Method for detecting 1, 3-bis (3-dimethylaminopropyl) urea and impurities thereof

Abstract

The invention relates to the technical field of substance detection, in particular to a method for detecting 1, 3-bis (3-dimethylaminopropyl) urea and impurities of the 1, 3-bis (3-dimethylaminopropyl) urea. The detection method comprises the following steps: treating a sample to be detected by utilizing an internal standard working solution, then detecting by adopting gas chromatography, and analyzing by adopting an internal standard method, the conditions of the gas chromatography comprise that a CP-Sil 8CB or HP-5 chromatographic column is adopted, the split ratio is (45-55): 1, and the heating procedure comprises the following steps: keeping the temperature at 40-80 DEG C for 2-10 minutes, then heating to 100-110 DEG C, keeping the temperature for 2-10 minutes, then heating to 135-145 DEG C, keeping the temperature for 2-10 minutes, and keeping the temperature at 135-145 DEG C for 2-10 minutes. And then raising the temperature to 260-280 DEG C and keeping the temperature for 2-10 minutes. The detection method can be widely applied, is simple and rapid, has good stability and high accuracy, and can be used for simultaneously detecting the contents of 3-dimethylaminopropyl urea and 1, 3-bis (3-dimethylaminopropyl) urea.

Description

Technical Field

[0001] The present invention relates to the technical field of substance detection, and in particular to a method for detecting 1,3-bis(3-dimethylaminopropyl)urea and its impurities. Background Art

[0002] 1,3-Bis(3-dimethylaminopropyl)urea (CAS No.: 52338-87-1) is referred to as DPU, molecular formula: C 11 H 26 N 4 O, the structural formula is as follows:

[0003]

[0004] 1,3-bis(3-dimethylaminopropyl)urea is widely used, for example, in the pharmaceutical, pesticide, dye, electroplating intermediate, petrochemical, semiconductor manufacturing and polymer industries, and is an important fine organic chemical intermediate. For example, 1,3-bis(3-dimethylaminopropyl)urea can be used to synthesize polyquaternary ammonium salts, which are widely used in daily chemicals, textiles, medicine, water treatment and electroplating. It can be used as a high-performance bactericide and algaecide, slime stripping agent, electroplating additive, excellent conditioner in shampoo products, moisturizer in skin creams, antistatic agent, dust-proof agent and moisturizer in textile products, and mordant in inkjet printing.

[0005] In the prior art, 1,3-bis(3-dimethylaminopropyl)urea is generally obtained by organic synthesis, specifically by reacting urea (CAS No.: 57-13-6) and N,N-dimethyl-1,3-diaminopropane (CAS No.: 109-55-7). However, during the reaction, the impurity 3-dimethylaminopropylurea (CAS No.: 31506-43-1) is formed, and there may be residues of the raw material N,N-dimethyl-1,3-diaminopropane, and the residues of these impurities will affect the subsequent reaction or the performance of 1,3-bis(3-dimethylaminopropyl)urea. Therefore, it is necessary to test the finished product of 1,3-bis(3-dimethylaminopropyl)urea or monitor its reaction process to determine whether the above impurities exist, and it is best to confirm their content.

[0006] In the prior art, high performance liquid chromatography is generally used for determination. For example, EP2657237 A1 reports a high performance liquid method for determining 1,3-bis(3-dimethylaminopropyl)urea, with acetonitrile and phosphate buffer solution as mobile phases, and ultraviolet visible light detectors for detecting 1,3-bis(3-dimethylaminopropyl)urea. However, this method is expensive in terms of instrumentation, and the solvent acetonitrile used is highly toxic, and the phosphate buffer solution is highly corrosive, which is not conducive to the health of the experimenter. At the same time, from the perspective of detection cost, detection simplicity, etc., gas chromatography is more recommended than liquid chromatography. However, there are few documents on the use of gas chromatography to detect 1,3-bis(3-dimethylaminopropyl)urea in the prior art, and the conditions of specific gas chromatography cannot be clearly defined. Therefore, gas chromatography cannot be used to perform qualitative and quantitative detection of 1,3-bis(3-dimethylaminopropyl)urea.

[0007] In view of this, the present invention is proposed. Summary of the invention

[0008] The purpose of the present invention is to provide a method for detecting 1,3-bis(3-dimethylaminopropyl)urea and its impurities. The method can be widely used, is simple and fast, has good stability and high accuracy, and can simultaneously detect the contents of 3-dimethylaminopropylurea and 1,3-bis(3-dimethylaminopropyl)urea.

[0009] The present invention is achieved in that:

[0010] In a first aspect, the present invention provides a method for detecting 1,3-bis(3-dimethylaminopropyl)urea and its impurities, comprising: treating a sample to be tested with an internal standard working solution, then detecting it with gas chromatography, and analyzing it with an internal standard method, wherein the gas chromatography conditions include a CP-Sil 8CB or HP-5 chromatographic column, a split ratio of (45-55):1, and a heating program including: maintaining at 40-80°C for 2-10 min, then heating to 100-110°C at 5-20°C / min and maintaining for 2-10 min, then heating to 135-145°C at 5-20°C / min and maintaining for 2-10 min, and then heating to 260-280°C at 5-20°C / min and maintaining for 2-10 min.

[0011] In an optional embodiment, in the method for detecting 3-bis(3-dimethylaminopropyl)urea and its impurities, the solvent forming the internal standard working solution is selected from C1-C3 alcohol solvents; preferably any one of methanol, ethanol and isopropanol.

[0012] In an optional embodiment, in the method for detecting 3-bis(3-dimethylaminopropyl)urea and its impurities, the internal standard in the internal standard working solution is bis(3-dimethylaminopropyl)aminoisopropanol and / or n-decanol.

[0013] In an optional embodiment, in the method for detecting 3-bis(3-dimethylaminopropyl)urea and its impurities, the concentration of the internal standard working solution is 0.05-1.00 mg / mL.

[0014] In an optional embodiment, the method for detecting 3-bis(3-dimethylaminopropyl)urea and its impurities, the gas chromatography conditions also include: an injection temperature of 300-340°C, an injection volume of 1-3 μL, and a detector temperature of 300-340°C.

[0015] In an optional embodiment, the method for detecting 3-bis(3-dimethylaminopropyl)urea and its impurities further comprises: preparing a standard solution, and detecting the standard solution by gas chromatography;

[0016] Preferably, the method comprises: mixing the standard with an internal standard working solution.

[0017] In an optional embodiment, in the method for detecting 3-bis(3-dimethylaminopropyl)urea and its impurities, the concentration of the standard solution is 0.05 mg / mL-4.00 mg / mL.

[0018] In an optional embodiment, a method for detecting 3-bis(3-dimethylaminopropyl)urea and its impurities, the 1,3-bis(3-dimethylaminopropyl)urea and its impurities include 1,3-bis(3-dimethylaminopropyl)urea and N,N-dimethyl-1,3-diaminopropane and / or 3-dimethylaminopropyl urea.

[0019] In an optional embodiment, the method for detecting 3-bis(3-dimethylaminopropyl)urea and its impurities uses the following formula to analyze the gas chromatography test results:

[0020] in,

[0021] W represents: the mass percentage of 1,3-bis(3-dimethylaminopropyl)urea;

[0022] S i Indicates: peak area of ​​1,3-bis(3-dimethylaminopropyl)urea;

[0023] S 0 Represents the peak area of ​​the internal standard in the internal standard working solution;

[0024] C 0 Indicates the concentration of the internal standard working solution, in mg / mL;

[0025] f i Indicates: relative correction factor of 1,3-bis(3-dimethylaminopropyl)urea;

[0026] M represents the weight of the sample to be tested, unit: g;

[0027] Calculation of relative correction factor of 1,3-bis(3-dimethylaminopropyl)urea:

[0028] f i =K;

[0029] The K value represents: the slope of the standard curve drawn with the ratio of the peak area of ​​1,3-bis(3-dimethylaminopropyl)urea to the peak area of ​​the internal standard in the internal standard working solution as the horizontal coordinate; the ratio of the mass of 1,3-bis(3-dimethylaminopropyl)urea to the mass of the internal standard in the internal standard working solution as the vertical coordinate.

[0030] In an optional embodiment, in the method for detecting 3-bis(3-dimethylaminopropyl)urea and its impurities, the sample to be tested treated with the internal standard working solution is filtered before being detected by gas chromatography.

[0031] The present invention has the following beneficial effects: by using a gas chromatograph to detect the sample to be tested, it can effectively ensure that 1,3-bis(3-dimethylaminopropyl)urea and impurities 3-dimethylaminopropyl urea and N,N-dimethyl-1,3-diaminopropane are effectively separated, and the peak shape is excellent. The sample to be tested is diluted with an internal standard working solution, and then under the gas chromatography conditions provided in the embodiment of the present invention, it can be ensured that 1,3-bis(3-dimethylaminopropyl)urea with a boiling point of 377.8±27.0°C is completely vaporized, the gas phase system has no residue, and 3-dimethylaminopropyl urea and N,N-dimethyl-1,3-diaminopropane with low content can be detected. The present invention can realize the separation, qualitative and quantitative analysis of 3-dimethylaminopropyl urea, N,N-dimethyl-1,3-diaminopropane and 1,3-bis(3-dimethylaminopropyl)urea at the same time, and provides a method for improving the production process of 1,3-bis(3-dimethylaminopropyl)urea. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for use in the embodiments are briefly introduced below. It should be understood that the following drawings only show certain embodiments of the present invention and therefore should not be regarded as limiting the scope. For ordinary technicians in this field, other related drawings can be obtained based on these drawings without creative work.

[0033] Figure 1 The gas chromatogram of the finished sample A1 to be tested provided in an embodiment of the present invention in CP-Sil 8CB;

[0034] Figure 2The gas chromatogram of the crude sample B1 to be tested provided in an embodiment of the present invention in CP-Sil 8CB;

[0035] Figure 3 A gas chromatogram of crude sample B1 to be tested using a CAM chromatographic column is provided for comparative example 1 of the present invention;

[0036] Figure 4 A gas chromatogram of crude sample B1 to be tested using an HP-5 chromatographic column is provided for comparative example 1 of the present invention;

[0037] Figure 5 A liquid chromatogram of the finished sample A1 to be tested using the high performance liquid chromatography method provided in EP2657237 A1 is provided for comparative example 2 of the present invention;

[0038] Figure 6 Provided for comparative example 3 of the present invention are gas chromatograms of the finished sample A1 to be tested at split ratios of 5:1 and 50:1 under CP-Sil 8CB;

[0039] Figure 7 This is the chromatogram of comparative example 4 of the present invention: the starting temperature is 70°C and maintained for 2 minutes; the temperature is increased to 105°C at 20°C / min and maintained for 5 minutes; the temperature is increased to 270°C at 15°C / min; and maintained for 5 minutes;

[0040] Figure 8 This is the chromatogram of comparative example 4 of the present invention: the starting temperature is 70°C and maintained for 2 minutes; the temperature is increased to 105°C at 20°C / min and maintained for 5 minutes; the temperature is increased to 140°C at 8°C / min and maintained for 5 minutes; the temperature is increased to 270°C at 15°C / min and maintained for 5 minutes;

[0041] Fig. 9 This is a gas chromatogram provided for Comparative Example 5 of the present invention. DETAILED DESCRIPTION

[0042] In order to make the purpose, technical scheme and advantages of the embodiments of the present invention clearer, the technical scheme in the embodiments of the present invention will be described clearly and completely below. If the specific conditions are not specified in the embodiments, they are carried out according to conventional conditions or conditions recommended by the manufacturer. If the manufacturer of the reagents or instruments used is not specified, they are all conventional products that can be purchased commercially.

[0043] At present, the mainstream method for detecting 1,3-bis(3-dimethylaminopropyl)urea is high performance liquid chromatography, and gas chromatography is less popular. The inventors found that 1,3-bis(3-dimethylaminopropyl)urea has a high boiling point and is difficult to completely vaporize. Therefore, it is not convenient to use gas chromatography for detection. If solvent dilution is used during the detection process, it will make it difficult to detect low-content 3-dimethylaminopropyl urea and N,N-dimethyl-1,3-diaminopropane, affecting the accuracy of the detection. On the other hand, 1,3-bis(3-dimethylaminopropyl)urea and 3-dimethylaminopropyl urea have high polarity, and the peak shape is easy to cause tailing, especially when the peak area of ​​3-dimethylaminopropyl urea is small, which also causes inaccurate detection results.

[0044] In order to overcome the above technical problems, the embodiment of the present invention provides a method for detecting 1,3-bis(3-dimethylaminopropyl)urea and its impurities to fill the gap in the determination of 3-dimethylaminopropyl urea and 1,3-bis(3-dimethylaminopropyl)urea by gas chromatography. The detection method can be applied to the production process of 1,3-bis(3-dimethylaminopropyl)urea to achieve real-time monitoring of 1,3-bis(3-dimethylaminopropyl)urea and its impurities, and can also be directly applied to the detection of 1,3-bis(3-dimethylaminopropyl)urea finished products to achieve the detection of the final finished product.

[0045] Specifically, the detection process is as follows:

[0046] (1) Prepare internal standard working solution;

[0047] The internal standard substance is mixed with a solvent to form an internal standard working solution, wherein the concentration of the internal standard working solution is 0.05-1.00 mg / mL, for example, any value between 0.05 mg / mL, 0.06 mg / mL, 0.07 mg / mL, 0.08 mg / mL, 0.09 mg / mL and 1.00 mg / mL.

[0048] The internal standard in the internal standard working solution is bis(3-dimethylaminopropyl)aminoisopropanol and / or decanol. The solvent is selected from C1-C3 alcohol solvents; preferably any one of methanol, ethanol and isopropanol. If other solvents are used, the detection may be inaccurate or even impossible to detect. For example, if toluene is used, the peak of toluene overlaps with the peak of impurities, and then it cannot be effectively detected. If chloromethane such as dichloromethane is used, chloromethane will react with 3-dimethylaminopropyl urea, which will also lead to undetectable results. Selecting the solvent provided in the embodiment of the present invention can achieve effective and accurate detection.

[0049] (2) Preparation of standard solution:

[0050] The standards of 1,3-bis(3-dimethylaminopropyl)urea and N,N-dimethyl-1,3-diaminopropane and / or 3-dimethylaminopropylurea were mixed with the above internal standard working solution to form the corresponding standard stock solutions, and stored in the dark.

[0051] Use a pipette to draw different volumes of standard stock solution, dilute it with the above internal standard working solution to prepare standard substance working solutions of different concentrations, ranging from 0.05 mg / mL to 4.00 mg / mL, and store in a dark place.

[0052] (3) Sample processing;

[0053] Accurately weigh 0.0020 g of sample (accurate to 0.0001 g), put it into a 10 mL volumetric flask, dilute it to volume with the internal standard working solution, and shake it evenly.

[0054] (4) Detection and analysis;

[0055] The samples of step (2) and step (3) were respectively filtered through a 0.22 μm polytetrafluoroethylene membrane and introduced into a gas chromatograph for analysis.

[0056] Among them, the gas chromatography conditions include CP-Sil 8CB or HP-5 chromatographic columns with dimensions of 30m×0.32mm×1.00μm or equivalent;

[0057] The heating program includes: 40-80°C for 2-10min, then heating to 100-110°C at 5-20°C / min for 2-10min, then heating to 135-145°C at 5-20°C / min for 2-10min, then heating to 260-280°C at 5-20°C / min for 2-10min; for example, 40-80°C for 2-10min, heating to 105°C at 20°C / min, holding for 2-10min, heating to 140°C at 8°C / min, holding for 2-10min; heating to 270°C at 15°C / min, holding for 2-10min;

[0058] The split ratio is (45-55):1, the injection temperature is 300-340°C, the injection volume is 1-3 μL, and the detector temperature is 300-340°C.

[0059] The above conditions can be used to accurately perform the test. If the conditions are changed, such as changing the selection of the chromatographic column or changing the heating program, the test results will be inaccurate.

[0060] Then the internal standard method is used for analysis. Specifically, the gas chromatography test results are analyzed using the following formula:

[0061] in,

[0062] W represents: the mass percentage of 1,3-bis(3-dimethylaminopropyl)urea;

[0063] S i Indicates: peak area of ​​1,3-bis(3-dimethylaminopropyl)urea;

[0064] S 0 Represents the peak area of ​​the internal standard in the internal standard working solution;

[0065] C 0 Indicates the concentration of the internal standard working solution, in mg / mL;

[0066] f i Indicates: relative correction factor of 1,3-bis(3-dimethylaminopropyl)urea;

[0067] M represents the weight of the sample to be tested, unit: g;

[0068] Calculation of relative correction factor of 1,3-bis(3-dimethylaminopropyl)urea:

[0069] f i =K;

[0070] The K value represents: the slope of the standard curve drawn with the ratio of the peak area of ​​1,3-bis(3-dimethylaminopropyl)urea to the peak area of ​​the internal standard in the internal standard working solution as the horizontal coordinate; the ratio of the mass of 1,3-bis(3-dimethylaminopropyl)urea to the mass of the internal standard in the internal standard working solution as the vertical coordinate.

[0071] The relative correction factor calculation method for 3-dimethylaminopropyl urea is the same as that for 1,3-bis(3-dimethylaminopropyl)urea.

[0072] The features and performance of the present invention are further described in detail below in conjunction with the embodiments.

[0073] Example 1

[0074] This embodiment provides a method for detecting a finished product of 1,3-bis(3-dimethylaminopropyl)urea, comprising:

[0075] Samples: 1,3-bis(3-dimethylaminopropyl)urea (Aladdin standard product purity 97.0%), 3-dimethylaminopropyl urea (Hangzhou Moku Biotechnology Co., Ltd. purity 98.0%), N,N-dimethyl-1,3-diaminopropane (Aladdin purity 99.0%), sample to be tested - finished product of 1,3-bis(3-dimethylaminopropyl)urea (Meside (Jilin) ​​New Materials Co., Ltd.).

[0076] Gas chromatograph (Agilent 7820A); 0.22 μm polytetrafluoroethylene membrane filter (Jinteng Company); electronic balance (Changzhou Lucky Electronic Equipment Co., Ltd.); volumetric flasks, pipettes and transfer pipettes (Grade A, various specifications).

[0077] (1) Preparation of methanol stock solution of n-decanol: Accurately weigh n-decanol (accurate to 0.0001 g), use methanol as solvent, accurately prepare a methanol stock solution of n-decanol with a concentration of 0.25 mg / mL, and store in the dark.

[0078] (2) Preparation of standard stock solution: Accurately weigh each standard substance (accurate to 0.0001 g), dilute to volume with n-decyl methanol stock solution, prepare a standard stock solution with a concentration of 1.00 mg / mL, and store in a dark place.

[0079] Preparation of standard working solution: Use a pipette to draw different volumes of standard stock solution, make up to volume with methanol stock solution of n-decanol, prepare standard substance working solutions of different concentrations, including 0.06 mg / mL, 0.12 mg / mL, 0.25 mg / mL, 0.50 mg / mL, 1.00 mg / mL, 2.00 mg / mL, and 4.00 mg / mL, and store in a dark place.

[0080] During the test, the sample is filtered and fed into the gas chromatograph for detection and analysis.

[0081] The gas chromatogram was analyzed and processed, and a standard curve was established with the ratio of the peak area of ​​each standard substance to the peak area of ​​n-decanol as the abscissa and the ratio of the mass of each standard substance to the peak mass of n-decanol as the ordinate.

[0082] 1,3-bis(3-dimethylaminopropyl)urea standard curve: Y=3.9188X;

[0083] 3-Dimethylaminopropylurea standard curve: Y=3.5789X;

[0084] N,N-dimethyl-1,3-diaminopropane standard curve: Y=1.0768X;

[0085] The linear range and correlation coefficient (r) of the three standards are shown in Table 1.

[0086] Table 1 Linear range and correlation coefficient (r) of standard products

[0087] sequence Target Linear range (mg / mL) <![CDATA[R 2 ]]> 1 1,3-Bis(3-dimethylaminopropyl)urea 0.06-4.00 0.9993 2 3-Dimethylaminopropyl urea 0.06-4.00 0.9996 3 N,N-Dimethyl-1,3-diaminopropane 0.06-4.00 0.9997

[0088] (3) Accurately weigh 0.0020 g of the sample to be tested (accurate to 0.0001 g) (select 4 samples from the same batch for testing) and put them into a 10 mL volumetric flask. Make up to volume with the methanol stock solution of n-decanol, shake well, take a sample and filter it through a 0.22 μm polytetrafluoroethylene filter. Then, inject it into the gas chromatograph for detection and analysis.

[0089] The gas chromatograph detection conditions are:

[0090] Capillary column: CP-Sil 8CB capillary column, size 30m×0.32mm×1.00μm or equivalent;

[0091] Program temperature rise: Initial temperature: 70℃, hold for 5 min, increase the temperature to 105℃ at 20℃ / min, hold for 5 min, increase the temperature to 140℃ at 8℃ / min, hold for 10 min; increase the temperature to 270℃ at 15℃ / min, hold for 10 min;

[0092] Inlet temperature: 320°C; split ratio: 50:1; injection volume: 1 μL; detector temperature: 320°C.

[0093] The test results of the sample to be tested (sample number A1 below) are shown in Figure 1 .

[0094] The gas chromatogram of the sample to be tested is analyzed and processed, and the ratio of the peak area of ​​each standard substance in the sample to the peak area of ​​n-decanol is substituted into the calculation formula to obtain the mass percentage of each standard substance in the sample.

[0095] in,

[0096] W represents: the mass percentage of 1,3-bis(3-dimethylaminopropyl)urea;

[0097] S i Indicates: peak area of ​​1,3-bis(3-dimethylaminopropyl)urea;

[0098] S 0 Represents the peak area of ​​the internal standard in the internal standard working solution;

[0099] C 0 Indicates the concentration of the internal standard working solution, in mg / mL;

[0100] f i Indicates: relative correction factor of 1,3-bis(3-dimethylaminopropyl)urea;

[0101] M represents the weight of the sample to be tested, unit: g;

[0102] Calculation of relative correction factor of 1,3-bis(3-dimethylaminopropyl)urea:

[0103] f i =K

[0104] The K value represents: the slope of the standard curve drawn with the ratio of the peak area of ​​1,3-bis(3-dimethylaminopropyl)urea to the peak area of ​​the internal standard in the internal standard working solution as the horizontal coordinate; the ratio of the mass of 1,3-bis(3-dimethylaminopropyl)urea to the mass of the internal standard in the internal standard working solution as the vertical coordinate.

[0105] The relative correction factor calculation method for 3-dimethylaminopropyl urea is the same as that for 1,3-bis(3-dimethylaminopropyl)urea.

[0106] The calculation results are shown in Table 2.

[0107] Table 2 Gas chromatography detection of 1,3-bis (3-dimethylaminopropyl) urea finished product content

[0108]

[0109] Reference example 1

[0110] The same sample to be tested was tested with reference to the high performance liquid chromatography method provided in EP2657237 A1, and the test results are shown in Table 3.

[0111] Table 3 Liquid chromatography detection of 1,3-bis (3-dimethylaminopropyl) urea finished product content

[0112] Serial number serial number 1,3-Bis(3-dimethylaminopropyl)urea content (%) 1 A1 94.98 2 A2 95.11 3 A3 95.61 4 A4 95.97 5 Aladdin Standard 97.89

[0113] According to the test results of Example 1 and Reference Example 1, for the finished 1,3-bis(3-dimethylaminopropyl)urea, the 1,3-bis(3-dimethylaminopropyl)urea content determined by the gas chromatography method provided by the present invention and the high performance liquid chromatography method provided by patent EP2657237 A1 are basically consistent, and the data are accurate.

[0114] Example 2

[0115] This embodiment provides a method for detecting a crude 1,3-bis(3-dimethylaminopropyl)urea product, comprising:

[0116] Sample to be tested: Meside (Jilin) ​​New Materials Co., Ltd.

[0117] The detection method is basically the same as that in Example 1, with the following differences:

[0118] Accurately weigh 0.0020 g of the sample to be tested (accurate to 0.0001 g) (select 20 samples from the same batch for testing) and put it into a 10 mL volumetric flask. Make up to volume with the methanol stock solution of n-decanol, shake well, take a sample and pass it through a 0.22 μm polytetrafluoroethylene filter membrane, and inject it into the gas chromatograph for analysis.

[0119] The test results of the sample to be tested (sample number B1 below) are shown in Figure 2 .

[0120] Then, the gas chromatogram of the sample to be tested is analyzed and processed, and the ratio of the peak area of ​​each standard substance of the sample to be tested to the peak area of ​​1-decanol is substituted into the calculation formula to obtain the mass percentage of each standard substance in the sample. The calculation results are shown in Table 4.

[0121] Table 4 Gas chromatography detection of 1,3-bis (3-dimethylaminopropyl) urea crude content

[0122]

[0123]

[0124] Reference example 2

[0125] The same sample to be tested was tested with reference to the high performance liquid chromatography method provided in EP2657237 A1, and the test results are shown in Table 5.

[0126] Table 5 Liquid chromatography detection of 1,3-bis (3-dimethylaminopropyl) urea crude content

[0127]

[0128]

[0129] According to the test results of Example 2 and Reference Example 2, for the finished 1,3-bis(3-dimethylaminopropyl)urea, the 1,3-bis(3-dimethylaminopropyl)urea content determined by the gas chromatography method provided by the present invention and the high performance liquid chromatography method provided by patent EP2657237 A1 are basically consistent, and the data are accurate.

[0130] Verification Example 1—Testing the Separation Precision and Recovery

[0131] This verification example analyzes the precision and recovery rate of detection and separation using the present invention (specific test conditions are the same as in Example 1).

[0132] The spike recovery experiment was carried out with pure 1,3-bis(3-dimethylaminopropyl)urea as the sample matrix. The addition levels of 1,3-bis(3-dimethylaminopropyl)urea, 3-dimethylaminopropylurea and N,N-dimethyl-1,3-diaminopropane were mg / mL. The pretreatment and instrument analysis were carried out according to the embodiment of the present invention. Each level was repeated 8 times, and the average recovery rate could reach more than 94%, and the relative standard deviation was less than 5%, as shown in Table 6.

[0133] Table 6 Average recovery and relative standard deviation of each standard substance

[0134]

[0135]

[0136] Verification Example 2—Maximum Concentration of Completely Vaporized 1,3-Bis(3-dimethylaminopropyl)urea

[0137] Using methanol as solvent, the 1,3-bis(3-dimethylaminopropyl)urea standard (97%) was investigated under fixed gas phase conditions (conditions refer to Example 1), and the content of 1,3-bis(3-dimethylaminopropyl)urea at different concentrations was calculated by area normalization method to confirm the maximum concentration at which 1,3-bis(3-dimethylaminopropyl)urea can be completely vaporized, see Table 7.

[0138] Table 7 Content of 1,3-bis(3-dimethylaminopropyl)urea standard at different concentrations

[0139] Serial number 1,3-Bis(3-dimethylaminopropyl)urea(mg / mL) 1,3-Bis(3-dimethylaminopropyl)urea(%) 1 10 81.29 2 8 92.46 3 6 95.28 4 5 96.54 5 4 97.12 6 2 97.23 7 1 97.34

[0140] It can be seen from Table 7 that the maximum concentration at which 1,3-bis(3-dimethylaminopropyl)urea can be completely vaporized is 4 mg / mL.

[0141] Comparative Example 1

[0142] Referring to the gas chromatography conditions provided in Example 1, different types of chromatographic columns were selected for detection, and the sample to be tested was B1. The peak shapes of 3-dimethylaminopropyl urea, 1,3-bis(3-dimethylaminopropyl)urea and N,N-dimethyl-1,3-diaminopropane were examined. Figure 2-Figure 4 . Figure 2 Among them, N,N-dimethyl-1,3-diaminopropane: 5.84min; 3-dimethylaminopropyl urea: 23.11min; 1,3-bis(3-dimethylaminopropyl)urea: 27.66min. Figure 3 Medium N,N-dimethyl-1,3-diaminopropane: 3.75min. Figure 4N,N-dimethyl-1,3-diaminopropane: 5.84min; 3-dimethylaminopropyl urea: 23.11min; 1,3-bis(3-dimethylaminopropyl)urea: 27.66min.

[0143] according to Figure 2-Figure 4 It can be seen that (1) due to the low upper temperature limit of the CAM column, at the highest temperature of the column, 3-dimethylaminopropyl urea and 1,3-bis(3-dimethylaminopropyl) urea did not emit peaks, and N,N-dimethyl-1,3-diaminopropane had peak tailing.

[0144] (2) Under the HP-5 column, 3-dimethylaminopropyl urea, 1,3-bis(3-dimethylaminopropyl) urea and N,N-dimethyl-1,3-diaminopropane all eluted as peaks, but 3-dimethylaminopropyl urea and N,N-dimethyl-1,3-diaminopropane showed peak tailing, and the peak area response value of 3-dimethylaminopropyl urea was also relatively small.

[0145] (3) On the CP-Sil 8CB column, 3-dimethylaminopropyl urea, 1,3-bis(3-dimethylaminopropyl) urea and N,N-dimethyl-1,3-diaminopropane had the best peak shapes, and the peak area response value of 3-dimethylaminopropyl urea with a lower content was also higher.

[0146] Comparative Example 2

[0147] The finished product A1 was tested according to the HPLC method provided in EP2657237 A1. The results are shown in Figure 5 . Figure 5 Medium 1,3-bis(3-dimethylaminopropyl)urea: 8.18min.

[0148] Under the high performance liquid chromatography method, 1,3-bis(3-dimethylaminopropyl)urea has a peak. Since EP2657237A1 does not detect 3-dimethylaminopropyl urea and N,N-dimethyl-1,3-diaminopropane, the high performance liquid chromatography method is temporarily unable to detect 3-dimethylaminopropyl urea and N,N-dimethyl-1,3-diaminopropane in the crude product.

[0149] Comparative Example 3

[0150] Referring to the gas chromatography conditions provided in Example 1, a CP-Sil 8CB column was selected, and different splits were selected for testing. The sample to be tested was the A1 sample of Comparative Example 1. Figure 6 . Figure 6 N,N-dimethyl-1,3-diaminopropane: 5.84min; 3-dimethylaminopropyl urea: 23.11min; 1,3-bis(3-dimethylaminopropyl)urea: 27.66min.

[0151] according to Figure 6 It can be seen that at a split ratio of 5:1, the baseline signal difference near 1,3-bis(3-dimethylaminopropyl)urea is large, and the peak area reproducibility is poor; at a split ratio of 50:1, the baseline near 1,3-bis(3-dimethylaminopropyl)urea is stable, and the peak area reproducibility is good.

[0152] Comparative Example 4

[0153] Referring to the gas chromatography conditions provided in Example 1, a CP-Sil 8CB column was selected, the split ratio was 50:1, and different program heating was selected to conduct the test. The sample to be tested was the A1 sample of Comparative Example 1. The results are shown in Figure 7-Figure 8 . Figure 7 n-Decanol and impurities co-elute: 14.80min. Figure 8 n-Decanol: 19.50min; impurities: 19.78min.

[0154] Figure 7 Chromatogram of starting temperature at 70°C and maintaining for 2 min; heating to 105°C at 20°C / min and maintaining for 5 min; heating to 270°C at 15°C / min and maintaining for 5 min.

[0155] Figure 8 The chromatogram is as follows: starting temperature at 70°C and maintaining for 2 minutes; heating to 105°C at 20°C / min and maintaining for 5 minutes; heating to 140°C at 8°C / min and maintaining for 5 minutes; heating to 270°C at 15°C / min and maintaining for 5 minutes.

[0156] Depend on Figure 7 , Figure 8 It can be seen that by adjusting the programmed temperature conditions, the internal standard n-decanol and impurities can be effectively separated to ensure the accuracy of quantitative analysis.

[0157] Comparative Example 5

[0158] Referring to the gas chromatography conditions provided in Example 1, the A1 sample in Comparative Example 1 was used as the sample to be tested, and different solvents were selected as the solvents of the internal standard working solution, specifically toluene, methanol and ethanol for detection. The chromatogram with toluene as the solvent is shown in Fig. 9 The chromatogram with methanol as solvent is shown in Figure 1 . Fig. 9 The toluene impurity peak overlaps with N,N-dimethyl-1,3-diaminopropane (retention time 5.51 min).

[0159] according to Fig. 9It can be seen that although toluene has stronger solubility, the peak of toluene impurity overlaps with N,N-dimethyl-1,3-diaminopropane and cannot be separated; methanol is selected as the solvent. On the one hand, methanol is miscible with various substances and there is no interference in the peak. On the other hand, methanol forms an azeotrope with 1,3-bis(3-dimethylaminopropyl)urea, and 1,3-bis(3-dimethylaminopropyl)urea is easier to vaporize.

[0160] In summary, the embodiment of the present invention provides a method for detecting 1,3-bis(3-dimethylaminopropyl)urea and its impurities. The samples to be tested include 1,3-bis(3-dimethylaminopropyl)urea finished products and 1,3-bis(3-dimethylaminopropyl)urea crude products or intermediates containing N,N-dimethyl-1,3-diaminopropane and 3-dimethylaminopropyl urea. The detection method provided by the embodiment of the present invention can achieve the separation of 3-dimethylaminopropyl urea, 1,3-bis(3-dimethylaminopropyl)urea and N,N-dimethyl-1,3-diaminopropane, and the peak shape of each substance is good. The above method provided by the embodiment of the present invention solves the problems of separation, qualitative and quantitative analysis of 3-dimethylaminopropyl urea, 1,3-bis(3-dimethylaminopropyl)urea and N,N-dimethyl-1,3-diaminopropane by gas chromatography, and can provide a detection method for the improvement of the production process of 1,3-bis(3-dimethylaminopropyl)urea. The detection method provided by the present invention has the advantages of being widely applicable, simple and fast, having good stability, high accuracy, convenient calculation method, good repeatability and good recovery rate.

[0161] Specifically, compared with the prior art, the detection method provided by the embodiment of the present invention has the following beneficial effects:

[0162] (1) The solution provided by the embodiment of the present invention fills the blank of simultaneous determination of 3-dimethylaminopropyl urea, 1,3-bis(3-dimethylaminopropyl)urea and N,N-dimethyl-1,3-diaminopropane by gas chromatography, ensuring that the high-boiling-point 1,3-bis(3-dimethylaminopropyl)urea can be completely vaporized at the injection port, and selecting a specific chromatographic column to ensure that 3-dimethylaminopropyl urea, 1,3-bis(3-dimethylaminopropyl)urea and N,N-dimethyl-1,3-diaminopropane can be completely separated and have a good peak shape. Among them, the preferred chromatographic column CP-Sil 8CB has a higher response value for 3-dimethylaminopropyl urea than HP-5, ensuring the detection of low-content 3-dimethylaminopropyl urea;

[0163] (2) The detection method provided in the embodiment of the present invention uses low-toxic, non-corrosive solvents, which are health-friendly to the experimenters. Inexpensive gas chromatographs are more widely used than high-performance liquid chromatographs, which lowers the threshold of the detection method. Using bis(3-dimethylaminopropyl)aminoisopropanol and n-decanol as internal standards can ensure good compatibility with various standard substances and no interference, and achieve rapid and accurate qualitative and quantitative determination; the sample recovery rate is greater than 94%, and the relative standard deviation is less than 5%.

[0164] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A method for detecting 1,3-bis(3-dimethylaminopropyl)urea and its impurities, characterized in that: include: The sample to be tested is treated with an internal standard working solution, and then detected by gas chromatography and analyzed by an internal standard method, wherein the gas chromatography conditions include a CP-Sil 8CB or HP-5 chromatographic column, a split ratio of (45-55):1, and a heating program including: 40-80°C for 2-10 minutes, then heating to 100-110°C at 5-20°C / min for 2-10 minutes, then heating to 135-145°C at 5-20°C / min for 2-10 minutes, and then heating to 260-280°C at 5-20°C / min for 2-10 minutes.

2. The method for detecting 1,3-bis(3-dimethylaminopropyl)urea and its impurities according to claim 1, characterized in that: The solvent for forming the internal standard working solution is selected from C1-C3 alcohol solvents; preferably any one of methanol, ethanol and isopropanol.

3. The method for detecting 1,3-bis(3-dimethylaminopropyl)urea and its impurities according to claim 1, characterized in that: The internal standard substance in the internal standard working solution is bis(3-dimethylaminopropyl)aminoisopropanol and / or n-decanol.

4. The method for detecting 1,3-bis(3-dimethylaminopropyl)urea and its impurities according to any one of claims 1 to 3, characterized in that: The concentration of the internal standard working solution is 0.05-1.00 mg / mL.

5. The method for detecting 1,3-bis(3-dimethylaminopropyl)urea and its impurities according to claim 1, characterized in that: The gas chromatography conditions also include: injection temperature of 300-340°C, injection volume of 1-3 μL, and detector temperature of 300-340°C.

6. The method for detecting 1,3-bis(3-dimethylaminopropyl)urea and its impurities according to claim 1, characterized in that: Also includes: preparing a standard solution, and subjecting the standard solution to gas chromatography for detection; Preferably, the method comprises: mixing the standard with an internal standard working solution.

7. The method for detecting 1,3-bis(3-dimethylaminopropyl)urea and its impurities according to claim 6, characterized in that: The concentration of the standard solution is 0.05 mg / mL-4.00 mg / mL.

8. The method for detecting 1,3-bis(3-dimethylaminopropyl)urea and its impurities according to claim 1, characterized in that: The 1,3-bis(3-dimethylaminopropyl)urea and its impurities include 1,3-bis(3-dimethylaminopropyl)urea and N,N-dimethyl-1,3-diaminopropane and / or 3-dimethylaminopropyl urea.

9. The method for detecting 1,3-bis(3-dimethylaminopropyl)urea and its impurities according to claim 1, characterized in that: The following formula is used to analyze the gas chromatography test results: in, W represents: the mass percentage of 1,3-bis(3-dimethylaminopropyl)urea; S i Indicates: peak area of ​​1,3-bis(3-dimethylaminopropyl)urea; S0 represents the peak area of ​​the internal standard in the internal standard working solution; C0 represents the concentration of the internal standard working solution, in mg / mL; f i Indicates: relative correction factor of 1,3-bis(3-dimethylaminopropyl)urea; M represents the weight of the sample to be tested, unit: g; Calculation of relative correction factor of 1,3-bis(3-dimethylaminopropyl)urea: f i =K; The K value represents: the slope of the standard curve drawn with the ratio of the peak area of ​​1,3-bis(3-dimethylaminopropyl)urea to the peak area of ​​the internal standard in the internal standard working solution as the horizontal coordinate; the ratio of the mass of 1,3-bis(3-dimethylaminopropyl)urea to the mass of the internal standard in the internal standard working solution as the vertical coordinate.

10. The method for detecting 1,3-bis(3-dimethylaminopropyl)urea and its impurities according to claim 1, characterized in that: Before detection by gas chromatography, the sample to be tested treated with the internal standard working solution is filtered.

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