CN113777204B - Detection method of p-hydroxyacetophenone related substances - Google Patents
Detection method of p-hydroxyacetophenone related substances Download PDFInfo
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- CN113777204B CN113777204B CN202110873039.4A CN202110873039A CN113777204B CN 113777204 B CN113777204 B CN 113777204B CN 202110873039 A CN202110873039 A CN 202110873039A CN 113777204 B CN113777204 B CN 113777204B
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
- G01N2030/8809—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample
- G01N2030/884—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample organic compounds
Abstract
The invention relates to the technical field of drug analysis and detection, and particularly discloses a detection method of p-hydroxyacetophenone related substances. The invention adopts gas chromatography to measure related substances, and the chromatographic conditions are as follows: a chromatographic column: a capillary column with phenyl-dimethyl polysiloxane as stationary liquid; carrier gas flow rate: 0.5-1.5 ml/min; the split ratio is as follows: 8-12: 1; temperature rising procedure: the initial temperature is 45-55 ℃, the temperature is increased to 215-225 ℃ at the rate of 8-12 ℃ per minute, and the temperature is maintained for 5-10 minutes; sample inlet temperature: 240-260 ℃; the detector is a hydrogen flame ionization detector, and the temperature of the detector is 240-260 ℃. The detection method provided by the invention can realize effective separation of p-hydroxyacetophenone and 2 '-hydroxyacetophenone, 3' -hydroxyacetophenone, phenol and phenol acetate ester, and accurately detect the content of related substances in the p-hydroxyacetophenone. The method is sensitive, accurate and good in reproducibility, provides reliable guarantee for improving and better controlling the quality of the p-hydroxyacetophenone, and has very important significance for improving the medication safety.
Description
Technical Field
The invention relates to the technical field of drug analysis and detection, in particular to a detection method of p-hydroxyacetophenone related substances.
Background
The salbutamol sulfate is named as 1- (4-hydroxy-3-hydroxymethyl phenyl) -2- (tert-butylamino) ethanol sulfate, has the main function of selectively exciting beta 2-receptors on bronchial smooth muscle to relax the bronchial smooth muscle, so as to relieve bronchial smooth muscle spasm, and has better treatment effect on respiratory diseases such as bronchial spasm of patients with asthmatic bronchitis, bronchial asthma and emphysema.
P-hydroxyacetophenone is an important starting material in the synthesis of salbutamol sulfate, in the synthesis process of the p-hydroxyacetophenone, related substances of the p-hydroxyacetophenone, including isomers of the p-hydroxyacetophenone, namely 2 '-hydroxyacetophenone and 3' -hydroxyacetophenone, and phenol, phenol acetate and other impurities, inevitably occur, and the related substances of the p-hydroxyacetophenone not only affect the subsequent reaction, but also affect the purity of a final finished product, so the content of the related substances of the p-hydroxyacetophenone needs to be strictly controlled. However, the detection methods of related substances of p-hydroxyacetophenone are not recorded in pharmacopoeias of various countries at present. Therefore, the research and development of a detection method capable of detecting related substances of p-hydroxyacetophenone is of great significance for improving the quality control of p-hydroxyacetophenone and improving the medication safety of patients.
Disclosure of Invention
In order to solve the technical problems, the invention provides a method for detecting p-hydroxyacetophenone related substances. The detection method can realize effective separation of the p-hydroxyacetophenone from the isomers 2 '-hydroxyacetophenone and 3' -hydroxyacetophenone, can also effectively separate the p-hydroxyacetophenone from phenol and phenol acetate, accurately detect the content of the related substances of the p-hydroxyacetophenone, and simultaneously accurately detect the content of the related substances of the p-hydroxyacetophenone, thereby overcoming the defects of the prior art.
In order to achieve the purpose, the invention adopts the following technical scheme:
the embodiment of the invention provides a method for detecting p-hydroxyacetophenone related substances, wherein the related substances comprise 2 '-hydroxyacetophenone, 3' -hydroxyacetophenone, phenol and phenol acetate, and the method is characterized in that methanol and water are used as solvents to prepare a solution to be detected, and a gas chromatography method is used for determining the related substances, wherein the chromatographic conditions of the gas chromatography method are as follows:
a chromatographic column: a capillary column with phenyl-dimethyl polysiloxane as stationary liquid;
flow rate of carrier gas: 0.5-1.5 ml/min;
the split ratio is as follows: 8-12: 1;
temperature rising procedure: the initial temperature is 45-55 ℃, the temperature is increased to 215-225 ℃ at the rate of 8-12 ℃ per minute, and the temperature is maintained for 5-10 minutes;
sample inlet temperature: 240-260 ℃;
the detector is a hydrogen flame ionization detector, and the temperature of the detector is 240-260 ℃.
The related substances of p-hydroxyacetophenone in the invention comprise isomers of p-hydroxyacetophenone, namely 2 '-hydroxyacetophenone and 3' -hydroxyacetophenone, and also comprise phenol and phenol acetate. Compared with the prior art, the detection method of the p-hydroxyacetophenone related substances does not need derivatization treatment and a chiral chromatographic column, only takes a capillary column with phenyl-dimethyl polysiloxane as a stationary liquid as the chromatographic column, takes methanol and water as solvents to prepare a solution to be detected, and measures the related substances in a sample injection mode of directly injecting the solution by controlling the temperature rise program of the gas chromatography, so that the method not only can realize effective separation of the p-hydroxyacetophenone from the isomers of the p-hydroxyacetophenone, namely 2 '-hydroxyacetophenone and 3' -hydroxyacetophenone, but also can realize effective separation of the p-hydroxyacetophenone from 2 '-hydroxyacetophenone, 3' -hydroxyacetophenone, phenol and phenol acetate, thereby accurately detecting the content of the related substances in the p-hydroxyacetophenone. The method provided by the invention is discovered through methodology research and verification such as specificity, sensitivity and the like, the method is high in sensitivity, good in accuracy and reproducibility, can realize accurate quantitative detection on the p-hydroxyacetophenone related substances through simple and rapid operation, overcomes the defect that the detection on the p-hydroxyacetophenone related substances is not recorded in the prior art, provides reliable guarantee for better controlling the quality of the p-hydroxyacetophenone, and has very important significance for improving the medication safety.
Preferably, the chromatographic column is a capillary column using 5% phenyl-95% dimethylpolysiloxane as a stationary liquid.
The method can realize the effective separation of the p-hydroxyacetophenone from the isomers 2 '-hydroxyacetophenone and 3' -hydroxyacetophenone without a chiral chromatographic column.
More preferably, the column is Agilent J & W HP-5, the specification is 30m × 0.32mm, and the filler particle size is 0.25 μm.
The chromatographic column specification of the invention can be matched with the temperature-rising program of the invention, so that the peak shape, the resolution and the detection sensitivity of each component are good, and the baseline interference is small, thereby being beneficial to the effective separation of p-hydroxyacetophenone, 2 '-hydroxyacetophenone, 3' -hydroxyacetophenone, phenol and phenol acetate, and having accurate and reliable result and good repeatability.
Preferably, in the above temperature raising procedure, the initial temperature is 50 ℃, the temperature is raised to 220 ℃ at a rate of 10 ℃ per minute, and the temperature is maintained for 8 minutes.
The temperature-raising program of the invention is matched with the chromatographic column of the invention, can improve the separation degree and the detection sensitivity between the p-hydroxyacetophenone and the 2 '-hydroxyacetophenone, the 3' -hydroxyacetophenone, the phenol and the phenol acetate, and ensure that the detection result is quantitative and accurate and has high precision.
Preferably, the injection port temperature is 250 ℃.
Preferably, the detector temperature is 250 ℃.
Preferably, the carrier gas for the above gas chromatography is nitrogen.
Preferably, the carrier gas flow rate is 1.0 ml/min.
Preferably, the split ratio is 10: 1.
Preferably, the injection volume is 1 μ L.
The preferable detection conditions can ensure that the p-hydroxyacetophenone, the 2 '-hydroxyacetophenone, the 3' -hydroxyacetophenone, the phenol and the phenol acetate ester have higher separation degree, so as to ensure the effective detection of the related substances of the p-hydroxyacetophenone, thereby achieving the purpose of effectively and accurately controlling the content of the related substances of the p-hydroxyacetophenone.
Preferably, the volume ratio of methanol to water in the solvent is 99: 1.
Preferably, the detection method comprises the steps of: step a, preparing a reference solution and a test solution by using methanol and water as solvents; and b, measuring the reference substance solution by using a gas chromatography, and calculating the content of the related substances of the p-hydroxyacetophenone in the test solution according to the measurement data by a peak area according to an external standard method.
The detection method provided by the invention can realize effective separation of p-hydroxyacetophenone and 2 '-hydroxyacetophenone, 3' -hydroxyacetophenone, phenol and phenol acetate, accurately detect the content of the related substances of the p-hydroxyacetophenone, has simple and rapid operation and high sensitivity, provides a reliable method for the preparation process of the p-hydroxyacetophenone and the quality control of the product, and is beneficial to improving the medication safety of patients.
Drawings
FIG. 1 is a chromatogram of a blank solvent under the specificity term in example 1;
FIG. 2 is a chromatogram of a control solution under the specificity term of example 1;
FIG. 3 is a chromatogram of a test solution under the special attribute items in example 1.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
Example 1
The embodiment of the invention provides a method for detecting p-hydroxyacetophenone related substances
1.1 materials and methods
The instrument comprises the following steps: gas chromatograph, hydrogen flame ionization detector, measuring flask, electronic balance.
Blank solvent: 99% methanol and 1% water.
1.2 preparation of the solution
Control solution: taking a proper amount of phenol, phenol acetate, 2 '-hydroxyacetophenone and 3' -hydroxyacetophenone, precisely weighing, and preparing a reference solution containing 50 mu g of phenol, 50 mu g of phenol acetate, 50 mu g of 2 '-hydroxyacetophenone and 50 mu g of 3' -hydroxyacetophenone in every 1mL of the reference solution by using 99% methanol and 1% water.
Test solution: taking a proper amount of p-hydroxyacetophenone sample, precisely weighing, and preparing 10mg of p-hydroxyacetophenone sample per 1mL of sample solution by using 99% methanol and 1% water.
1.3 detection method of p-hydroxyacetophenone related substances
Detection and analysis are carried out according to the following chromatographic conditions:
a chromatographic column: agilent J & W HP-530 m.times.0.32 mm, 0.25 μm;
flow rate of carrier gas: 1.0 ml/min;
the split ratio is as follows: 10: 1;
temperature rising procedure: the initial temperature is 50 ℃, the temperature is increased to 220 ℃ at the rate of 10 ℃ per minute, and the temperature is maintained for 8 minutes;
sample inlet temperature: 250 ℃;
detector temperature: at 250 ℃ to obtain a mixture.
1.4 methodological validation:
(1) specificity
Sampling a blank solvent, a test solution and a reference solution according to the gas chromatography conditions, detecting, wherein the sample injection amount is 1 mu L, recording a chromatogram, wherein the chromatogram peak of the blank solvent is shown in figure 1, the chromatogram peak of the reference solution is shown in figure 2, the chromatogram peak of the test solution is shown in figure 3, wherein the chromatogram peak 1 of the test solution is phenol, the peak 2 is phenol acetate, the peak 3 is 2 '-hydroxyacetophenone, the peak 4 is 3' -hydroxyacetophenone, the peak 5 is p-hydroxyacetophenone, and the experimental results of the test solution are shown in table 1:
TABLE 1
Test results show that the base line is stable and has no interference, and blank solvents have no interference to the detection of 2 '-hydroxyacetophenone, 3' -hydroxyacetophenone, p-hydroxyacetophenone, phenol and phenol acetate; the separation degrees of the p-hydroxyacetophenone and the 2 '-hydroxyacetophenone, the 3' -hydroxyacetophenone, the phenol and the phenol acetate are all larger than 1.5, the separation degrees of the p-hydroxyacetophenone and the 2 '-hydroxyacetophenone, the separation degrees of the 3' -hydroxyacetophenone, the separation degrees of the p-hydroxyacetophenone and the phenol acetate are all larger than 1.5, the separation degrees of the p-hydroxyacetophenone and the 2 '-hydroxyacetophenone, the separation degrees of the 3' -hydroxyacetophenone, the phenol and the phenol acetate are not interfered, and the method is suitable for detecting related substances of the p-hydroxyacetophenone, and the detection method provided by the invention is good in specificity.
(2) Detection limit
And (3) taking the concentration of each impurity with the signal-to-noise ratio of 3:1 as a detection limit and the concentration of each impurity with the signal-to-noise ratio of 10:1 as a quantification limit, carrying out sample injection detection respectively according to the chromatographic conditions, carrying out sample injection on the quantification limit solution for 6 times continuously, and calculating the RSD of the peak area. The results of the limit of quantitation and limit of detection tests are shown in table 2, and the results of the limit of quantitation reproducibility tests are shown in table 3:
TABLE 2 quantitation Limit and detection Limit test results
TABLE 3 quantitative limit repeatability test results
| Composition (I) | 1 | 2 | 3 | 4 | 5 | 6 | RSD％ |
| Phenol and its preparation | 873 | 870 | 897 | 949 | 902 | 944 | 3.75 |
| Phenol acetate ester | 888 | 877 | 830 | 842 | 857 | 853 | 2.51 |
| 2' -hydroxyacetophenones | 988 | 1057 | 1043 | 1049 | 969 | 1009 | 3.53 |
| 3' -hydroxyacetophenone | 1074 | 1027 | 1026 | 1161 | 940 | 1110 | 7.27 |
| P-hydroxyacetophenone | 941 | 931 | 1123 | 965 | 1053 | 918 | 8.26 |
The detection method provided by the invention has high sensitivity according to the quantitative limit and detection limit test results, and the RSD for repeatedly measuring the peak area for 6 times is 8.26 percent, which shows that the method provided by the scheme has good quantitative limit repeatability.
(3) Linear range
Accurately weighing appropriate amount of 2 '-hydroxyacetophenone, 3' -hydroxyacetophenone, phenol and phenol acetate, diluting with blank solvent to obtain linear solution with series concentration, and detecting according to the above chromatographic conditions and detection method. Precisely measuring 1. mu.L of each linear solution, injecting into a gas chromatograph, recording the chromatogram, measuring the peak area, and performing linear regression with the peak area A as the ordinate and the concentration C as the abscissa, with the results shown in tables 4 to 7.
TABLE 4 phenol Linear test results
TABLE 5 phenol acetate Linear test results
TABLE 62' -hydroxyacetophenone Linear test results
TABLE 73 Linear test results for hydroxyacetophenone
The test result shows that the linear relation of each component is good, which shows that the linear relation is good in the detection method provided by the invention.
(4) Recovery rate
Precisely weighing appropriate amount of 2 '-hydroxyacetophenone, 3' -hydroxyacetophenone, phenol and phenol acetate, preparing mixed solution with 99% methanol and 1% water to 10 times of limit concentration, and storing as reference solution; taking about 100mg of p-hydroxyacetophenone sample, accurately weighing, placing in a 10ml measuring flask, preparing 9 parts in parallel, respectively and accurately adding 0.3ml, 0.4ml and 1.0ml of reference substance storage solutions, using 99% methanol and 1% water to fix the volume to a scale, wherein each concentration is 3 parts in parallel, taking the solution as a recovery rate sample solution, and detecting according to the chromatographic conditions and the detection method, wherein the recovery rate results of each component are shown in tables 8 to 11.
TABLE 8 phenol recovery test results
TABLE 9 detection results of phenol acetate recovery
TABLE 102' -hydroxyacetophenone recovery test results
TABLE 113 detection of hydroxyacetophenone recovery
The data show that the recovery rate of each component is between 80% and 106%, and the RSD is 5.29%, which indicates that the detection method provided by the invention has good accuracy.
(5) Repeatability of
Taking 3 parts of test solution, detecting according to the chromatographic conditions and the detection method, recording a chromatogram, and calculating the content of each related substance in the p-hydroxyacetophenone test solution, wherein the result is shown in Table 12.
TABLE 12 results of the repeatability tests
| Composition (I) | Retention time/min | 1 | 2 | 3 |
| Phenol and its preparation | 6.051 | 0.239 | 0.256 | 0.234 |
| Phenol acetate ester | 7.26 | 0.221 | 0.235 | 0.216 |
| 2' -hydroxyacetophenone | 8.771 | 0.221 | 0.235 | 0.217 |
| 3' -hydroxyacetophenone | 11.771 | 0.181 | 0.18 | 0.181 |
| P-hydroxyacetophenone | 12.651 | 99.138 | 99.094 | 99.152 |
The test result shows that the detection results of 3 test sample solutions have no obvious difference, and the detection method provided by the invention has good repeatability.
(6) Stability of solution
Precisely weighing appropriate amount of each component, preparing sample solution according to 1.2 solution preparation method, detecting at 0h, 2h, 4h, 8h, 12h, 24h and 48h respectively according to the above chromatographic conditions and detection method, and the solution stability results are shown in Table 13:
watch 13
Test results show that all components are stable when the kit is placed at room temperature for 48 hours, and the solution stability of the detection method provided by the invention is good.
(7) Durability
Taking a plurality of parts of test solution, respectively changing the temperature of the injection port, the initial temperature, the heating rate and the temperature of the detector, observing the change of the chromatographic behavior of the instrument, and showing the durability results in tables 14 to 17:
TABLE 14 temperature separation at different injection ports
| Composition (I) | The sample inlet is 245 DEG C | A sample inlet of 250 DEG C | Sample inlet 255 deg.C |
| Phenol and its preparation | - | - | - |
| Acetic acid phenol ester | 24.286 | 24.174 | 24.356 |
| 2' -hydroxyacetophenones | 28.733 | 28.664 | 28.760 |
TABLE 15 degrees of separation at different initial temperatures
| Composition (I) | Initial temperature of 48 deg.C | Initial temperature 50 deg.C | Initial temperature 52 deg.C |
| Phenol and its preparation | - | - | - |
| Phenol acetate ester | 24.354 | 24.174 | 24.116 |
| 2' -hydroxyacetophenones | 28.779 | 28.664 | 28.533 |
| 3' -hydroxyacetophenone | 55.407 | 55.787 | 55.278 |
TABLE 16 degrees of separation at different ramp rates
| Composition (I) | The temperature rise rate is 9 ℃/min | The heating rate is 10 ℃/min | The heating rate is 11 ℃/min |
| Phenol and its preparation | - | - | - |
| Phenol acetate ester | 25.359 | 24.174 | 23.406 |
| 2' -hydroxyacetophenones | 29.812 | 28.664 | 27.75 |
| 3' -hydroxyacetophenone | 57.891 | 55.787 | 53.192 |
TABLE 17 temperature resolution of different detectors
| Composition (I) | Detector 245 deg.c | Detector 250 deg.c | Detector 255 deg.c |
| Phenol as the starting material | - | - | - |
| Phenol acetate ester | 24.375 | 24.174 | 24.279 |
| 2' -hydroxyacetophenone | 28.623 | 28.664 | 28.585 |
| 3' -hydroxyacetophenone | 55.107 | 55.787 | 55.017 |
And the separation degree of each component meets the requirement by changing various conditions, which shows that the detection method provided by the invention has good durability.
(8) Test solution detection
The test solution is detected according to the above chromatographic conditions, and the chromatogram is shown in FIG. 3. The related substances in the test solution are respectively calculated by mixing the reference solution according to an external standard method. The results are shown in Table 18.
TABLE 18 test results of related substances of the test articles
The data show that the separation degree of each impurity is more than or equal to 1.5, which meets the requirements, and the p-hydroxyacetophenone can be effectively separated from the 2 '-hydroxyacetophenone, the 3' -hydroxyacetophenone, the phenol and the phenol acetate.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents or improvements made within the spirit and principle of the present invention should be included in the scope of the present invention.
Claims (9)
1. A method for detecting related substances of p-hydroxyacetophenone, wherein the related substances comprise 2 '-hydroxyacetophenone, 3' -hydroxyacetophenone, phenol and phenol acetate, is characterized in that a p-hydroxyacetophenone solution is prepared as a test solution by taking methanol and water as solvents, and the related substances are measured by a gas chromatography method, wherein the chromatographic conditions of the gas chromatography method are as follows:
a chromatographic column: a capillary column with phenyl-dimethyl polysiloxane as stationary liquid;
carrier gas flow rate: 0.5-1.5 ml/min;
the split ratio is as follows: 8-12: 1;
temperature rising procedure: the initial temperature is 45-55 ℃, the temperature is increased to 215-225 ℃ at the rate of 8-12 ℃ per minute, and the temperature is maintained for 5-10 minutes;
sample inlet temperature: 240-260 ℃;
the detector is a hydrogen flame ionization detector, and the temperature of the detector is 240-260 ℃; wherein the chromatographic column is a capillary column taking 5% of phenyl-95% of dimethyl polysiloxane as a stationary liquid.
2. The method for detecting p-hydroxyacetophenone-related substances according to claim 1, wherein the chromatographic column is Agilent J & W HP-5, the specification is 30m x 0.32mm, and the particle size of the filler is 0.25 μm.
3. The method for detecting p-hydroxyacetophenone-related substance according to claim 1, wherein the temperature raising process is carried out at a rate of 10 ℃ per minute with a starting temperature of 50 ℃ to 220 ℃ for 8 minutes.
4. The method for detecting p-hydroxyacetophenone-related substance according to claim 1, wherein the injection port temperature is 250 ℃.
5. The method for detecting p-hydroxyacetophenone-related substance according to claim 1, wherein the temperature of the detector is 250 ℃.
6. The method for detecting p-hydroxyacetophenone-related substance according to claim 1, wherein the carrier gas in the gas chromatography is nitrogen; and/or
The flow rate of the carrier gas is 1.0 ml/min; and/or
The split ratio was 10: 1.
7. The method for detecting p-hydroxyacetophenone-related substance according to claim 1, wherein the injection volume is 1 μ L.
8. The method for detecting p-hydroxyacetophenone-related substance according to claim 1, wherein the volume ratio of methanol to water in the solvent is 99: 1.
9. The method for detecting p-hydroxyacetophenone-related substance according to any one of claims 1 to 8, characterized in that the method comprises the steps of: step a, preparing a reference solution and a test solution by using the methanol and the water as solvents; and b, measuring the reference substance solution by using the gas chromatography, and calculating the content of the related substances of the p-hydroxyacetophenone in the test solution according to the measurement data by using a peak area according to an external standard method.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0170483A2 (en) * | 1984-07-24 | 1986-02-05 | Celanese Corporation | Process for producing acyloxy aromatic carboxylic acid |
| CN85101149A (en) * | 1984-06-04 | 1987-01-17 | 塞拉尼丝公司 | The preparation method of N-acyl group-hydroxyl and N-acyl group-acyloxy aromatic amine |
| US4663485A (en) * | 1986-07-22 | 1987-05-05 | Celanese Corporation | Process for purifying 4-hydroxyacetophenone |
| CN106645537A (en) * | 2017-01-23 | 2017-05-10 | 中国烟草总公司郑州烟草研究院 | Method for simultaneously measuring 19 smoke incense ingredients in main stream smoke of cigarette |
-
2021
- 2021-07-30 CN CN202110873039.4A patent/CN113777204B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN85101149A (en) * | 1984-06-04 | 1987-01-17 | 塞拉尼丝公司 | The preparation method of N-acyl group-hydroxyl and N-acyl group-acyloxy aromatic amine |
| EP0170483A2 (en) * | 1984-07-24 | 1986-02-05 | Celanese Corporation | Process for producing acyloxy aromatic carboxylic acid |
| US4663485A (en) * | 1986-07-22 | 1987-05-05 | Celanese Corporation | Process for purifying 4-hydroxyacetophenone |
| CN106645537A (en) * | 2017-01-23 | 2017-05-10 | 中国烟草总公司郑州烟草研究院 | Method for simultaneously measuring 19 smoke incense ingredients in main stream smoke of cigarette |
Non-Patent Citations (7)
| Title |
|---|
| A STUDY ON THE MECHANISM OF FRIES REACTION;Y. OGATA 等;《Tetrahedron》;19641231;第20卷;1661-1666 * |
| Fries rearrangement in methane sulfonic acid,an environmental friendly acid;Annie Commarieu 等;《Journal of Molecular Catalysis A: Chemical 》;20021231;第182-183卷;137-141 * |
| Gas-Liquid Chromatographic Separation of Methyl- and Methoxy-substituted Benzenes,Phenols, Phenylacetates, and Acetophenols;H. L. Louwerse 等;《JOURNAL OF GAS CHROMATOGRAPH》;19681130;第6卷;563-566 * |
| 乙酸苯酯Fries重排反应的研究;吕丽莉;《中国优秀博硕士学位论文全文数据库(硕士)工程科技Ⅰ辑》;20050915(第05期);B014-19 * |
| 化学和化工过程绿色化-Y型沸石催化乙酸苯酯Fries重排反应;吕丽莉等;《化学世界》;20051231(第06期);323-324，327，351 * |
| 微波加热三氯化铝催化合成邻羟基苯乙酮;刘现国等;《化工中间体》;20091231(第09期);31-33 * |
| 活性炭载铁催化剂上几种典型芳烃一步羟基化反应研究;钟永科;《中国优秀博硕士学位论文全文数据库(博士)工程科技Ⅰ辑》;20080415(第04期);B014-28 * |
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