A kind of purity analysis method of 1-methylpyrazole

Abstract

The invention discloses a purity analysis method of 1-methylpyrazole, belonging to the technical field of chemical substance detection. 1-methylpyrazole has a wide range of applications in both military and civilian industries, and is the main raw material of 1-methyl-3,4,5-trinitropyrazole (MTNP), but its purity analysis method has not been established so far. By exploring the gas chromatography separation system of 1-methylpyrazole and main impurity dimethyl carbonate, a purity analysis method of 1-methylpyrazole is established, and the best test conditions are obtained: SE-54 capillary column (50m×0.25mm×0.25μm) stationary phase is: 5% phenyl, 95% dimethylpolysiloxane, vaporization chamber temperature 220℃, detector temperature 220℃, column temperature 90℃, carrier gas pressure 0.14MPa, injection volume 1uL, and each substance separation degree is greater than 1.5. The internal standard method was used for quantitative analysis, and the internal standard curve was measured. The linear correlation coefficient was greater than 0.999, the spiked recovery rate was between 96.3% and 99%, and the RSD was less than 0.5, with good accuracy and precision.

Description

Technical Field

[0001] The invention belongs to the technical field of chemical substance detection, and particularly relates to a purity analysis method of 1-methylpyrazole. Background Art

[0002] 1-Methylpyrazole is an organic chemical raw material, which is widely used in various fields, such as medicine, electronics and agricultural products. The molecular formula is C4H6N2, and the structural formula is shown in Figure 6. The boiling point is 127.00℃, and it is a colorless liquid at room temperature with a refractive index of 1.477. It can also be used as a raw material for energetic materials 1-methyl-3,4,5-trinitropyrazole (MTNP). MTNP is superior to any previous potential substitute for TNT due to its high-energy insensitivity, and provides an excellent candidate for the leap in the comprehensive performance of high-energy insensitive ammunition charges. At present, various countries are conducting research on its synthesis method, process, melt-cast explosive formula and process. However, as the main raw material of MTNP, the research on its preparation process and purity analysis has not made further progress, which directly affects the synthesis, cost and application research of MTNP.

[0003] Chromatography is one of the fastest growing and most widely used analytical methods in analytical chemistry. Chromatography has powerful component separation, qualitative and quantitative functions, making it an indispensable and powerful means for component separation and analysis of complex samples. Since 1-methylpyrazole has no ultraviolet absorption and a low boiling point, it is detected by gas chromatography. Gas chromatography has the advantages of high selectivity, high sensitivity, high accuracy and high precision. It can be used for qualitative and quantitative analysis of gas, volatile liquid and solid samples. Due to its high separation efficiency, fast analysis speed, small sample dosage, good selectivity, high sensitivity and simple operation, it has a wide range of applications in many fields, and gas chromatography instruments have become very popular analytical instruments.

[0004] The preparation methods of 1-methylpyrazole have always been mainly pyrazole methylation and aldehyde amine condensation. In these two methods, whether it is dimethyl sulfate, alkyl halide or hydrazine and its derivatives, they are highly toxic, and some raw materials are expensive, which is not suitable for the current requirements of environmental protection and green chemical industry. Therefore, an experimental study on the methylation of pyrazole to synthesize 1-methylpyrazole was carried out using dimethyl carbonate as a methylation reagent. There are relatively complete preparation processes and purity analysis methods for dimethyl carbonate and pyrazole. HP-INNOWax capillary column and hydrogen flame ionization detector (FID) are used for dimethyl carbonate. The gas chromatography method for determining the content of dimethyl carbonate is established by using a second-order programmed temperature and n-butanol as the internal standard. Pyrazole can be quantitatively analyzed by using an OV-17 capillary column and n-hexadecane as the internal standard. However, the method for purity analysis of 1-methylpyrazole has not yet been established. In this study, a purity analysis method for 1-methylpyrazole based on high performance gas chromatography was established. The internal standard method was used for quantitative detection of 1-methylpyrazole and its main impurity dimethyl carbonate, providing technical support for the industrial production of 1-methylpyrazole and product quality control. Summary of the invention

[0005] In view of the problem that a purity analysis method of 1-methylpyrazole has not been established so far, the present invention provides a purity analysis method of 1-methylpyrazole.

[0006] In order to achieve the above object, the present invention adopts the following technical solutions:

[0007] A purity analysis method for 1-methylpyrazole comprises the following steps:

[0008] Step 1, preparation of 1-methylpyrazole standard solution: Use a microsyringe to accurately measure 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, and 0.8 mL of 1-methylpyrazole standard sample into a 10 mL volumetric flask, accurately add 0.5 mL of 1,2-dichloroethane as an internal standard, dilute to the scale with methanol, and shake well to make the volume fractions of 1-methylpyrazole 2%, 3%, 4%, 5%, 6%, 7%, and 8%, respectively;

[0009] Step 2, 1-methylpyrazole sample solution preparation: Take 0.5 mL of 1-methylpyrazole sample into a 10 mL volumetric flask, accurately add 0.5 mL of 1,2-dichloroethane, dilute to the scale with methanol, and shake well;

[0010] Step 3, determination: under chromatographic conditions, after the instrument is stable, sample is injected for determination, first the 1-methylpyrazole standard solution is determined, then the 1-methylpyrazole sample solution is determined, and the peak areas of 1-methylpyrazole and the internal standard 1,2-dichloroethane are recorded respectively;

[0011] Step 4, content calculation: linearly regress the peak area ratio of the 1-methylpyrazole standard sample and the internal standard 1,2-dichloroethane in the solution with the 1-methylpyrazole content to obtain a linear regression equation; substitute the peak area ratio of 1-methylpyrazole and the internal standard 1,2-dichloroethane in the 1-methylpyrazole sample solution into the linear regression equation to obtain the content of 1-methylpyrazole in the 1-methylpyrazole sample solution, and then convert it into the actual content of 1-methylpyrazole in the 1-methylpyrazole sample.

[0012] The chromatographic conditions are: chromatographic column: SE-54 capillary chromatographic column (50m×0.25mm×0.25μm); stationary phase: 5% phenyl, 95% dimethylpolysiloxane; vaporization chamber temperature: 220°C; detector temperature: 220°C; column temperature: 90°C; injection volume 1uL; carrier gas: high-purity nitrogen ≥99.99%, carrier gas pressure of 0.14MPa.

[0013] Compared with the prior art, the present invention has the following advantages:

[0014] The present invention establishes a purity analysis method of 1-methylpyrazole by exploring the gas chromatography separation system of 1-methylpyrazole and the main impurity dimethyl carbonate, and obtains the best test conditions: SE-54 capillary column (50m×0.25mm×0.25μm) stationary phase: 5% phenyl, 95% dimethylpolysiloxane; vaporization chamber temperature 220℃; detector temperature 220℃; column temperature 90℃; carrier gas pressure 0.14MPa; injection volume 1uL, and the separation degree of each substance is greater than 1.5. The internal standard method is used for quantitative analysis, and the internal standard standard curve is measured, the linear correlation coefficient is greater than 0.999, the spike recovery rate is between 96.3% and 99%, and the RSD is not greater than 0.5, with good accuracy and precision. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 Gas phase diagram of 1-methylpyrazole standard sample and internal standard 1,2-dichloroethane;

[0016] Figure 2 Gas phase diagram of 1-methylpyrazole sample and internal standard 1,2-dichloroethane;

[0017] Figure 3 Schematic diagram of the separation of methanol, 1-methylpyrazole, and 1,2-dichloroethane at different column temperatures;

[0018] Figure 4 Schematic diagram of the separation of methanol, 1-methylpyrazole, and 1,2-dichloroethane at different carrier gas pressures;

[0019] Figure 5 Schematic diagram of 1-methylpyrazole standard curve;

[0020] Figure 6 Schematic diagram of the structural formula of 1-methylpyrazole. DETAILED DESCRIPTION

[0021] Example 1

[0022] 1.1 Main instruments and reagents

[0023] Gas chromatograph: Shanghai Kechuang GC9800, with hydrogen flame ionization detector (FID) and matching chromatography data processing workstation;

[0024] KCA-2LP air generator; KCH-300Ⅱ hydrogen generator;

[0025] Methanol chromatography grade: purity ≥99.90, Tianjin Concord Technology Co., Ltd.;

[0026] 1,2-Dichloroethane: purity ≥99.0, Tianjin Fengchuan Chemical Reagent Technology Co., Ltd.;

[0027] Dimethyl carbonate: purity ≥98.0%, Shanghai Aladdin Biochemical Technology Co., Ltd.;

[0028] 1-Methylpyrazole: standard sample ≥98.0%, San Chemical Technology Co., Ltd.;

[0029] Laboratory synthesis of 1-methylpyrazole samples;

[0030] 1.2 Chromatographic conditions:

[0031] Chromatographic column: SE-54 capillary column (50m×0.25mm×0.25μm), stationary phase: 5% phenyl, 95% dimethylpolysiloxane; vaporization chamber temperature: 220℃; detector temperature: 220℃; column temperature: 90℃; injection volume 1uL; carrier gas: high-purity nitrogen (≥99.99%), carrier gas pressure is 0.14MPa.

[0032] 1.3 Purity analysis method of 1-methylpyrazole

[0033] Step 1, preparation of 1-methylpyrazole standard solution: Use a microsyringe to accurately measure 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, and 0.8 mL of 1-methylpyrazole standard sample into a 10 mL volumetric flask, accurately add 0.5 mL of 1,2-dichloroethane as an internal standard, dilute to the scale with methanol, and shake well to make the volume fractions of 1-methylpyrazole 2%, 3%, 4%, 5%, 6%, 7%, and 8%, respectively;

[0034] Step 2, 1-methylpyrazole sample solution preparation: Take 0.5 mL of 1-methylpyrazole sample into a 10 mL volumetric flask, accurately add 0.5 mL of 1,2-dichloroethane, dilute to the scale with methanol, and shake well;

[0035] Step 3, determination: under chromatographic conditions, after the instrument is stable, sample is injected for determination, first the 1-methylpyrazole standard solution is determined, then the 1-methylpyrazole sample solution is determined, and the peak areas of 1-methylpyrazole and the internal standard 1,2-dichloroethane are recorded respectively;

[0036] Step 4, content calculation: linearly regress the peak area ratio of the 1-methylpyrazole standard sample and the internal standard 1,2-dichloroethane in the solution with the 1-methylpyrazole content to obtain a linear regression equation; substitute the peak area ratio of 1-methylpyrazole and the internal standard 1,2-dichloroethane in the 1-methylpyrazole sample solution into the linear regression equation to obtain the content of 1-methylpyrazole in the 1-methylpyrazole sample solution, and then convert it into the actual content of 1-methylpyrazole in the 1-methylpyrazole sample.

[0037] Example 2 Selection of chromatographic column

[0038] HP-INNOWax, SE-54, and SE-30 capillary columns were selected for comparative tests. The test results showed that the SE-54 capillary column had the best separation effect, fast peak elution, and symmetrical peak shape. The 1-methylpyrazole peak, the main impurity dimethyl carbonate peak, and the solvent methanol peak were all effectively separated. The chromatograms of the 1-methylpyrazole standard sample and the laboratory synthesized 1-methylpyrazole sample are shown in Figure 1. Figure 1 Figure 2 As shown, Figure 1 The characteristic peaks in the middle represent 1-methanol, 2-1,2-dichloroethane, and 3-1-methylpyrazole; Figure 2 The characteristic peaks in the middle represent 1-methanol, 2-dimethyl carbonate, 3-1,2-dichloroethane, and 4-1-methylpyrazole.

[0039] Example 3 Chromatographic column temperature

[0040] Temperature is one of the important operating variables in gas chromatography analysis, which directly affects the selectivity of the chromatographic column, the separation efficiency and the stability of the detector sensitivity. The basic principle of column temperature selection is to shorten the analysis time as much as possible while ensuring that the components are fully separated. Increasing the column temperature can improve the gas phase mass transfer rate and speed up this process, which is beneficial to improving column efficiency. However, the serious impact of increasing the column temperature is that the column selectivity is reduced and the separation effect becomes worse. Therefore, the separation of each component was tested under the conditions of column temperatures of 80°C, 90°C, and 100°C. The results are as follows: Figure 3 As shown, the peak shape of 1-methylpyrazole is asymmetric at 80℃, while the peak shapes of each component are symmetric at 90℃ and 100℃. Therefore, under the premise of ensuring the symmetry and separation degree of the peak shapes of each component, the peak separation effect of each component in gas chromatography is best when the column temperature is 90℃.

[0041] Example 4 Carrier Gas Pressure

[0042] If the carrier gas pressure is too low, the retention time of the sample components in the chromatographic column will be prolonged, and the separation effect of each component will be poor. If the carrier gas pressure is too high, the separation efficiency will be reduced. The carrier gas pressure of 0.12, 0.13, 0.14, and 0.15 MPa was selected for the test. Figure 4 As shown in the figure, the experimental results show that when the carrier gas pressure is 0.12 and 0.13, the components cannot be separated; when the carrier gas pressure is 0.14 and 0.15, the components are well separated, and the peaks are symmetrical. In order not to reduce the separation efficiency, a small carrier gas pressure is selected as much as possible, so the carrier gas pressure of 0.14MPa is selected in this experiment.

[0043] Example 5 Working curve

[0044] Under the optimal chromatographic conditions, 1-methylpyrazole standard solutions in different concentration ranges were analyzed by HPLC. The samples were injected in order from low to high concentrations, and each concentration was injected three times. The standard curve of the internal standard method is shown in the figure below. Figure 5 As shown. Figure 5 It can be seen that the linear range of 1-methylpyrazole is 0.2-0.8 mL, the linear equation is Y=2.6527X-0.251, where the 1-methylpyrazole content is X, the peak area ratio of 1-methylpyrazole to the internal standard 1,2-dichloroethane is Y, and the correlation coefficient r=0.99911.

[0045] Example 6 Separation

[0046] In order to examine whether each component meets the requirements of quantitative analysis, the separation degree (R) between adjacent components is calculated. Generally, when the separation degree R>1.5, it is regarded as a sign that two adjacent peaks can be completely separated. Through the analysis of the experimental results shown in Table 1, it can be seen that each component meets the requirements of quantitative analysis.

[0047] Separation calculation method: R = 2(t2-t1) / (Y1+Y2), where: t1, t2 are the retention time of two adjacent components; Y1, Y2 are the peak bottom widths of the corresponding components.

[0048] Table 1 Separation degree of each component

[0049]

[0050]

[0051] Example 7 Qualitative determination

[0052] This test is qualitatively determined based on the same retention time of the unknown and known components. Considering that the products are mainly dimethyl carbonate and 1-methylpyrazole, 1-methylpyrazole, dimethyl carbonate and internal standard 1,2-dichloroethane and their mixture are analyzed under the selected chromatographic conditions for the consistency of the determination conditions. The results are shown in Table 2.

[0053] Table 2 Qualitative test results

[0054]

[0055] Example 8 Precision Test

[0056] Under chromatographic conditions, different 1-methylpyrazole samples were determined according to the experimental method, and the results are shown in Table 3. As shown in Table 3, the relative standard deviations of the 1-methylpyrazole content in the three samples were 0.4641%, 0.1659%, and 0.0988, respectively, indicating that the precision of this method is good.

[0057] Table 3 Precision test results

[0058]

[0059] Example 9 Spiked Recovery Test

[0060] The accuracy of the results of the quantitative analysis was determined by the spike recovery test. The closer the recovery was to 100%, the higher the accuracy of the method was. Under chromatographic conditions, different 1-methylpyrazole samples were determined by the experimental method, and then a certain amount of 1-methylpyrazole standard samples were added. The 1-methylpyrazole content was determined by the same method. The content difference before and after the addition of the 1-methylpyrazole standard sample was the content of the 1-methylpyrazole standard sample in the sample, and then divided by the actual volume of the sample added to calculate the recovery. The results are shown in Table 2. As shown in Table 2, the spike recovery of 1-methylpyrazole is shown in Table 4, indicating that the accuracy of this method is high.

[0061] Table 4 Spike recovery test results

[0062]

[0063] In summary, the present invention aims at the demand for quantitative analysis of purity detection of products in 1-methylpyrazole synthesis reaction, and carries out research on the construction, verification and detection of impurities of analysis methods based on gas chromatography.

[0064] (1) By comparing the relevant factors that affect gas chromatography analysis, such as the selection of capillary columns, the determination of carrier gas flow rate, column temperature, injector temperature, and detector temperature, the optimal conditions for the purity analysis of 1-methylpyrazole were established. 1-Methylpyrazole and its main impurity, dimethyl carbonate, were efficiently separated, with a separation degree of each substance greater than 1.5 and symmetrical peak shapes.

[0065] (2) 1,2-Dichloroethane was selected as the internal standard, and the internal standard method was used to quantitatively analyze 1-methylpyrazole. The sensitivity, accuracy, and precision of this method met the requirements of high performance gas chromatography for qualitative and quantitative analysis.

[0066] (3) This method is used for quantitative detection of each component in the method of synthesizing 1-methylpyrazole by methylating pyrazole with dimethyl carbonate, and can accurately obtain the purity of the product 1-methylpyrazole.

[0067] The contents not described in detail in the specification of the present invention belong to the prior art known to the professional and technical personnel in the field. Although the illustrative specific embodiments of the present invention are described above to facilitate the understanding of the present invention by the technical personnel in the field, it should be clear that the present invention is not limited to the scope of the specific embodiments. For the ordinary technical personnel in the field, as long as various changes are within the spirit and scope of the present invention defined and determined by the attached claims, these changes are obvious, and all inventions and creations using the concept of the present invention are protected.

Claims

1. A purity analysis method for 1-methylpyrazole, characterized in that: The following steps are involved: Step 1, preparation of 1-methylpyrazole standard solution: Use a microsyringe to accurately measure 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, and 0.8 mL of 1-methylpyrazole standard sample into a 10 mL volumetric flask, accurately add 0.5 mL of 1,2-dichloroethane as an internal standard, dilute to the scale with methanol, and shake well to make the volume fractions of 1-methylpyrazole 2%, 3%, 4%, 5%, 6%, 7%, and 8%, respectively; Step 2, 1-methylpyrazole sample solution preparation: take 0.5mL 1-methylpyrazole sample into a 10mL volumetric flask, accurately add 0.5mL 1,2-dichloroethane, dilute to the scale with methanol, and shake well; Step 3, determination: under chromatographic conditions, after the instrument is stable, sample is injected for determination, first the 1-methylpyrazole standard solution is determined, then the 1-methylpyrazole sample solution is determined, and the peak areas of 1-methylpyrazole and the internal standard 1,2-dichloroethane are recorded respectively; Step 4, content calculation: linearly regress the peak area ratio of the 1-methylpyrazole standard sample and the internal standard 1,2-dichloroethane in the solution with the 1-methylpyrazole content to obtain a linear regression equation; substitute the peak area ratio of 1-methylpyrazole and the internal standard 1,2-dichloroethane in the 1-methylpyrazole sample solution into the linear regression equation to obtain the content of 1-methylpyrazole in the 1-methylpyrazole sample solution, and then convert it into the actual content of 1-methylpyrazole in the 1-methylpyrazole sample; The chromatographic conditions are: chromatographic column: SE-54 capillary chromatographic column 50m×0.25mm, 0.25μm; stationary phase: 5% phenyl, 95% dimethylpolysiloxane; vaporization chamber temperature: 220°C; detector temperature: 220°C; Column temperature: 90°C; injection volume: 1uL; Carrier gas: high purity nitrogen ≥99.99%, carrier gas pressure is 0.14MPa.

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