Method for determining content of benzobicyclon intermediate

Abstract

The present invention relates to the technical field of chemical analysis, in particular to a method for determining the content of the intermediate of tembotrione. The intermediate of tembotrione is 3-bromo-2-methyl-6-methylsulfonyl-α-chlorobenzaldoxime, and the method for determining the content comprises the following steps: (1) Dissolving the standard substance and the sample to be measured with methanol as the solvent respectively to prepare a standard sample and a test sample; (2) Analyzing the standard sample and the test sample obtained in step (1) by a reverse-phase high-performance liquid chromatography method, wherein the chromatographic column is chromatographic column VP-ODS, the mobile phase is a mixed system of acetonitrile and aqueous acetic acid solution, the flow rate of the mobile phase is 0.5-1.5 mL / min, the detection wavelength is 254-270 nm, and the mass fraction of 3-bromo-2-methyl-6-methylsulfonyl-α-chlorobenzaldoxime in the sample to be measured is calculated according to the formula of the external standard method. The method of the present invention has strong specificity, good precision and high recovery rate, and is applicable to the quality control of pesticide intermediate products.

Description

Technical Field

[0001] The present invention relates to the technical field of chemical analysis, in particular to a method for determining the content of an intermediate of pyraoxystrobin. Specifically, the present invention will be used to detect the content of 3-bromo-2-methyl-6-methylsulfonyl-α-chlorobenzaldehyde oxime. Background Art

[0002] Pyraoxystrobin is the first benzyl pyrazolone herbicide discovered and developed by BASF. It has the characteristics of high safety, excellent selectivity, broad-spectrum herbicidal activity, long duration and strong compatibility. It is the herbicide with the highest safety in corn fields and one of the herbicides with the lowest toxicity to mammals.

[0003] 3-Bromo-2-methyl-6-methylsulfonyl-α-chlorobenzaldehyde oxime is an important intermediate for synthesizing pyraoxystrobin, and its structure is shown in formula (Ⅰ). In order to accurately determine the content of 3-bromo-2-methyl-6-methylsulfonyl-α-chlorobenzaldehyde oxime in the production process and effectively guide the adjustment of workshop process parameters, it is necessary to develop a quantitative detection method for 3-bromo-2-methyl-6-methylsulfonyl-α-chlorobenzaldehyde oxime.

[0004] Summary of the Invention

[0005] Aiming at the technical blank of the existing detection method for the content of 3-bromo-2-methyl-6-methylsulfonyl-α-chlorobenzaldehyde oxime, the present invention provides a method for detecting its content by high performance liquid chromatography. This method has strong specificity, good precision and high recovery rate, and is applicable to the quality control of pesticide intermediate products.

[0006] The technical solution of the present invention is as follows:

[0007] A method for determining the content of an intermediate of pyraoxystrobin, wherein the intermediate of pyraoxystrobin is 3-bromo-2-methyl-6-methylsulfonyl-α-chlorobenzaldehyde oxime, and the content determination method comprises the following steps:

[0008] (1) Dissolve the standard substance and the sample to be tested with methanol as the solvent respectively to prepare a standard sample and a test sample;

[0009] (2) Analyze the standard sample and the test sample obtained in step (1) by using a reverse-phase high performance liquid chromatography analysis method. The chromatographic column is chromatographic column VP-ODS, the mobile phase is a mixed system of acetonitrile and acetic acid aqueous solution, the flow rate of the mobile phase is 0.5-1.5 mL / min, the detection wavelength is 254-270 nm, and calculate the mass fraction of 3-bromo-2-methyl-6-methylsulfonyl-α-chlorobenzaldehyde oxime in the sample to be tested according to the external standard method formula.

[0010] Further, the column length of the chromatographic column is 150 mm, the column inner diameter is 4.6 mm, and the column particle size is 5 μm.

[0011] Further, the temperature of the chromatographic column is 35 - 50 °C, preferably 40 °C.

[0012] Further, the volume percentage concentration of the glacial acetic acid aqueous solution is 0.8%.

[0013] Further, the volume ratio of acetonitrile to the glacial acetic acid aqueous solution is 50:50.

[0014] Further, the flow rate of the mobile phase is 1 mL / min.

[0015] Further, after the instrument baseline is stable, the samples are injected in the order of standard sample, test sample, test sample, and standard sample.

[0016] Further, in order to achieve better detection effect and accuracy, the sample volume for each injection is 1 - 10 μL, preferably 5 μL.

[0017] Further, the formula of the external standard method is as follows:

[0018]

[0019] In the formula, A1 is the average value of the peak areas of 3 - bromo - 2 - methyl - 6 - methylsulfonyl - α - chlorobenzaldehyde oxime in the standard sample,

[0020] A2 is the average value of the peak areas of 3 - bromo - 2 - methyl - 6 - methylsulfonyl - α - chlorobenzaldehyde oxime in the test sample,

[0021] m1 is the mass of the standard sample,

[0022] m2 is the mass of the test sample,

[0023] P1 is the mass fraction of 3 - bromo - 2 - methyl - 6 - methylsulfonyl - α - chlorobenzaldehyde oxime in the standard sample,

[0024] X1 is the mass fraction of 3 - bromo - 2 - methyl - 6 - methylsulfonyl - α - chlorobenzaldehyde oxime in the test sample.

[0025] The method for determining the content of 3 - bromo - 2 - methyl - 6 - methylsulfonyl - α - chlorobenzaldehyde oxime provided by the present invention can also be used for the quality control of the intermediate product of the topramezone technical.

[0026] The beneficial effects of the present invention are as follows:

[0027] The method for determining the content of 3-bromo-2-methyl-6-methylsulfonyl-α-chlorobenzaldehyde oxime provided by the present invention fills the technical gap in the prior art that there is no corresponding high-performance liquid chromatography detection method. Using this method to detect the mass fraction of 3-bromo-2-methyl-6-methylsulfonyl-α-chlorobenzaldehyde oxime, the chromatographic peak shape is good, the integral calculation result is accurate and has good repeatability, the obtained result is more accurate, timely and has high credibility, providing strong data support for the production of the technical drug intermediate, being particularly suitable for the quality control of the intermediate products of the technical pesticide, and playing an important role and practical significance in ensuring the quality of the final product. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required for use in the description of the embodiments or the prior art. Obviously, for those of ordinary skill in the art, without creative efforts, other drawings can also be obtained based on these drawings.

[0029] Figure 1 It is the chromatogram of the standard sample in Example 1.

[0030] Figure 2 It is the chromatogram of the test sample in Example 1.

[0031] Figure 3 It is the chromatogram of the standard sample in Example 2.

[0032] Figure 4 It is the chromatogram of the test sample in Example 2.

[0033] Figure 5 It is the linear relationship diagram at a wavelength of 254 nm in Verification Example 2.

[0034] Figure 6 It is the linear relationship diagram at a wavelength of 235 nm in Verification Example 2.

[0035] Figure 7 It is the linear relationship diagram at a wavelength of 270 nm in Verification Example 2.

[0036] Figures 1-4 In it, the abscissa represents time (min), and the ordinate represents absorbance; Figures 6-7 In it, the abscissa represents concentration (μg / mL), and the ordinate represents peak area. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0037] To enable those skilled in the art to better understand the technical solutions in the present invention, the following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0038] The high-performance liquid chromatograph used in the following examples is the LC-20AT infusion pump and SPD-20A ultraviolet detector of Shimadzu Corporation.

[0039] Example 1

[0040] In production batch 001, 360 kg of 3-bromo-2-methyl-6-methylsulfonyl-α-chlorobenzaldehyde oxime was obtained, and the content analysis of the product was carried out.

[0041] Chromatographic conditions: A chromatographic column VP-ODS with octadecylsilane-bonded silica gel as the filler, column length of 150 mm, column inner diameter of 4.6 mm, column particle size of 5 μm, column temperature of 40 °C, a mixed system of acetonitrile and 0.8% (v / v) acetic acid aqueous solution with a volume ratio of 50:50 as the mobile phase, the flow rate of the mobile phase is 1 mL / min, the detection wavelength is 254 nm, and the injection volume is 5 μL.

[0042] The detection steps are as follows:

[0043] (1) Accurately weigh 0.0511 g of 3-bromo-2-methyl-6-methylsulfonyl-α-chlorobenzaldehyde oxime standard sample, place it in a 100 mL volumetric flask, add 80 mL of methanol, dissolve it by ultrasonic oscillation, cool it to room temperature, and then dilute it to the mark with methanol to obtain the standard sample for standby;

[0044] Accurately weigh 0.0588 g of 3-bromo-2-methyl-6-methylsulfonyl-α-chlorobenzaldehyde oxime sample, place it in a 100 mL volumetric flask, add 80 mL of methanol, dissolve it by ultrasonic oscillation, cool it to room temperature, and then dilute it to the mark with methanol to obtain the sample for standby;

[0045] (2) After the instrument baseline is stable, inject several needles of the standard sample continuously, calculate the relative response values of each needle. After the relative response values of adjacent two needles change less than 1.5%, inject samples for detection in the order of standard sample, sample, sample, and standard sample. The chromatograms are as shown in Figure 1 、 2 shown, and the data are as shown in Table 1 below:

[0046] Table 1 Detection Results of Example 1

[0047]

[0048] Substitute into the formula of external standard method

[0049]

[0050] In the formula, A1 is the average value of the peak area of 3-bromo-2-methyl-6-methylsulfonyl-α-chlorobenzaldehyde oxime in the standard sample,

[0051] A2 is the average value of the peak area of 3-bromo-2-methyl-6-methylsulfonyl-α-chlorobenzaldehyde oxime in the sample,

[0052] m1 is the mass of the standard sample,

[0053] m2 is the mass of the sample,

[0054] P1 is the mass fraction of 3-bromo-2-methyl-6-methylsulfonyl-α-chlorobenzaldehyde oxime in the standard sample,

[0055] X1 is the mass fraction of 3-bromo-2-methyl-6-methylsulfonyl-α-chlorobenzaldehyde oxime in the sample;

[0056] It can be calculated that the mass fraction of 3-bromo-2-methyl-6-methylsulfonyl-α-chlorobenzaldehyde oxime in the sample is 92.22%.

[0057] Example 2

[0058] In production batch 003, 400 kg of 3-bromo-2-methyl-6-methylsulfonyl-α-chlorobenzaldehyde oxime was obtained, and the content analysis of the product was carried out.

[0059] Chromatographic conditions: The chromatographic column VP-ODS filled with octadecylsilane chemically bonded silica gel was used, with a column length of 150 mm, a column inner diameter of 4.6 mm, a column particle size of 5 μm, a chromatographic column temperature of 40 °C, a mixed system of acetonitrile and 0.8% (v / v) acetic acid aqueous solution with a volume ratio of 50:50 as the mobile phase, a flow rate of the mobile phase of 1 mL / min, a detection wavelength of 254 nm, and an injection volume of 5 μL.

[0060] The detection steps are as follows:

[0061] (1) Accurately weigh 0.0476 g of the standard sample of 3-bromo-2-methyl-6-methylsulfonyl-α-chlorobenzaldehyde oxime, place it in a 100 mL volumetric flask, add 80 mL of methanol, dissolve it by ultrasonic oscillation, cool it to room temperature, and then dilute it to the mark with methanol to obtain the standard sample for standby;

[0062] Accurately weigh 0.0453 g of the sample of 3-bromo-2-methyl-6-methylsulfonyl-α-chlorobenzaldoxime, place it in a 100 mL volumetric flask, add 80 mL of methanol, dissolve it by ultrasonic oscillation, cool it to room temperature, and then dilute it to the mark with methanol to obtain the sample for standby;

[0063] (2) After the instrument baseline is stable, inject several needles of the standard sample continuously, calculate the relative response value of each needle. After the relative response value of adjacent two needles changes less than 1.5%, inject the samples for detection in the order of standard sample, sample, sample, and standard sample. The chromatograms are as shown in Figure 3 、 4 shown, and the data are as shown in Table 2 below:

[0064] Table 2 Detection Results of Example 2

[0065]

[0066] Substitute into the external standard method formula (the same as Example 1), and it can be calculated that the mass fraction of 3-bromo-2-methyl-6-methylsulfonyl-α-chlorobenzaldoxime in the sample is 92.73%.

[0067] Verification Example 1 Stability Test

[0068] Take the sample solution in Example 1 as the object of investigation, analyze it every two hours at room temperature. The determination method and chromatographic conditions are the same as those in Example 1, record the peak area, and the data are as shown in Table 3 below.

[0069] Table 3 Stability Test Results

[0070]

[0071] By comparing the peak areas, the RSD is less than 1%, indicating that the method of the present invention has good stability.

[0072] Verification Example 2 Linear Test

[0073] Weigh appropriate amounts of the standard sample of 3-bromo-2-methyl-6-methylsulfonyl-α-chlorobenzaldoxime respectively, dissolve them with methanol and prepare a group of standard sample solutions with concentrations of 369 μg / mL, 463 μg / mL, 529 μg / mL, 674 μg / mL, and 749 μg / mL. Analyze them in sequence. The determination method and chromatographic conditions are the same as those in Example 1, record the peak area, and the data are as shown in Table 4 below.

[0074] Table 4 Linear Test Results

[0075] Sample weighing amount g Standard sample concentration μg / mL Peak area 1 Peak area 2 Average peak area 0.0369 369 2876903 2880328 2878615.5 0.0463 463 3598892 3601125 3600009 0.0529 529 4132515 4135518 4134016.5 0.0674 674 5251514 5244643 5248078.5 0.0749 749 5838905 5840698 5839801.5

[0076] As shown in Figure 5 shown, taking the peak area as the ordinate and the sample concentration as the abscissa, perform linear regression, and the obtained regression equation is y = 7792.1x + 1476, and its correlation coefficient R2 For 1,3-bromo-2-methyl-6-methylsulfonyl-α-chlorobenzaldehyde oxime, the linear relationship is good in the range of 369 - 749 μg / mL, indicating that the linearity of this method meets the requirements.

[0077] On the basis of Verification Example 2, the detection wavelength was adjusted, and linear verifications were carried out at detection wavelengths of 235 nm and 270 nm respectively. The results are shown in Tables 5, 6 and Figure 6 , 7 as follows.

[0078] Table 5 Results of linearity test at 235 nm wavelength

[0079] Weighing amount / g Concentration / (μg / mL) Chromatographic peak area 1 Chromatographic peak area 2 Average peak area 0.0369 369 7892681 7898074 7895377.5 0.0463 463 9852367 9857258 9854812.5 0.0529 529 11289380 11301299 11295339.5 0.0674 674 14269716 14294810 14282263 0.0749 749 15833828 15853725 15843776.5

[0080] Performing linear regression on the sample concentration based on the average peak area obtained from the detection, the regression equation at 235 nm wavelength is obtained:

[0081] y = 20917x + 187807, R 2 = 0.9999.

[0082] Table 6 Results of linearity test at 270 nm wavelength

[0083] Weighing amount / g Concentration / (μg / mL) Chromatographic peak area 1 Chromatographic peak area 2 Average peak area 0.0369 369 3370727 3373363 3372045 0.0463 463 4216320 4221506 4218913 0.0529 529 4840795 4848174 4844484.5 0.0674 674 6146031 6156771 6151401 0.0749 749 6840663 5840698 6843668

[0084] Performing linear regression on the sample concentration based on the average peak area obtained from the detection, the regression equation at 270 nm wavelength is obtained:

[0085] y = 9132.7x + 706.47, R 2 = 1.

[0086] It can be seen that at a wavelength of 235 nm, although the linear correlation coefficient R 2 value is also greater than 0.99, the intercept is very large. If the single standard comparison method in the present invention is used for sample analysis, the error is relatively large; under the condition of 270 nm, the correlation coefficient R 2 is 1, and the linear relationship of 1,3-bromo-2-methyl-6-methylsulfonyl-α-chlorobenzaldehyde oxime is good in the range of 369 - 749 μg / mL, indicating that the linearity of this experiment meets the requirements. Therefore, any wavelength within the range of 254 - 270 nm can be selected for content analysis.

[0087] Verification Example 3 Precision test

[0088] Weigh the standard sample of 3-bromo-2-methyl-6-methylsulfonyl-α-chlorobenzaldehyde oxime and 5 samples of Example 2 (accurate to 0.0002 g) respectively, place them in 100 mL volumetric flasks, add 80 mL of methanol, dissolve by ultrasonic oscillation, cool to room temperature, and then dilute to the mark with methanol; analyze them in sequence, the determination method and chromatographic conditions are the same as in Example 1, record the peak areas, and the data are shown in Table 7 below.

[0089] Table 7 Results of precision test

[0090]

[0091]

[0092] Calculate and compare the contents of the five parallel samples. The RSD value is less than 1%, indicating that the precision of the method of the present invention is good.

[0093] Verification Example 4 Recovery test

[0094] Weigh the standard sample of 3-bromo-2-methyl-6-methylsulfonyl-α-chlorobenzaldehyde oxime and 5 samples of Example 2 (accurate to 0.0002 g) respectively, and add different masses of the standard sample to the samples. Analyze them in sequence according to the chromatographic conditions and determination method of Example 1, calculate the recovery rate of the added standard sample, and the data are shown in Table 8 below.

[0095] Table 8 Results of recovery test

[0096]

[0097] It can be seen from Table 8 that the recovery rates are all between 98% and 102%, and the average recovery rate is 99.21%, indicating that the recovery rate of this experiment meets the requirements.

[0098] In summary, the analytical method for the content of 3-bromo-2-methyl-6-methylsulfonyl-α-chlorobenzaldehyde oxime provided by the present invention has high accuracy and good operability, and can be widely applied to the analysis and detection of the content of 3-bromo-2-methyl-6-methylsulfonyl-α-chlorobenzaldehyde oxime.

[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, those of ordinary skill in the art can make various equivalent modifications or substitutions to the embodiments of the present invention, and these modifications or substitutions should all be within the scope of the present invention. / Any person skilled in the art within the technical scope disclosed by the present invention can easily think of changes or substitutions, and all should be covered within the protection scope of the present invention.

Claims

1. A method for determining the content of an intermediate of tembotrione, characterized in that, The benzobicyclon intermediate is 3-bromo-2-methyl-6-methylsulfonyl-α-chlorobenzaldehyde oxime, and the content determination method includes the following steps: (1) Dissolve the standard substance and the sample to be tested with methanol as the solvent respectively to prepare a standard sample and a test sample; (2) Analyze the standard sample and the test sample obtained in step (1) by reverse-phase high-performance liquid chromatography. The chromatographic column is chromatographic column VP-ODS, and the mobile phase is a mixed system of acetonitrile and aqueous acetic acid solution with a volume ratio of 50:

50. The volume percentage concentration of the aqueous acetic acid solution is 0.8%. The flow rate of the mobile phase is 0.5-1.5 mL / min, and the detection wavelength is 254-270 nm. Calculate the mass fraction of 3-bromo-2-methyl-6-methylsulfonyl-α-chlorobenzaldehyde oxime in the sample to be tested according to the external standard method formula.

2. The content determination method according to claim 1, wherein The column length of the chromatographic column is 150 mm, the column inner diameter is 4.6 mm, and the column particle size is 5 μm.

3. The content determination method according to claim 1, wherein The column temperature of the chromatographic column is 35-50 °C.

4. The content determination method according to claim 3, characterized in that, The column temperature of the chromatographic column is 40 °C.

5. The content determination method according to claim 1, wherein The flow rate of the mobile phase is 1 mL / min.

6. The content determination method according to claim 1, wherein, After the instrument baseline is stable, inject samples in the order of standard sample, test sample, test sample, and standard sample in turn.

7. The content determination method according to claim 1, characterized in that, The sample volume for each injection is 1-10 μL.

8. The content determination method according to claim 7, characterized in that, The sample volume for each injection is 5 μL.

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