CN111965208A - Method for measuring content of 1-bromoethyl acetate and structural analogue thereof - Google Patents
Method for measuring content of 1-bromoethyl acetate and structural analogue thereof Download PDFInfo
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- 238000000034 method Methods 0.000 title claims abstract description 44
- IIASCQBFNHWZBE-UHFFFAOYSA-N 1-bromoethyl acetate Chemical compound CC(Br)OC(C)=O IIASCQBFNHWZBE-UHFFFAOYSA-N 0.000 title claims abstract description 36
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 claims abstract description 44
- WOZVHXUHUFLZGK-UHFFFAOYSA-N dimethyl terephthalate Chemical compound COC(=O)C1=CC=C(C(=O)OC)C=C1 WOZVHXUHUFLZGK-UHFFFAOYSA-N 0.000 claims abstract description 33
- 239000001257 hydrogen Substances 0.000 claims abstract description 25
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 25
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 23
- 238000001228 spectrum Methods 0.000 claims abstract description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 17
- 238000012360 testing method Methods 0.000 claims abstract description 16
- 239000002904 solvent Substances 0.000 claims abstract description 13
- 230000003595 spectral effect Effects 0.000 claims abstract description 9
- 238000005481 NMR spectroscopy Methods 0.000 claims abstract description 6
- 238000005259 measurement Methods 0.000 claims abstract description 6
- 238000004445 quantitative analysis Methods 0.000 claims abstract description 6
- 239000000523 sample Substances 0.000 claims description 37
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 claims description 26
- 239000000243 solution Substances 0.000 claims description 14
- 239000012488 sample solution Substances 0.000 claims description 13
- 238000005070 sampling Methods 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 7
- 238000005303 weighing Methods 0.000 claims description 6
- 238000002347 injection Methods 0.000 claims description 5
- 239000007924 injection Substances 0.000 claims description 5
- 238000006243 chemical reaction Methods 0.000 claims description 4
- 239000012535 impurity Substances 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- 239000008186 active pharmaceutical agent Substances 0.000 claims description 3
- 238000004090 dissolution Methods 0.000 claims description 3
- 238000001208 nuclear magnetic resonance pulse sequence Methods 0.000 claims description 3
- 239000012491 analyte Substances 0.000 claims description 2
- 239000012085 test solution Substances 0.000 claims 2
- 238000010408 sweeping Methods 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 7
- 238000002474 experimental method Methods 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- KEJCWVGMRLCZQQ-YJBYXUATSA-N Cefuroxime axetil Chemical compound N([C@@H]1C(N2C(=C(COC(N)=O)CS[C@@H]21)C(=O)OC(C)OC(C)=O)=O)C(=O)\C(=N/OC)C1=CC=CO1 KEJCWVGMRLCZQQ-YJBYXUATSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 229960002620 cefuroxime axetil Drugs 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 150000002739 metals Chemical class 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000005457 optimization Methods 0.000 description 2
- 238000010966 qNMR Methods 0.000 description 2
- 238000005464 sample preparation method Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- VLJNHYLEOZPXFW-BYPYZUCNSA-O (2S)-2-carbamoylpyrrolidin-1-ium Chemical compound NC(=O)[C@@H]1CCC[NH2+]1 VLJNHYLEOZPXFW-BYPYZUCNSA-O 0.000 description 1
- REIDAMBAPLIATC-UHFFFAOYSA-N 4-methoxycarbonylbenzoic acid Chemical compound COC(=O)C1=CC=C(C(O)=O)C=C1 REIDAMBAPLIATC-UHFFFAOYSA-N 0.000 description 1
- 229930186147 Cephalosporin Natural products 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 229940124587 cephalosporin Drugs 0.000 description 1
- 150000001780 cephalosporins Chemical class 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000005311 nuclear magnetism Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000005220 pharmaceutical analysis Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000004451 qualitative analysis Methods 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000012113 quantitative test Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000013557 residual solvent Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000002912 waste gas Substances 0.000 description 1
- 239000002699 waste material Substances 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
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- Pathology (AREA)
- Investigating Or Analyzing Non-Biological Materials By The Use Of Chemical Means (AREA)
Abstract
A method for measuring the content of 1-bromoethyl acetate and structural analogues thereof is characterized by comprising the following steps: quantitative measurement is carried out by adopting a nuclear magnetic resonance hydrogen spectrum quantitative method, using CDCl3 as a solvent and dimethyl terephthalate as an internal standard, and nuclear magnetic quantitative parameters are as follows: sw (spectral width) =20.0ppm, o1p (center frequency) =7.4ppm, using "zg 30" pulse program, D1=20s, ns (number of samples) =32 times, TD =64K, process window parameter lb =0.3, temperature 298K. The method is suitable for content test of unstable compounds sensitive to extreme degrees such as water, air and the like, and has good repeatability.
Description
Technical Field
The invention relates to a method for measuring the content of 1-bromoethyl acetate and structural analogues thereof based on a hydrogen nuclear magnetic quantitative analysis technology.
Background
Cefuroxime axetil is a synthetic second-generation cephalosporin drug, has the characteristics of broad spectrum, strong bactericidal power, inherent stability to beta-2 lactamase, good human pharmacokinetics and the like, and has large market demand. In the synthesis of cefuroxime axetil, 1-bromoethyl acetate is used as the esterification raw material of carboxyl. The 1-bromoethyl acetate is extremely unstable, easy to oxidize and sensitive to water due to the structure, and can react with certain metals, so that the conventional content analysis method cannot accurately analyze the 1-bromoethyl acetate. This also results in that most of the currently commercially available 1-bromoethyl acetate is labeled with purity and is the purity value of nuclear magnetic testing, or part of the suppliers directly replace the content with nuclear magnetic purity.
At present, chromatography is mostly used for analyzing the content of a sample in pharmaceutical analysis, but the method is not suitable for compounds which are extremely unstable and easily react with water or partial metal parts. The hydrogen nuclear magnetic method of quantification has many unique advantages over chromatography. Since the area of the proton absorption peak in nuclear magnetism is proportional to the contained proton, the absolute content of the compound can be measured by taking an internal standard with known content as a reference, the interference of water and residual solvent in a sample is avoided, and qualitative and quantitative analysis can be synchronously completed. And the quantitative nuclear magnetic method adopts a nuclear magnetic tube to contain sample solution, does not directly contact with instrument parts, and has no damage to the sample. The reaction of the unstable compound with water can also be avoided by controlling the water content in the organic solvent.
Disclosure of Invention
The invention provides a method for measuring the content of 1-bromoethyl acetate and structural analogues thereof by adopting the characteristics of a hydrogen nuclear magnetic quantitative method, and the method is used for analyzing the content of unstable compounds such as 1-bromoethyl acetate which are extremely sensitive to water, air and partial metals.
The technical scheme of the invention is as follows:
a method for measuring the content of 1-bromoethyl acetate and structural analogues thereof is characterized by comprising the following steps:
quantitative measurement is carried out by adopting a nuclear magnetic resonance hydrogen spectrum quantitative method, using CDCl3 as a solvent and dimethyl terephthalate as an internal standard, and nuclear magnetic quantitative parameters are as follows: sw (spectral width) =20.0ppm, o1p (center frequency) =7.4ppm, using "zg 30" pulse program, D1=20s, ns (number of samples) =32 times, TD =64K, process window parameter lb =0.3, temperature 298K.
The method for determining the content of the 1-bromoethyl acetate and the structural analogue thereof adopts the following experimental instruments:
bruker Avance III HD 400M NMR spectrometer, Mettler XP6 model analytical balance; and (3) testing the sample: 1-bromoethyl acetate, batch No.: 1-YJK-147-1, CDCl3, Merck, batch number: s5747996837; DMSO-d 6: CIL company, batch number: PR-29532104048DM1, dimethyl terephthalate control: sigma corporation, lot number: BCBT9974, content: 99.95 percent.
The method for determining the content of the 1-bromoethyl acetate and the structural analogue thereof adopts an HNMR spectrum acquired under a zg30 pulse sequence (298K); the specific experimental parameters were set as: spectral Width (SWH) 5000Hz, center frequency (O1) 2100Hz, number of sampling points (TD): 64K, relaxation delay time (D1) 20s, sampling Number (NS) 32 times, and null scan number (DS) 4 times.
The method further comprises the preparation of a sample solution: adding 0.5ml of CDCl3 into a sample injection vial, and precisely weighing 40mg of a sample to be tested in a mode of dropwise adding the sample into a solvent; then weighing 10mg of internal standard into the solution, continuously adding 0.5ml of CDCl3, and shaking to test complete dissolution; transferring the sample solution into a standard nuclear magnetic tube with the diameter of 5 mm to obtain the product.
The method also includes selection of internal standard and quantitation peaks: because the product is liquid and reacts with water, CDCl3 or DMSO-d6 is primarily selected as a solvent; the appropriate amount of sample was dissolved in CDCl3 or DMSO-d6, respectively, and the spectra were recorded. During the sample adding process, the sample is observed to have light yellow change at the moment of being added into DMSO-d6, and an impurity peak in a spectrogram is enhanced, which is presumed that a small amount of water in DMSO-d6 is possibly reacted with the sample; because CDCl3 contains very little water, it is not prone to significant reaction. The solvent was further determined to be CDCl 3.
The method selects 6.71ppm (1H, q) of hydrogen as the quantitative peak selection of the substance to be detected; the peak at 8.12pm (4H, s) was used as a quantitation peak for the internal standard.
The method further comprises selection of pulse width: the pulse program "zg 30" was commonly used on a Bruker AVANCE instrument, and was used in this study.
The experimental conditions of the method are as follows: spectral width sw =20.0ppm, center frequency o1p =7.4ppm, "zg 30" pulse program, sampling times ns =32 times, TD =64K, process window parameter lb =0.3, temperature 298K. The d1 values were measured at 2s, 4s, 10s, 20s, and 30s, respectively.
The invention has the beneficial effects that:
the invention establishes a faster, more accurate and simpler method, and the method hardly generates waste liquid and waste gas, thereby saving energy and protecting environment. The invention is suitable for content test of unstable compounds sensitive to extreme degrees such as water, air and the like, and has better repeatability.
Drawings
FIG. 1 is a chart of the hydrogen spectrum (DMSO-d 6) of 1-bromoethyl acetate according to the present invention.
FIG. 2 is a chart of the hydrogen spectrum (CDCl 3) of 1-bromoethyl acetate according to the present invention.
FIG. 3 is a diagram of the hydrogen spectrum (CDCl 3) of dimethyl terephthalate according to the present invention.
FIG. 4 is a chart of the hydrogen spectrum (CDCl 3) of a mixture of dimethyl terephthalate and 1-bromoethyl acetate according to the present invention.
FIG. 5 is a standard graph of 1-bromoethyl acetate according to the present invention.
Figure 6 is a line graph of L prolinamide impurity a.
Detailed Description
The present invention will be described in further detail with reference to the following examples:
as shown in fig. 1-6.
1. Examples of the embodiments
1.1 instruments and reagents
Bruker Avance III HD 400M NMR spectrometer, Mettler XP6 model analytical balance.
The test sample (1-bromoethyl acetate, batch number: 1-YJK-147-1),
CDCl3 (Merck company, batch number: S5747996837)
DMSO-d6 (CIL Corp., batch: PR-29532104048DM 1),
dimethyl terephthalate control (Sigma Co., batch No.: BCBT9974, content: 99.95%)
1.2 Experimental conditions
HNMR spectra acquired under zg30 pulse sequence (298K) were used for the experiments. The specific experimental parameters were set as: spectral Width (SWH) 5000Hz, center frequency (O1) 2100Hz, number of sampling points (TD): 64K, relaxation delay time (D1) 20s, sampling Number (NS) 32 times, and null scan number (DS) 4 times.
1.3 sample solution preparation
Preparation of sample solution: adding 0.5ml of CDCl3 into a sample injection vial, and precisely weighing 40mg of a sample to be tested in a mode of dropwise adding the sample into a solvent; then 10mg of internal standard was weighed into the above solution, 0.5ml of CDCl3 was added further, and the dissolution was tried to be complete by shaking. Transferring the sample solution into a standard nuclear magnetic tube with the diameter of 5 mm to obtain the product.
2. Results and discussion
2.1 selection of internal Standard and quantitation peaks
Because the product is liquid and reacts with water, CDCl3 or DMSO-d6 is primarily selected as a solvent. The appropriate amount of sample was dissolved in CDCl3 or DMSO-d6, respectively, and the spectra were recorded. During the sample loading process, a light yellow change of the sample is observed in the instant of DMSO-d6 addition, and an impurity peak in the spectrum (shown in figure 1) is enhanced, which is presumed to be that a small amount of water in DMSO-d6 reacts with the sample. Because CDCl3 contains very little water, it is not prone to significant reaction. The solvent was further determined to be CDCl 3.
As shown in FIG. 2, the hydrogen spectrum (CDCl 3) of 1-bromoethyl acetate has three sets of signal peaks, but the methyl peaks of the two sets of high-field regions are close to each other, and a hetero peak is nearby, so that the hydrogen spectrum is not suitable for being used as a quantitative peak. Therefore, only 6.71ppm (1H, q) of hydrogen can be selected as a quantitative peak of the analyte.
As shown in FIG. 3, the dimethyl terephthalate hydrogen spectrum has two single peaks of 8.12pm (4H, s) and 3.97pm (6H, s), and the peak of 8.12pm (4H, s) is more suitable for being used as the quantitative peak of the internal standard according to the principle that the quantitative peaks are adjacent as much as possible and have good separation degree.
On the hydrogen spectrum of the mixture of methyl terephthalate and 1-bromoethyl acetate (FIG. 4), it can be seen that the quantitative hydrogen signal of dimethyl terephthalate is 8.12ppm, and has better separation degree with the hydrogen signal of 1-bromoethyl acetate at 6.71ppm, and the signals do not interfere with each other. Thus, quantitative nuclear magnetic analysis of 1-bromoethyl acetate determined using CDCl3 as solvent and dimethyl terephthalate as internal standard, and the peak at 8.12ppm was taken as the quantitative peak.
2.2 selection of pulse Width
The key to QNMR is to allow the relaxation of the signal of each quantitative peak employed to fully return to equilibrium, typically with a smaller pulse width (i.e., using a smaller flip angle θ) in order to shorten d1 time, in conjunction with the literature, typically with a 30 ° flip angle, on a Bruker AVANCE instrument, a pulse program of "zg 30" is commonly used, and this study employed the pulse program described above.
2.3 optimization of relaxation delay time (D1)
The experimental conditions are as follows: sw (spectral width, same below) =20.0ppm, o1p (center frequency, same below) =7.4ppm (center frequency should be guaranteed to be in the middle of two quantitative peaks as much as possible), "zg 30" pulse program, ns (sampling times, same below) =32 times, TD =64K, processing window parameter lb =0.3, temperature 298K. The d1 values were measured at 2s, 4s, 10s, 20s, and 30s, respectively. The results are shown in Table 1.
TABLE 1 Effect of delay time on relative area of peaks
The experimental results show that: when d1 is 20 s-30 s, the peak area ratio of the sample to the internal standard is not changed any more, but when the d1 time is set to 30s, the sample collection time is greatly increased. Therefore, the delay time in the quantitative test should be determined to be 20 s.
2.4 optimization of the Experimental temperature
The experimental conditions are as follows: sw =20.0ppm, o1p =7.4ppm, "zg 30" pulse program, ns =32 times, d1=20s, TD =64K, lb =0.3, sample solutions were measured at temperatures of 293K, 298K and 303K, respectively. The results are shown in the table.
TABLE 2 Effect of experiment temperature on the relative area of the peaks
The experimental results show that: the stability of the sample solution at each temperature is good, the content determination result is not obviously influenced, and the experimental temperature is determined to be 298K at the conventional temperature.
And (4) conclusion: through the selection of the above experimental conditions, the experimental conditions are finally determined: sw =20.0ppm, o1p =7.4ppm, "zg 30" pulse program, ns =32 times, d1=20s, TD =64K, lb =0.3, temperature 298K.
2.5 Linear test
Preparation of a series of solutions: respectively and precisely weighing 27.665, 33.319, 40.254, 44.828 and 53.615mg of 1-bromoethyl acetate samples in sample injection vials, respectively and precisely adding 10.81, 10.537, 10.180, 10.222 and 10.715 mg of internal standards, preparing 5 parts of series solutions according to a sample solution preparation method, transferring the obtained series solutions into a 5 mm nuclear magnetic tube, and determining the hydrogen spectrum of each series solution according to a method. The peak area ratio of the sample and the internal standard mass ratio is regressed, and the regression equation is y =0.2853x +0.0163, r2=0.9997, x is the mass ratio of sample to internal standard, and y is the peak area ratio of sample to internal standard.
Table 3: results of the Linear test
2.6 precision of the instrument
Taking a middle point linear sample solution, continuously measuring 6 times of hydrogen spectrum, obtaining the hydrogen spectrum, adjusting the phase, carrying out baseline integration, and calculating the ratio of the quantitative peak to the internal standard peak area, wherein the result RSD =0.28%, and meets the requirement.
Table 4: results of instrumental precision measurement
2.7 repeatability test
39.461, 40.859, 40.588, 40.327 and 39.009mg of 1-bromoethyl acetate samples are accurately weighed in each sample injection vial respectively, 10.388, 10.660, 10.519, 10.224 and 10.686 mg of internal standard are accurately added respectively, 5 parts of parallel solution is prepared according to a sample preparation method, the content of the sample is calculated, and the repeatability of the method is judged by the RSD of 6 parts of parallel solution which is the total of the intermediate point linear solution and the intermediate point linear solution. The results are shown in Table 5.
TABLE 5 results of the repeatability tests
And (4) conclusion: the results showed RSD of 0.47%, less than 1%, for 6 consecutive measurements. Meets the requirements.
2.8 intermediate precision test
Different testers respectively and precisely weigh 39.949, 39.337, 38.872, 39.023, 39.228 and 42.601mg of 1-bromoethyl acetate samples in different time periods, respectively add 10.665, 10.161, 10.882, 10.417, 10.775 and 10.611 mg of internal standard, prepare 6 parts of parallel solution according to a sample preparation method, and calculate results. The intermediate precision of the method is judged according to the RSD value of 6 groups of data of the repeatability test. The results are shown in Table 6.
TABLE 6 intermediate precision test results
And (4) conclusion: the results showed RSD of 0.47%, less than 2%, for a total of 12 results with reproducibility. Meets the requirements.
2.9 solution stability
Taking the middle point linear sample solution, standing at room temperature, determining the hydrogen spectrum according to the method at 0h, 1h, 2h, 4h and 8h respectively, and recording the integral area ratio of the sample to the internal standard quantitative peak. The results of the experiments are shown in Table 7 below.
TABLE 7 examination of solution stability of samples
And (4) conclusion: the experimental result shows that the sample solution is placed at room temperature, and the RSD is 0.79% (n = 12) and less than 2% within 8h, which meets the requirement.
3 quantitative results
The quantitative results are shown in 2.7, and the contents of the samples obtained in six replicates are respectively 99.77%, 98.44%, 99.21%, 99.43%, 99.01%, 99.51% and the average content is 99.23%.
Content% = [ ()As/ns)×Ms×mr]/ [(Ar/nr)×Mr×ms]×Wr
Wherein,Asis the integrated area of the quantitative peak of 1-bromoethyl acetate;ns is the hydrogen number represented by the quantitative peak of the 1-bromoethyl acetate;Ms is the relative molecular mass of 1-bromoethyl acetate;Ar is the integral area of the quantitative peak of dimethyl terephthalate;nr is the number of hydrogen represented by the dimethyl terephthalate quantitative peak;Mr is the relative molecular mass of dimethyl terephthalate;mr is the mass of dimethyl terephthalate;Wr is the mass fraction of dimethyl terephthalate;ms is the mass of 1-bromoethyl acetate.
4. Conclusion
The established method for measuring the content of the 1-bromoethyl acetate by qNMR has the advantages of simple sample preparation and quick measurement process. The method is suitable for content test of the unstable compounds.
The foregoing shows and describes the general principles, essential features, and advantages of the invention. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, and the preferred embodiments of the present invention are described in the above embodiments and the description, and are not intended to limit the present invention. The scope of the invention is defined by the appended claims and equivalents thereof.
Claims (4)
1. A method for measuring the content of 1-bromoethyl acetate and structural analogues thereof is characterized by comprising the following steps:
quantitative measurement is carried out by adopting a nuclear magnetic resonance hydrogen spectrum quantitative method, using CDCl3 as a solvent and dimethyl terephthalate as an internal standard, and nuclear magnetic quantitative parameters are as follows: sw (spectral width) =20.0ppm, o1p (center frequency) =7.4ppm, using "zg 30" pulse program, D1=20s, ns (number of samples) =32 times, TD =64K, process window parameter lb =0.3, temperature 298K; the method for determining the content of the 1-bromoethyl acetate and the structural analogue thereof adopts the following experimental instruments:
bruker Avance III HD 400M NMR spectrometer, Mettler XP6 model analytical balance; and (3) testing the sample: 1-bromoethyl acetate, batch No.: 1-YJK-147-1, CDCl3, Merck, batch number: s5747996837; DMSO-d 6: CIL company, batch number: PR-29532104048DM1, dimethyl terephthalate control: sigma corporation, lot number: BCBT9974, content: 99.95 percent; the method for determining the content of the 1-bromoethyl acetate and the structural analogue thereof adopts an HNMR spectrum acquired under a zg30 pulse sequence (298K); the specific experimental parameters were set as: spectral Width (SWH) 5000Hz, center frequency (O1) 2100Hz, number of sampling points (TD): 64K, relaxation delay time (D1) 20s, sampling times (NS) 32 times, and null sweeping times (DS) 4 times; the method further comprises the preparation of a sample solution: adding 0.5ml of CDCl3 into a sample injection vial, and precisely weighing 40mg of a sample to be tested in a mode of dropwise adding the sample into a solvent; then weighing 10mg of internal standard into the solution, continuously adding 0.5ml of CDCl3, and shaking to test complete dissolution; transferring the test solution into a standard nuclear magnetic tube with the diameter of 5 mm to obtain the test solution; the method also includes selection of internal standard and quantitation peaks: because the product is liquid and reacts with water, CDCl3 or DMSO-d6 is primarily selected as a solvent; respectively dissolving a proper amount of sample and CDCl3 or DMSO-d6, and recording a spectrogram; during the sample adding process, the sample is observed to have light yellow change at the moment of being added into DMSO-d6, and an impurity peak in a spectrogram is enhanced, which is presumed that a small amount of water in DMSO-d6 is possibly reacted with the sample; because the CDCl3 has little water content, obvious reaction is not easy to occur; the solvent was further determined to be CDCl 3.
2. The method for determining the content of 1-bromoethyl acetate and structural analogs thereof according to claim 1, wherein 6.71ppm (1H, q) of hydrogen is selected as a quantitative peak of the analyte; the peak at 8.12pm (4H, s) was used as a quantitation peak for the internal standard.
3. The method of claim 1, wherein the method further comprises selecting the pulse width of: the pulse program "zg 30" was commonly used on a Bruker AVANCE instrument, and was used in this study.
4. The method of claim 1, wherein the experimental conditions are as follows: spectral width sw =20.0ppm, center frequency o1p =7.4ppm, "zg 30" pulse program, sampling times ns =32 times, TD =64K, process window parameter lb =0.3, temperature 298K; the d1 values were measured at 2s, 4s, 10s, 20s, and 30s, respectively.
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Application publication date: 20201120 |