Method for determining content of 3-(dimethylaminoformyl) pyridine-2-sulfonyl chloride by precolumn derivatization method

Abstract

The invention relates to the technical field of chemical detection, in particular to a method for determining the content of 3-(dimethyl carbamoyl) pyridine-2-sulfonyl chloride through a pre-column derivatization method, which is characterized in that corresponding 3-(dimethyl carbamoyl) pyridine-2-sulfonic acid methyl ester can be effectively generated through the reaction of a derivatization agent methanol and 3-(dimethyl carbamoyl) pyridine-2-sulfonyl chloride, and the content of 3-(dimethyl carbamoyl) pyridine-2-sulfonyl chloride can be measured through the pre-column derivatization method. The method comprises the following steps: taking a sample solution to be detected as a mobile phase to avoid decomposition in the mobile phase to generate 3-(dimethylaminoformyl) pyridine-2-sulfonic acid, then carrying out high performance liquid chromatography analysis on the sample solution and a standard sample solution, taking a mixture of methanol and a phosphoric acid aqueous solution as the mobile phase, and comparing with a standard sample to calculate the content of 3-(dimethylaminoformyl) pyridine-2-sulfonyl chloride in the sample to be detected. The method provided by the invention has the advantages of strong specificity and good precision, is especially suitable for quality evaluation and control of organic synthesis intermediates, and has important effect and practical significance for ensuring the quality of final products.

Description

Technical Field

[0001] The present invention relates to the technical field of chemical detection, and specifically relates to a method for determining the content of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride by pre-column derivation method. Background Art

[0002] As a precursor of the nicosulfuron intermediate 2-chloro-N,N-dimethylnicotinamide, 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride can be used to obtain the nicosulfuron intermediate 2-chloro-N,N-dimethylnicotinamide by dropping ammonia water. The quality of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride affects the quality of the subsequent intermediate, thereby affecting the quality of the final product nicosulfuron. At the same time, according to the content of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride, the yield of this section can be calculated, which has important guiding significance for stabilizing the quality and increasing the yield of this section.

[0003] After consulting relevant domestic and foreign literatures, there is no relevant report on the analysis method for the content of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride. Based on this, it is necessary to propose a method for determining the content of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride by pre-column derivation method with good chromatographic peak shape and high credibility of the obtained results. Summary of the Invention

[0004] Aiming at the blank of the analysis method for the content of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride in the prior art, the present invention provides a method for determining the content of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride by pre-column derivation method. The method of the present invention uses pre-column derivation high performance liquid chromatography to detect the content of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride. By reacting the derivatizing agent methanol with 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride, the corresponding methyl 3-(dimethylcarbamoyl)pyridine-2-sulfonate can be effectively generated, avoiding the decomposition of 3-(dimethylcarbamoyl)pyridine-2-sulfonic acid in the mobile phase. At the same time, methanol is used as the mobile phase, avoiding the polarization effect between the solvent and the mobile phase, ensuring the accuracy and credibility of the content analysis.

[0005] The present invention provides a method for determining the content of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride by pre-column derivation method, which specifically includes the following steps: (1) The sample to be tested and the standard sample are respectively dissolved and derivatized with methanol, and then diluted to obtain a sample solution and a standard sample solution, and the linear concentration range of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride is controlled to be 200 mg / L - 700 mg / L; (2) Perform high performance liquid chromatography analysis on the sample solution and the standard sample solution obtained in step (1), using a mixture of methanol and phosphoric acid aqueous solution as the mobile phase. By comparing with the standard sample, calculate the content of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride in the sample to be tested.

[0006] Further, in step (1), the derivatization time is 0.5 - 1.5 h, and the derivatization temperature is 20 - 40 °C; Preferably, the derivatization time is 1 h, and the derivatization temperature is 30 °C.

[0007] Further, in step (1), using methanol as the solvent and also as the derivatizing agent, under the above conditions, it can be completely derivatized into its methyl ester product, that is, methyl 3-(dimethylcarbamoyl)pyridine-2-sulfonate, and its structure is: .

[0008] The above-derived methyl 3-(dimethylcarbamoyl)pyridine-2-sulfonate avoids the decomposition of 3-(dimethylcarbamoyl)pyridine-2-sulfonic acid in the mobile phase. At the same time, using methanol as the mobile phase avoids the polarization effect between the solvent and the mobile phase, ensuring the accuracy and reliability of the content analysis; methanol is used as the derivatizing agent at the same time, and its dosage is extremely low and does not affect its role as a solvent. Therefore, methanol in step (1) of this application is far in excess as a derivatizing agent, and only the dosage as a solvent needs to be considered when adding.

[0009] Further, in step (2), a packed column with silica gel bonded C18 is used, the column length of the chromatographic column is 150 mm, the column temperature is 30 °C, the theoretical plate number is 5000, the detection wavelength is 245 - 280 nm, and preferably, the detection wavelength is 265 nm.

[0010] Further, in step (2), the volume ratio of methanol to phosphoric acid aqueous solution in the mobile phase is 35:65 - 45:55, where the volume percentage of phosphoric acid in the phosphoric acid aqueous solution is 0.05% - 0.1%, and the flow rate of the mobile phase is 0.8 - 1.2 mL / min.

[0011] Preferably, the volume ratio of methanol to phosphoric acid aqueous solution is 40:60, and the volume percentage of phosphoric acid in the phosphoric acid aqueous solution is 0.1%. Utilizing the characteristics of different polarities of different mobile phases, by changing the mobile phase ratio, the polarity of the mobile phase is changed, thereby affecting the distribution ratio of the sample between the mobile phases and achieving the separation result; at the same time, using methanol as the derivatizing agent and the mobile phase can effectively avoid the polarization effect between the solvent and the mobile phase, ensuring the stability of the chromatographic peak area during detection, thereby ensuring its accuracy and reliability. Using the above mobile phase can obtain a better separation effect.

[0012] Further, in step (2), after the instrument baseline is stable, samples are injected in the order of standard sample, sample, sample, and standard sample, and the sample volume for each injection is 5 μL.

[0013] Compared with the prior art, the beneficial effects of the present invention are as follows: The method for determining the content of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride by pre-column derivation high-performance liquid chromatography provided by the present invention fills the blank in this field. By reacting the derivatizing agent methanol with 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride, the corresponding methyl ester product can be effectively generated, avoiding the decomposition of the corresponding acid in the mobile phase. At the same time, methanol is used as the mobile phase, avoiding the polarization effect between the solvent and the mobile phase, ensuring the accuracy and reliability of the content analysis. When the above method is used to detect the mass fraction of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride, the chromatographic peak shape is good, the integral calculation result is accurate and has good repeatability, and the obtained result is highly credible and more accurate and timely; the method of the present invention has strong specificity and good precision, is particularly suitable for the quality evaluation and control of organic synthesis intermediates, and has important significance and practical significance for ensuring the quality of the final product. Description of the Drawings

[0014] Figure 1 It is the chromatogram of the standard sample in Example 1; Figure 2 It is the chromatogram of the sample in Example 1; Figure 3 It is the linear relationship diagram in Test Example 2; Figure 4 It is the chromatogram of derivatization at 20 °C for 1.0 h in Test Example 5. Detailed Embodiments

[0015] In order 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 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 of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative work shall fall within the protection scope of the present invention.

[0016] Example 1 A method for determining the content of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride by pre-column derivation 10.8 g of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride was obtained by small-scale synthesis, and its content was analyzed. The content analysis method specifically includes the following steps: ① Preparation of the standard sample stock solution Accurately weigh 0.0514 g (accurate to 0.0002 g) of the methyl ester standard sample of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride and place it in a 100 mL volumetric flask. Add 80 mL of methanol, dissolve it by ultrasonic oscillation, heat it in a water bath at 30 °C for 1 h, cool it to room temperature, then dilute it to the mark with methanol, shake well and set aside.

[0017] ② Preparation of sample stock solution Accurately weigh 0.0522 g (accurate to 0.0002 g) of the sample containing 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride and place it in a 100 mL volumetric flask. Add 80 mL of methanol, dissolve it by ultrasonic oscillation, heat it in a water bath at 30 °C for 1 h, cool it to room temperature, then dilute it to the mark with methanol, shake well and set aside.

[0018] ③ Testing and data processing The high-performance liquid chromatograph used is the LC-20ATvp infusion pump and SPD-20Avp ultraviolet detector of Shimadzu Corporation. The chromatographic column is a packed column with silica gel bonded C18 (Dalian Elite Hypersil ODS2 150 mm * 4.6 μm, column temperature is 30 °C, theoretical plate number is 5000). The mobile phase is methanol: 0.1% phosphoric acid aqueous solution with a volume ratio of 40:60, and the flow rate is 1.0 mL / min; After the machine self-check is passed, under the specified operating conditions, 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 change between adjacent two needles is less than 1.5%, inject samples in the order of standard sample, sample, sample, standard sample in turn. The injection volume each time is 5 μL, and detect at a wavelength of 265 nm. Its chromatogram is as Figure 1 and 2 shown. In the figure, 6.029 min is the chromatographic peak of methyl 3-(dimethylcarbamoyl)pyridine-2-sulfonate, the derivative of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride. The impurities are completely separated, the peak shape is good, and the data shown in Table 1 below are obtained: Table 1 Detection results of Example 1 Calculate the mass fraction X of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride in the sample according to the following formula 1： In the formula: A1—the average value of the peak area of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride in the standard sample; A2—the average value of the peak area of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride in the sample; m1—the mass of the standard sample; m2—the mass of the sample; P1—Mass fraction of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride in the standard sample; X1—Mass fraction of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride in the sample; 1.016—Conversion coefficient of sulfonyl chloride to methyl ester.

[0019] It can be calculated that the mass fraction of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride in the sample of Example 1 is 96.31%.

[0020] Example 2 A method for determining the content of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride by pre-column derivation 11.5 g of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride was obtained by small-scale synthesis, and its content was analyzed. The content analysis method specifically includes the following steps: ① Preparation of standard sample stock solution Accurately weigh 0.0526 g (accurate to 0.0002 g) of the methyl ester standard sample of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride and place it in a 100 mL volumetric flask. Add 80 mL of methanol, dissolve it by ultrasonic oscillation, then place it in a 30 °C water bath and heat for 1 h. After cooling to room temperature, dilute it to the scale with methanol and shake well for standby.

[0021] ② Preparation of sample stock solution Accurately weigh 0.0531 g (accurate to 0.0002 g) of the sample containing 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride and place it in a 100 mL volumetric flask. Add 80 mL of methanol, dissolve it by ultrasonic oscillation, then place it in a 30 °C water bath and heat for 1 h. After cooling to room temperature, dilute it to the scale with methanol and shake well for standby.

[0022] ③ Testing and data processing The high-performance liquid chromatograph used is the LC-20ATvp infusion pump and SPD-20Avp ultraviolet detector of Shimadzu Corporation. The chromatographic column is a packed column with silica gel bonded C18 (Dalian Elite Hypersil ODS2 150 mm * 4.6 μm, column temperature is 30 °C, and the theoretical plate number is 5000). The mobile phase is methanol: 0.1% phosphoric acid aqueous solution volume ratio = 45:55, and the flow rate is 0.8 mL / min.

[0023] Table 2 Detection results of Example 2 Calculated according to the formula in Example 1, it can be calculated that the mass fraction of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride in the sample of Example 2 is 95.51%.

[0024] In summary, through the reaction of the derivatizing agent methanol with 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride, the corresponding methyl 3-(dimethylcarbamoyl)pyridine-2-sulfonate can be effectively generated, avoiding the decomposition of 3-(dimethylcarbamoyl)pyridine-2-sulfonic acid in the mobile phase. At the same time, methanol is used as the mobile phase, avoiding the polarization effect between the solvent and the mobile phase, ensuring the accuracy and reliability of the content analysis.

[0025] Test Example 1 Repeatability Test ① Preparation of standard sample stock solution Accurately weigh 0.0518 g of the methyl ester standard sample of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride (accurate to 0.0002 g) and place it in a 100 mL volumetric flask. Add 80 mL of methanol, dissolve it by ultrasonic oscillation, heat it in a water bath at 30 °C for 1 h, cool it to room temperature, and dilute it to the mark with methanol. Mix well and set aside.

[0026] ② Preparation of test sample stock solution Accurately weigh 6 portions of the test sample containing 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride (from the same batch as the sample in Example 2) and place them in a 100 mL volumetric flask. Add 80 mL of methanol, dissolve it by ultrasonic oscillation, heat it in a water bath at 30 °C for 1 h, cool it to room temperature, and dilute it to the mark with methanol. Mix well and set aside.

[0027] ③ Testing and data processing Detect the 6 test samples respectively according to the method of Example 1. The impurities are completely separated and the peak shape is good. Calculate the content of the active ingredient of the test sample according to the formula in Example 1, and obtain the data shown in Table 3 below. It can be seen that the experimental results of this method have good repeatability; Table 3 Detection Results of Test Example 1 .

[0028] Test Example 2 Linear Determination ① Preparation of test sample stock solution Weigh the standard product, methyl 3-(dimethylcarbamoyl)pyridine-2-sulfonate, that is, methyl 3-(dimethylcarbamoyl)pyridine-2-sulfonate, and dissolve and dilute it with methanol to prepare a group of methyl 3-(dimethylcarbamoyl)pyridine-2-sulfonate test samples containing 204 μg / ml, 312 μg / ml, 408 μg / ml, 516 μg / ml, 603 μg / ml, 664 μg / ml, and 712 μg / ml for standby; ② Testing and data processing Detect the 6 test samples respectively according to the method of Example 1. The impurities are completely separated and the peak shape is good, as Figure 3As shown, at a wavelength of 265 nm, the samples in each group were sequentially detected. A linear regression was performed with the peak area (A) on the y-axis against the sample concentration (μg / ml) on the x-axis, and the resulting regression equation was as follows: y = 6082.1x - 4028.5, R 2 = 0.9997, It can be seen that methyl 3-(dimethylcarbamoyl)pyridine-2-sulfonate has a good linear relationship in the range of 200 - 700 μg / mL.

[0029] Test Example 3 Intermediate Precision Test ① Preparation of sample stock solution Six persons accurately weighed 0.05 g (accurate to 0.0002 g) of the sample containing 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride in different laboratories and placed them in 100 mL volumetric flasks respectively. 80 mL of methanol was added, and the mixture was dissolved by ultrasonic oscillation. After derivatization at 30 °C for 1 h and cooling to room temperature, it was diluted to the mark with methanol to obtain 6 portions of sample stock solution; Different persons operated according to the method of Example 1 in different laboratories respectively; ② Testing and data processing Different persons detected the samples according to the method of Example 1 in different laboratories respectively and obtained the data shown in Table 4 below. It can be seen that the intermediate precision of the experimental results of this method is good; Table 4 Detection Results of Test Example 3 .

[0030] Test Example 4 Stability Test ① Preparation of sample stock solution Accurately weigh 0.05 g (accurate to 0.0002 g) of the sample containing 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride and place it in a 100 mL volumetric flask respectively. 80 mL of methanol was added, and the mixture was dissolved by ultrasonic oscillation. After derivatization at 30 °C for 1 h and cooling to room temperature, it was diluted to the mark with methanol; ② Testing and data processing After preparation, the samples were detected according to the method of Example 1 at 0, 1, 2, 4, 8, and 24 hours respectively. The impurities were completely separated and the peak shape was good. The content of the active ingredient of the sample was calculated according to the formula in Example 1, and the data shown in Table 5 below were obtained. It can be seen that the time stability of the experimental results of this method is good; Table 5 Detection Results of Test Example 4 .

[0031] Test Example 5 Derivatization Time and Temperature Test ① Preparation of sample stock solution Accurately weigh 9 samples each containing 0.05 g of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride (accurate to 0.0002 g) and place them separately in 100 mL volumetric flasks. Add 80 mL of methanol, dissolve by ultrasonic oscillation, derivatize at 20 °C, 30 °C, and 40 °C for 0.5 h, 1 h, and 1.5 h respectively, then cool to room temperature and dilute to the mark with methanol; ② Testing and data processing After preparation, the samples were detected according to the method of Example 1 respectively. The impurities were completely separated, the peak shape was good, and the injection was carried out continuously for 5 times. According to the chromatogram and the change of peak area, it can be seen that the reaction can be completed completely by derivatizing at 30 °C for 1 h and at 40 °C for 1 h. When the derivatization temperature is low or the derivatization time is short, the derivatization is not complete, and 3-(dimethylcarbamoyl)pyridine-2-sulfonic acid is produced by the hydrolysis of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride during detection. As Figure 4 shown, in the case of derivatizing at 20 °C for 1 h, the derivatization is incomplete. Not only does the sample decompose into acid ( Figure 4 the peak at the 1.6 min position in Figure 4 ), but also there is a chromatographic peak of sulfonyl chloride ( the peak at the 7.9 min position in In summary, the method for determining the content of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride by the pre-column derivatization method 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-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride.

[0032] 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, which should all be covered by the protection scope of the present invention. Therefore, the protection scope of the present invention should be subject to the protection scope described in the claims.

Claims

1. A method for determining the content of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride by pre-column derivation method, which is characterized in that, The content analysis method specifically includes the following steps: (1) After the sample to be tested and the standard sample are respectively dissolved and derivatized with the solvent methanol and then diluted, a sample solution and a standard sample solution are obtained; the derivatization time is 0.5 - 1.5 h, and the derivatization temperature is 20 - 40 °C; (2) The sample solution and the standard sample solution obtained in step (1) are subjected to high performance liquid chromatography analysis. A mixture of methanol and phosphoric acid aqueous solution is used as the mobile phase. By comparing with the standard sample, the content of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride in the sample to be tested is calculated.

2. The method for determining the content of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride by pre-column derivation method according to claim 1, characterized in that, In step (1), the derivatization time is 1 h and the derivatization temperature is 30 °C.

3. The method for determining the content of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride by pre-column derivation method according to claim 1, characterized in that, The product after derivatization of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride is methyl 3-(dimethylcarbamoyl)pyridine-2-sulfonate.

4. The method for determining the content of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride by pre-column derivation method according to claim 1, characterized in that, The linear concentration range of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride is 200 mg / L - 700 mg / L.

5. The method for determining the content of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride by pre-column derivation method according to claim 1, characterized in that, In step (2), a packed column with silica gel bonded C18 is used, the column temperature is 30 °C, the theoretical plate number is 5000, and the detection wavelength is 245 - 280 nm.

6. The method for determining the content of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride by pre-column derivation method according to claim 1, characterized in that, In step (2), the detection wavelength is 265 nm.

7. The method for determining the content of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride by pre-column derivation method according to claim 1, characterized in that, In step (2), the volume ratio of methanol to phosphoric acid aqueous solution in the mobile phase is 35:65 - 45:55, the volume percentage of phosphoric acid in the phosphoric acid aqueous solution is 0.05% - 0.1%, and the flow rate of the mobile phase is 0.8 - 1.2 mL / min.

8. The method for determining the content of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride by pre-column derivation method according to claim 1, characterized in that, In step (2), the volume ratio of methanol to phosphoric acid aqueous solution in the mobile phase is 40:

60.

9. The method for determining the content of 3-(dimethylcarbamoyl)pyridine-2-sulfonyl chloride by pre-column derivation method according to claim 1, characterized in that, In step (2), after the instrument baseline is stable, samples are injected in the order of standard sample, sample, sample, standard sample in sequence, and the sample volume for each injection is 5 μL.

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