CN113899838B - Method for detecting purity of benzene ring anhydride compound - Google Patents

Method for detecting purity of benzene ring anhydride compound Download PDF

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CN113899838B
CN113899838B CN202111063320.8A CN202111063320A CN113899838B CN 113899838 B CN113899838 B CN 113899838B CN 202111063320 A CN202111063320 A CN 202111063320A CN 113899838 B CN113899838 B CN 113899838B
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benzene ring
anhydride compound
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liquid
ratio
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CN113899838A (en
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孙长军
薛单单
杨建华
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Quzhou Kangpeng Chemical Co ltd
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    • 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
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    • 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
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Abstract

The invention provides a method for detecting purity of benzene ring anhydride compounds, which comprises the following steps: and adding a derivatization reagent and an organic solvent into the benzene ring anhydride compound sample, heating, cooling to obtain a liquid to be detected, detecting by adopting a liquid chromatography, comparing the retention time for qualitative determination, and determining the relative contents of the benzene ring anhydride compound and ring-opening impurities in the liquid to be detected by a peak area normalization method so as to determine the purity of the benzene ring anhydride compound. The method for detecting the purity of the benzene ring anhydride compound can realize the complete separation of the benzene ring anhydride compound and related impurities, and has good precision and accuracy and accurate result.

Description

Method for detecting purity of benzene ring anhydride compound
Technical Field
The invention belongs to the technical field of purity detection of organic compounds, and relates to a method for detecting purity of benzene ring anhydride compounds.
Background
Benzene ring anhydride compounds can be widely used in fine chemical products, such as: ODPA, chemical name 4,4' -oxydiphthalic anhydride, is a key intermediate of high molecular materials, and is used in composite materials, foams, adhesives, molded parts, films, and the like. The polyimide is an important raw material for preparing polyimide, and can be widely used for packaging LED lamps, alignment films of liquid crystal screens and parts in automobiles. Another example is: 6FDA, chemical name 4,4' - (hexafluoroisopropylidene) diphthalic anhydride, is one of the six most widely used dianhydride monomers, and is the dianhydride monomer used in the largest amount in the current colorless transparent polyimide. Polyimide synthesized by 6FDA has a glass transition temperature of usually 300 ℃ or higher, and has a good balance of mechanical properties and electrical properties, and thus far is the most representative fluorine-containing polyimide.
The benzene ring anhydride compound can be hydrolyzed to lead to open the ring of the anhydride to generate open-ring impurities, which influence the cyclization ratio of the compound, and the content of the open-ring impurities directly influences the quality of downstream polymerization products, so that the accurate detection of the cyclization ratio of the compound has very important significance. At present, the compounds are commonly used in the following two detection means: 1. the alkaline hydrolysis compound is firstly used, then HPLC is used for grafting measurement, and the impurity content is counted into the main component, so that the purity cannot truly reflect the quality of the compound. 2. Analysis by titration method can not reflect the content of single ring-opening impurity, and also leads to inaccuracy of the cyclization ratio.
Disclosure of Invention
In view of the above-mentioned drawbacks of the prior art, an object of the present invention is to provide a method for detecting purity of a benzene ring anhydride compound, which can effectively detect the benzene ring anhydride compound and its ring-opened impurities by using a derivatization pretreatment method, so as to effectively control the purity of the benzene ring anhydride compound.
To achieve the above and other related objects, the present invention provides a method for detecting purity of a benzene ring anhydride compound, comprising: and adding a derivatization reagent and an organic solvent into the benzene ring anhydride compound sample, heating, cooling to obtain a liquid to be detected, detecting by adopting a liquid chromatography, comparing the retention time for qualitative determination, and determining the relative contents of the benzene ring anhydride compound and ring-opening impurities in the liquid to be detected by a peak area normalization method so as to determine the purity of the benzene ring anhydride compound.
Preferably, the derivatizing agent is selected from one of methanol, ethanol, cyclopentylamine or cyclohexylamine.
Preferably, the derivatizing agent is cyclohexylamine.
Preferably, the organic solvent is acetonitrile.
Preferably, the ratio of the mass g added to the benzene ring anhydride compound sample to the volume ml added to the derivatization reagent is 0.5-1.5:200.
Preferably, the ratio of the mass g added to the sample of the benzene ring anhydride compound to the volume ml added to the derivatizing agent is 1:200.
Preferably, the ratio of the added mass g of the benzene ring anhydride compound sample to the added volume ml of the organic solvent is 0.5-1.5:1000.
Preferably, the ratio of the mass g added to the benzene ring anhydride compound sample to the volume ml added to the organic solvent is 1:1000.
Preferably, the temperature of the heating is 70-90 ℃. Preferably, the temperature of the heating is 80 ℃.
Preferably, the heating time is 2-5 hours. Preferably, the heating time is 3 hours.
Preferably, the heating is performed using an oven.
Preferably, the cooling is to room temperature. The room temperature is 20-30 ℃.
Preferably, the detection by liquid chromatography comprises the following steps:
1) Adding water into a benzene ring anhydride compound standard substance and a ring-opening impurity standard substance, adding a derivatization reagent and an organic solvent, heating and cooling to obtain a positioning solution;
2) Mixing the derivatization reagent with an organic solvent, heating and cooling to obtain a blank solution;
3) Detecting the liquid to be detected, the positioning solution in the step 1) and the blank solution in the step 2) by adopting a liquid chromatography (HPLC), comparing the retention time for qualitative determination, determining the peak positions of the benzene ring anhydride compounds and the ring-opened impurities in the liquid to be detected, and determining the relative contents of the benzene ring anhydride compounds and the ring-opened impurities in the liquid to be detected by a peak area normalization method.
Preferably, in step 1), the benzene ring anhydride compound standard is selected from one of 4,4 '-oxydiphthalic anhydride (ODPA), 4' - (hexafluoroisopropylidene) diphthalic anhydride (6 FDA) or 3,3', 4' -biphenyl tetracarboxylic dianhydride.
The CAS number for the 4,4' -oxydiphthalic anhydride (ODPA) was 1823-59-2. The CAS number of the 4,4' - (hexafluoroisopropylidene) diphthalic anhydride (6 FDA) is 1107-00-2. The CAS number of the 3,3', 4' -biphenyl tetracarboxylic dianhydride is 2420-87-3.
More preferably, the benzene ring anhydride compound standard is 4,4' -oxydiphthalic anhydride derivative and isomer of 4,4' -oxydiphthalic anhydride derivative contained in 4,4' -oxydiphthalic anhydride (ODPA).
Further preferably, the 4,4' -oxydiphthalic anhydride derivative has the structural formula
Further preferably, the isomer of the 4,4' -oxydiphthalic anhydride derivative has the structural formula
Preferably, in step 1), the open-loop impurity standard comprises ODPA double-sided open-loop impurity, ODPA single-sided open-loop impurity, and isomer of ODPA single-sided open-loop impurity.
More preferably, the ODPA double-sided ring-opening impurity is 4, 4-oxydiphthalic acid. The CAS number of the 4, 4-oxydiphthalic acid is 7717-76-2.
More preferably, the ODPA single-side ring-opened impurity has the structural formula ofWherein R is selected from CH 3O、C2H5 O,/>One of them. And R is a functional group structure connected after the reaction of the derivatization reagent.
Further preferably, the ODPA single-side ring-opened impurity has the structural formula of
More preferably, the isomer of the ODPA single-sided ring-opened impurity has the structural formula ofWherein R is selected from CH 3O、C2H5 O,/>One of them. And R is a functional group structure connected after the reaction of the derivatization reagent.
Further preferably, the isomer of the single-sided ring-opened impurity of ODPA has the structural formula of
Preferably, in the step 1), the ratio of the mass g of the benzene ring anhydride compound standard substance added to the volume ml of water added is 0.5-1.5:100.
Preferably, in step 1), the ratio of the mass g of the standard substance of the benzene ring anhydride compound added to the volume ml of the derivatizing agent added is 0.5-1.5:200, preferably 1:200.
Preferably, in the step 1), the ratio of the mass g of the benzene ring anhydride compound standard substance added to the volume ml of the organic solvent added is 0.5-1.5:1000, preferably 1:1000.
Preferably, in step 1), the ratio of the mass g of the addition of the ring-opened impurity standard substance to the volume ml of the addition of water is 0.5-1.5:100.
Preferably, in step 1), the ratio of the mass g of the ring-opened impurity standard addition to the volume ml of the derivatization reagent addition is 0.5-1.5:200, preferably 1:200.
Preferably, in step 1), the ratio of the mass g of the ring-opened impurity standard addition to the volume ml of the organic solvent addition is 0.5-1.5:1000, preferably 1:1000.
Preferably, in step 1), the derivatizing agent is selected from one of methanol, ethanol, cyclopentylamine or cyclohexylamine, preferably cyclohexylamine.
Preferably, in step 1), the organic solvent is acetonitrile.
In step 2), the blank solution is used for blank deduction.
Preferably, in step 2), the ratio of the volume of the derivatizing agent to the volume of the organic solvent added is 150 to 250:1000, preferably 200:1000.
Preferably, in step 1) or 2), the heating temperature is 70-90 ℃. More preferably, the temperature of the heating is 80 ℃.
Preferably, in step 1) or 2), the heating time is 2 to 5 hours. More preferably, the heating time is 3 hours.
Preferably, in step 1) or 2), the heating is performed using an oven.
Preferably, in step 1) or 2), the cooling is to room temperature. The room temperature is 20-30 ℃.
Preferably, in step 3), the detector employed in the liquid chromatography is an ultraviolet detector (UV).
Preferably, in the step 3), the chromatographic column adopted in the liquid chromatography is an octadecylsilane chemically bonded silica gel packed chromatographic column, the length of the chromatographic column is 15-25cm, the inner diameter is 0.40-0.50mm, and the thickness of the stationary phase film is 3.5-5 μm.
More preferably, the chromatographic column used in the liquid chromatography is AgilentZorbax XDB-C18, the column length is 15cm, the inner diameter is 0.46mm, and the stationary phase film thickness is 5 μm.
Preferably, in step 3), the column temperature used in the liquid chromatography is 30-40 ℃. More preferably, the column temperature used in the high performance liquid chromatography is 35 ℃.
Preferably, in step 3), the sample injection amount used in the liquid chromatography is 5.0-20.0 μl. More preferably, the sample injection amount used in the liquid chromatography is 10.0. Mu.L.
Preferably, in step 3), the flow rate used in the liquid chromatography is 0.8-1.2mL/min. More preferably, the flow rate employed in the liquid chromatography is 1.0mL/min.
Preferably, in step 3), the detection wavelength used in the liquid chromatography is 205-215nm. More preferably, the detection wavelength used in the liquid chromatography is 210nm.
Preferably, in the step 3), in the liquid chromatography, the mobile phase is 0.05-0.2% phosphoric acid aqueous solution-acetonitrile, wherein the phase A is 0.05-0.2% phosphoric acid aqueous solution, and the phase B is acetonitrile; the analysis time is 70min; gradient elution.
More preferably, in the liquid chromatography, the mobile phase is 0.1% phosphoric acid aqueous solution-acetonitrile, wherein the a phase is 0.1% phosphoric acid aqueous solution, and the B phase is acetonitrile; the analysis time is 70min; gradient elution.
The 0.05-0.2% phosphoric acid aqueous solution is 0.05-0.2% phosphoric acid aqueous solution by volume percent. The 0.1% phosphoric acid aqueous solution is a phosphoric acid aqueous solution with a volume percentage of 0.1%.
More preferably, as shown in table 1, the specific procedure of the gradient elution is:
0-5min, phase A: the volume ratio of the phase B is 90:10-90:10;
5-30min, phase A: the volume ratio of the phase B is 90:10-50:50;
30-40min, phase A: the volume ratio of the phase B is 50:50-5:95;
40-50min, phase A: the volume ratio of the phase B is 5:95-5:95;
50-55.01min, phase A: the volume ratio of the phase B is 5:95-90:10;
55.01-70min, phase A: the volume ratio of the phase B is 90:10-90:10.
TABLE 1
Preferably, in step 3), the peak area normalization method means: and detecting the benzene ring anhydride compound sample by HPLC, calculating to obtain chromatographic peak areas of the benzene ring anhydride compound and ring-opened impurities in the liquid to be detected, and calculating the sum of the areas of the chromatographic peaks after the blank solution is subtracted from the liquid to be detected to obtain the total chromatographic peak area. Then dividing the chromatographic peak area of the benzene ring anhydride compound by the total chromatographic peak area to obtain the percentage of the chromatographic peak area of the benzene ring anhydride compound to the total chromatographic peak area, namely the relative content of the benzene ring anhydride compound in the liquid to be detected.
Preferably, in step 3), the peak area normalization method is performed according to formula (1),
The formula (1) is: Wherein w i is the relative content of benzene ring anhydride compounds in the liquid to be detected; a i is the chromatographic peak area of the benzene ring anhydride compound in the liquid to be detected; sigma A i is the total chromatographic peak area of the liquid to be measured.
The water is pure water.
As described above, the method for detecting the purity of the benzene ring anhydride compound can realize the complete separation of the benzene ring anhydride compound and related impurities, thereby effectively measuring the purity of the benzene ring anhydride compound. The method can realize the effective separation of the benzene ring anhydride compound and the ring-opening impurity thereof, has good precision and accuracy and accurate result, can correctly reflect the purity quality of the benzene ring anhydride compound, and has very important significance for monitoring the quality of the benzene ring anhydride compound.
Drawings
Fig. 1 shows a liquid chromatogram of a blank solution for ODPA determination in the present invention.
Fig. 2 shows a liquid chromatogram of a positioning solution for determining ODPA in the present invention, wherein a is an ODPA double-sided ring-opened impurity, b is an ODPA single-sided ring-opened impurity, c is an isomer of the ODPA single-sided ring-opened impurity, d is an ODPA derivative, and e is an isomer of the ODPA derivative.
FIG. 3 shows a liquid chromatogram of a sample for determining actual benzene ring anhydride compounds in the present invention.
Detailed Description
The invention is further illustrated below in connection with specific examples, which are to be understood as being illustrative of the invention and not limiting the scope of the invention.
Other advantages and effects of the present invention will become apparent to those skilled in the art from the following disclosure, which describes the embodiments of the present invention with reference to specific examples. The invention may be practiced or carried out in other embodiments that depart from the specific details, and the details of the present description may be modified or varied from the spirit and scope of the present invention.
It should be understood that the process equipment or devices not specifically identified in the examples below are all conventional in the art; all pressure values and ranges refer to relative pressures.
Furthermore, it is to be understood that the reference to one or more method steps in this disclosure does not exclude the presence of other method steps before or after the combination step or the insertion of other method steps between these explicitly mentioned steps, unless otherwise indicated; it should also be understood that the combined connection between one or more devices/means mentioned in the present invention does not exclude that other devices/means may also be present before and after the combined device/means or that other devices/means may also be interposed between these two explicitly mentioned devices/means, unless otherwise indicated. Moreover, unless otherwise indicated, the numbering of the method steps is merely a convenient tool for identifying the method steps and is not intended to limit the order of arrangement of the method steps or to limit the scope of the invention in which the invention may be practiced, as such changes or modifications in their relative relationships may be regarded as within the scope of the invention without substantial modification to the technical matter.
The reagents and instrumentation used in the following examples were as follows:
1. Reagent(s)
4,4' -Oxybisphthalic anhydride Compound sample (Zhuo pharmaceutical chemical materials Co., ltd., changzhou). 4,4' -oxydiphthalic anhydride standard (purity >99.8%, boehmeria chemical industry development limited) in which both 4,4' -oxydiphthalic anhydride derivative and isomer of 4,4' -oxydiphthalic anhydride derivative are present. Open-loop impurity standard (merck, germany) in which an ODPA double-sided open-loop impurity, an ODPA single-sided open-loop impurity, and an isomer of ODPA single-sided open-loop impurity are present at the same time. Methanol, ethanol, cyclopentylamine, cyclohexylamine (purity not less than 99.9%, sigma-aldich); acetonitrile (chromatographic purity, merck, germany); pure water (self-made by Milibo pure water meter).
2. Instrument for measuring and controlling the intensity of light
Agilent type 1200 liquid chromatograph (Agilent, usa) equipped with an ultraviolet detector; agilentZorbax XDB-C18 (150X 0.46mm,5 μm) (Agilent, USA).
Example 1
1. Sample pretreatment
0.05G of benzene ring anhydride compound ODPA sample is taken, and derivatization reagent is added: cyclohexylamine 10ml and organic solvent: after 50ml of acetonitrile is mixed, the mixture is placed in an oven at 80 ℃ for heating for 3 hours, and the solution to be measured is obtained after cooling. Wherein, the concentration of the ODPA sample in the liquid to be tested is 0.05g (i.e. 50 mg)/50 mL=1 mg/mL.
Taking 0.05g of benzene ring anhydride compound standard substance and 0.05g of ring-opening impurity standard substance, adding 5ml of pure water, and then adding a derivatization reagent: cyclohexylamine 10ml and organic solvent: after 50ml of acetonitrile was mixed, the mixture was heated in an oven at 80℃for 3 hours, and the resultant was cooled to obtain a positioning solution. The benzene ring anhydride compound standard is 4,4' -oxydiphthalic anhydride derivative contained in 4,4' -oxydiphthalic anhydride (ODPA) and isomer of 4,4' -oxydiphthalic anhydride derivative.
Taking a derivatizing reagent: cyclohexylamine 10ml and organic solvent: after 50ml of acetonitrile was mixed, the mixture was heated in an oven at 80℃for 3 hours, and cooled to obtain a blank solution.
2. Measurement
And (2) detecting the liquid to be detected, the positioning solution and the blank solution prepared in the step (1) by adopting HPLC, comparing the retention time according to the measured value of the positioning solution, determining the peak positions of the benzene ring anhydride compound and the ring-opened impurity in the liquid to be detected, and determining the relative contents of the benzene ring anhydride compound and the ring-opened impurity in the liquid to be detected by a peak area normalization method. The liquid chromatogram of the specific measurement result is shown in figures 1,2 and 3, and the comparison of figures 1,2 and 3 shows that the separation effect of benzene ring anhydride compounds and ring-opening impurities in the positioning solution and the liquid to be measured is obvious. In fig. 2, a is ODPA double-sided ring-opened impurity: 4, 4-oxydiphthalic acid; b is ODPA unilateral ring-opening impurity with the structural formula ofC is an isomer of ODPA unilateral ring-opening impurity, and the structural formula isD is an ODPA derivative of the formula/>E is an isomer of an ODPA derivative having the structural formula/>
In specific measurement, the detection conditions of the HPLC method were: the detector is an ultraviolet detector (UV); the chromatographic column is AgilentZorbax XDB-C18 chromatographic column (150X0.46 mm,5 μm); the sample injection amount is 10 mu L; the flow rate is 1.0mL/min; the column temperature is 35 ℃; the detection wavelength is 210nm; the mobile phase is 0.1% phosphoric acid aqueous solution-acetonitrile, wherein the A phase is 0.1% phosphoric acid aqueous solution, and the B phase is acetonitrile; the analysis time is 70min; gradient elution.
The specific procedure for gradient elution is shown in table 1, as follows:
0-5min, phase A: the volume ratio of the phase B is 90:10-90:10;
5-30min, phase A: the volume ratio of the phase B is 90:10-50:50;
30-40min, phase A: the volume ratio of the phase B is 50:50-5:95;
40-50min, phase A: the volume ratio of the phase B is 5:95-5:95;
50-55.01min, phase A: the volume ratio of the phase B is 5:95-90:10;
55.01-70min, phase A: the volume ratio of the phase B is 90:10-90:10.
The peak area normalization method refers to: and detecting the benzene ring anhydride compound sample by HPLC, calculating to obtain chromatographic peak areas of the benzene ring anhydride compound and the ring-opened impurities in the liquid to be detected, and calculating the sum of the areas of all chromatographic peaks in the liquid to be detected to obtain the total chromatographic peak area. Then dividing the chromatographic peak area of the benzene ring anhydride compound by the total chromatographic peak area to obtain the percentage of the chromatographic peak area of the benzene ring anhydride compound to the total chromatographic peak area, namely the relative content of the benzene ring anhydride compound in the liquid to be detected.
The peak area normalization method is calculated according to a formula (1), wherein the formula (1) is as follows:
Wherein w i is the relative content of benzene ring anhydride compounds in the liquid to be detected; a i is the chromatographic peak area of the benzene ring anhydride compound in the liquid to be detected; sigma A i is the total chromatographic peak area of the liquid to be measured.
Example 2
1. Sample pretreatment
60Mg benzene ring anhydride compound ODPA sample is taken and put into a glass bottle which can be heated and sealed, 10mL cyclohexane and 50mL acetonitrile are added, and the glass bottle is placed into an oven at 80 ℃ for heating for 3 hours, and the liquid to be detected is obtained after cooling.
60Mg of benzene ring anhydride compound standard substance and 60mg of ring-opening impurity standard substance are taken to be placed in a glass bottle which can be heated and sealed, 5mL of pure water is added, 10mL of cyclohexylamine and 50mL of acetonitrile are added, and the mixture is placed in an oven at 80 ℃ to be heated for 3 hours, and then a positioning solution is obtained after cooling. The benzene ring anhydride compound standard is 4,4' -oxydiphthalic anhydride derivative contained in 4,4' -oxydiphthalic anhydride (ODPA) and isomer of 4,4' -oxydiphthalic anhydride derivative.
After adding 10mL of cyclohexylamine and 50mL of acetonitrile, the mixture was heated in an oven at 80 ℃ for 3 hours, and a blank solution was obtained after cooling.
2. Measurement
And (2) detecting the liquid to be detected, the positioning solution and the blank solution prepared in the step (1) by adopting HPLC, comparing the retention time according to the measured value of the positioning solution, determining the peak positions of the benzene ring anhydride compound and the ring-opened impurity in the liquid to be detected, and determining the relative contents of the benzene ring anhydride compound and the ring-opened impurity in the liquid to be detected by a peak area normalization method. The liquid chromatogram of the specific measurement results are shown in figures 1, 2 and 3, and the comparison of figures 1, 2 and 3 shows that the method has very good separation effect on benzene ring anhydride compounds and ring-opening impurities.
In specific measurement, the detection conditions of the HPLC method were: the detector is an ultraviolet detector (UV); the chromatographic column is AgilentZorbax XDB-C18 chromatographic column (150X0.46 mm,5 μm); the sample injection amount is 10 mu L; the flow rate is 1.0mL/min; the column temperature is 35 ℃; the detection wavelength is 210nm; the mobile phase is 0.1% phosphoric acid aqueous solution-acetonitrile, wherein the A phase is 0.1% phosphoric acid aqueous solution, and the B phase is acetonitrile; the analysis time is 70min; gradient elution.
The specific procedure for gradient elution is shown in table 1, as follows:
0-5min, phase A: the volume ratio of the phase B is 90:10-90:10;
5-30min, phase A: the volume ratio of the phase B is 90:10-50:50;
30-40min, phase A: the volume ratio of the phase B is 50:50-5:95;
40-50min, phase A: the volume ratio of the phase B is 5:95-5:95;
50-55.01min, phase A: the volume ratio of the phase B is 5:95-90:10;
55.01-70min, phase A: the volume ratio of the phase B is 90:10-90:10.
The peak area normalization method refers to: and detecting the benzene ring anhydride compound sample by HPLC, calculating to obtain chromatographic peak areas of the benzene ring anhydride compound and the ring-opened impurities in the liquid to be detected, and calculating the sum of the areas of all chromatographic peaks in the liquid to be detected to obtain the total chromatographic peak area. Then dividing the chromatographic peak area of the benzene ring anhydride compound by the total chromatographic peak area to obtain the percentage of the chromatographic peak area of the benzene ring anhydride compound to the total chromatographic peak area, namely the relative content of the benzene ring anhydride compound in the liquid to be detected.
The peak area normalization method is calculated according to a formula (1), wherein the formula (1) is as follows:
Wherein w i is the relative content of benzene ring anhydride compounds in the liquid to be detected; a i is the chromatographic peak area of the benzene ring anhydride compound in the liquid to be detected; sigma A i is the total chromatographic peak area of the liquid to be measured.
Example 3
3 Benzene ring anhydride compounds ODPA samples produced by different manufacturers are respectively taken, the numbers are 1#, 2#, 3#, a liquid to be detected, a positioning solution and a blank solution are prepared according to the step 1 in the example 2, the measurement is carried out according to the step 2 in the example 2, and the relative content of the ODPA in the liquid to be detected is respectively calculated according to the formula (1). Each identical sample was assayed 5 times in parallel and the results are shown in tables 2 and 3. As can be seen from tables 2 and 3, the relative content of ODPA was measured by this method, RSD was less than 0.2%, and the ring-opened impurity of ODPA was measured: the RSD of the relative content measurement result of the ODPA unilateral ring-opening impurity derivative is less than 0.1 percent, and the method has high precision and good repeatability.
Table 2 precision results of sample determination of ODPA relative content (n=5)
Table 3 sample precision results (n=5) for determining the relative content of open-loop impurities of ODPA
Example 4
Taking a 4,4' -oxydiphthalic anhydride standard (purity is > 99.8%) as a sample, preparing a liquid to be detected, a positioning solution and a blank solution according to the step 1 in the example 2, measuring according to the step 2 in the example 2, comparing the measured value with a standard identification value, and respectively calculating the relative content of ODPA in the liquid to be detected through a formula (1). The results of 5 replicates are shown in Table 4. As is clear from Table 4, the relative content of ODPA was measured by this method, and the RSD was less than 0.05%, and the accuracy of the measurement was high.
Table 4 method accuracy test results validation data
Example 5
Taking ODPA sample numbered 2# in example 3, preparing a test sample according to step 1 and preparing a positioning solution according to step 2 in example 2, and eluting with different proportions of mobile phases when detecting the test solution by HPLC, wherein the measurement results are shown in Table 5.
TABLE 5 determination of the different eluent ratios
As is clear from Table 5, when the gradient elution is performed under the preferable conditions according to the present invention in step 2 of example 2, the main peak and the adjacent impurity can be effectively separated by combining the factors such as the degree of separation of the main peak from the adjacent impurity components, the peak shape and the impurity elution.
In summary, the method for detecting the purity of the benzene ring anhydride compound can realize complete separation of the benzene ring anhydride compound and related ring-opening impurities, and has the advantages of good precision, accurate result, simple quantitative method and good repeatability. Therefore, the invention effectively overcomes various defects in the prior art and has high industrial utilization value.
The above embodiments are merely illustrative of the principles of the present invention and its effectiveness, and are not intended to limit the invention. Modifications and variations may be made to the above-described embodiments by those skilled in the art without departing from the spirit and scope of the invention. Accordingly, it is intended that all equivalent modifications and variations of the invention be covered by the claims, which are within the ordinary skill of the art, be within the spirit and scope of the present disclosure.

Claims (6)

1. A method for detecting purity of benzene ring anhydride compounds comprises the following steps: adding a derivatization reagent and an organic solvent into a benzene ring anhydride compound sample, heating, cooling to obtain a liquid to be detected, detecting by adopting a liquid chromatography, comparing the retention time for qualitative determination, and determining the relative contents of the benzene ring anhydride compound and ring-opening impurities in the liquid to be detected by a peak area normalization method so as to determine the purity of the benzene ring anhydride compound;
the derivatizing agent is cyclohexylamine; the benzene ring anhydride compound is 4,4' -oxydiphthalic anhydride;
the detection by liquid chromatography comprises the following steps:
1) Adding water into a benzene ring anhydride compound standard substance and a ring-opening impurity standard substance, adding a derivatization reagent and an organic solvent, heating and cooling to obtain a positioning solution;
2) Mixing the derivatization reagent with an organic solvent, heating and cooling to obtain a blank solution;
3) Detecting the liquid to be detected, the positioning solution in the step 1) and the blank solution in the step 2) by adopting a liquid chromatography method, comparing the retention time for qualitative determination, determining the peak positions of the benzene ring anhydride compounds and the ring-opening impurities in the liquid to be detected, and determining the relative contents of the benzene ring anhydride compounds and the ring-opening impurities in the liquid to be detected by a peak area normalization method;
In the step 1), the standard substance of the benzene ring anhydride compound is 4,4' -oxydiphthalic anhydride;
In the step 1), the open-loop impurity standard substance comprises ODPA double-side open-loop impurities, ODPA single-side open-loop impurities and isomers of the ODPA single-side open-loop impurities; the ODPA bilateral ring-opening impurity is 4, 4-oxydiphthalic acid; the structural formula of the ODPA unilateral ring-opening impurity is The structural formula of the isomer of the ODPA unilateral ring-opened impurity is/>The R is a functional group structure connected after the reaction of the derivatization reagent, and the R is
In step 3), the liquid chromatography includes the following detection conditions: the detector is an ultraviolet detector UV; the chromatographic column adopts octadecylsilane chemically bonded silica filler chromatographic column; the detection wavelength is 205-215nm; the mobile phase is 0.05-0.2% phosphoric acid aqueous solution-acetonitrile, wherein, the A phase is 0.05-0.2% phosphoric acid aqueous solution, and the B phase is acetonitrile; the analysis time is 70min; gradient elution;
The specific procedure of the gradient elution is as follows: 0-5min, phase A: the volume ratio of the phase B is 90:10-90:10;5-30min, phase A: the volume ratio of the phase B is 90:10-50:50;30-40min, phase A: the volume ratio of the phase B is 50:50-5:95;40-50min, phase A: the volume ratio of the phase B is 5:95-5:95;50-55.01min, phase A: the volume ratio of the phase B is 5:95-90:10;55.01-70min, phase A: the volume ratio of the phase B is 90:10-90:10.
2. The method for detecting purity of benzene ring anhydride compound according to claim 1, characterized by comprising any one or more of the following conditions:
a1 The organic solvent is acetonitrile;
A2 The ratio of the added mass of the benzene ring anhydride compound sample to the added volume of the derivatization reagent is 0.5-1.5:200, g/ml;
A3 The ratio of the added mass of the benzene ring anhydride compound sample to the added volume of the organic solvent is 0.5-1.5:1000,
g/ml；
A4 The temperature of the heating is 70-90 ℃;
A5 The heating time is 2-5 hours.
3. The method for detecting purity of benzene ring anhydride compound according to claim 1, wherein in step 1), the benzene ring anhydride compound standard substance is an isomer containing 4,4' -oxydiphthalic anhydride derivative and 4,4' -oxydiphthalic anhydride derivative in 4,4' -oxydiphthalic anhydride.
4. The method for detecting purity of benzene ring anhydride compound according to claim 1, wherein any one or more of the following conditions are included in step 1) or 2):
B1 In the step 1), the ratio of the added mass of the standard substance of the benzene ring anhydride compound to the added volume of water is 0.5-1.5:100, g/ml;
B2 In the step 1), the ratio of the added mass of the standard substance of the benzene ring anhydride compound to the added volume of the derivatization reagent is 0.5-1.5:200, g/ml;
B3 In the step 1), the ratio of the added mass of the standard substance of the benzene ring anhydride compound to the added volume of the organic solvent is 0.5-1.5:1000, g/ml;
B4 In the step 1), the ratio of the added mass of the ring-opened impurity standard substance to the added volume of water is 0.5-1.5:100,
g/ml；
B5 In step 1), the ratio of the added mass of the ring-opened impurity standard substance to the added volume of the derivatization reagent is 0.5-1.5:200, g/ml;
B6 In the step 1), the ratio of the added mass of the ring-opened impurity standard substance to the added volume of the organic solvent is 0.5-1.5:1000, g/ml;
B7 In step 2), the ratio of the derivatizing agent to the volume of organic solvent added is 150-250:1000;
b8 In step 1) or 2), the heating temperature is 70-90 ℃;
b9 In step 1) or 2), the heating time is 2-5 hours.
5. The method for detecting purity of benzene ring anhydride compound according to claim 1, wherein in step 3), the liquid chromatography further comprises the following detection conditions: the column temperature is 30-40 ℃; the sample injection amount is 5.0-20.0 mu L; the flow rate is 0.8-1.2mL/min.
6. The method for detecting purity of benzene ring anhydride compound according to claim 1, wherein in step 3), the peak area normalization method is calculated according to formula (1), and formula (1) is: Wherein w i is the relative content of benzene ring anhydride compounds in the liquid to be detected; a i is the chromatographic peak area of the benzene ring anhydride compound in the liquid to be detected; sigma A i is the total chromatographic peak area of the liquid to be measured.
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