A method for determining pseudoactivity in cumyl peroxyneodecanoate

Abstract

The invention provides a method for determining pseudoactivity in cumyl peroxide neodecanoate, which relates to the field of detection methods and comprises the following steps: (1) preparation of a standard solution: dissolving a cumyl peroxide standard substance in a solvent to prepare a standard solution; (2) drawing a standard curve: diluting the standard solution with a solvent to different concentration gradients, detecting by HPLC, and drawing a standard curve with the peak area as the ordinate and the concentration as the abscissa; (3) sample processing: dissolving the sample with a solvent to prepare a detection solution; (4) sample detection and analysis: detecting and analyzing the detection solution by HPLC under the same chromatographic conditions to obtain an accurate volume content of pseudoactivity. The determination method of the invention can accurately determine the pseudoactivity component and content in cumyl peroxide neodecanoate, does not require a complicated determination process, has high accuracy, solves the problem that pseudoactivity in cumyl peroxide neodecanoate cannot be detected, and can be widely used in the quality detection of cumyl peroxide neodecanoate products.

Description

Technical Field

[0001] The invention belongs to the field of detection methods, and in particular relates to a method for determining pseudoactivity in cumyl peroxyneodecanoate. Background Art

[0002] Cumyl peroxide neodecanoate (CNP) is a colorless or light yellow free-flowing liquid, mainly used as an initiator for polyvinyl chloride polymerization. Compared with common azo initiators, cumyl peroxide neodecanoate has a small dosage in the polymer polymerization process, is easy to disperse in the polymerization system, has a uniform exothermic reaction during the polymerization, has a higher initiation efficiency, is easy to control, and has excellent product performance. It is a safe, efficient, and stable product quality initiator for polymer synthesis, and has a large market demand.

[0003] At present, the preparation of cumyl peroxyneodecanoate is mainly prepared by using cumyl hydroperoxide and neodecanoyl chloride as reaction raw materials. In order to improve the yield of the product, cumyl hydroperoxide is added in excess, so the obtained product often contains residual raw material cumyl hydroperoxide (CHP), and the pseudoactivity in cumyl peroxyneodecanoate refers to the residual cumyl hydroperoxide in the product.

[0004] The structural formula of cumene hydroperoxide is as follows:

[0005]

[0006] The structural formula of cumyl peroxyneodecanoate is as follows:

[0007]

[0008] From the structural formula, we can see that the structure of cumyl peroxide neodecanoate is similar to cumyl hydroperoxide. At present, the content analysis of CNP and CHP generally adopts the iodine titration method. This method can only detect the total content of CNP and CHP in the product, and cannot accurately analyze the small amount of CHP content in the CNP product.

[0009] Chinese invention patent CN104535675 discloses a method for determining impurities of cumene hydroperoxide, which can be used for the detection of cumene hydroperoxide compounds in raw materials such as dexlansoprazole, and selects siloxane bonded silica gel as the stationary phase, and uses the first mixed solvent of organic solution and alkaline aqueous solution as the mobile phase gradient elution. Chinese invention patent CN113125582 discloses a method for detecting cumene hydroperoxide and its impurities, and 12 impurities including 2-phenyl-2-propanol, acetophenone, cumene, and dicumyl peroxide can be detected by high performance liquid chromatography, and the impurity recovery rate can reach 98.13-103.29%, and the RSD is as low as 0.85-2.7%. However, several detection methods currently disclosed can only separate and detect multiple impurities in drugs such as CHP and dexlansoprazole, or in the process of synthesizing cumene hydroperoxide, without separating and detecting the pseudo-active component CHP in CNP.

[0010] The rapid detection of CHP content in CNP has important practical significance for the quality control of the high-efficiency initiator cumyl peroxyneodecanoate. Summary of the invention

[0011] The invention aims at the problems existing in the prior art and provides a method for determining the pseudo-activity in cumyl peroxide neodecanoate. The method adopts the working principle of high performance liquid chromatography and can accurately determine the pseudo-active components and content in cumyl peroxide neodecanoate without complicated determination process. The method has high accuracy, can efficiently separate CHP in CNP, and can accurately obtain the CHP content. The problem that the pseudo-activity in cumyl peroxide neodecanoate cannot be detected is solved. The method can be widely used in the quality detection of cumyl peroxide neodecanoate products.

[0012] To achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0013] In one aspect, the present invention provides a method for determining pseudoactivity in cumyl peroxyneodecanoate, comprising the steps of:

[0014] (1) Preparation of standard solution: dissolve cumene hydroperoxide standard in a solvent to prepare a standard solution;

[0015] (2) Drawing of standard curve: The standard solution is diluted with solvent to different concentration gradients, and detected by HPLC. The standard curve is drawn with the peak area as the ordinate and the concentration as the abscissa;

[0016] (3) Sample processing: The sample is dissolved in a solvent to form the test solution;

[0017] (4) Sample detection and analysis: The test solution is subjected to HPLC analysis under the same chromatographic conditions to obtain the accurate pseudoactive volume content; according to the formula The pseudo-activity mass content can be obtained, where w is the mass concentration of pseudo-activity in the sample to be tested, in wt%; p is the volume concentration of the diluted sample, in g / L; m is the mass of the sample weighed, in g;

[0018] The chromatographic conditions of the HPLC method are:

[0019] Chromatographic column: C18 column;

[0020] Mobile phase: mixture of water and methanol;

[0021] Elution: isocratic elution;

[0022] Flow rate: 0.5-2.0mL / min;

[0023] Column temperature: 30-50°C;

[0024] Injection volume: 0.1-2.0 μL;

[0025] Detector: UV-visible dual wavelength detector;

[0026] Detection wavelength: 200-220nm;

[0027] Data collection time: 36-120min.

[0028] Preferably, in steps (1)-(3), the solvent is selected from at least one of methanol, ethanol, tetrahydrofuran and acetonitrile.

[0029] More preferably, the solvent is selected from at least one of methanol and acetonitrile.

[0030] More preferably, the solvent is methanol.

[0031] Preferably, the concentration of the standard solution in step (1) is 20-60 g / L.

[0032] Preferably, in step (2), the different concentration gradients are at least 5 concentration gradients between 0.01-10 g / L.

[0033] Preferably, in step (3), the detection solution has a cumene hydroperoxide content of 0-80 wt%.

[0034] Further preferably, the content of cumene hydroperoxide in the detection solution is 0.5-20 wt %.

[0035] Preferably, in step (4), the specification of the chromatographic column is Shimadzu WONDASIL C18-WR 5 μm, 4.6×250 mm.

[0036] Preferably, in step (4), the mobile phase is a mixture of water and methanol, wherein, calculated by volume, water accounts for 0-40% and methanol accounts for 60-100%.

[0037] More preferably, water accounts for 20% and methanol accounts for 80% in the mobile phase.

[0038] Preferably, in step (4), the flow rate is 0.5-2.0 mL / min, the column temperature is 30-50° C., the injection volume is 0.1-2.0 μL, the detection wavelength is 200-220 nm, and the data acquisition time is 36-120 min.

[0039] Further preferably, the flow rate is 0.5-1.5 mL / min, the column temperature is 35-45° C., the injection volume is 0.1-1.0 μL, the detection wavelength is 210-220 nm, and the data acquisition time is 36-60 min.

[0040] More preferably, the flow rate is 1.0 mL / min, the column temperature is 40° C., the injection volume is 0.5 μL, the detection wavelength is 210 nm, and the data acquisition time is 45 min.

[0041] On the other hand, the present invention provides the application of the above-mentioned determination method in the quality detection of cumyl peroxyneodecanoate product.

[0042] Compared with the prior art, the present invention has the following beneficial effects:

[0043] The determination method of the invention can accurately determine the false activity in cumyl peroxide neodecanoate, does not require a complicated determination process, has high accuracy, solves the problem that the false activity in cumyl peroxide neodecanoate cannot be detected, and can be widely used in the quality detection of cumyl peroxide neodecanoate products. BRIEF DESCRIPTION OF THE DRAWINGS

[0044] Figure 1 This is a HPLC graph of cumene hydroperoxide standard solution under the chromatographic conditions of Example 1 of the present invention;

[0045] Figure 2 is an HPLC graph of cumyl peroxyneodecanoate after spike addition under the chromatographic conditions of Example 1 of the present invention;

[0046] Figure 3 It is a standard curve diagram under the chromatographic conditions of Example 1 of the present invention. DETAILED DESCRIPTION

[0047] The following non-limiting examples can enable those skilled in the art to more fully understand the present invention, but do not limit the present invention in any way. The following content is merely an exemplary description of the scope of protection claimed in this application, and those skilled in the art can make various changes and modifications to the invention of this application based on the disclosed content, which should also fall within the scope of protection claimed in this application.

[0048] The present invention is further described below by way of specific examples. The various chemical reagents used in the examples of the present invention are obtained through conventional commercial channels unless otherwise specified. The contents described below are all by mass.

[0049] CHP recovery % = detected CHP concentration / actual CHP concentration in the sample.

[0050] Example 1

[0051] HPLC chromatographic conditions:

[0052] Chromatographic column: C18 chromatographic column (Shimadzu WONDASIL C18-WR 5 μm, 4.6 × 250 mm, filled with high-purity spherical silica gel);

[0053] Flow rate: 1.0 mL / min;

[0054] Column temperature: 40°C;

[0055] Mobile phase: volume ratio, water 20%, methanol 80%;

[0056] Injection volume: 0.5 μL;

[0057] Detector: UV-visible dual wavelength detector;

[0058] Detection wavelength: 210nm;

[0059] Data collection time: 45 minutes.

[0060] Experimental steps:

[0061] (1) Preparation of standard solution: Accurately weigh cumene hydroperoxide standard and dissolve it in methanol to prepare a standard solution with a concentration of 20 g / L for later use;

[0062] (2) Standard curve drawing: The standard solution was diluted with solvent to 6 concentration gradients, and detected by HPLC. The standard curve was drawn with the peak area as the ordinate and the concentration as the abscissa. The curve equation was: y = 1.49729 × 10 6 x+101019,R 2 =0.9994, showing a good linear relationship;

[0063] (3) Sample treatment: Weigh 6 portions of cumyl peroxide neodecanoate samples, 5.0 g (accurate to 0.0001 g) each, add 28 mL of standard solution, dilute to 100 mL with methanol, shake well, and obtain the test solution for use; the cumyl peroxide neodecanoate sample is a pure sample without false activity. After spiked, the concentration of the false active ingredient isopropyl hydrogen peroxide is 5.6 g / L;

[0064] (4) Sample detection and analysis: The test solution was analyzed under the same chromatographic conditions to obtain the accurate pseudo-active volume content. The results are shown in Table 1.

[0065] Table 1

[0066]

[0067]

[0068] Recording chromatograms: Figure 1 It shows that the peak time of CHP is 4.1min. Figure 2 This indicates that CHP is well separated from CNP under this chromatographic condition; Figure 3 This indicates that the standard curve has a good linear relationship, the average recovery rate is 100.47%, close to 1; the relative standard deviation RSD is 0.70%, and this method can be used for the qualitative and / or quantitative detection of CHP in CNP.

[0069] Example 2

[0070] The HPLC chromatographic conditions were the same as those in Example 1.

[0071] The difference from Example 1 is that the CHP content of the sample selected in step (3) is different. Sample processing: weigh 5.0 g (accurate to 0.0001 g) of 1 portion of isopropyl peroxide neodecanoate sample, add 50 mL of standard solution, dilute to 100 ml with methanol, shake well, and obtain the test solution for use; wherein the isopropyl peroxide neodecanoate sample is the same sample as that in Example 1 and does not contain false activity. After the addition of the standard, the concentration of the false active ingredient isopropyl hydrogen peroxide is 10.0 g / L; the remaining steps are the same, the standard curve used is the standard curve of Example 1, and the same sample is measured 5 times and the results are shown in Table 2.

[0072] Table 2

[0073]

[0074] Table 2 shows that the average value of cumyl peroxide neodecanoate with known CHP content was 10.02 g / L and the relative standard deviation RSD was 0.29%, indicating that the method has good precision and can be used for the qualitative and / or quantitative detection of CHP in CNP.

[0075] Example 3

[0076] The HPLC chromatographic conditions were the same as those in Example 1.

[0077] The difference from Example 1 is that the sample selected in step (3) is different. The sample used is the reaction solution of different reaction times during the preparation of cumyl peroxide neodecanoate. Sample treatment: Weigh 5.0 g (accurate to 0.0001 g) of each cumyl peroxide neodecanoate sample and dilute to 100 ml with methanol, shake well, and obtain the test solution. The remaining steps are the same. The standard curve used is the standard curve of Example 1. The volume concentration of the pseudo-active ingredient in the sample is calculated by the standard curve according to the formula: The mass concentration of the pseudo-active ingredient can be calculated. The results are shown in Table 3.

[0078] Table 3

[0079] serial number Sample volume, g / L Measured value, g / L CHP mass fraction / % CNP-reaction 30min 5.0042 3.266 6.53 CNP-reaction 60min 4.9971 3.061 6.13 CNP-reaction 90min 5.1003 2.899 5.68

[0080] Table 3 shows that as the synthesis reaction of cumyl peroxy neodecanoate proceeds, the reactant cumyl hydroperoxide is constantly reduced, and the detection method of the present invention can be used to judge the degree of progress of the synthesis reaction of cumyl peroxy neodecanoate.

[0081] Example 4

[0082] The HPLC chromatographic conditions were the same as those in Example 1.

[0083] The difference from Example 1 is that the cumyl peroxide neodecanoate selected in step (3) is a cumyl peroxide neodecanoate product that has been washed and purified. Sample processing: Weigh 5.0 g (accurate to 0.0001 g) of different cumyl peroxide neodecanoate samples and dilute to 100 ml with methanol, shake well, and obtain the test solution. The remaining steps are the same, and the standard curve used is the standard curve of Example 1. The volume concentration of the pseudo-active ingredient in the sample is calculated by the standard curve, according to the formula: The mass concentration of the pseudo-active ingredient can be calculated. The results are shown in Table 4.

[0084] Table 4

[0085]

[0086]

[0087] Table 4 shows that the residual amount of cumene hydroperoxide in product 2 is less than that in product 1, and the quality of product 2 is better than that of product 1. Therefore, this method can be used to judge the quality of cumyl peroxyneodecanoate products.

[0088] Comparative Example 1

[0089] The isopropyl peroxyneodecanoate sample in Example 3 was detected by conventional method (iodine titration), and the specific steps were based on standard T / CPCIF 0094-2021. The results were 76.09%, 88.64%, and 93.16%, respectively, which were the total contents of CNP and CHP in the reaction solution. The specific content of CHP could not be determined.

[0090] The results show that the CNP pseudo-activity test method of the present invention has high precision, the recovery rate of detected CHP is close to 100%, and cumene hydroperoxide in cumyl peroxyneodecanoate can be well separated.

[0091] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions of the technical solution of the present invention by ordinary technicians in this field do not deviate from the essence and scope of the technical solution of the present invention.

Claims

1. A method for determining pseudoactivity in cumyl peroxyneodecanoate, characterized in that: Includes steps: (1) Preparation of standard solution: Dissolve cumene hydroperoxide standard in solvent to prepare standard solution; (2) Drawing of standard curve: dilute the standard solution with solvent to different concentration gradients, detect it by HPLC, and draw a standard curve with peak area as the ordinate and concentration as the abscissa; (3) Sample processing: The sample is dissolved in a solvent to form the test solution; (4) Sample detection and analysis: The test solution is subjected to HPLC analysis under the same chromatographic conditions to obtain the accurate pseudoactive volume content; according to the formula The pseudo-activity mass content can be obtained, where w is the mass concentration of pseudo-activity in the sample to be tested, in wt%; p is the volume concentration of the diluted sample, in g / L; m is the mass of the sample weighed, in g; The chromatographic conditions of the HPLC method are: Chromatographic column: C18 column; Mobile phase: a mixture of water and methanol, with a volume ratio of water to methanol of 20:80; Elution: isocratic elution; Flow rate: 0.5-2.0mL / min; Column temperature: 30-50°C; Injection volume: 0.1-2.0 μL; Detector: UV-visible dual wavelength detector, detection wavelength 200-220nm; Data collection time: 36-120min.

2. The measuring method according to claim 1, characterized in that The solvent in steps (1) to (3) is at least one selected from methanol, ethanol, tetrahydrofuran and acetonitrile.

3. The measuring method according to claim 2, characterized in that The solvent is methanol.

4. The measuring method according to claim 1, characterized in that In step (1), the concentration of the standard solution is 20-60 g / L.

5. The measuring method according to claim 1, characterized in that In step (2), the different concentration gradients are at least 5 concentration gradients between 0.01-10 g / L.

6. The measuring method according to claim 1, characterized in that In step (3), the cumene hydroperoxide content of the detection solution is 0-80wt%.

7. The measuring method according to claim 1, characterized in that In step (4), the flow rate is 0.5-2.0 mL / min, the column temperature is 30-50° C., the injection volume is 0.1-2.0 μL, the detection wavelength is 200-220 nm, and the data acquisition time is 36-120 min.

8. The measuring method according to claim 7, characterized in that The flow rate was 1.0 mL / min, the column temperature was 40° C., the injection volume was 0.5 μL, the detection wavelength was 210 nm, and the data acquisition time was 45 min.

9. Application of the assay method described in any one of claims 1 to 8 in the quality detection of cumyl peroxyneodecanoate product.

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