technical Field

[0001] The invention relates to the technical field of chemical analysis, and in particular to a method for analyzing the content of a flufenacet intermediate 2-(acetoxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide. Background Art

[0002] Flufenacet is an aromatic amide herbicide developed by Bayer in Germany in 1988. Flufenacet works by inhibiting the cell growth and division of weeds and can be used to control weeds in soybeans, cotton, rice, corn and other crops. Flufenacet can be combined with herbicides such as sulfamethoxam, metribuzin and diflufenicol for controlling broadleaf weeds to expand the weed control spectrum. Compared with mefenacet, flufenacet has higher activity and is suitable for controlling weeds in more crops.

[0003] 2-(Acetyloxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide (CAS No.: 150164-68-4) is an intermediate in the synthesis of flufenacet. Currently, there is no analytical method for accurately detecting the content of 2-(acetyloxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide, and its content accuracy directly affects the accuracy of its downstream products, thereby affecting the accuracy of flufenacet content. Finding an analytical method for stably and accurately detecting the content of 2-(acetyloxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide is of great importance and practical significance for ensuring the quality of flufenacet products. Summary of the invention

[0004] In view of the gap in the technology for detecting the content of 2-(acetyloxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide, the present invention provides an analytical method for the content of a flufenacet intermediate, which fills the technical gap and has strong specificity, good precision, high recovery rate, good repeatability, and is particularly suitable for quality control of pesticide technical intermediates.

[0005] The technical solution of the present invention is as follows:

[0006] A method for analyzing the content of a flufenacet intermediate, using high performance liquid chromatography to analyze the flufenacet intermediate 2-(acetyloxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide, comprising the following steps:

[0007] (1) using methanol as a solvent to dissolve the standard and the sample to be tested respectively, to prepare a standard solution and a sample solution to be tested;

[0008] (2) setting the detection wavelength to within the range of 200-250 nm, and after the baseline of the instrument is stable, injecting and analyzing the standard, the sample to be tested, the sample to be tested, and the standard in sequence, wherein the chromatographic conditions include: the chromatographic column is an ODS-C18 reverse phase chromatographic column, the chromatographic column temperature is 30-50° C., the mobile phase is a mixed system of acetonitrile and 0.8% (v / v) glacial acetic acid aqueous solution, and the volume ratio of acetonitrile to glacial acetic acid aqueous solution is 70-20:30-80;

[0009] (3) Calculate the average peak area of ​​2-(acetoxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide in the standard solution and the sample solution to be tested, and calculate the mass fraction X1 of 2-(acetoxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide in the sample to be tested according to the external standard method formula:

[0010]

[0011] Wherein, A1 is the average peak area of ​​2-(acetyloxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide in the standard solution;

[0012] A2——the average peak area of ​​2-(acetyloxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide in the sample solution to be tested;

[0013] m1——the mass of the standard;

[0014] m2——the mass of the sample to be tested;

[0015] P1——Mass fraction of 2-(acetyloxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide in the standard.

[0016] Furthermore, the concentration ranges of the standard solution and the sample solution to be tested are both 0.3-0.8 mg / mL.

[0017] Furthermore, the column length of the chromatographic column is 150 mm, the inner diameter of the column is 4.5-5 mm, preferably 4.6 mm, and the column particle size is 3.5 μm.

[0018] Furthermore, the temperature of the chromatographic column is 40°C.

[0019] Furthermore, the detection wavelength is 225 nm.

[0020] Furthermore, the volume ratio of acetonitrile to the glacial acetic acid aqueous solution is 40:60.

[0021] Furthermore, the HPLC conditions also include: the sample volume for each injection is 5 μL.

[0022] Furthermore, the HPLC conditions also include: the flow rate of the mobile phase is 0.8-1.2 mL / min, preferably 1.0 mL / min.

[0023] The beneficial effects of the present invention are:

[0024] (1) The present invention uses acetonitrile and glacial acetic acid aqueous solution to effectively separate the target substance from impurities, and is more economical than other solvents. Under corresponding chromatographic conditions, its content can be accurately determined, filling the technical gap in the corresponding field of the prior art;

[0025] (2) The mass fraction of 2-(acetyloxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide detected by the method of the present invention is stable and accurate, the detection accuracy and stability are improved, the impurities and the main peak can be completely separated, the chromatographic peak shape is good, the retention time is stable, the integral calculation results are accurate and reproducible, and the results obtained are highly credible. It is particularly suitable for the quality control of pesticide technical intermediates, and plays an important role and practical significance in ensuring the quality of the final product. At the same time, the results obtained are more accurate and timely, providing strong data support for the production of flufenacet. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, for ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0027] Figure 1 It is the chromatogram of the standard solution in Example 1.

[0028] Figure 2 It is the chromatogram of the sample solution to be tested in Example 1.

[0029] Figure 3 It is the chromatogram of the standard solution in Example 2.

[0030] Figure 4 It is the chromatogram of the sample solution to be tested in Example 2.

[0031] Figure 5 It is the chromatogram of the standard solution in Example 3.

[0032] Figure 6 It is the chromatogram of the sample solution to be tested in Example 3.

[0033] Figure 7 This is a linear relationship diagram at a detection wavelength of 225 nm in Experimental Example 4.

[0034] Figure 8This is a linear relationship diagram at a detection wavelength of 245 nm in Experimental Example 4. DETAILED DESCRIPTION

[0035] In order to enable those skilled in the art to better understand the technical solutions in the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work should fall within the scope of protection of the present invention.

[0036] Example 1

[0037] During the production, 73 batches were produced, and 680 kg of solid samples of 2-(acetoxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide were obtained. The content of 2-(acetoxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide in the product was analyzed. The method comprises the following steps:

[0038] (1) Accurately weigh 51.6 mg of 2-(acetoxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide standard and place it in a 100 mL volumetric flask, add 90 mL of methanol, shake to dissolve, and dilute to the mark with methanol to obtain a standard solution for use. The mass fraction of 2-(acetoxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide in the standard solution is 98.5%;

[0039] Accurately weigh 53.8 mg of the sample to be tested and place it in a 100 mL volumetric flask, add 90 mL of methanol, shake to dissolve, and dilute to the scale with methanol to obtain the sample solution to be tested for later use;

[0040] (2) A high performance liquid chromatograph with a diode array detector was used. The chromatographic column was an ODS-C18 reverse phase column. The column length was 150 mm, the column inner diameter was 4.6 mm, and the column particle size was 3.5 μm. The temperature of the chromatographic column was 40°C. The mobile phase was a mixture of acetonitrile and 0.8% (v / v) glacial acetic acid aqueous solution, and the volume ratio of acetonitrile to glacial acetic acid aqueous solution was 40:60. The sample volume for each injection was 5 μL, and the flow rate of the mobile phase was 1 mL / min. The detection wavelength was set to 225 nm.

[0041] (3) After the instrument baseline is stable, the samples are injected in the order of standard, sample to be tested, sample to be tested, and standard. The average peak area of ​​2-(acetoxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide of the standard solution and the sample solution to be tested is calculated respectively. The test data are shown in Table 1 below:

[0042] Table 1 Test results of Example 1

[0043]

[0044] (4) Calculate the mass fraction X1 of 2-(acetyloxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide in the sample to be tested according to the external standard method formula. The specific formula is as follows:

[0045]

[0046] Wherein, A1 is the average peak area of ​​2-(acetyloxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide in the standard solution;

[0047] A2——the average peak area of ​​2-(acetyloxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide in the sample solution to be tested;

[0048] m1——the mass of the standard;

[0049] m2——the mass of the sample to be tested;

[0050] P1——Mass fraction of 2-(acetoxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide in the standard;

[0051] The mass fraction of 2-(acetyloxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide in the sample to be tested was calculated to be 98.2%.

[0052] Figure 1 , Figure 2 They are the chromatograms of the standard product and the sample to be tested in this embodiment respectively. Figure 1 In the analysis, the peak corresponding to the position of 8.280 min is 2-(acetoxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide; Figure 2 In the analysis, the peak at 8.282 min corresponds to 2-(acetyloxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide.

[0053] Example 2

[0054] The test sample 20220614 batches, obtained 48.3g of solid, the product of 2- (acetoxy) -N- (4-fluorophenyl) -N- (1-methylethyl) acetamide content was analyzed, the method comprising the following steps:

[0055] (1) Accurately weigh 51.7 mg of 2-(acetoxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide standard and place it in a 100 mL volumetric flask, add 90 mL of methanol, shake to dissolve, and dilute to the mark with methanol to obtain a standard solution for use. The mass fraction of 2-(acetoxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide in the standard solution is P1=98.5%;

[0056] Accurately weigh 51.5 mg of the sample to be tested and place it in a 100 mL volumetric flask, add 90 mL of methanol, shake to dissolve, and dilute to the scale with methanol to obtain the sample solution to be tested for later use;

[0057] (2) A high performance liquid chromatograph with a diode array detector was used. The chromatographic column was an ODS-C18 reverse phase column. The column length was 150 mm, the column inner diameter was 4.6 mm, and the column particle size was 3.5 μm. The temperature of the chromatographic column was 40°C. The mobile phase was a mixture of acetonitrile and 0.8% (v / v) glacial acetic acid aqueous solution, and the volume ratio of acetonitrile to glacial acetic acid aqueous solution was 40:60. The sample volume for each injection was 5 μL, and the flow rate of the mobile phase was 1 mL / min. The detection wavelength was set to 225 nm.

[0058] (3) After the instrument baseline is stable, the standard solution, the sample to be tested, the sample to be tested, and the standard solution are injected in sequence, and the average peak area of ​​2-(acetoxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide of the standard solution and the sample solution to be tested is calculated respectively. The test data are shown in Table 2 below:

[0059] Table 2 Example 2 Test results

[0060]

[0061] (4) The mass fraction of 2-(acetoxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide in the sample to be tested is calculated according to the external standard method formula. The specific formula is the same as that in Example 1. The mass fraction of 2-(acetoxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide in the sample to be tested is calculated to be 97.9%.

[0062] Figure 3 , Figure 4 They are the chromatograms of the standard product and the sample to be tested in this embodiment respectively. Figure 3 In the analysis, the peak at 8.276 min corresponds to 2-(acetoxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide; Figure 4 In the analysis, the peak at 8.273 min corresponds to 2-(acetyloxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide.

[0063] Example 3

[0064] In 98 batches of production, 1546 kg of solid samples of 2-(acetoxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide were obtained. The content of 2-(acetoxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide in the product was analyzed. The method comprises the following steps:

[0065] (1) Accurately weigh 51.2 mg of 2-(acetoxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide standard and place it in a 100 mL volumetric flask, add 90 mL of methanol, shake to dissolve, and dilute to the mark with methanol to obtain a standard solution for use. The mass fraction of 2-(acetoxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide in the standard solution is P1=98.5%;

[0066] Accurately weigh 54.2 mg of the sample to be tested and place it in a 100 mL volumetric flask, add 90 mL of methanol, shake to dissolve, and dilute to the scale with methanol to obtain the sample solution to be tested for later use;

[0067] (2) A high performance liquid chromatograph with a diode array detector was used. The chromatographic column was an ODS-C18 reverse phase column. The column length was 150 mm, the column inner diameter was 4.6 mm, and the column particle size was 3.5 μm. The temperature of the chromatographic column was 40°C. The mobile phase was a mixture of acetonitrile and 0.8% (v / v) glacial acetic acid aqueous solution, and the volume ratio of acetonitrile to glacial acetic acid aqueous solution was 40:60. The sample volume for each injection was 5 μL, and the flow rate of the mobile phase was 1 mL / min. The detection wavelength was set to 225 nm.

[0068] (3) After the instrument baseline is stable, the samples are injected in the order of standard, sample to be tested, sample to be tested, and standard. The average peak area of ​​2-(acetoxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide of the standard solution and the sample solution to be tested is calculated respectively. The test data are shown in Table 3 below:

[0069] Table 3 Example 3 test results

[0070]

[0071] (4) The mass fraction of 2-(acetoxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide in the sample to be tested is calculated according to the external standard method formula. The specific formula is the same as that in Example 1. The mass fraction of 2-(acetoxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide in the sample to be tested is calculated to be 98.4%.

[0072] Figure 5 , Figure 6 They are the chromatograms of the standard product and the sample to be tested in this embodiment respectively. Figure 5 In the analysis, the peak corresponding to the position of 8.139 min is 2-(acetoxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide; Figure 6 In the analysis, the peak at 8.144 min corresponds to 2-(acetyloxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide.

[0073] Test Example 1 Stability Test

[0074] The standard solution in Example 1 was taken as the object of investigation, and a high performance liquid chromatograph with a diode array detector was used to analyze it once at regular intervals at room temperature for a total of 5 times, and the peak area was recorded simultaneously. The analysis conditions were the same as in Example 1.

[0075] The results are shown in Table 4 below. The retention time of the chromatographic peak is stable, and the RSD is less than 1% by comparing the peak areas, indicating that the analytical method of the present invention has good stability.

[0076] Table 4 Stability test results

[0077]

[0078] Test Example 2: Precision Test

[0079] Take the 2-(acetoxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide of the pilot sample 20220624 of Example 2 as the object of investigation, weigh the standard and five parallel samples to be tested, and inject them in the order of the standard, the sample to be tested, the sample to be tested, and the standard, and calculate the mass fraction of 2-(acetoxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide in the five parallel samples to be tested. The analysis conditions are the same as those in Example 1.

[0080] The results are shown in Table 5 below. By comparing the mass fractions of 2-(acetyloxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide, the RSD was less than 1%, indicating that the analytical method of the present invention has good precision.

[0081] Table 5 Precision test results

[0082]

[0083]

[0084] Test Example 3 Recovery Test

[0085] Take the 2-(acetoxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide of the small test sample 20220624 of Example 2 as the object of investigation, weigh the standard and five samples of different masses to be tested, add different masses of standard samples to the samples to be tested, inject the samples, and calculate the spiked recovery rate. The analysis conditions are the same as those in Example 1.

[0086] The results are shown in Table 6 below. The recovery rates are all between 98% and 102%, and the average recovery rate is 99.82%, indicating that the recovery rate of this experiment meets the requirements.

[0087] Table 6 Recovery test results

[0088]

[0089]

[0090] Test Example 4 Linear Test

[0091] A series of standard products of different masses were weighed, placed in a 100 mL volumetric flask, dissolved and fixed to volume with methanol, and the relationship between the peak area and the solution concentration was examined after injection. The analysis conditions were the same as those in Example 1.

[0092] The results are shown in Table 7 and Figure 7 As shown, the correlation coefficient is 1, indicating that the linearity of the analysis method meets the requirements at this detection wavelength.

[0093] Table 7 Linearity test results at 225nm detection wavelength

[0094] Serial number Sample weight / g Standard solution concentration / g / L Peak area 1 Peak area 2 Average peak area 1 0.0332 0.332 3337091 3339105 3338098 2 0.0441 0.441 4434730 4438291 4436510.5 3 0.0554 0.554 5556977 5560749 5558863 4 0.0663 0.663 6677221 6680965 6679093 5 0.0776 0.776 7779760 7790269.00 7785014.5

[0095] The detection wavelength was adjusted from 225 nm to 245 nm, and the above linear test was repeated. The results are shown in Table 8 and Figure 8 As shown, the correlation coefficient is 1, and the intercept is too large. The linear test results at two detection wavelengths of 225nm and 245nm show that the linearity of the analysis method provided by the present invention meets the requirements, and the detection wavelength of 225nm is better.

[0096] Table 8 Linearity test results at 245nm detection wavelength

[0097] Serial number Sample weight / g Standard solution concentration / g / L Peak area 1 Peak area 2 Average peak area 1 0.0332 0.332 5821541 5796541 5809041 2 0.0441 0.441 7772012 7789846 7780929 3 0.0554 0.554 9798287 9818482 9808384.5 4 0.0663 0.663 11818681 11806974 11812827.5 5 0.0776 0.776 13847972 13796350 13822161

[0098] Based on the above test examples 1-4, it can be seen that the analysis method for the content of 2-(acetyloxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide provided by the present invention has high accuracy and good operability, and can be widely used in the analysis and detection of the content of 2-(acetyloxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide.

[0099] Although the present invention has been described in detail by referring to the accompanying drawings and in combination with the preferred embodiments, the present invention is not limited thereto. Without departing from the spirit and essence of the present invention, a person of ordinary skill in the art may make various equivalent modifications or substitutions to the embodiments of the present invention, and these modifications or substitutions shall be within the scope of the present invention. Any person of ordinary skill in the art may easily think of changes or substitutions within the technical scope disclosed by the present invention, and these shall be within the scope of protection of the present invention. Therefore, the scope of protection of the present invention shall be subject to the scope of protection described in the claims.

Claims

1. A method for analyzing the content of flufenacet intermediates, characterized in that: The analysis of the flufenacet intermediate 2-(acetyloxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide by high performance liquid chromatography includes the following steps: (1) using methanol as a solvent to dissolve the standard and the sample to be tested respectively, to prepare a standard solution and a sample solution to be tested; (2) setting the detection wavelength to within the range of 200-250 nm, and after the baseline of the instrument is stable, injecting and analyzing in the order of standard, sample to be tested, sample to be tested, and standard, wherein the chromatographic conditions include: the chromatographic column is an ODS-C18 reverse phase chromatographic column, the chromatographic column temperature is 30-50° C., the mobile phase is a mixed system of acetonitrile and 0.8% glacial acetic acid aqueous solution, and the volume ratio of acetonitrile to glacial acetic acid aqueous solution is 70-20:30-80; (3) Calculate the average peak area of ​​2-(acetoxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide in the standard solution and the sample solution to be tested, and calculate the mass fraction X1 of 2-(acetoxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide in the sample to be tested according to the external standard method formula: Wherein, A1 is the average peak area of ​​2-(acetyloxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide in the standard solution; A2——the average peak area of ​​2-(acetyloxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide in the sample solution to be tested; m1——the mass of the standard; m2——the mass of the sample to be tested; P1——Mass fraction of 2-(acetyloxy)-N-(4-fluorophenyl)-N-(1-methylethyl)acetamide in the standard.

2. The analysis method according to claim 1, characterized in that The concentration ranges of the standard solution and the sample solution to be tested are both 0.3-0.8 mg / mL.

3. The analysis method according to claim 1, characterized in that The column length of the chromatographic column is 150 mm, the inner diameter of the column is 4.5-5 mm, and the particle size of the column is 3.5 μm.

4. The analysis method according to claim 1, characterized in that The temperature of the column was 40°C.

5. The analysis method according to claim 1, characterized in that The detection wavelength is 225 nm.

6. The analysis method according to claim 1, characterized in that The volume ratio of acetonitrile to glacial acetic acid aqueous solution is 40:

60.

7. The analysis method according to claim 1, characterized in that The HPLC conditions also include: the sample volume for each injection is 5 μL.

8. The analysis method according to claim 1, characterized in that The HPLC conditions also include: a flow rate of the mobile phase of 0.8-1.2 mL / min.

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