Analysis method of N-methyl-N-isopropyl amino sulfonamide

Abstract

The invention relates to a detection and analysis method of N-methyl-N-isopropyl amino sulfonamide. The analysis method is a high performance liquid chromatography. According to the method, methanol is used for dissolving a sample, water and acetonitrile are used as mobile phases, the to-be-detected sample is eluted at low wavelength, after elution, the separation degree of N-methyl-N-isopropyl amino sulfonamide and impurities is high, and peak patterns are sharp and symmetrical. And integrating the spectrogram by adopting an area normalization method to obtain a detection result of the N-methyl-N-isopropylamino sulfonamide, so that the content of the N-methyl-N-isopropylamino sulfonamide in the sample can be effectively detected.

Description

Technical Field

[0001] The invention belongs to the technical field of chemical analysis and specifically relates to a high performance liquid phase analysis method and a quantitative analysis method of N-methyl-N-isopropylaminosulfonamide. Background Art

[0002] N-methyl-N-isopropylaminosulfonamide is a white solid with a molecular weight of 152.22 and a boiling point of 238.7±23.0℃ (Predicted). It is soluble in acetone and dichloromethane; it is easily soluble in methanol and is a key intermediate for the preparation of the herbicide saflufenacil. Saflufenacil is a herbicide developed by BASF and can be used as a lethal herbicide. It can effectively control a variety of broadleaf weeds, including weeds resistant to glyphosate, ALS and triazines. It has a fast lethal effect and soil residues degrade rapidly. It can be mixed with grass weed herbicides, such as glyphosate, with good results. It can be applied in a variety of crop fields and non-arable land, with few restrictions on crop rotation. 70% saflufenacil water-dispersible granules are already on the market, which can be used to control broadleaf weeds in wheat fields.

[0003] In the production process of saflufenacil, accurate analysis of N-methyl-N-isopropylaminosulfonamide content is crucial to guide production.

[0004] At present, there are few literature reports on the analysis and detection methods of N-methyl-N-isopropylaminosulfonamide. In the actual production process, factories are generally limited to using gas chromatography detection, but the peak shape and separation effect are poor, and it is impossible to separate N-methyl-N-isopropylaminosulfonamide and the main impurities contained therein well, and it is impossible to accurately analyze the quality of the product.

[0005] Therefore, it is a very urgent need for production companies to develop an analytical detection method and a quantitative method for N-methyl-N-isopropylaminosulfonamide that is simple to operate and has accurate results. Summary of the invention

[0006] Those skilled in the art know that in the process of establishing the HPLC analysis method: 1. Certain solvents absorb strong light at <210nm, which will interfere with the detection of compounds. 2. The baseline of the instrument chromatogram is unstable at <210nm, which will affect the peak shape of the spectrum. Therefore, it is necessary to avoid overlap with the absorption wavelength of these solvents. Usually, wavelengths less than 210nm are not selected as detection wavelengths, and chromatographic wavelengths of 210nm-400nm are selected as crop detection wavelengths. In the actual detection process, the applicant found that although the chromatographic wavelength of 210nm-400nm can detect the product, the separation effect of N-methyl-N-isopropylaminosulfonamide and the impurities therein is not ideal.

[0007] The invention aims at the lack of an analytical method capable of accurately analyzing N-methyl-N-isopropylaminosulfonamide in the prior art, in particular, an analytical method capable of well separating N-methyl-N-isopropylaminosulfonamide from impurities therein.

[0008] The applicant has found through unremitting research that when the detection wavelength is selected to be 190-200 nm and a composition of water and acetonitrile is used as an eluent, N-methyl-N-isopropylaminosulfonamide and its main impurities 1 and 2 can be well separated on the liquid phase spectrum. In view of this, the present invention has been completed.

[0009] Specifically, the present invention provides a high performance liquid phase analysis method for N-methyl-N-isopropylaminosulfonamide, comprising preparing a sample, setting a sample injection program, integrating a spectrum using an area normalization method, and obtaining detection results of N-methyl-N-isopropylaminosulfonamide and impurities, wherein the detection wavelength is 190 to 200 nm, the mobile phase comprises a combination of water and acetonitrile, and methanol is used to prepare the sample.

[0010] The present invention also provides a quantitative analysis method for N-methyl-N-isopropylaminosulfonamide, wherein the high performance liquid phase analysis method of the present invention is used in the quantitative process.

[0011] Beneficial effects of the present invention

[0012] 1) The separation effect of the high performance liquid phase analysis method of the present invention is better than that of the prior art; the separation of N-methyl-N-isopropylaminosulfonamide and impurities is high, the peak position is moderate, and the peak shape is sharp and symmetrical;

[0013] 2) The analytical method of the present invention is more accurate in the quantitative analysis of N-methyl-N-isopropylaminosulfonamide;

[0014] 3) If a certain proportion of acetonitrile is contained in the mobile phase of the present invention, the compounds and impurities can be better separated, and the separation effect and peak shape are better than using conventional methanol;

[0015] 4) Selecting appropriate sample preparation conditions can accurately analyze N-methyl-N-isopropylaminosulfonamide. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 This is the spectrum obtained by high performance liquid chromatography in Example 1, wherein 5.245 min is the peak of impurity 1, 6.134 min is the peak of N-methyl-N-isopropylaminosulfonamide, and 7.345 min is the peak of impurity 2.

[0017] Figure 2This is the spectrum obtained by high performance liquid chromatography in Example 2, wherein 7.097min is the peak of impurity 1, 7.953min is the peak of N-methyl-N-isopropylaminosulfonamide, and 8.528min is the peak of impurity 2.

[0018] Figure 3 This is the spectrum obtained by high performance liquid chromatography in Example 3, wherein 5.076min is the peak of N-methyl-N-isopropylaminosulfonamide containing impurity 1, and 5.721min is the peak of impurity 2.

[0019] Figure 4 This is the spectrum obtained by high performance liquid chromatography in Example 8, wherein 5.970 min is the peak of impurity 1, and 6.107 min is the peak of N-methyl-N-isopropylaminosulfonamide.

[0020] Figure 5 This is the spectrum obtained by high performance liquid chromatography in Example 11, wherein 7.431 min is the peak of impurity 1, and 7.609 min is the peak of N-methyl-N-isopropylaminosulfonamide containing impurity 2.

[0021] Figure 6 This is the spectrum obtained by high performance liquid chromatography in Example 12, wherein 4.925 min is the peak of impurity 1, and 5.049 min is the peak of N-methyl-N-isopropylaminosulfonamide containing impurity 2.

[0022] Figure 7 This is the spectrum obtained by high performance liquid chromatography in Example 13, wherein 5.222min is the peak of impurity 1, 5.590min is the peak of N-methyl-N-isopropylaminosulfonamide, and 6.423min is the peak of impurity 2.

[0023] Figure 8 This is the spectrum obtained by high performance liquid chromatography in Comparative Example 1, wherein 9.744 min is the peak of N-methyl-N-isopropylaminosulfonamide containing impurities 1 and 2.

[0024] Fig. 9 This is the spectrum obtained by gas chromatography in Comparative Example 2, wherein 2.893 min is the peak of impurity 1, 3.151 min is the peak of N-methyl-N-isopropylaminosulfonamide, and 3.229 min is the peak of impurity 2. DETAILED DESCRIPTION

[0025] Now, various exemplary embodiments of the present invention are described in detail, which should not be considered as limiting the present invention, but should be understood as a more detailed description of certain aspects, characteristics and embodiments of the present invention. It should be understood that the terms described in the present invention are only for describing a particular embodiment and are not used to limit the present invention. In addition, for the numerical range in the present invention, it should be understood that the upper and lower limits of the range and each intermediate value between them are specifically disclosed. Each smaller range between the intermediate value in any stated value or stated range and any other stated value or intermediate value in the range is also included in the present invention. The upper and lower limits of these smaller ranges may be independently included or excluded in the range. Unless otherwise specified, all technical and scientific terms used herein have the same meanings as commonly understood by conventional technicians in the field to which the present invention belongs. Although the present invention only describes preferred methods and materials, any methods and materials similar or equivalent to those described herein may also be used in the implementation or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe methods and / or materials related to the documents. In the event of a conflict with any incorporated document, the content of this specification shall prevail. The samples to be tested used in the present invention come from the applicant's factory; the reagents used in the analytical method for detection are chromatographic grade solvents from commercial channels.

[0026] Specifically, the present invention first provides a high performance liquid phase analysis method for N-methyl-N-isopropylaminosulfonamide, comprising preparing a sample, setting an injection program, integrating a spectrum using an area normalization method, and obtaining detection results of N-methyl-N-isopropylaminosulfonamide and impurities. The method is characterized in that the chromatographic column is a reverse chromatographic column, preferably a C18 and a C8 column; the detection wavelength is 190 to 200 nm, the mobile phase comprises a combination of water and acetonitrile, and methanol is used to prepare the sample.

[0027] In the above analysis method, the sample preparation step includes preparing the sample to be tested with a solvent to a suitable concentration, the solvent is acetonitrile, methanol or acetone, preferably methanol, and the suitable concentration is 1-5 mg / ml, preferably 2.5 mg / ml.

[0028] In the above analysis method, the injection procedure uses a mobile phase to perform gradient elution on the sample; preferably, the gradient elution conditions are, based on water in the mobile phase, the elution gradient is: 0-8min: 75-85%; 8-20min: 5-15%; 20-25min: 75-85%.

[0029] In a preferred embodiment, the gradient elution conditions are: based on water in the mobile phase, the elution gradient is: 0-8 min: 80%; 8-20 min: 10%; 20-25 min: 80%.

[0030] In some preferred embodiments, the flow rate of the mobile phase is 0.8-1.2 mL / min, preferably 1 mL / min.

[0031] In the above analysis method, the column temperature of the chromatographic column is 25-35°C, preferably 30°C.

[0032] Preferably, in an embodiment, the detection wavelength is 194 nm.

[0033] In some embodiments, the injection volume set in the injection program is 5 to 15 μL, preferably 10 μL.

[0034] The above preferred conditions have a better effect on the analysis of N-methyl-N-isopropylaminosulfonamide and a better separation effect.

[0035] The present invention also provides a quantitative analysis method for N-methyl-N-isopropylaminosulfonamide, which comprises adopting the above-mentioned high performance liquid phase analysis method of the present invention, using methanol as a solvent to dissolve a sample and a standard product of N-methyl-N-isopropylaminosulfonamide to prepare the sample.

[0036] The following examples are given to further illustrate the present invention. It is necessary to point out that the following examples cannot be understood as limiting the scope of protection of the present invention. If a person skilled in the art makes some non-essential improvements and adjustments to the present invention based on the above content of the present invention, it still belongs to the scope of protection of the present invention.

[0037] 1. Analytical Method Example

[0038] Example 1

[0039] This embodiment provides a method for detecting and analyzing N-methyl-N-isopropylaminosulfonamide using high performance liquid chromatography, which is as follows:

[0040] (1) Solution preparation: Take a sample of N-methyl-N-isopropylaminosulfonamide and use methanol to prepare a 2.5 mg / ml sample to be tested.

[0041] (2) Detection instrument: Agilent 1260 series liquid chromatograph.

[0042] (3) Stationary phase: ZORBAX Eclipse Plus C18, 4.6×250 mm, 5 μm;

[0043] (4) Eluent: Solvent A is water, solvent B is acetonitrile.

[0044] (5) The elution gradient is shown in the following table (the time in the table is the time point when the volume ratio is changed):

[0045] Volume ratio of solvent A to solvent B 0min 80:20 8min 80:20 12min 10:90 20min 10:90 22min 80:20 25min 80:20

[0046] (5) Elution parameter setting:

[0047] The flow rate was 1 mL / min, the column temperature was 30 °C, the detection wavelength was 194 nm, and the injection volume was 10 μL.

[0048] (6) Data analysis:

[0049] The above test results are as follows Figure 1 As shown, it can be seen from the spectrum that the separation effect between N-methyl-N-isopropylaminosulfonamide and impurities is good, the peak position is moderate, and the peak shape is sharp.

[0050] Example 2

[0051] The difference from Example 1 is that the elution gradient is as shown in the following table (the time in the table is the time node of changing the volume ratio)

[0052] Volume ratio of solvent A to solvent B 0min 85:15 8min 85:15 12min 10:90 20min 10:90 22min 85:15 25min 85:15

[0053] The test results of Example 2 are as follows Figure 2 As shown, the separation peak shape is better, but compared with Example 1, the elution position of N-methyl-N-isopropylaminosulfonyl is later.

[0054] Example 3

[0055] The difference from Example 1 is that the elution gradient is as shown in the following table (the time in the table is the time node of changing the volume ratio)

[0056] Volume ratio of solvent A to solvent B 0min 70:30 8min 70:30 12min 10:90 20min 10:90 22min 70:30 25min 70:30

[0057] The test results of Example 3 are as follows Figure 3 It is shown that compared with Example 1, N-methyl-N-isopropylaminosulfonamide and the impurities are not completely separated, and the separation effect is poor.

[0058] Example 4

[0059] The difference from Example 1 is that the column temperature is 25°C.

[0060] Example 5

[0061] The difference from Example 1 is that the column temperature is 35°C.

[0062] Example 6

[0063] The difference from Example 1 is that the detection wavelength is 190 nm.

[0064] Example 7

[0065] The difference from Example 1 is that the detection wavelength is 200 nm.

[0066] Example 8

[0067] The difference from Example 1 is that the detection wavelength is 220nm, the absorption is very weak, and the peak area is very small. The results are as follows Figure 4 As shown, N-methyl-N-isopropylaminosulfonamide has very low responses to impurity 1, while impurity 2 has no response, resulting in a larger error.

[0068] Example 9

[0069] The difference from Example 1 is that the injection volume is 5 μL.

[0070] Example 10

[0071] The difference from Example 1 is that the injection volume is 15 μL.

[0072] Embodiment 11

[0073] The difference from Example 1 is that the flow rate is 0.8 mL / min. Figure 5 As shown, N-methyl-N-isopropylaminosulfonamide was not separated from the impurities.

[0074] Example 12

[0075] The difference from Example 1 is that the flow rate is 1.2 mL / min. The results are as follows Figure 6 As shown, N-methyl-N-isopropylaminosulfonamide was not separated from the impurities.

[0076] Embodiment 13

[0077] The difference from Example 1 is that the Rx-C8 chromatographic column is used. The results are as follows Figure 7 shown.

[0078] The results of the above embodiments show that within the preferred elution gradient range of the present invention, the separation effect of N-methyl-N-isopropylaminosulfonamide from impurities 1 and 2 is better, and the particularly preferred elution gradient has the best effect; the column temperature, detection wavelength, and injection volume of the chromatographic column have little effect on the separation degree of N-methyl-N-isopropylaminosulfonamide and impurities; under the preferred conditions of the present invention, the separation degree can be further improved.

[0079] Comparative Example 1

[0080] The difference from Example 1 is that the mobile phase acetonitrile is replaced by methanol, and the peak shape is not good. The results are as follows Figure 8 As shown, impurities were not separated.

[0081] Comparative Example 2

[0082] The method for detecting and analyzing the reaction solution of N-methyl-N-isopropylaminosulfonamide by gas chromatography is as follows:

[0083] (1) Solution preparation: The reaction solution was prepared with methanol as solvent to prepare 2 mg / ml of the sample to be tested.

[0084] (2) Detection instrument: Agilent 7820B gas chromatograph with flame ionization (FID) detector.

[0085] (3) Chromatographic column: HP-5, 30 m, 0.32 mm, 0.25 μm capillary column;

[0086] (4) Inlet temperature: 250°C, detector temperature: 270°C, column temperature program: 150°C (1 min) -20°C

[0087] -260℃(6min);

[0088] (5) Injection volume: 1 μL;

[0089] (6) N2 flow rate: 1.0 mL / min;

[0090] (7) Split ratio: 30:1

[0091] The above test results are as follows Fig. 9 As shown, it can be seen from the spectrum that the separation effect of N-methyl-N-isopropylaminosulfonamide and impurities is not good.

[0092] 2. Quantitative Analysis Example

[0093] The quantitative analysis operating conditions and steps of N-methyl-N-isopropylaminosulfonamide of the present invention are as follows:

[0094] (1) Detection instrument: Agilent 1260 series liquid chromatograph.

[0095] (2) Stationary phase: ZORBAX Eclipse Plus C18, 4.6×250 mm, 5 μm;

[0096] (3) Eluent: Solvent A is water, solvent B is acetonitrile.

[0097] (4) The elution gradient is shown in the following table (the time in the table is the time point when the volume ratio is changed):

[0098] Volume ratio of solvent A to solvent B 0min 80:20 8min 80:20 12min 10:90 20min 10:90 22min 80:20 25min 80:20

[0099] (5) Elution parameter setting:

[0100] The flow rate was 1 mL / min, the column temperature was 30 °C, the detection wavelength was 194 nm, and the injection volume was 10 μL.

[0101] (6) Solution preparation: 1. Accurately weigh 120 mg of N-methyl-N-isopropylaminosulfonamide (purity: 98.0%) standard into a 50 mL volumetric flask, dissolve it with methanol, dilute to the mark, and shake well for later use. 2. Weigh approximately 120 mg of sample five times into a 50 mL volumetric flask, dissolve it with methanol, dilute to the mark, and shake well for later use.

[0102] After the instrument is stable, inject several injections of standard solution continuously until the relative deviation of the peak area between two adjacent injections is less than 1%. Then inject in the following order: standard solution 1, sample solution 1, sample solution 2, sample solution 3, sample solution 4, sample solution 5…

[0103] calculate

[0104]

[0105] in:

[0106] A: Peak area of ​​N-methyl-N-isopropylaminosulfonamide in the sample solution;

[0107] As: peak area of ​​N-methyl-N-isopropylaminosulfonamide in standard solution;

[0108] m: sample weight (mg);

[0109] ms: standard sample weight (mg);

[0110] Ps: standard purity (wt / wt, %);

[0111] The relative standard errors of the quantitative analysis results are shown in Table 1:

[0112] Table 1:

[0113]

[0114] From the data in the above table, we can see that the relative standard deviation is 0.12%, which is within the standard requirement.

[0115] The applicant declares that the present invention illustrates the detailed process equipment and process flow of the present invention through the above-mentioned embodiments, but the present invention is not limited to the above-mentioned detailed process equipment and process flow, that is, it does not mean that the present invention must rely on the above-mentioned detailed process equipment and process flow to be implemented. Those skilled in the art should understand that any improvement of the present invention, equivalent replacement of various raw materials of the product of the present invention, addition of auxiliary components, selection of specific methods, etc., all fall within the protection scope and disclosure scope of the present invention.

Claims

1. A high performance liquid phase analysis method for N-methyl-N-isopropylaminosulfonamide, comprising preparing a sample, setting a sample injection program, integrating the spectrum using an area normalization method, and obtaining the detection results of N-methyl-N-isopropylaminosulfonamide and impurities, characterized in that: The chromatographic column is a reverse chromatographic column, preferably a C18 or C8 column; the detection wavelength is 190-200 nm, the mobile phase comprises water and acetonitrile, and the sample preparation uses methanol as a solvent.

2. The analysis method according to claim 1, characterized in that The injection procedure uses a mobile phase to perform gradient elution on the sample; preferably, the gradient elution conditions are, based on water in the mobile phase, the elution gradient is: 0-8min: 75-85%; 8-20min: 5-15%; 20-25min: 75-85%.

3. The analysis method according to any one of claims 1 or 2, characterized in that The gradient elution condition is that, based on the water in the mobile phase, the elution gradient is: 0-8min: 80%; 8-20min: 10%; 20-25min: 80%.

4. The analysis method according to any one of claims 1 to 3, characterized in that The flow rate of the mobile phase is 0.8-1.2 mL / min, preferably 1 mL / min.

5. The analysis method according to any one of claims 1 to 4, characterized in that: The column temperature of the chromatographic column is 25-35°C, preferably 30°C.

6. The detection and analysis method according to any one of claims 1 to 5, characterized in that: The detection wavelength is 194 nm.

7. The analysis method according to any one of claims 1 to 6, characterized in that: The injection volume set in the injection program is 5 to 15 μL, preferably 10 μL.

8. The detection and analysis method according to any one of claims 1 to 7, characterized in that: The chromatographic column is a Plus-C18 or Rx-C8 chromatographic column.

9. A high performance liquid phase analysis method for determining the content of N-methyl-N-isopropylaminosulfonamide by external standard method, characterized in that: The analysis method adopts the analysis method described in any one of claims 1 to 8, and methanol is used as a solvent to dissolve the sample and standard of N-methyl-N-isopropylaminosulfonamide.

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