Method for detecting various aromatic ether compounds in sample

Abstract

The invention provides a method for qualitatively and / or quantitatively detecting aromatic ether compounds in a sample, which comprises the following steps: detecting the sample by using liquid chromatography, and measuring the retention time and peak area integral value of each aromatic ether compound in the sample; and detecting the standard sample retention time standard curve by using a standard sample, comparing with the sample, and determining the nature and / or quantity of the aromatic ether compound in the sample. According to the method, qualitative and quantitative detection of various different aromatic ether compounds in the sample can be realized through simple and convenient steps, the detection time is shorter, and the method has excellent sensitivity and reproducibility.

Description

Technical Field

[0001] This invention belongs to the field of analytical chemistry and relates to a technique for detecting the types and contents of target compounds in a sample. Specifically, it relates to a method for qualitative and / or quantitative analysis of multiple aromatic ether compounds contained in a sample. Background Technology

[0002] Various aromatic ether compounds are widely used in various fields. Examples include p-hydroxyanisole, o-hydroxyanisole, and anisole. Among them, p-hydroxyanisole (also known as p-methoxyphenol, hydroquinone monomethyl ether, or hydroquinone monomethyl ether) is not only used as a highly efficient polymerization inhibitor in the production, storage, and transportation of alkenyl monomers such as (meth)acrylic acid and (meth)acrylates, but also as an important intermediate in the synthesis of pharmaceuticals, fragrances, pesticides, and other fine chemical products, demonstrating its wide range of applications. o-hydroxyanisole (also known as guaiacol or o-methoxyphenol) is an important raw material in pesticides, fragrances, and fine chemical intermediates. Its primary use is as a raw material for the synthesis of vanillin, an expensive and widely used high-end fragrance. Anisole (also known as anethole) is an important fine chemical intermediate with wide applications in pesticides, dyes, and pharmaceuticals. With the increasing demand in these fields year by year, the scale of synthesis processes for these aromatic ether compounds is also continuously expanding.

[0003] The synthesis of these aromatic ether compounds often involves multiple designs. For example, there are four main methods for synthesizing hydroxyanisole: the dimethyl sulfate method and the methanol method using hydroquinone as a raw material; the p-aminoanisole method using p-aminoanisole as a raw material; and the anisole hydroxylation method using anisole as a raw material. The main methods for synthesizing o-hydroxyanisole include the diazotization-hydrolysis process using o-aminoanisole as a raw material, the hydroxylation-reduction process using o-nitrochlorobenzene as a raw material, and the etherification process using catechol as a raw material. The industrial synthesis method for anisole mainly involves methylating phenol as a raw material.

[0004] The aforementioned synthetic processes often yield reaction materials containing multiple aromatic ether compounds. During or after the synthesis process, it is necessary to qualitatively and quantitatively characterize the types and relative contents of these aromatic ether compounds in the reaction materials. This allows for targeted separation, purification, and recovery of the reaction materials, as well as effective monitoring and adjustment of the synthesis process. However, the problem lies in the fact that, in existing technologies, these different aromatic ether compounds are often characterized using different techniques. Therefore, when a sample contains multiple different aromatic ether compounds, it is necessary to first separate, purify, and concentrate these different aromatic ether compounds through complex and time-consuming steps. Only then can different detection devices and apparatuses be used based on different detection principles to qualitatively and quantitatively characterize the resulting single aromatic ether compound. This approach is not only time-consuming and labor-intensive, requiring large amounts of reagents, but also suffers from poor detection accuracy. Moreover, differences in separation, purification, and concentration steps, as well as detection techniques, can significantly affect the quantitative detection results to varying degrees, severely hindering the development of aromatic ether compound synthesis processes.

[0005] Therefore, there is an urgent need in the field to develop a new detection method that can simultaneously and accurately qualitatively and quantitatively analyze different aromatic ether compounds in a simple manner without requiring additional separation of the different aromatic ether compounds in the sample. Summary of the Invention

[0006] In response to the above problems, the inventors of this application, through extensive and in-depth research, have successfully developed a novel detection method that unexpectedly solves the problems in the prior art.

[0007] This invention provides a detection method for qualitative and / or quantitative detection of each aromatic ether compound in a sample containing at least two aromatic ether compounds, the method comprising: Step A: Use liquid chromatography to detect the sample and measure the retention time and peak area integral value of each aromatic ether compound in the sample; Step B1: Use the liquid chromatography to detect the standard retention time of the aromatic ether compound standard; Step B2: Compare the retention time of the standard sample measured in Step B1 with the retention time measured in Step A to qualitatively identify the aromatic ether compounds in the sample; Step C1: Use the liquid chromatography to detect the peak area integral values ​​of a series of samples with different concentrations of aromatic ether compound standards, and obtain a standard curve accordingly; Step C2: Compare the standard curve obtained in step C1 with the peak area integral value obtained in step A to quantify the aromatic ether compounds in the sample.

[0008] According to one embodiment of this application, the aromatic ether compound has the molecular structure shown in Formula 1: Formula 1 In Formula 1, R1 is selected from one or more of the following: C1-C12 alkyl, C3-C12 cycloalkyl, C6-C16 aryl, C4-C16 heteroaryl; and R1 is not substituted, or R1 is substituted by one or more of the following substituents: hydroxyl, halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 hydroxyalkyl, nitro, amino; R2, R3, R4, R5 and R6 are each independently selected from one or more of the following: hydrogen atom, hydroxyl group, C1-C8 alkyl group, C1-C8 alkoxy group, halogen, C1-C8 haloalkyl group, C1-C8 haloalkoxy group, nitro group, amino group.

[0009] According to another embodiment of this application, the sample includes two or more aromatic ether compounds selected from the following: anisole, o-hydroxyanisole, m-hydroxyanisole, p-hydroxyanisole, o-nitroanisole, m-nitroanisole, p-nitroanisole, o-aminoanisole, m-aminoanisole, and p-aminoanisole.

[0010] According to another embodiment of this application, the sample further comprises a solvent selected from one or more of the following: water, methanol, ethanol, n-propanol, isopropanol, acetone, acetonitrile, chloroform, dichloromethane, diethyl ether, diethylamine, dimethyl sulfoxide, methyl tert-butyl ether, and tetrahydrofuran.

[0011] According to another embodiment of this application, the sample is derived from the product of anisole hydroxylation (oxidation) reaction, which includes anisole, p-hydroxyanisole, and o-hydroxyanisole.

[0012] According to another embodiment of this application, the liquid chromatograph includes a UV-Vis detector.

[0013] According to another embodiment of this application, the chromatographic column used in the liquid chromatograph is an octadecylsilane bonded chromatographic column, and the inner diameter of the chromatographic column is 1-10 mm, the length is 100-1000 mm, and the particle size of the packing material is 0.1-8.0 μm.

[0014] According to another embodiment of this application, the mobile phase used in the liquid chromatography includes one or more of the following: water, methanol, acetonitrile, n-hexane, tetrahydrofuran, ethanol, diethyl ether, and isopropanol.

[0015] According to another embodiment of this application, the liquid chromatography is operated under the following process conditions: column temperature of 30-45℃, injection volume of 5-20 μL, detector wavelength of 260-290 nm, and column flow rate of 0.5-1.5 mL / min.

[0016] According to another embodiment of this application, in step C1, the peak area integral values ​​of 5-10 samples of aromatic ether compound standards at different concentrations are detected using the liquid chromatography, and a standard curve is obtained accordingly.

[0017] According to another embodiment of this application, for quantitative testing, the column of the liquid chromatography is first rinsed with a mobile phase for 0.5-2 hours, and the liquid chromatography test is performed after the baseline has stabilized.

[0018] In the detailed description section below, the method and polymer product of this application will be further described with reference to the accompanying drawings. Attached Figure Description

[0019] Figure 1 The liquid chromatogram of a sample from one embodiment of the present invention is shown; Figure 2 This shows a standard curve of p-hydroxyanisole according to one embodiment of this application; Figure 3 This shows a standard curve of o-hydroxyanisole according to one embodiment of this application; Figure 4 A standard curve of anisole according to one embodiment of this application is shown. Detailed Implementation

[0020] The “range” disclosed in this document takes the form of a lower limit and an upper limit. It can be one or more lower limits and one or more upper limits, respectively. A given range is defined by selecting a lower limit and an upper limit. The selected lower and upper limits define the boundaries of the particular range. All ranges that can be defined in this way are inclusive and composable; that is, any lower limit can be combined with any upper limit to form a range. For example, if ranges of 60-120 and 80-110 are listed for a specific parameter, it is also expected that ranges of 60-110 and 80-120 are also included. Furthermore, if the minimum range values ​​are listed as 1 and 2, and if the maximum range values ​​are listed as 3, 4, and 5, then the following ranges are all expected: 1-3, 1-4, 1-5, 2-3, 2-4, and 2-5.

[0021] In this application, unless otherwise stated, the numerical range "ab" is a shortened representation of any combination of real numbers from a to b, where a and b are real numbers. For example, the numerical range "0-5" means that all real numbers between "0-5" have been listed in this document, and "0-5" is simply a shortened representation of these numerical combinations.

[0022] Unless otherwise specified in this application, all embodiments and preferred embodiments mentioned herein can be combined to form new technical solutions.

[0023] Unless otherwise specified, all technical features and preferred features mentioned herein can be combined to form new technical solutions.

[0024] In this application, unless otherwise specified, the term "comprising" as used herein can be either open-ended or closed-ended. For example, "comprising" may mean that it may also include other components not listed, or it may only include the listed components.

[0025] The sample being processed by the method of the present invention contains two or more aromatic ether compounds having the structure shown in Formula 1 below, for example, the sample contains two, three, four, five or six aromatic ether compounds having the structure shown in Formula 1 below: Formula 1 In Formula 1, R1 is selected from one or more of the following: C1-C12 alkyl, C3-C12 cycloalkyl, C6-C16 aryl, C4-C16 heteroaryl; preferably, R1 is selected from one or more of the following: C1-C8 alkyl, C3-C8 cycloalkyl, C6-C12 aryl, C4-C12 heteroaryl; more preferably, R1 is selected from one or more of the following: C1-C6 alkyl, C3-C10 cycloalkyl, C6-C12 aryl, C4-C12 heteroaryl; even more preferably, R1 is selected from one or more of the following: C1-C3 alkyl, C3-C6 cycloalkyl, C6-C8 aryl, C4-C8 heteroaryl. For example, R1 can be methyl.

[0026] The R1 group in Formula 1 may be unsubstituted, or R1 may be further substituted by one or more substituents selected from the following: hydroxyl, halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 hydroxyalkyl, nitro, amino.

[0027] In this invention, halogens include one or more of the following: fluorine, chlorine, bromine, and iodine.

[0028] According to another embodiment of this application, R2, R3, R4, R5 and R6 are each independently selected from one or more of the following: hydrogen atom, hydroxyl group, C1-C8 alkyl group, C1-C8 alkoxy group, halogen, C1-C8 haloalkyl group, C1-C8 haloalkoxy group, nitro group, amino group; or R2, R3, R4, R5 and R6 are each independently selected from one or more of the following: hydrogen atom, hydroxyl group, C1-C6 alkyl group, C1-C6 alkoxy group, halogen, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, nitro group, amino group; or R2, R3, R4, R5 and R6 are each independently selected from one or more of the following: hydrogen atom, hydroxyl group, C1-C3 alkyl group, C1-C3 alkoxy group, halogen, C1-C3 haloalkyl group, C1-C3 haloalkoxy group, nitro group, amino group.

[0029] According to one exemplary embodiment of this application, the aromatic ether compound contained in the sample is selected from two or more of the following: anisole, o-hydroxyanisole, m-hydroxyanisole, p-hydroxyanisole, o-nitroanisole, m-nitroanisole, p-nitroanisole, o-aminoanisole, m-aminoanisole, and p-aminoanisole. According to another exemplary embodiment of this application, the sample contains anisole, o-hydroxyanisole, and p-hydroxyanisole.

[0030] According to another embodiment of this application, the sample may also contain a solvent, that is, the sample may be a solution of the two or more aromatic ether compounds in the solvent, wherein the solvent is selected from one or more of the following: water, methanol, ethanol, n-propanol, isopropanol, acetone, acetonitrile, chloroform, dichloromethane, diethyl ether, diethylamine, dimethyl sulfoxide, methyl tert-butyl ether, tetrahydrofuran.

[0031] According to another embodiment of this application, the sample may be obtained from the reaction system used to prepare the above-mentioned aromatic ether compounds. The sample may be taken during the reaction or after the reaction is completed. Therefore, the sample may contain the target product (e.g., p-hydroxyanisole), the reaction raw material (e.g., anisole), and the by-product (e.g., o-hydroxyanisole).

[0032] According to another embodiment of this application, the reaction for preparing aromatic ether compounds described above is, for example, a reaction using anisole as a starting material to synthesize p-hydroxyanisole via a hydroxylation (oxidation) reaction. For example, this reaction can involve adding a catalyst and an oxidant to a solution of anisole in a solvent to cause the starting material to undergo a hydroxylation (oxidation) reaction to prepare the target product p-hydroxyanisole. The process for preparing p-hydroxyanisole via the hydroxylation (oxidation) reaction of anisole and the selection of various reagents are known in the art. In addition to generating the target product p-hydroxyanisole, this reaction inevitably generates the byproduct o-hydroxyanisole; therefore, samples obtained from this reaction system will contain p-hydroxyanisole, o-hydroxyanisole, and unreacted starting material anisole.

[0033] As described above, the inventive point of this invention is that, unlike existing technologies, it eliminates the need for separation, purification, and / or concentration of various aromatic ether compounds in a sample, followed by separate qualitative and quantitative analysis of each isolated aromatic ether compound. The method of this invention can simultaneously perform qualitative and quantitative analysis of two or more aromatic ether compounds contained in a sample.

[0034] According to one embodiment of this application, before using the method of the present invention for detection, the sample may be filtered as needed to remove solid impurities (e.g., catalysts).

[0035] According to one embodiment of this application, the sample volume taken from the reaction system can be 0.1-10 mL, for example 1-8 mL, or 1.5-5 mL. The sample can be diluted as needed with the solvent described above, for example, to 10-100 mL. The above dilution needs to be performed with high precision, and the dilution ratio should be recorded so that the content of various components in the sample can be accurately determined.

[0036] The method of the present invention includes characterizing the sample to be tested and the standard prepared using a liquid chromatography device to obtain their respective retention times and peak area integral values.

[0037] According to one embodiment of this application, the liquid chromatography apparatus used may be equipped with an octadecylsilane-bonded column and a UV-Vis detector. The octadecylsilane-bonded column indicates that the packing material used in the column is octadecylsilane-bonded silica gel. According to another embodiment of this application, the average particle size of the packing material is 0.1-8.0 micrometers, for example, 1.0-7.0 micrometers, or 2.0-6.0 micrometers, or 3.0-5.0 micrometers.

[0038] According to another embodiment of this application, the inner diameter of the chromatographic column is 1-10 mm, or 2-8 mm, or 3-6 mm, or 4-5 mm. The length of the chromatographic column can be 100-1000 mm, for example 150-800 mm, or 200-600 mm, or 250-500 mm. According to another embodiment of this application, the column temperature of the liquid chromatography is 30-45°C.

[0039] According to one embodiment of this application, the injection volume of the liquid chromatograph is 5-20 μL, or 8-15 μL, or 10-12 μL.

[0040] According to one embodiment of this application, the mobile phase used in the liquid chromatography is selected from one or more of the following: water, methanol, acetonitrile, n-hexane, tetrahydrofuran, ethanol, diethyl ether, and isopropanol. When two or more mobile phases are used, these different mobile phases can form mixtures of different concentrations, for example, using a mixture of water and methanol as the mobile phase, wherein the volume ratio of methanol is 30-50%. According to another embodiment of this application, the composition of the mobile phase can undergo a gradient change during elution; for example, when using a mixture of water and methanol as the mobile phase, the methanol content in the mobile phase can gradually increase or decrease over time.

[0041] According to another embodiment of this application, the flow rate in the chromatographic column of the liquid chromatography is 0.5-1.5 mL / min. According to another embodiment of this application, the detection wavelength of the ultraviolet-visible detector equipped with the chromatogram is 260-290 nm.

[0042] According to another embodiment of this application, before quantitative testing of a sample or standard, the column of the liquid chromatograph is first flushed with a mobile phase for 0.5-2 hours. After the baseline stabilizes, the sample or standard is injected into the liquid chromatograph to detect its signal peak integral value, and the sample / standard is quantitatively analyzed based on the signal peak integral value.

[0043] The method of the present invention includes steps A, B1, B2, C1, and C2 as described below. The order of steps A, B1, and C1 can be adjusted as needed. For example, (1) step A can be performed first, followed by steps B1 and C1; or (2) steps A, B1, and C1 can be performed simultaneously by different operators; or (3) steps B1 and / or C1 can be performed first, and the retention time and standard curve of specific aromatic ether compounds (especially those aromatic ether compounds contained in the sample) can be determined in advance using standard samples, and then step A can be performed. This allows for convenient and quick qualitative and quantitative analysis based on the retention time and peak area integral value of various aromatic ether compounds in the sample. According to one embodiment of the present application, in the actual operation of the method of the present application, the types of aromatic ether compounds contained in the sample can be roughly predicted based on experience according to the source of the sample (e.g., materials from the reaction process of synthesizing p-hydroxyanisole by the hydroxylation reaction (oxidation reaction) of anisole or the final product material). In this case, the above-mentioned approach (3) can significantly improve the efficiency of qualitative and / or quantitative analysis.

[0044] According to one embodiment of this application, in step A, liquid chromatography is used to detect the sample, and the retention time and peak area integral value of each aromatic ether compound in the sample are measured. In step B1, the retention time of the aromatic ether compound standard is detected using liquid chromatography. In step B2, the retention time of the standard measured in step B1 is compared with the retention time measured in step A to qualitatively identify the aromatic ether compounds in the sample. In step C1, the peak area integral values ​​of a series of aromatic ether compound standard samples with different concentrations are detected using liquid chromatography, and a standard curve is obtained accordingly. In step C2, the standard curve obtained in step C1 is compared with the peak area integral value obtained in step A to quantitatively identify the aromatic ether compounds in the sample.

[0045] In steps A to C2 of the present invention, the liquid chromatography equipment of the present invention operates under exactly the same conditions for each injection (whether it is a sample or a standard), so that the retention time and peak area integral value are not affected by changes in equipment or fluctuations in process conditions. Therefore, each specific aromatic ether compound has a specific retention time, and each specific concentration of aromatic ether compound corresponds to a specific peak area integral value.

[0046] According to another embodiment of this application, in step C1, a standard curve is obtained by preparing a series of standard solutions of different concentrations using an aromatic ether compound standard (e.g., p-hydroxyanisole, anisole, or o-hydroxyanisole). Each series may contain 5-20, 5-15, or 5-10 standard solutions of different concentrations. The specific concentrations can vary between the upper and lower limits of detection in liquid chromatography, for example, within the range of 5-500 ppm. Furthermore, different aromatic ether compounds have different linear ranges for the peak area integral value versus sample concentration standard curve (i.e., within this range, the peak area integral value and sample concentration are directly proportional, thus the standard curve is a straight line). For example, for p-hydroxyanisole, the linear range is 23-298 ppm; for o-hydroxyanisole, the linear range is 13-161 ppm; and for anisole, the linear range is 218-2807 ppm.

[0047] In the following examples, the reaction product material for the preparation of p-hydroxyanisole by hydroxylation (oxidation) of anisole was used as an example, and the method of the present invention was used to perform qualitative and quantitative detection on it.

[0048] Example

[0049] All reagents used in the following examples were commercially available chromatographically pure reagents and were used directly without further treatment. All water used in the following examples was deionized water.

[0050] The liquid chromatograph used in the following examples was an LC-20AD model purchased from Shimadzu Corporation. The chromatographic column was also purchased from Shimadzu, with an inner diameter of 4.6 mm and a length of 250 mm. The packing material was octadecyl-bonded silica particles with a particle size of 5.0 μm. The column temperature was 30°C, the mobile phase was a methanol-water mixture at a flow rate of 1 mL / min, with a methanol content of 40% by volume. Each injection volume was 10 μL. The liquid chromatograph was equipped with a UV-Vis detector with a detection wavelength of 275 nm.

[0051] Example 1

[0052] Accurately weigh 0.5265 g of p-hydroxyanisole, dissolve it in 10 mL of ethanol in a beaker, then transfer the solution to a 100 mL volumetric flask. Wash the beaker three times with a small amount of ethanol, and transfer the washings into the volumetric flask as well. Then dilute to volume with ethanol to obtain a p-hydroxyanisole standard solution with a concentration of 5265 ppm.

[0053] Accurately weigh 0.2821 g of o-hydroxyanisole, dissolve it in 10 mL of ethanol in a beaker, then transfer the solution to a 100 mL volumetric flask. Wash the beaker three times with a small amount of ethanol, and transfer the washings into the volumetric flask as well. Then dilute to volume with ethanol to obtain an o-hydroxyanisole standard solution with a concentration of 2821 ppm.

[0054] Accurately weigh 5.1223 g of anisole, dissolve it in 10 mL of ethanol in a beaker, then transfer the solution to a 100 mL volumetric flask. Wash the beaker three times with a small amount of ethanol, and transfer the washings into the volumetric flask as well. Then dilute to volume with ethanol to obtain an anisole standard solution with a concentration of 51223 ppm.

[0055] Accurately measure 1 mL of p-hydroxyanisole standard solution, 1 mL of o-hydroxyanisole standard solution, and 1 mL of anisole solution using a pipette, add them to a 100 mL volumetric flask, and then dilute to volume with ethanol to obtain a mixed solution containing 52.65 ppm p-hydroxyanisole, 28.21 ppm o-hydroxyanisole, and 512.23 ppm anisole.

[0056] In this embodiment, a mixed solution prepared as described above is used to simulate a sample of "product of synthesis of p-hydroxyanisole by hydroxylation (oxidation) of anisole".

[0057] The sample was pre-washed with a mobile phase for approximately 1 hour until the baseline stabilized. Then, 10.00 μL of the sample was precisely injected into the liquid chromatograph using an injector to obtain... Figure 1 The spectrum shown has signal peaks at 7.893 min, 10.345 min, and 32.690 min. The peak area integration of these three signal peaks was performed using chromatographic software, and the area integration values ​​of the three peaks were determined to be 466559, 396194, and 4123911, respectively.

[0058] Qualitative experiment: Using an injector, 10.00 μL of the above-mentioned p-hydroxyanisole, o-hydroxyanisole, and anisole reference solutions were injected independently into the liquid chromatograph, and the chromatographic data were recorded and summarized in Table 1: Table 1: Retention time determination results of various aromatic ether compounds

[0059] As can be seen, the three peaks in the sample's chromatogram correspond to p-hydroxyanisole, o-hydroxyanisole, and anisole, respectively, which allows for accurate identification of the substances corresponding to these three peaks.

[0060] Quantitative Experiment: In this quantitative experiment, a series of p-hydroxyanisole standard solutions with concentrations of 0.023 mg / mL, 0.043 mg / mL, 0.064 mg / mL, 0.128 mg / mL, 0.171 mg / mL, 0.212 mg / mL, and 0.298 mg / mL were prepared. 10 μL of each solution was taken for liquid chromatography (HPLC) analysis (the chromatogram was flushed with mobile phase for approximately 1 hour before each test until the baseline stabilized). A standard curve was plotted based on the peak area integral value versus concentration for these seven standard solutions, as shown below. Figure 2 As shown.

[0061] A series of o-hydroxyanisole standard solutions with concentrations of 0.013 mg / mL, 0.023 mg / mL, 0.035 mg / mL, 0.069 mg / mL, 0.092 mg / mL, 0.114 mg / mL, and 0.161 mg / mL were prepared. 10 μL of each solution was subjected to high-performance liquid chromatography (HPLC) (the chromatogram was flushed with mobile phase for approximately 1 hour before each test until the baseline was stable). A standard curve was plotted based on the peak area integral value versus concentration for these seven standard solutions, as shown below. Figure 3 As shown.

[0062] A series of anisole standard solutions with concentrations of 0.218 mg / mL, 0.404 mg / mL, 0.606 mg / mL, 1.204 mg / mL, 1.604 mg / mL, 2.004 mg / mL, and 2.807 mg / mL were prepared. 10 μL of each solution was subjected to high-performance liquid chromatography (HPLC) (the chromatogram was flushed with mobile phase for approximately 1 hour before each test until the baseline was stable). A standard curve was plotted based on the peak area integral versus concentration for these seven standard solutions, as shown below. Figure 4 As shown.

[0063] Table 2: Standard curve information for p-hydroxyanisole, o-hydroxyanisole, and anisole

[0064] As shown in Table 2, p-hydroxyanisole exhibits good linearity in the concentration range of 23-298 ppm, o-hydroxyanisole exhibits good linearity in the concentration range of 13-161 ppm, and anisole exhibits good linearity in the concentration range of 218-2807 ppm.

[0065] Substituting the peak area integrals of the three peaks measured for the sample as described above into the equation of the standard curve, the concentration of the component in the sample is determined and compared with the true concentration determined when the sample was prepared: Table 3: Concentration of each component in the sample

[0066] Example 2

[0067] In this embodiment, 4.15 mL of the p-hydroxyanisole standard solution prepared in Example 1, 1.09 mL of the o-hydroxyanisole standard solution prepared in Example 1, and 1.44 mL of the anisole solution prepared in Example 1 were accurately measured using a pipette and added to a 100 mL volumetric flask. The solution was then diluted to volume with ethanol to obtain a mixed solution containing 218.31 ppm p-hydroxyanisole, 30.62 ppm o-hydroxyanisole, and 737.79 ppm anisole.

[0068] In this embodiment, a mixed solution prepared as described above is used to simulate a sample of "product of synthesis of p-hydroxyanisole by hydroxylation (oxidation) of anisole".

[0069] The sample was pre-washed with a mobile phase for about 1 hour until the baseline stabilized. Then, 10.00 μL of the sample was precisely injected into the liquid chromatograph using an injector. Signal peaks were observed at 7.919 min, 10.384 min, and 32.791 min. The peak area integrals of these three peaks were calculated using chromatographic software, and the area integral values ​​of the three peaks were determined to be 1919808, 434962, and 5929160, respectively.

[0070] The peak area integrals of the three peaks obtained in this way are substituted into the equation of the standard curve obtained in Example 1 to determine the component concentration in the sample, and compared with the true concentration determined when the sample was prepared: Table 4: Concentration of each component in the sample

[0071] As can be seen from the above embodiments, the method of the present invention can achieve simultaneous qualitative and quantitative detection of these compounds without the need for individual separation, purification and concentration of various aromatic ether compounds in the sample, and achieves excellent sensitivity and accuracy.

Claims

1. A detection method, said method for qualitative and / or quantitative detection of each aromatic ether compound in a sample containing at least two aromatic ether compounds, said method comprising: Step A: Use liquid chromatography to detect the sample and measure the retention time and peak area integral value of each aromatic ether compound in the sample; Step B1: Use the liquid chromatography to detect the standard retention time of the aromatic ether compound standard; Step B2: Compare the retention time of the standard sample measured in Step B1 with the retention time measured in Step A to qualitatively identify the aromatic ether compounds in the sample; Step C1: Use the liquid chromatography to detect the peak area integral values ​​of a series of samples with different concentrations of aromatic ether compound standards, and obtain a standard curve accordingly; Step C2: Compare the standard curve obtained in step C1 with the peak area integral value obtained in step A to quantify the aromatic ether compounds in the sample.

2. The detection method according to claim 1, characterized in that, The aromatic ether compounds have the molecular structure shown in Formula 1: Formula 1 In Formula 1, R1 is selected from one or more of the following: C1-C12 alkyl, C3-C12 cycloalkyl, C6-C16 aryl, C4-C16 heteroaryl; and R1 is not substituted, or R1 is substituted by one or more of the following substituents: hydroxyl, halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 hydroxyalkyl, nitro, amino; R2, R3, R4, R5 and R6 are each independently selected from one or more of the following: hydrogen atom, hydroxyl group, C1-C8 alkyl group, C1-C8 alkoxy group, halogen, C1-C8 haloalkyl group, C1-C8 haloalkoxy group, nitro group, amino group.

3. The detection method according to claim 1, characterized in that, The sample includes two or more aromatic ether compounds selected from the following: anisole, o-hydroxyanisole, m-hydroxyanisole, p-hydroxyanisole, o-nitroanisole, m-nitroanisole, p-nitroanisole, o-aminoanisole, m-aminoanisole, and p-aminoanisole.

4. The detection method according to claim 1, characterized in that, The sample also contains a solvent selected from one or more of the following: water, methanol, ethanol, n-propanol, isopropanol, acetone, acetonitrile, chloroform, dichloromethane, diethyl ether, diethylamine, dimethyl sulfoxide, methyl tert-butyl ether, and tetrahydrofuran.

5. The detection method according to claim 1, characterized in that, The sample is derived from the product of the hydroxylation (oxidation) reaction of anisole, which includes anisole, p-hydroxyanisole, and o-hydroxyanisole.

6. The detection method according to claim 1, characterized in that, The liquid chromatograph includes a UV-Vis detector; The liquid chromatograph uses an octadecylsilane bonded column, and the inner diameter of the column is 1-10 mm, the length is 100-1000 mm, and the particle size of the packing material is 0.1-8.0 μm.

7. The detection method according to claim 1, characterized in that, The mobile phase used in the liquid chromatography includes one or more of the following: water, methanol, acetonitrile, n-hexane, tetrahydrofuran, ethanol, diethyl ether, and isopropanol.

8. The detection method according to claim 1, characterized in that, The liquid chromatography is operated under the following conditions: column temperature 30-45℃, injection volume 5-20 μL, detector wavelength 260-290 nm, and column flow rate 0.5-1.5 mL / min.

9. The detection method according to claim 1, characterized in that, In step C1, the peak area integral values ​​of 5-10 samples of aromatic ether compound standards at different concentrations are detected using liquid chromatography, and a standard curve is obtained accordingly.

10. The detection method according to claim 1, characterized in that, For quantitative testing, first flush the column with a mobile phase for 0.5-2 hours, and then perform the liquid chromatography test after the baseline has stabilized.

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