CN114166883A - Detection method for measuring HBIW purity by nuclear magnetic resonance hydrogen spectrometry - Google Patents
Detection method for measuring HBIW purity by nuclear magnetic resonance hydrogen spectrometry Download PDFInfo
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- 238000005481 NMR spectroscopy Methods 0.000 title claims abstract description 39
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 title claims abstract description 37
- 229910052739 hydrogen Inorganic materials 0.000 title claims abstract description 37
- 239000001257 hydrogen Substances 0.000 title claims abstract description 37
- 238000001514 detection method Methods 0.000 title claims abstract description 14
- 238000004611 spectroscopical analysis Methods 0.000 title claims abstract description 11
- 239000000126 substance Substances 0.000 claims abstract description 38
- 238000000034 method Methods 0.000 claims abstract description 26
- 238000001228 spectrum Methods 0.000 claims abstract description 21
- ZPTVNYMJQHSSEA-UHFFFAOYSA-N 4-nitrotoluene Chemical compound CC1=CC=C([N+]([O-])=O)C=C1 ZPTVNYMJQHSSEA-UHFFFAOYSA-N 0.000 claims abstract description 18
- 238000012360 testing method Methods 0.000 claims abstract description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical group CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 12
- CSCPPACGZOOCGX-WFGJKAKNSA-N deuterated acetone Substances [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 claims description 12
- 239000003153 chemical reaction reagent Substances 0.000 claims description 9
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 claims description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 claims description 5
- 230000005284 excitation Effects 0.000 claims description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 claims description 3
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 claims description 3
- 238000005303 weighing Methods 0.000 claims description 3
- 239000004576 sand Substances 0.000 claims description 2
- 238000004458 analytical method Methods 0.000 abstract description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract description 7
- 238000004128 high performance liquid chromatography Methods 0.000 abstract description 5
- 238000012216 screening Methods 0.000 abstract description 3
- 239000007859 condensation product Substances 0.000 abstract description 2
- 238000010813 internal standard method Methods 0.000 abstract description 2
- IUKZSMGVHPBEHK-UHFFFAOYSA-N hexabenzilisovyurtsitan Chemical compound C=1C=CC=CC=1CN(C1C(N(CC=2C=CC=CC=2)C(N2CC=3C=CC=CC=3)C3N1CC=1C=CC=CC=1)N1CC=4C=CC=CC=4)C1C2N3CC1=CC=CC=C1 IUKZSMGVHPBEHK-UHFFFAOYSA-N 0.000 description 65
- 230000000052 comparative effect Effects 0.000 description 19
- 239000012535 impurity Substances 0.000 description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
- 238000013094 purity test Methods 0.000 description 6
- NDYLCHGXSQOGMS-UHFFFAOYSA-N CL-20 Chemical compound [O-][N+](=O)N1C2N([N+]([O-])=O)C3N([N+](=O)[O-])C2N([N+]([O-])=O)C2N([N+]([O-])=O)C3N([N+]([O-])=O)C21 NDYLCHGXSQOGMS-UHFFFAOYSA-N 0.000 description 5
- 238000004364 calculation method Methods 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 238000001225 nuclear magnetic resonance method Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- NINQAYBICGTGQD-UHFFFAOYSA-N 1-(6,8,12-triacetyl-4,10-dibenzyl-2,4,6,8,10,12-hexazatetracyclo[5.5.0.03,11.05,9]dodecan-2-yl)ethanone Chemical compound CC(=O)N1C2C(N3CC=4C=CC=CC=4)N(C(=O)C)C1C(N1C(C)=O)N(C(C)=O)C3C1N2CC1=CC=CC=C1 NINQAYBICGTGQD-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- CZZYITDELCSZES-UHFFFAOYSA-N diphenylmethane Chemical group C=1C=CC=CC=1CC1=CC=CC=C1 CZZYITDELCSZES-UHFFFAOYSA-N 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 description 2
- 238000007327 hydrogenolysis reaction Methods 0.000 description 2
- 150000002894 organic compounds Chemical class 0.000 description 2
- -1 oxalyl dibenzylamine Chemical compound 0.000 description 2
- 238000004445 quantitative analysis Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- YGSFNCRAZOCNDJ-TXHXQZCNSA-N [2H]C(C(=O)C([2H])([2H])[2H])([2H])[2H].CC(=O)C Chemical group [2H]C(C(=O)C([2H])([2H])[2H])([2H])[2H].CC(=O)C YGSFNCRAZOCNDJ-TXHXQZCNSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 229940015043 glyoxal Drugs 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- BSCHIACBONPEOB-UHFFFAOYSA-N oxolane;hydrate Chemical group O.C1CCOC1 BSCHIACBONPEOB-UHFFFAOYSA-N 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000012113 quantitative test Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 238000012916 structural analysis Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N24/00—Investigating or analyzing materials by the use of nuclear magnetic resonance, electron paramagnetic resonance or other spin effects
- G01N24/08—Investigating or analyzing materials by the use of nuclear magnetic resonance, electron paramagnetic resonance or other spin effects by using nuclear magnetic resonance
- G01N24/087—Structure determination of a chemical compound, e.g. of a biomolecule such as a protein
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/38—Diluting, dispersing or mixing samples
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Abstract
The invention relates to a detection method for measuring HBIW purity by a nuclear magnetic resonance hydrogen spectrometry, and belongs to the technical field of condensation product purity analysis. The method adopts a nuclear magnetic resonance hydrogen spectrum internal standard method to detect the purity of the HBIW sample for the first time, and selects a 4-nitrotoluene standard substance as an internal standard substance according to the structural characteristics of the HBIW sample, an H peak on a methyl existing at delta 2.34 is an internal standard substance characteristic peak, and an H peak on a CH on a cage body at delta 3.42 is an HBIW characteristic peak; through screening the delay time and the scanning times in the nuclear magnetic resonance hydrogen spectrum test, the accuracy of sample purity detection is improved, and the error rate is as low as +/-0.7%. The method can effectively measure the purity of HBIW, and has the advantages of simple operation, cheap and easily-obtained internal standard substance, good repeatability, safety and high efficiency compared with the traditional high performance liquid chromatography.
Description
Technical Field
The invention relates to a detection method for measuring HBIW purity by a nuclear magnetic resonance hydrogen spectrometry, and belongs to the technical field of condensation product purity analysis.
Background
Hexanitrohexaazaisowurtzitane (HNIW, also known as CL-20) is the single explosive with the highest energy level which is prepared in batches at present. The synthesis of CL-20 firstly needs to construct a cage structure by simple small molecule condensation, and the current production line for preparing CL-20 by engineering uses Hexabenzylhexaazaisowurtzitane (HBIW) as a cage parent. HBIW is easy to decompose under acidic conditions and can not be directly nitrified, Tetraacetyldibenzylhexaazaisowurtzitane (TADB) is obtained by primary hydrogenolysis with a noble metal catalyst, but a plurality of side reactions exist in the HBIW synthesis process, which causes the purity of HBIW to be reduced, for example, in the prior art, HBIW is prepared by aldehyde-amine condensation reaction of glyoxal and benzylamine under the catalysis of acid, and oxalyl dibenzylamine impurities exist in the HBIW product prepared by the method, so that the catalyst is poisoned by the impurities, and the hydrogenolysis efficiency is reduced or even fails.
At present, an effective HBIW purity analysis technology is not available, High Performance Liquid Chromatography (HPLC) is generally adopted for analysis, but the method has too short retention time and is easily interfered by other components, and the mobile phase is tetrahydrofuran and water, so that the instrument is corroded, and the human body is greatly damaged. Therefore, it is very necessary to establish a convenient, efficient, safe and reliable HBIW purity detection method.
The quantitative nuclear magnetic resonance hydrogen spectrum technology is mainly used for the structure determination of organic compounds, is also an important means for the quantitative analysis of the organic compounds, and has the basic principle that1The area of a formant in H-NMR is proportional to the number of hydrogen atoms contained in the formant, and when a quantitative measurement is performed, the absolute content can be determined by comparing only the integral value of a formant generated by a proton on a predetermined group in a compound to be measured with the integral value of a formant generated by a proton on a predetermined group in a reference standard. The basic principle of internal standard peak selection of the quantitative nuclear magnetic resonance method is that the internal standard substance is a high-purity or easily refined compound, does not react with any component in a determination solution, has a simple nuclear magnetic spectrum, can preferably generate a single resonance peak, and the position of a determination signal of a sample and the internal standard substance has at least 30Hz interval.
The quantitative nuclear magnetic resonance hydrogen spectrometry has the advantages of rapidness, accuracy, less required sample amount, no need of using a pure product of the sample as a reference standard, no damage to the sample in the measurement process and the like, and the current pharmacopoeias of many countries and regions contain quantitative nuclear magnetic analysis methods. Due to the structural characteristics of the HBIW substance, the selection of an internal standard substance and the selection of a sample characteristic peak have difficulty, and the accuracy of a purity test result is greatly influenced by the screening and setting of quantitative nuclear magnetic scanning parameters. Reports on the determination of HBIW purity by quantitative hydrogen nuclear magnetic resonance spectroscopy are not seen at present.
Disclosure of Invention
In order to overcome the defects in the prior art, the invention aims to provide a detection method for measuring HBIW purity by a nuclear magnetic resonance hydrogen spectrometry.
In order to achieve the purpose of the invention, the following technical scheme is provided.
A detection method for measuring HBIW purity by a nuclear magnetic resonance hydrogen spectrometry method comprises the following steps:
(1) respectively quantitatively weighing 1 mg-10 mg HBIW sample and 1 mg-10 mg internal standard substance, dissolving in 0.5 mL-1.0 mL deuterated reagent, setting the hydrogen spectrum determination conditions for nuclear magnetic resonance, and performing hydrogen spectrum test for nuclear magnetic resonance;
wherein the mass ratio of the HBIW sample to the internal standard substance is 1: 1-1: 2.
Preferably, the ratio of the HBIW sample mass (mg) to the deuterated reagent volume (mL) is 7.8: 1-10.3: 1.
The internal standard substance is a 4-nitrotoluene standard substance.
The deuterated reagent is deuterated Acetone (Acetone-d6), deuterated chloroform or deuterated dimethyl sulfoxide, and is preferably deuterated Acetone.
The nuclear magnetic resonance hydrogen spectrum determination conditions are as follows:
the resonance frequency of the nuclear magnetic spectrometer is above 400MHz, preferably 400 MHz-600 MHz;
the delay time is 20 s-30 s;
the number of scans was 32 to 128.
Preferably, the temperature is 20-30 ℃;
preferably, the excitation pulse angle is 30 °;
(2) determining the hydrogen nuclear magnetic resonance spectrum of step (1)Measuring characteristic peaks of HBIW and internal standard substance, and determining relative integral area A of characteristic peak of HBIWSAnd the relative integral area A of the characteristic peak of the internal standard substanceRSubstituting the data into formula (1) to calculate the quality score P of HBIWS％。
Wherein, PRIs the purity of the internal standard; a. theRIs the integral area of the characteristic peak of the internal standard substance; wSThe mass of the HBIW sample; wRIs the mass of the internal standard.
ESFor HBIW proton equivalent, it can be specifically calculated by equation (2):
wherein M isSRelative molecular mass for HBIW; n is a radical ofSThe number of protons for the characteristic peak was chosen for HBIW.
ERThe proton equivalent of the internal standard can be specifically calculated by the following formula (3):
wherein M isRRelative molecular mass as internal standard; n is a radical ofRThe proton number is the characteristic peak of the internal standard substance.
The structural formula of HBIW is shown in the following figure, wherein 1-12 represent the number of the original element on the cage body.
According to1H-NMR spectrum, HBIW has four groups of peaks,1four sets of peaks in the H-NMR spectrum correspond to the following positions in the HBIW structure as shown above: the peak at delta 3.42 is the H peak on C (1) and C (7) CH on the cage, delta 3.98 ℃The peak at 3.99 is benzyl CH2The peak at delta 4.10 is the H peak on CH at C (3), C (5), C (9) and C (11) positions on the cage body, and the peak at delta 7.12-7.13 is the H peak on a benzyl benzene ring. According to the structure and the property of an HBIW sample, in the actual experiment and calculation process, the distance between the peak at the position delta 3.98-3.99 and the peak at the position delta 4.10 is too close to be easily distinguished; the peak at delta 7.12-7.13 is the H peak on the benzene ring of benzyl, the H peak on the benzene ring of the impurity oxalyl dibenzylamine also exists at the position, and the characteristic peak at 7.12-7.13 leads to higher measurement result because of the existence of the impurity, so the H peaks on the CH positions of C (1) and C (7) on the cage body at delta 3.42 are selected as the characteristic peaks of the sample HBIW.
According to1In an H-NMR spectrum, 4-nitrotoluene has three groups of peaks, namely a peak at delta 2.34 which is an H peak on a methyl group, peaks at delta 7.32-7.35 which are H peaks on a 2-position and a 6-position on a benzene ring, and peaks at delta 7.99-8.01 which are H peaks on a 3-position and a 5-position on the benzene ring. According to the basic principle of internal standard substance characteristic peak selection of the quantitative nuclear magnetic resonance method, the peak at delta 2.34 is an H peak on a methyl group, is not the same as four groups of peaks of a sample HBIW in type, and does not influence the quantitative test result; and the distance interval between the peak at delta 2.34 and the characteristic peak delta 3.42 of the HBIW sample is moderate, so that the methyl peak at delta 2.34 of 4-nitrotoluene is selected as the characteristic peak of the internal standard substance for calculation and analysis.
The peak at δ 1.91 is the deuterated acetone solvent peak, and the peak at δ 2.67 is the peak of residual water in the solvent.
Advantageous effects
1. The invention provides a method for detecting HBIW purity, which adopts a nuclear magnetic resonance hydrogen spectrum internal standard method to detect the purity of an HBIW sample for the first time, improves the accuracy of sample purity detection by screening delay time and scanning times, and reduces the error rate to +/-0.7%.
2. The invention provides a method for detecting HBIW purity, which is characterized in that according to the structural characteristics of an HBIW sample, a 4-nitrotoluene standard substance is selected as an internal standard substance, 4-nitrotoluene has an H peak on a methyl at delta 2.34, and from structural analysis, the peak is not the same as four groups of peaks in the HBIW sample in type, and the quantitative analysis of a product is not influenced; according to the analysis on the peak position, the sample to be detected has no peak near delta 2.34, so that the sample to be detected cannot be interfered, and the accuracy of the purity detection is improved by accurately selecting the internal standard substance.
3. The invention provides a method for detecting HBIW purity, which selects a 4-nitrotoluene standard substance as an internal standard substance according to the structure and the property of HBIW, and takes an H peak on CH on a cage body at delta 3.42 as an HBIW characteristic peak; the method can effectively measure the purity of HBIW, and has the advantages of simple operation, cheap and easily-obtained internal standard substance, good repeatability, safety and high efficiency compared with the traditional high performance liquid chromatography.
Drawings
FIG. 1 is a NMR chart of example 1.
Detailed Description
The invention is described in detail below with reference to the drawings and specific examples, but the invention is not limited thereto.
The materials used in the following examples and comparative examples are all conventionally commercially available unless otherwise specified.
4-nitrotoluene as a standard substance, with a purity of 99.5%, was purchased from Shanghai Aladdin Biochemical Co., Ltd.
The liquid chromatography instrument model is Agilent high performance liquid chromatograph 1260.
The model of the nuclear magnetic resonance spectrometer is a Bruker ADVANCE 400 type superconducting nuclear magnetic resonance spectrometer.
Example 1
A detection method for measuring HBIW purity by a nuclear magnetic resonance hydrogen spectrometry method comprises the following steps:
(1) respectively quantitatively weighing 3.91mg of HBIW sample and 4.01mg of 4-nitrotoluene, placing the HBIW sample and the 4.01mg of 4-nitrotoluene in a sample bottle, adding 0.5mL of deuterated acetone, setting the determination conditions of the nuclear magnetic resonance hydrogen spectrum, and performing the nuclear magnetic resonance hydrogen spectrum test;
the nuclear magnetic resonance hydrogen spectrum determination conditions are as follows: the resonance frequency of the nuclear magnetic spectrometer is 400 MHz; the scanning times are 32 times, the delay time is 20s, and the temperature is 25 ℃; the excitation pulse angle is 30 degrees; (2) and (3) determining characteristic peaks of HBIW and the internal standard substance in the nuclear magnetic resonance hydrogen spectrum in the step (1). Example 1 NMR results are shown in FIG. 1, in which the peak No. 1 is HBIW and the peak No. 2 is 4-nitrotoluenePeaks, HBIW had four sets of peaks, respectively: the peak at delta 3.42 is the H peak on the CH at the C (1) and C (7) positions on the cage body, and the peak at delta 3.98-3.99 is benzyl CH2The peak at delta 4.10 is the H peak on CH at C (3), C (5), C (9) and C (11) positions on the cage body, and the peak at delta 7.12-7.13 is the H peak on a benzyl benzene ring. According to the structure and the property of the HBIW sample and impurities, in the practical experiment and calculation process, the peak at the position delta 3.42 is minimally affected by the impurities, and the H peak on CH on the cage body at the position delta 3.42 of the HBIW sample is selected as a characteristic peak by the method.
The 4-nitrotoluene has three groups of peaks, wherein the peak at delta 2.34 is an H peak on a methyl group, the peaks at delta 7.32-7.35 are H peaks on a 2-position and a 6-position on a benzene ring, and the peaks at delta 7.99-8.01 are H peaks on a 3-position and a 5-position on the benzene ring. According to the basic principle of internal standard peak selection of the quantitative nuclear magnetic resonance method, a methyl peak at delta 2.34 of 4-nitrotoluene is selected as an internal standard peak for calculation and analysis.
The peak at δ 1.91 is the deuterated acetone solvent peak, and the peak at δ 2.67 is the peak of residual water in the solvent.
Determination of the relative integral area A of the characteristic peaks of HBIWSIs 2, relative integral area A of characteristic peak of internal standard substanceRAt 17.33, substituting the data into equation (1) calculates the HBIW quality score PSThe% is 91.34%.
ESFor HBIW proton equivalent, it can be specifically calculated by equation (2):
wherein M isSRelative molecular mass 708.92 for HBIW; n is a radical ofSThe number of protons for the characteristic peak selected for HBIW was 2, ES＝354.46。
ERThe proton equivalent of the internal standard can be specifically calculated by the following formula (3):
wherein M isRRelative molecular mass 137.14 for internal standard; n is a radical ofRThe number of protons is 3 for the characteristic peak of the internal standard substance, ER＝45.71。
Example 2
Example 2 on the basis of example 1, only the delay time in step (1) was replaced from 20s to 30s, and the remaining parameters and conditions were unchanged.
Example 3
Example 3 on the basis of example 1, only the number of scans in step (1) was changed from 32 to 64, and the remaining parameters and conditions were unchanged.
Example 4
Example 4 on the basis of example 1, only the number of scans in step (1) was changed from 32 to 128, and the remaining parameters and conditions were unchanged.
Example 5
Example 5 on the basis of example 1, only the deuterated reagent in step (1) was replaced by deuterated chloroform from deuterated acetone, and the rest parameters and conditions were not changed.
Example 6
Example 6 on the basis of example 1, only the deuterated reagent in step (1) is replaced by deuterated acetone and deuterated dimethyl sulfoxide, and the rest parameters and conditions are not changed.
Example 7
Example 7 on the basis of example 1, only the temperature in step (1) was changed from 25 ℃ to 28 ℃, and the remaining parameters and conditions were not changed.
Example 8
Example 8 on the basis of example 1, only the nuclear magnetic resonance frequency in step (1) was replaced from 400MHz to 600MHz, and the remaining parameters and conditions were unchanged.
Example 9
Example 9 on the basis of example 1, 3.91mg of HBIW and 4.01mg of 4-nitrotoluene in step (1) were replaced with 5.84mg of HBIW and 5.74mg of 4-nitrotoluene, and 0.5mL of deuterated acetone was replaced with 0.7mL of deuterated acetone, with the remaining parameters and conditions unchanged.
Example 10
Example 10 on the basis of example 1, only 3.91mg of HBIW and 4.01mg of 4-nitrotoluene in step (1) were replaced with 9.27mg of HBIW and 9.42mg of 4-nitrotoluene, and 0.5mL of deuterated acetone was replaced with 0.9mL of deuterated acetone, with the remaining parameters and conditions being unchanged.
Comparative example 1
The purity of the HBIW sample was tested using conventional high performance liquid chromatography.
The specific test conditions are as follows: the chromatographic column is H & E C18(5 μm, 100A; 4.6X 250 mm); the mobile phase is tetrahydrofuran-water (75/25, V/V); the flow rate is 0.8 mL/min; the column temperature is 25 ℃; the detection wavelength was 241 nm.
Comparative example 2
Comparative example 2 on the basis of example 1, only the delay time in step (1) was replaced from 20s to 2s, and the remaining parameters and conditions were unchanged.
Comparative example 3
Comparative example 3 on the basis of example 1, only the delay time in step (1) was replaced from 20s to 5s, and the remaining parameters and conditions were unchanged.
Comparative example 4
Comparative example 4 on the basis of example 1, only the delay time in step (1) was replaced from 20s to 10s, and the remaining parameters and conditions were unchanged.
Comparative example 5
Comparative example 5 on the basis of example 1, only the number of scans in step (1) was changed from 32 to 4, and the remaining parameters and conditions were unchanged.
Comparative example 6
Comparative example 6 on the basis of example 1, only the number of scans in step (1) was changed from 32 to 8, and the remaining parameters and conditions were unchanged.
Comparative example 7
Example 7 on the basis of example 1, only the number of scans in step (1) was changed from 32 to 16, and the remaining parameters and conditions were unchanged.
The NMR spectra of examples 2 to 10 and comparative examples 2 to 7 were similar to that of example 1. The index parameters and the corresponding purity test results of the HBIW sample in examples 1-10 and comparative examples 2-7 and the purity test results of the HBIW sample in comparative example 1 are shown in Table 1.
Table 1 shows each index parameter in examples 1 to 10 and comparative examples 2 to 7, and corresponding HBIW purity test results, and HBIW purity test results in comparative example 1
The experimental result shows that the delay time and the scanning times are key parameters influencing the accuracy of the purity of the HBIW (hydrogen nuclear magnetic resonance) of the HBIW. When the delay time is 20-30 s and the scanning times are 32-128 times, the error of the purity of the HBIW measured by the quantitative nuclear magnetic resonance hydrogen spectrum and the purity measured by the traditional high performance liquid chromatography in the comparative example 1 is within +/-0.7 percent, and the purity test requirement of the HBIW is met. The method is simple to operate, the internal standard substance is cheap and easy to obtain, the repeatability is good, the method is safe and efficient, and the method can be used as a preferred method for analyzing the purity of HBIW.
Claims (7)
1. A detection method for measuring HBIW purity by a nuclear magnetic resonance hydrogen spectrometry is characterized by comprising the following steps: the method comprises the following steps:
(1) respectively quantitatively weighing 1 mg-10 mg HBIW sample and 1 mg-10 mg internal standard substance, dissolving in 0.5 mL-1.0 mL deuterated reagent, setting the hydrogen spectrum determination conditions for nuclear magnetic resonance, and performing hydrogen spectrum test for nuclear magnetic resonance;
wherein the mass ratio of the HBIW sample to the internal standard substance is 1: 1-1: 2;
the deuterated reagent is deuterated acetone, deuterated chloroform or deuterated dimethyl sulfoxide;
the internal standard substance is a 4-nitrotoluene standard substance;
the nuclear magnetic resonance hydrogen spectrum determination conditions are as follows:
the resonance frequency of the nuclear magnetic spectrometer is above 400 MHz;
the delay time is 20 s-30 s;
the scanning times are 32-128 times;
(2) determining characteristic peaks of HBIW and internal standard substance in hydrogen nuclear magnetic resonance spectrum, and determining relative integral area A of HBIW characteristic peakSAnd the relative integral area A of the characteristic peak of the internal standard substanceRSubstituting the data into formula (1) to calculate the quality score P of HBIWS％；
Wherein, PRIs the purity of the internal standard; a. theRIs the integral area of the characteristic peak of the internal standard substance; wSThe mass of the HBIW sample; wRIs the mass of the internal standard;
ESfor HBIW proton equivalent, it can be specifically calculated by equation (2):
wherein M isSRelative molecular mass for HBIW; n is a radical ofSSelecting the proton number of the characteristic peak for HBIW;
ERthe proton equivalent of the internal standard can be specifically calculated by the following formula (3):
wherein M isRRelative molecular mass as internal standard; n is a radical ofRThe number of protons is the characteristic peak of the internal standard substance;
selecting HBIW1Delta 3.42 position in H-NMR spectrumThe peak of (a) is a characteristic peak of the sample HBIW;
of 4-nitrotoluene1The peak at delta 2.34 in the H-NMR spectrum is taken as the characteristic peak of the internal standard substance.
2. The detection method for detecting the purity of HBIW by the hydrogen nuclear magnetic resonance spectroscopy according to claim 1, which is characterized in that: the volume ratio of the HBIW sample mass to the deuterated reagent is 7.8: 1-10.3: 1.
3. The method for detecting the purity of HBIW by hydrogen nuclear magnetic resonance spectroscopy according to claim 1 or 2, which is characterized in that: the deuterated reagent is deuterated acetone.
4. The method for detecting the purity of HBIW by hydrogen nuclear magnetic resonance spectroscopy according to claim 1 or 2, which is characterized in that: the resonance frequency of the nuclear magnetic spectrometer is 400 MHz-600 MHz.
5. The method for detecting the purity of HBIW by hydrogen nuclear magnetic resonance spectroscopy according to claim 1 or 2, which is characterized in that: the temperature for measuring the hydrogen spectrum of nuclear magnetic resonance is 20-30 ℃.
6. The method for detecting the purity of HBIW by hydrogen nuclear magnetic resonance spectroscopy according to claim 1 or 2, which is characterized in that: the excitation pulse angle was 30 ° as measured by nmr hydrogen spectroscopy.
7. The method for detecting HBIW purity by NMR spectroscopy according to claim 4, wherein the method comprises the following steps: the nuclear magnetic resonance hydrogen spectrum measuring temperature is 20-30 ℃; the excitation pulse angle was 30 ° as measured by nmr hydrogen spectroscopy.
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