Method for synchronous detection of deuterium content and mass fraction in deuterated acid solution

Abstract

The application discloses a kind of synchronous detection methods of deuterium degree and mass fraction in deuterated acid solution, belongs to medical analysis technical field.The application provides a kind of synchronous detection methods of deuterium degree and mass fraction in deuterated acid solution, comprising the following steps: (1) the deuterated acid solution sample to be measured and internal standard are weighed;(2) the internal standard is placed in nuclear magnetic sample tube with the deuterated acid solution sample to be measured;(3) collection 1 H NMR, 2 H NMR and / or 19 F NMR spectrum;(4) the characteristic peak area integration of nuclear magnetic spectrum after testing is carried out, and the deuterium degree and mass fraction of the deuterated acid solution sample to be measured are calculated;The method provided by the application can obtain the deuterium degree and mass fraction of deuterated acid solution simultaneously, without respectively using titration method and nuclear magnetic resonance spectroscopy to carry out two sets of independent detection, both reduce the detection step and the error accumulation caused by multi-method combination, also greatly shorten detection period.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical analysis technology, and more specifically, relates to a method for simultaneous detection of deuteration degree and mass fraction in deuterated acid solutions. Background Technology

[0002] Deuterated acids, especially deuterated organic sulfonic acids and deuterated organic carboxylic acids, are widely used in deuteration synthesis, deuterated drug preparation, isotope labeling reactions, and related catalytic processes. In these systems, the degree of deuteration (the extent to which a target hydrogen site in the molecular structure is replaced by a deuterium atom, usually expressed as a percentage; for deuterated acid systems, the degree of deuteration represents the proportion of active hydrogen sites replaced by deuterium) directly affects the system's ability to provide a deuterium source and the deuteration level of the target product. The mass fraction of the deuterated acid directly affects the catalyst feed rate, acid strength, reaction kinetics, and process repeatability. Therefore, both the degree of deuteration and the mass fraction are key quality attributes that require careful control.

[0003] In practical production and application scenarios, the water content of deuterated acids fluctuates significantly due to differences in preparation methods and post-processing techniques. This is especially true for strongly acidic sulfonic acid compounds, whose extreme hygroscopicity and high miscibility with water make conventional dehydration methods insufficient to reduce their water content to ideal levels. In newly prepared acid-water systems, to maintain a sufficient deuterium source supply to meet the deuteration reaction requirements, it is usually necessary to add a sufficient amount of heavy water, rather than relying solely on the deuterated acid itself as the sole deuterium source. This results in a dynamic distribution of deuteration degree within the system. In recycled acid-water systems, the water content further increases after repeated use of the acid, and the amount of water is uncontrollable, leading to changes in both deuteration degree and mass fraction. Furthermore, the rapid hydrogen-deuterium exchange mechanism between acid and water means that the overall deuteration state of the system cannot be characterized by measuring the deuteration degree of the acid or water alone; only the overall deuteration degree of the active hydrogen sites needs to be measured. These characteristics dictate that the detection of deuterated acid samples requires analytical methods that can simultaneously cover different water contents and different deuteration degrees.

[0004] In existing technologies, the detection of deuteration degree typically employs mass spectrometry or nuclear magnetic resonance spectroscopy, with nuclear magnetic resonance spectroscopy being able to detect deuteration degree based on... 1 H NMR or 2 Analyzing deuteration using 1H NMR signals has become an important technique for detecting the deuterium abundance of deuterated compounds. For example, Chinese invention patent application CN112305007A discloses a method for determining the deuterium isotope abundance of deuterated compounds using 1H NMR or deuterium NMR spectroscopy. In contrast, the determination of mass fraction in existing technologies still mainly relies on independent analytical methods such as acid-base titration and potentiometric titration.

[0005] Therefore, in the actual detection of deuterated acid samples, it is usually necessary to measure the degree of deuteration and the mass fraction separately, and then comprehensively judge the sample quality attributes. Although this technical route can obtain the relevant parameters separately, the detection process is fragmented and involves many steps, which can easily introduce the superposition of errors caused by multiple measurements, making it unfavorable for rapid, accurate and uniform quality control of samples during research and development and production.

[0006] From the perspective of NMR quantification, existing methods are still limited by the applicability of internal standard systems. Existing NMR quantification methods mainly include the following categories: Firstly... 1 The 1H NMR single internal standard method typically uses all-hydrogen compounds such as DMF, maleic acid, and 1,4-dioxane as internal standards. The residual hydrogen content is calculated by integrating the hydrogen spectrum, indirectly inferring the deuterium abundance. This type of method usually requires combining other methods to determine the total purity of the sample, involving numerous pretreatment and calculation steps. Furthermore, there is a possibility of side reactions between the aforementioned internal standards and the acid sample being tested, interfering with the accuracy of the detection. Secondly... 1 H NMR and 2 Combined ¹H NMR and quantitative methods, such as those reported by Xie et al., involve the simultaneous use of ¹H NMR and ¹⁸O NMR. 1 H NMR and 2 A method for determining the isotopic abundance of deuterated compounds using ¹H NMR employs both total hydrogen and total deuterium internal standards to determine the hydrogen and deuterium content in the sample. While this improves the completeness of deuterium abundance determination, it still requires two sets of internal standard systems. A third method is a relative quantification method based on a fixed deuterium abundance internal standard, such as the OIV-OENO 527-2015 standard method which uses tetramethylurea as an internal standard. 2 H SNIF-NMR binding 1 H NMR determination of the D / H ratio of methyl sites in acetic acid is essentially an isotope ratio analysis, which makes it difficult to directly obtain the absolute deuteration degree and mass fraction of the sample. Furthermore, direct mixing of the sample with the internal standard can easily lead to sample mixing errors and non-recoverable samples.

[0007] Monakhova and Diehl proposed a model based on 2 A qNMR workflow with H integral normalization was used, employing isopropanol-d6 as a normalizing material containing both hydrogen and deuterium information for determining the deuteration degree of deuterated solvents. However, this approach still has limitations in its applicability to deuterated acid solutions, especially strongly acidic systems: firstly, isopropanol-d6 contains active hydrogen atoms in its hydroxyl group, which readily undergo H / D exchange in acidic environments; secondly, its residual... 1 When the sample contains aliphatic hydrogen signals, the H signal may cause overlap or neighboring interference, which is not conducive to high-accuracy quantitative analysis.

[0008] The above methods for quantitative determination of deuteration by NMR all have various defects, and due to the strong acidity of the deuterated acid system and the presence of easily exchangeable active hydrogen or active deuterium, they are difficult to apply directly to deuterated acid samples.

[0009] Furthermore, considering the requirement to test both deuteration degree and mass fraction, the conventional "potential titration combined with..." 1 The ¹H NMR method is suitable for samples with high deuteration degree and low mass fraction, where residual... 1 A weak H signal and a low mass fraction can easily amplify signal integration errors and titration relative errors; while for samples with low deuteration degree and high mass fraction, 2 The H signal is weak, and the exchange behavior under strong acid conditions further increases the difficulty of detection. This means that existing technologies often cannot simultaneously cover a wide range of samples from low to very high deuteration and from low to high mass fractions, especially lacking adaptability to extreme samples.

[0010] Therefore, although existing technologies provide methods for detecting deuteration degree and mass fraction respectively, for deuterated acid samples, especially strongly acidic systems with readily exchangeable active hydrogen and a wide detection range, there is still a lack of a method that can simultaneously obtain deuteration degree and mass fraction within a unified NMR detection framework. Based on this, it is necessary to develop a method for the simultaneous detection of deuteration degree and mass fraction in deuterated acid systems to meet the needs of related research and development, production, and quality control. Summary of the Invention

[0011] 1. The problem to be solved To address the problems in existing technologies where the degree of deuteration and mass fraction typically require separate analytical methods for determination, resulting in fragmented detection processes, cumbersome operations, numerous sources of error, and the potential for changes in sample reactivity due to the introduction of an internal standard, which could reduce detection accuracy and make existing methods unsuitable for deuterated acid systems, this invention provides a method for the simultaneous detection of the degree of deuteration and mass fraction in deuterated acid solutions.

[0012] 2. Technical Solution To solve the above problems, the technical solution adopted by the present invention is as follows: This invention provides a method for simultaneous detection of deuteration degree and mass fraction in deuterated acid solutions, comprising the following steps: (1) Weigh the sample of the deuterated acid solution to be tested and the internal standard; (2) The internal standard and the deuterated acid solution sample to be tested are placed in the NMR sample tube in a capillary-encapsulated and coaxial manner; (3) Based on the type of deuterated acid solution sample and internal standard, collect samples. 1 H NMR, 2H NMR and / or 19 F NMR spectrum; (4) Integrate the characteristic peak area of ​​the NMR spectrum after testing, and calculate the degree of deuteration and mass fraction of the deuterated acid solution sample based on the integrated area, the known molar amount of the corresponding nucleus in the internal standard, and the mass of the deuterated acid solution sample and the internal standard. The acid in the deuterated acid solution includes one or more organic sulfonic acids and organic carboxylic acids.

[0013] As a preferred embodiment of any technical solution of the present invention, according to the quantitative characteristics of nuclear magnetic resonance, the acid in the deuterated acid solution includes acids containing non-active hydrogen and acids without non-active hydrogen.

[0014] It should be noted that the active hydrogen is hydrogen directly bonded to O, N, or S, including alcohol hydroxyl hydrogen, phenolic hydroxyl hydrogen, carboxyl hydrogen, amino hydrogen, amide hydrogen, and mercapto hydrogen; the inactive hydrogen is hydrogen on carbon, such as alkyl hydrogen (-CH, -CH2, -CH3), aromatic hydrogen, and alkene hydrogen. As a preferred embodiment of any technical solution of the present invention, the acid containing inactive hydrogen is selected from one or more of organic sulfonic acids and organic carboxylic acids. The organic sulfonic acid includes one or more of alkyl sulfonic acids and aryl sulfonic acids; the organic carboxylic acid includes one or more of alkyl carboxylic acids and aryl carboxylic acids.

[0015] A further preferred embodiment is that the alkyl sulfonic acid comprises C1 to C4 alkyl sulfonic acids; The aryl sulfonic acid includes substituted or unsubstituted benzenesulfonic acid, wherein the substituents are independently selected from C1-C3 alkyl, C1-C3 alkoxy, halogen, nitro, cyano, C1-C4 alkoxycarbonyl, trifluoromethyl, phenyl, or five- or six-membered heteroaryl. The alkyl carboxylic acids include C2-C6 alkyl carboxylic acids; The aryl carboxylic acid includes substituted or unsubstituted benzoic acid, wherein the substituents are independently selected from C1-C3 alkyl, C1-C3 alkoxy, halogen, nitro, cyano, C1-C4 alkoxycarbonyl, trifluoromethyl, phenyl, or five- or six-membered heteroaryl.

[0016] More preferably, the alkyl sulfonic acid includes one or more of methanesulfonic acid, ethyl sulfonic acid, propyl sulfonic acid, isopropyl sulfonic acid, and butyl sulfonic acid; The aryl sulfonic acid includes one or more of benzenesulfonic acid, p-methylbenzenesulfonic acid, and 4-fluorobenzenesulfonic acid; The alkyl carboxylic acid includes one or more of acetic acid, propionic acid, isobutyric acid, and pivalic acid; The aryl carboxylic acid includes one or more of benzoic acid, p-fluorobenzoic acid, and p-methylbenzoic acid.

[0017] As a preferred embodiment of any technical solution of the present invention, the acid without non-active hydrogen includes perfluorinated substituted acids; the perfluorinated substituted acids include one or more of perfluorinated alkyl sulfonic acids and perfluorinated alkyl carboxylic acids.

[0018] More preferably, the perfluoroalkyl sulfonic acid includes C1 to C4 perfluoroalkyl sulfonic acids; The perfluoroalkyl carboxylic acids include C2-C8 perfluoroalkyl carboxylic acids.

[0019] Further preferably, the perfluoroalkyl sulfonic acid includes one or more of trifluoromethanesulfonic acid, perfluoroethanesulfonic acid, and perfluorobutyric acid; The perfluoroalkyl carboxylic acids include one or more of trifluoroacetic acid, perfluoropropionic acid, perfluorobutyric acid, and perfluorooctanoic acid.

[0020] As a preferred embodiment of any technical solution of the present invention, the internal standard includes one or more of dual-core internal standards or multi-core internal standards.

[0021] Further preferably, the dual-core internal standard includes one or more of hydrogen-deuterium dual-core internal standards, fluorine-hydrogen dual-core internal standards, and fluorine-deuterium dual-core internal standards, and the multi-core internal standard includes fluorine-hydrogen-deuterium tri-core internal standards.

[0022] It should be noted that the hydrogen-deuterium binuclear internal standard is an internal standard containing both hydrogen and deuterium atoms in the molecule; the fluorine-hydrogen binuclear internal standard is an internal standard containing both fluorine and hydrogen atoms in the molecule; the fluorine-deuterium binuclear internal standard is an internal standard containing both fluorine and deuterium atoms in the molecule; and the fluorine-hydrogen-deuterium trinuclear internal standard is an internal standard containing fluorine, hydrogen, and deuterium atoms in the molecule.

[0023] Further optimization involves using a hydrogen-deuterium dual-core internal standard when the acid in the deuterated acid solution to be tested is an acid containing inactive hydrogen. 1 H NMR spectrum and 2 ¹H NMR spectra were used to calculate the degree of deuteration and mass fraction.

[0024] Further preferred, when the acid in the deuterated acid solution to be tested is an acid without non-active hydrogen, the internal standard is one or more of the following: a combination of a hydrogen-deuterium binuclear internal standard and a fluorine-hydrogen binuclear internal standard; a combination of a hydrogen-deuterium binuclear internal standard and a fluorine-deuterium binuclear internal standard; a combination of a fluorine-hydrogen binuclear internal standard and a fluorine-deuterium binuclear internal standard; or a fluorine-hydrogen-deuterium trinuclear internal standard. 2 H NMR and 1 The degree of deuteration was calculated by H NMR, through 19 F NMR is used to calculate the mass fraction.

[0025] As a preferred embodiment of any technical solution of the present invention, the hydrogen-deuterium dual-core internal standard is selected from one or more of the following: deuterated toluene-d5, ethyl(benzene-d5), deuterated mesitylene-d3, deuterated p-tert-butylbromobenzene-d4, deuterated 1,4-di-tert-butylbenzene-d4, deuterated p-xylene-d4, deuterated o-xylene-d4, deuterated m-xylene-d4, deuterated p-methoxytoluene-d4, deuterated anisole-d5, deuterated methyl tert-butyl ether-d9, deuterated ethanol-d5, deuterated hydroxymethanol-d1, and deuterated hydroxyethanol-d1.

[0026] As a preferred embodiment of any technical solution of the present invention, the fluorine-hydrogen dual-core internal standard is selected from one or more of methyl trifluoroacetate, ethyl trifluoroacetate, 4-methyltrifluorotoluene, 3-methyltrifluorotoluene, trifluorotoluene, and 1-(tert-butyl)-4-(trifluoromethyl)benzene.

[0027] As a preferred embodiment of any technical solution of the present invention, the fluorine-deuterium dual-core internal standard is selected from one or more of deuterated fluorobenzene-d5, p-bromofluorobenzene-d4, and trifluorotoluene-d5.

[0028] As a preferred embodiment of any technical solution of the present invention, the fluorine-hydrodeuterium trinuclear internal standard is selected from... or .

[0029] As a preferred embodiment of any technical solution of the present invention, the H content of the effective characteristic peak of the internal standard is 8-100 mmol / g.

[0030] It should be noted that the H content of the effective characteristic peak of the internal standard refers to the H content corresponding to the effective hydrogen characteristic peak of a single internal standard in an internal standard system, such as a hydrogen-deuterium binary internal standard, or a combination of a hydrogen-deuterium binary internal standard and a fluorine-hydrogen binary internal standard. The D content and F content of the effective characteristic peak of the internal standard are interpreted in the same way.

[0031] Further preferably, the H content of the effective characteristic peak of the internal standard is 15-60 mmol / g.

[0032] Further preferably, the H content of the effective characteristic peak of the internal standard is 20-60 mmol / g.

[0033] Further preferably, the H content of the effective characteristic peak of the internal standard is 20-50 mmol / g.

[0034] As a preferred embodiment of any technical solution of the present invention, the D content of the effective characteristic peak of the internal standard is 8-100 mmol / g.

[0035] Further preferably, the D content of the effective characteristic peak of the internal standard is 15-50 mmol / g.

[0036] Further preferably, the D content of the effective characteristic peak of the internal standard is 20-50 mmol / g.

[0037] As a preferred embodiment of any technical solution of the present invention, the F content of the effective characteristic peak of the internal standard is 5-25 mmol / g.

[0038] Further preferably, the F content of the effective characteristic peak of the internal standard is 10-25 mmol / g.

[0039] Further preferably, the F content of the effective characteristic peak of the internal standard is 15-25 mmol / g.

[0040] As a preferred embodiment of any technical solution of the present invention, in step (2), the capillary encapsulation coaxial placement method is to place the internal standard into the NMR sample tube, and then place the capillary into the NMR sample tube containing the deuterated acid solution sample to be tested. It should be noted that using capillary encapsulation for testing not only avoids the risks of acid corrosion, proton exchange, or decomposition of the internal standard, ensuring the long-term stability of its chemical composition and spectroscopic properties, but also allows for the reuse of the internal standard and the recycling of the sample, making it environmentally friendly.

[0041] When the selected internal standard is a solid or viscous liquid that is difficult to inject directly into the capillary, an appropriate amount of NMR solvent can be added before packaging to dissolve it and prepare a homogeneous solution before injecting it into the capillary. The selected NMR solvent should meet the following conditions: (i) It has good solubility in the internal standard and does not react chemically with the internal standard; (ii) The position of its ²H NMR characteristic peak does not overlap with the position of the deuterium characteristic peak of the internal standard and the position of the deuterium characteristic peak in the acid solution sample to be tested, so as to avoid interfering with the accurate quantitative integration of the deuterium spectrum; (iii) Preferably a deuterated solvent to provide a clear ²H NMR reference signal.

[0042] When using capillary encapsulation for testing, one NMR sample tube corresponds to one capillary containing the encapsulated internal standard. For example, when the internal standard is a combination of a hydrogen-deuterium dual-core internal standard and a fluorine-hydrogen dual-core internal standard, the hydrogen-deuterium dual-core internal standard and the fluorine-hydrogen dual-core internal standard can be mixed and placed into the same capillary, or the hydrogen-deuterium dual-core internal standard and the fluorine-hydrogen dual-core internal standard can be placed into two separate capillary tubes, and then the two capillary tubes are placed in two NMR sample tubes containing the deuterated acid solution sample to be tested.

[0043] As a preferred embodiment of any technical solution of the present invention, after the capillary is placed in the NMR sample tube containing the deuterated acid solution sample to be tested, the liquid level in the capillary is basically consistent with the liquid level in the deuterated acid solution sample to be tested in the NMR tube; so as to reduce the quantitative error caused by the difference in detection geometry.

[0044] As a preferred embodiment of any technical solution of the present invention, in step (3), the collection... 1 For H NMR spectroscopy, the operating parameters of the NMR instrument are as follows: the field lock reagent is any one of heavy water (D2O), deuterated benzene (C6D6), or deuterated trifluoroacetic acid; the number of samplings (NS) is no less than 16; the spectral width (SW) is 15 to 25 ppm; the center frequency (O1P) is 5 to 8 ppm; the single sampling time (AQ) is 3 to 6 s; the pulse tilt angle is 90°; and the relaxation delay time (D1) is 6 to 70 s. collection 2 For H NMR spectroscopy, the operating parameters of the NMR instrument are as follows: the field-locking reagent is any one of heavy water (D2O), deuterated trifluoroacetic acid, or no-lock; the number of samplings (NS) is no less than 32; the spectral width (SW) is 15 to 25 ppm; the center frequency (O1P) is 2 to 6 ppm; the single sampling time (AQ) is 3 to 6 s; the pulse tilt angle is 90°; and the relaxation delay time (D1) is 6 to 70 s. collection 19 For F NMR spectroscopy, the operating parameters of the NMR instrument are as follows: the field lock reagent is either heavy water (D2O) or deuterated trifluoroacetic acid; the number of samplings (NS) is no less than 32; the spectral width (SW) is 200 to 300 ppm; the center frequency (O1P) is -100 to -70 ppm; the single sampling time (AQ) is 0.5 to 1.0 s; the pulse tilt angle is 90°; and the relaxation delay time (D1) is 1 to 15 s.

[0045] As a preferred embodiment of any technical solution of the present invention, in step (4), the formula for calculating the degree of deuteration of the deuterated acid solution sample is as shown in formula (1): ; Equation (1) Among them, S 样品D represent 2 The integral area of ​​the characteristic peak of active hydrogen in the H NMR spectrum of the sample to be tested; S 内标D represent 2 The integrated area of ​​the characteristic peak of the internal standard deuterium in the H NMR spectrum; S 样品H-1 represent 1 The integral area of ​​the characteristic peak of active hydrogen in the H NMR spectrum of the sample to be tested; S 内标H represent 1 The integral area of ​​the hydrogen characteristic peak of the internal standard in the 1H NMR spectrum; N D This represents the number of deuterium atoms corresponding to the deuterium characteristic peaks used for integration in the internal standard. NH This represents the number of hydrogen atoms corresponding to the hydrogen characteristic peaks used for integration in the internal standard. D 内标 It represents the degree of deuteration of the internal standard used.

[0046] As a preferred embodiment of any technical solution of the present invention, in step (4), when the acid in the deuterated acid solution to be tested is an acid containing non-active hydrogen, the formula for calculating the mass fraction of the deuterated acid solution sample is as shown in formula (2): ; Equation (2) Among them, S 内标H represent 1 The integral area of ​​the hydrogen characteristic peak of the internal standard in the 1H NMR spectrum; S 样品H-2 represent 1 The integral area of ​​the characteristic peak of non-active hydrogen in the H NMR spectrum of the sample to be tested. m 内标 The mass of the internal standard used in step (2), in g; M 内标 Represents the molar mass of the internal standard used in the labeled state, in g / mol; C 内标 This represents the purity of the internal standard used, % . N H This represents the number of hydrogen atoms corresponding to the hydrogen characteristic peaks used for integration in the internal standard. M 酸 The molar mass of the acid in the deuterated acid solution of the test sample under the labeled state is represented in g / mol. m 酸溶液 The amount of the deuterated acid solution sample to be tested in step (2), in g; O H represent 1 The integral area S of the characteristic peak of non-active hydrogen in the H NMR spectrum of the sample to be tested 样品H-2 The corresponding number of H's.

[0047] As a preferred embodiment of any technical solution of the present invention, in step (4), when the acid in the deuterated acid solution to be tested is an acid without non-active hydrogen, the formula for calculating the mass fraction of the deuterated acid solution sample is as shown in formula (3): ; Equation (3) Among them, S 内标F represent 19 The area of ​​the fluorine characteristic peak of the internal standard in the integrated F NMR spectrum; S 样品F represent 19 The area of ​​the characteristic fluorine peak in the fluorine-containing acid sample to be tested in the F NMR spectrum; m 内标 The mass of the internal standard used in step (2), in g; C 内标 This represents the purity of the internal standard used, % . M 内标 Represents the molar mass of the internal standard used in the labeled state, in g / mol; N F The integral area S of the characteristic fluorine peak of the internal standard used 内标F The corresponding F numbers; M 酸 The molar mass of the acid in the deuterated acid solution of the test sample under the labeled state is represented in g / mol. m 酸溶液 The amount of the deuterated acid solution sample to be tested in step (2), in g; P F represent 19 The integral area S of the fluorine characteristic peak in the fluorine sample in the F NMR spectrum 样品F The corresponding F numbers.

[0048] It should be noted here that the active hydrogen in the acid and water in the deuterated acid solution... 1 Addressing the problem of overlapping in H NMR spectra and the difficulty in directly quantifying using active hydrogen signals, this invention transforms mass fraction determination into the quantification of signals from inactive hydrogen or fluorine atoms in acid molecules, fundamentally avoiding interference from active hydrogen. Furthermore, this invention is applicable to two extreme types of samples: in high-deuteration-degree deuteration iterative reaction systems, even small differences in the mass fraction of the deuterated acid catalyst have a significant impact on reaction kinetics and product distribution. Therefore, accurate determination of low mass fractions is crucial for high-deuteration-degree, low-mass-fraction samples; however, conventional titration methods themselves have poor accuracy in determining mass fractions. This invention... 2 H NMR is the main component. 1 ¹H NMR was used as an auxiliary method to determine the degree of deuteration, and the signal of inactive hydrogen was utilized or 19 The F-signal is used to determine the mass fraction, thus taking into account both the strong deuterium signal at high deuteration degree and the large error of conventional titration at low mass fraction.

[0049] For samples with low deuteration degree and high mass fraction, conventional titration methods for strong acids are inherently difficult to determine the titration endpoint under high mass fraction conditions, and the corrosiveness of strong acids to the electrodes also affects the accuracy of the determination. For such samples, this invention addresses this issue by... 1 H NMR is the main component. 2 ¹H NMR is used as an auxiliary method to determine the degree of deuteration, while still employing inactive hydrogen signals or 19 The F signal is used to determine the quality fraction, avoiding the influence of conventional testing on low-deuteration and high-quality fractions.

[0050] As a preferred embodiment of any technical solution of the present invention, M in formulas (2) and (3) 酸 = Molar mass of the non-deuterated acid + Number of hydrogen atoms exchanged between hydrogen and deuterium in the molecular formula × Degree of deuteration; M 内标 = Molar mass of the non-deuterated internal standard + Number of hydrogens exchanged between hydrogen and deuterium in the molecular formula × Degree of deuteration.

[0051] 3. Beneficial effects Compared with the prior art, the beneficial effects of the present invention are as follows: (1) The method for simultaneous detection of deuteration degree and mass fraction in deuterated acid solution provided by the present invention acquires data simultaneously under the same NMR detection framework. 1 H NMR, 2 H NMR and / or 19 By analyzing the F NMR spectrum and performing calculations, the degree of deuteration and mass fraction of the deuterated acid solution can be obtained simultaneously. This eliminates the need for two separate detection methods, namely titration and nuclear magnetic resonance spectroscopy, reducing detection steps and error accumulation caused by using multiple methods in combination, and significantly shortening the detection cycle.

[0052] (2) The method for simultaneous detection of deuteration degree and mass fraction in deuterated acid solutions provided by this invention uses a binuclear or multinuclear organic compound with high chemical inertness, low hygroscopicity, and a definite stoichiometric relationship as an internal standard. A capillary coaxial encapsulation technique is used to achieve physical isolation between the internal standard and the acid solution sample to be tested. Simultaneously, the internal standard has a fixed molecular composition and a defined ¹H / ²H / ¹ ratio. 9 The F atom ratio allows for the provision of dual-nuclear or multi-nuclear internal standards for two or three nuclides using a single internal standard molecule. This not only overcomes the chemical instability of conventional internal standards in strongly acidic systems but also enables a single internal standard molecule to simultaneously provide dual-nuclear (e.g., F-nuclear) standards in the same NMR sample tube. 1 H+ 2 H, 1 H+ 19 F, 2 H+ 19 F) or triple-core ( 1 H+ 2 H + 19 The quantitative benchmark of F) enables simultaneous quantification of multiple nuclei in a single NMR experiment, significantly improving information acquisition efficiency and further reducing measurement errors; Furthermore, this invention provides differentiated internal standard selection schemes for acids with different chemical structures, covering almost all types of acids in the field of deuteration synthesis.

[0053] (3) The method for simultaneous detection of deuteration degree and mass fraction in deuterated acid solution provided by the present invention can achieve good repeatability and accuracy for samples of different types of acids, different mass fractions and different deuteration degree ranges. It can be adapted to the detection of a wide range of samples from low deuteration degree to high abundance deuteration degree (99.8%), low mass fraction (10.0wt%) to high mass fraction (99.0wt%), and has a good linear relationship.

[0054] (4) The method for simultaneous detection of deuteration degree and mass fraction in deuterated acid solution provided by the present invention has high accuracy. The RSD of deuteration degree determination can be as low as 0.05%, and the RSD of mass fraction determination can be as low as 0.15%. The results of deuteration degree and mass fraction determination are consistent with the sample preparation value or the results of classical titration method, indicating that the present invention has good practicality.

[0055] (5) The method for simultaneous detection of deuteration degree and mass fraction in deuterated acid solution provided by the present invention uses a reasonably designed internal standard with characteristic peaks that are single peaks or narrow multiple peaks, which do not overlap with the signal of the deuterated acid solution sample to be tested. The spectrum is easy to analyze and the integration accuracy is high. In addition, the effective characteristic peak nuclide concentration of the selected internal standard has been optimized (H content 8~100 mmol / g, D content 8~100 mmol / g, F content 5~25 mmol / g), ensuring that a high signal-to-noise ratio NMR signal can still be obtained with a small packaging volume, resulting in high quantitative accuracy. Attached Figure Description

[0056] Figure 1 In Example 1 1 H NMR spectrum; Figure 2 In Example 1 2 H NMR spectrum; Figure 3 In Example 1 19 F NMR spectrum; Figure 4 In Example 2 1 H NMR spectrum; Figure 5 In Example 2 2 H NMR spectrum; Figure 6 In Example 3 1 H NMR spectrum; Figure 7 In Example 3 2 H NMR spectrum. Detailed Implementation

[0057] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0058] Unless otherwise specified in the examples, the procedures should be performed under standard conditions or conditions recommended by the manufacturer. Reagents or instruments whose manufacturers are not specified are all commercially available products.

[0059] Concentration, amount, and other numerical data may be presented in range format herein. It should be understood that such range format is used solely for convenience and brevity and should be flexibly interpreted to include not only the values ​​explicitly stated as the limits of the range, but also all individual values ​​or subranges encompassed within the range, as if each value and subrange were explicitly stated. For example, a range of values ​​from about 1 to about 4.5 should be interpreted to include not only the explicitly stated limits of 1 to 4.5, but also individual numbers (such as 2, 3, 4) and subranges (such as 1 to 3, 2 to 4, etc.). The same principle applies to ranges that describe only a single value, such as "less than about 4.5," which should be interpreted to include all the values ​​and ranges described above. Furthermore, this interpretation should apply regardless of the breadth of the range or characteristic described.

[0060] The present invention will be further described below with reference to specific embodiments.

[0061] Information on raw materials and reagents used in the examples: Deuterated p-tert-butylbromobenzene-d4: Degree of deuteration 98.16%, purity >99.0%, Ningbo Cuiying Chemical Technology Co., Ltd.; Trifluorotoluene: Purity > 99.5%, Moisture ≤ 50 ppm (by K.F.), Shanghai Adamas Reagent Co., Ltd.; Deuteration degree 99.50%, purity >99.0%, Ningbo Cuiying Chemical Technology Co., Ltd.; Deuterated trimethylbenzene-d3: Deuteration degree 99.65%, purity >99.5%, Ningbo Cuiying Chemical Technology Co., Ltd.; Deuterated p-bromofluorobenzene-d4: Degree of deuteration 99.50%, purity >99.0%, Ningbo Cuiying Chemical Technology Co., Ltd.; Deuterated hydroxymethanol-d1: Deuteration degree 99.84%, purity >99.5%, Ningbo Cuiying Chemical Technology Co., Ltd.

[0062] Example 1: Determination of the degree of deuteration and mass fraction of trifluoromethanesulfonic acid solution (1) Prepare internal standard and sample of deuterated acid solution to be tested. 1-1) Internal Standard: The internal standard uses a combination of hydrogen-deuterium dual-core internal standard and fluorine-hydrogen dual-core internal standard. The hydrogen-deuterium dual-core internal standard is deuterated p-tert-butylbromobenzene-d4, and the fluorine-hydrogen dual-core internal standard is trifluorotoluene. The specific preparation procedures are as follows: Accurately weigh 41.7 mg of deuterated p-tert-butylbromobenzene-d4 (deuteration degree 98.16%, purity > 99.0%) and 224.2 mg of trifluorotoluene (purity > 99.5%), inject them into two capillary tubes respectively, and seal them.

[0063] 1-2) Deuterated acid solution samples to be tested: Trifluoromethanesulfonic acid aqueous solution with known deuteration degree and mass fraction (deuteration degree 99.4%, mass fraction 88.0%) is used as the deuterated acid solution to be tested. Accurately weigh 0.8125g and 0.4657g of the above trifluoromethanesulfonic acid aqueous solution, respectively, and label them as samples A-1 and A-2. Then, put samples A-1 and A-2 into NMR sample tubes respectively.

[0064] (2) Sample tube preparation: vertically place the capillary tube containing deuterated p-tert-butylbromobenzene-d4 in 1-1) into the NMR sample tube containing A-1 in 1-2), and vertically place the capillary tube containing trifluorotoluene in 1-1) into the NMR sample tube containing A-2 in 1-2). Adjust the height of the sealing solution in the capillary tube to be basically consistent with the height of the sample liquid in the NMR tube.

[0065] (3) Nuclear magnetic resonance acquisition: A 400 MHz nuclear magnetic resonance spectrometer was used with D2O field locking to acquire the nuclear magnetic resonance data of sample A-1. 1 H NMR spectrum, 2 H NMR spectra, collected from A-2 19 F NMR spectrum, where: 1 The acquisition conditions for the H NMR spectrum were: number of samples NS=64, spectral width SW=20.4799, center frequency O1P=6.175ppm, sampling time AQ=4s, pulse tilt angle of 90°, and relaxation delay time D1 of 20s. 2 The acquisition conditions for the H NMR spectrum were: number of samplings NS=32, spectral width SW=20.3457, center frequency O1P=4.000ppm, sampling time AQ=4s, pulse tilt angle of 90°, and relaxation delay time D1 of 10s. 19 The acquisition conditions for the F NMR spectrum were as follows: number of samples NS=32, spectral width SW=241.4, center frequency O1P=-100ppm, sampling time AQ=0.72s, pulse tilt angle of 90°, and relaxation delay time D1 of 10s.

[0066] The above NMR spectra were collected and measured in three parallel sessions.

[0067] (4) Data processing: 1 H NMR spectrum ( Figure 1 ), 2 H NMR spectrum ( Figure 2 ), 19 F NMR spectrum ( Figure 3 Integrate the corresponding characteristic peak areas of the internal standard and the sample to be tested.

[0068] Depend on 1 H NMR spectrum, 2 Integrating the H NMR spectrum yields S 内标D S 内标H S 样品H-1 S 样品D Calculate the degree of deuteration (D) of trifluoromethanesulfonic acid according to formula (1); 19 F NMR spectrum integration yields S 内标F S 样品F The mass fraction (ω) of trifluoromethanesulfonic acid was calculated according to formula (3); the results are shown in Table 1 below: Table 1. Deuteration test results of trifluoromethanesulfonic acid solution

[0069] Table 2. Results of Trifluoromethanesulfonic Acid Mass Fraction Test in Trifluoromethanesulfonic Acid Solution

[0070] Note: Samples A-1 and A-2 are trifluoromethanesulfonic acid solutions from the same batch, and they have the same degree of deuteration.

[0071] In this embodiment, the effective characteristic peak of the hydrogen-deuterium dual-core internal standard (deuterated p-tert-butylbromobenzene-d4) has an H content of 41.45 mmol / g and a D content of 9.21 mmol / g; the effective characteristic peak of the fluorine-hydrogen dual-core internal standard (trifluorotoluene) has an H content of 13.69 mmol / g and a F content of 20.53 mmol / g.

[0072] As shown in Table 1, the average value of the deuteration degree (D) of the trifluoromethanesulfonic acid aqueous solution measured in three parallel determinations was 99.48%, with an RSD of 0.06%, which is basically consistent with the set deuteration degree of 99.4%. As shown in Table 2, the average value of the mass fraction (ω) of the trifluoromethanesulfonic acid measured in three parallel determinations was 87.81%, with an RSD of 0.15%, which is basically consistent with the set mass fraction of 88.0%. The measured deuteration degree and mass fraction are basically consistent with the initial settings, indicating that the method of this embodiment is accurate and reliable.

[0073] Example 2: Determination of the degree of deuteration and mass fraction of methanesulfonic acid aqueous solution (1) Prepare internal standard and sample of deuterated acid solution to be tested. 1-1) Internal Standard: The internal standard used is a hydrogen-deuterium dual-core internal standard. Specifically, the hydrogen-deuterium dual-core internal standard is deuterated p-tert-butylbromobenzene-d4, and the preparation procedure is as follows: Accurately weigh 41.7 mg of deuterated p-tert-butylbromobenzene-d4 (deuteration degree of 98.16%, purity >99.0%) and inject it into a capillary for encapsulation.

[0074] 1-2) Deuterated acid solution sample to be tested: A methanesulfonic acid aqueous solution with known deuteration degree and mass fraction (deuteration degree 42.5%, mass fraction 24.5%) is used as the deuterated acid solution to be tested. Accurately weigh 0.5873g of the methanesulfonic acid aqueous solution, label it as sample B, and put sample B into an NMR sample tube.

[0075] (2) Sample tube preparation: vertically place the capillary tube containing the internal standard in 1-1) into the NMR sample tube in 1-2), and adjust the liquid level of the sealing solution in the capillary tube to be basically consistent with the liquid level of the sample to be tested in the NMR tube.

[0076] (3) Nuclear magnetic resonance (NMR) acquisition: acquisition 1 H NMR spectrum, 2 The H NMR spectrum was collected under the same conditions as in Example 1, and three parallel measurements were performed.

[0077] (4) Data processing: 1 H NMR spectrum ( Figure 4 ), 2 H NMR spectrum ( Figure 5 ), and perform area integration of the corresponding characteristic peaks of the internal standard and the sample to be tested.

[0078] Depend on 1 H NMR spectrum, 2 Integrating the H NMR spectrum yields S 内标D S 内标H S 样品H-1 S 样品D S 样品H-2 The degree of deuteration (D) of methanesulfonic acid was calculated according to formula (1), and the mass fraction (ω) of methanesulfonic acid was calculated according to formula (2); the results are shown in Table 3 below: Table 3. Test results of deuteration degree and mass fraction of sample B-methanesulfonic acid solution

[0079] In this embodiment, the effective characteristic peak of the hydrogen-deuterium dual-core internal standard (deuterated p-tert-butylbromobenzene-d4) has an H content of 41.45 mmol / g and a D concentration of 9.21 mmol / g.

[0080] As shown in Table 3, the average value of the three parallel determinations of the degree of deuteration (D) of the mesylate aqueous solution was 42.48%, with an RSD of 0.48%, which is basically consistent with the set deuteration degree of 42.5%. The average value of the mass fraction (ω) of the mesylate acid measured in three parallel determinations was 24.23%, with an RSD of 0.41%, which is basically consistent with the set mass fraction of 24.5%. The measured deuteration degree and mass fraction are consistent with the initial settings, indicating that the method of this embodiment is accurate and reliable. At the same time, the mass fraction of mesylate acid in the same mesylate aqueous solution sample was tested by conventional potentiometric titration, and the mass fraction of mesylate acid was measured to be 24.21%. The deviation from the 24.23% measured by the method of this embodiment is only 0.02%, proving that the method of this embodiment is accurate and reliable in determining the mass fraction of mesylate acid.

[0081] Example 3 The difference between this embodiment and Embodiment 2 is that the deuterated acid solution sample to be tested in 1-2) and the internal standard in 1-1) are different. The deuterated acid solution sample to be tested in this embodiment is a methanesulfonic acid aqueous solution with known deuteration degree and mass fraction (deuteration degree 44.0%, mass fraction 26.5%). In this embodiment, deuterated hydroxymethanol-d1 (deuteration degree 99.84%, purity > 99.5%) is used as a hydrogen-deuterium dual-core internal standard.

[0082] The 1H NMR and 2H NMR spectra obtained in this embodiment are as follows: Figure 6 , Figure 7 As shown in Table 4, the calculated degrees of deuteration and mass fraction of methanesulfonic acid in the aqueous solution are as follows: Table 4. Degree of deuteration and mass fraction of methanesulfonic acid aqueous solution obtained by testing with deuterated hydroxymethanol-d1 as internal standard.

[0083] The results showed that when hydroxydeuterated methanol was used as the internal standard for methanesulfonic acid aqueous solution, the average value of the three parallel determinations of the degree of deuteration (D) of the methanesulfonic acid aqueous solution was 44.16%, with an RSD of 0.73%, which deviated from the set degree of deuteration of 44.0% by 0.16%; the average value of the three parallel determinations of the mass fraction (ω) of methanesulfonic acid was 27.17%, with an RSD of 0.54%, which deviated from the set mass fraction of 27.0% by 0.17%.

[0084] Example 4: Determination of the degree of deuteration and mass fraction of trifluoromethanesulfonic acid solution using a deuterium-fluoride trinuclear internal standard. (1) Prepare internal standard and sample of deuterated acid solution to be tested. 1-1) Internal Standard: The internal standard used is a trinuclear internal standard of fluorine-hydrogen-deuterium, the structure of which is as follows: The deuteration degree is 99.50%. The specific preparation steps are as follows: Accurate weighing (Deuteration degree is 99.50%, purity > 99.0%) 36.8 mg, injected into capillary and sealed.

[0085] 1-2) Sample of deuterated acid solution to be tested: Use a trifluoromethanesulfonic acid aqueous solution with known deuteration degree and mass fraction (deuteration degree 99.4%, mass fraction 84.2%) as the sample of deuterated acid solution to be tested. Accurately weigh 0.8103g of the trifluoromethanesulfonic acid aqueous solution, label it as sample C, and put sample C into an NMR sample tube.

[0086] (2) Sample tube preparation: vertically place the capillary tube containing the internal standard in 1-1) into the NMR sample tube in 1-2), and adjust the liquid level of the sealing solution in the capillary tube to be basically consistent with the liquid level of the sample to be tested in the NMR tube.

[0087] (3) Nuclear magnetic resonance (NMR) acquisition: acquiring the NMR data of sample C. 1 H NMR spectrum, 2 H NMR spectrum, 19 F NMR spectra were obtained under the same conditions as in Example 1, and three parallel measurements were performed.

[0088] (4) Data processing: 1 H NMR spectrum, 2 H NMR spectrum, 19 F NMR spectra were used to integrate the corresponding characteristic peak areas of the internal standard and the sample to be tested.

[0089] Depend on 1 H NMR spectrum, 2 Integrating the H NMR spectrum yields S 内标D S 内标H S 样品H-1 S 样品D Calculate the degree of deuteration (D) of trifluoromethanesulfonic acid according to formula (1); 19 F NMR spectrum integration yields S 内标F S 样品F The mass fraction (ω) of trifluoromethanesulfonic acid was calculated according to formula (3); the results are shown in Table 5 below: Table 5. Test results of deuteration degree and mass fraction of sample C-trifluoromethanesulfonic acid solution

[0090] In this embodiment, the effective characteristic peaks of the internal standard prepared have an H content of 12.18 mmol / g, a D content of 18.28 mmol / g, and an F content of 18.28 mmol / g.

[0091] As shown in Table 5, the average value of the deuteration degree (D) of the trifluoromethanesulfonic acid aqueous solution measured in three parallel determinations was 99.49%, with an RSD of 0.05%, which is basically consistent with the set deuteration degree of 99.4%. The average value of the mass fraction (ω) of trifluoromethanesulfonic acid measured in three parallel determinations was 84.40%, with an RSD of 0.52%, which is basically consistent with the set mass fraction of 84.2%. The measured deuteration degree and mass fraction are consistent with the initial settings, indicating that the method of this embodiment is accurate and reliable.

[0092] Example 5: Determination of deuterated acid solutions with different degrees of deuteration and different mass fractions To verify that the method of this invention can test deuterated acid solutions with a large range of deuteration degree and mass fraction, this embodiment tests deuterated acid solutions with different deuteration degrees and mass fractions. The specific steps are as follows: (1) Preparation of the deuterated acid solution sample to be tested The following (Table 6) samples of deuterated acid solutions with different mass fractions and degrees of deuteration were prepared: Table 6. Deuterated acid solution samples with different mass fractions and degrees of deuteration

[0093] In preparing the above samples, high-abundance deuterated acids with known deuteration degrees were mixed with perhydroacids in a specific ratio, and the deuteration degree and mass fraction were adjusted using ordinary deionized water or heavy water. All preparation values ​​were accurately determined by weighing.

[0094] (2) Test the degree of deuteration and mass fraction of samples D-1 to F-4. 2-1) Samples D-1~D-3 and F-1~F-4, i.e., deuterated trifluoroacetic acid and trifluoromethanesulfonic acid solutions, were tested for deuteration degree and mass fraction according to the method in Example 1. The only difference between this example and Example 1 is the internal standard used. The internal standard used in this example is as follows: Accurately weigh 30.5 mg of deuterated trimethylbenzene-d3 (hydrogen-deuterium dual-core internal standard, deuteration degree 99.65%, purity >99.5%) and 86.6 mg of deuterated p-bromofluorobenzene-d4 (fluorodeuterium dual-core internal standard, deuteration degree 99.5%, purity >99.0%), inject them into two capillary tubes respectively, and seal them independently.

[0095] 2-2) Samples E-1 to E-3, i.e., deuterated methanesulfonic acid solutions, were tested for deuteration degree and mass fraction according to the method in Example 2. The only difference between this example and Example 2 is the internal standard used. The internal standard used in this example is as follows: Accurately weigh 30.2 mg of deuterated trimethylbenzene-d3 (hydrogen-deuterium dual-core internal standard, deuteration degree of 99.65%, purity >99.5%) and inject it into a capillary for encapsulation.

[0096] Among them, the effective characteristic peak of the hydrogen-deuterium dual-core internal standard (deuterated trimethylbenzene-d3) had an H content of 73.06 mmol / g and a D content of 24.35 mmol / g; the effective characteristic peak of the fluorine-deuterium dual-core internal standard (deuterated p-bromofluorobenzene-d4) had a D content of 11.17 mmol / g and a F content of 5.59 mmol / g.

[0097] The sampling quantity for each sample is as follows: Table 7. Sampling quantities for different test samples

[0098] The test results for samples D-1 to F-4 are shown in Table 8 below: Table 8. Test results of deuteration degree and mass fraction of samples D-1 to F-4

[0099] The results show that the method of the present invention has excellent detection performance for organic acid aqueous solution samples with different mass fractions (10.0-99.0 wt%) and different deuteration levels (45.0-99.8%). The RSD of deuteration is in the range of 0.09%-0.36%, and the RSD of mass fraction is in the range of 0.24%-0.65%.

[0100] Comparative Example 1 The mass fraction of trifluoromethanesulfonic acid in the aqueous solution sample of Example 1 (from the same batch as in Example 1 of this invention) was determined by conventional potentiometric titration. The specific procedure is as follows: Accurately weigh approximately 0.5 g of the trifluoromethanesulfonic acid aqueous solution sample to be tested, dilute with 50 mL of deionized water, and titrate using an automatic potentiometric titrator with 0.10 mol / L sodium hydroxide standard solution as the titrant. Determine the endpoint by the potential jump point. Perform the titration three times in parallel and calculate the mass fraction of trifluoromethanesulfonic acid. The results are shown in Table 9 below: Table 9. Results of mass fraction of trifluoromethanesulfonic acid in aqueous solution determined by potentiometric titration

[0101] The average mass fraction of trifluoromethanesulfonic acid measured by the method of the present invention is 87.81%, while the average mass fraction of trifluoromethanesulfonic acid measured by conventional potentiometric titration is 88.24%. The deviation between the two is 0.43%, indicating that the two results are highly consistent. This shows that the method of the present invention has the same accuracy as the classical titration method for determining the mass fraction of trifluoromethanesulfonic acid, and does not require cumbersome titration operations and sample processing.

[0102] Comparative Example 2 Using the conventional "potential titration combined" method in this field1 The deuteration degree of the above-mentioned batch of trifluoromethanesulfonic acid aqueous solution samples was determined by ¹H NMR. The specific operating steps are as follows: (1) The mass fraction of trifluoromethanesulfonic acid (i.e., the mass fraction of total acid) in the sample was determined according to the method described in Comparative Example 1, and denoted as C. 总酸 ; (2) Add the trifluoromethanesulfonic acid aqueous solution sample to be tested directly into the NMR tube (without adding internal standard), and collect samples. 1 The H NMR spectrum (acquisition conditions are the same as in Example 1) is used to calculate the concentration of residual hydrogen in the sample by integrating the peak area of ​​the characteristic peak of active hydrogen in the sample and combining it with the known sample mass and molar mass. (3) The degree of deuteration was calculated according to the formula “Deuteration (%) = (1 - residual hydrogen concentration / mass fraction of total acid) × 100%”. Three parallel determinations were performed, and the results are shown in Table 10 below. The average value and relative standard deviation (RSD) were calculated.

[0103] Table 10. Potentiometric titration combination 1 Results of HNMR analysis of the deuteration degree of trifluoromethanesulfonic acid solution

[0104] The method of this invention yielded an average deuteration degree of 99.48%, with a deviation of only 0.08% from the prepared value of 99.4%, and an RSD of 0.06%. In contrast, conventional titration methods... 1 The deviation of the H NMR method was 0.11% and the RSD was 0.07%, indicating that the accuracy and precision of the method of the present invention are better than those of the conventional indirect method. Moreover, the method of the present invention does not require titration, which reduces cumbersome steps and cumulative errors.

[0105] The above description provides an illustrative overview of the present invention and its embodiments. This description is not restrictive, and the embodiments shown are merely one example of the invention's implementation. Actual implementations are not limited to these examples. Therefore, if those skilled in the art are inspired by this description and design similar implementations and examples without departing from the spirit of the invention, such designs should fall within the scope of protection of the present invention.

Claims

1. A method for simultaneous detection of deuteration degree and mass fraction in deuterated acid solution, characterized in that, Includes the following steps: (1) Weigh the sample of the deuterated acid solution to be tested and the internal standard; (2) The internal standard and the deuterated acid solution sample to be tested are placed in the NMR sample tube in a capillary-encapsulated and coaxial manner; (3) Based on the type of deuterated acid solution sample and internal standard, collect samples. 1 H NMR, 2 H NMR and / or 19 F NMR spectrum; (4) Integrate the characteristic peak area of ​​the NMR spectrum after testing, and calculate the degree of deuteration and mass fraction of the deuterated acid solution sample based on the integrated area, the known molar amount of the corresponding nucleus in the internal standard, and the mass of the deuterated acid solution sample and the internal standard. The acid in the deuterated acid solution includes one or more organic sulfonic acids and organic carboxylic acids.

2. The method for simultaneous detection of deuteration degree and mass fraction in deuterated acid solution according to claim 1, characterized in that, According to the quantitative characteristics of nuclear magnetic resonance, the acids in the deuterated acid solution are divided into acids containing non-active hydrogen and acids without non-active hydrogen. The acid containing non-active hydrogen is selected from one or more of organic sulfonic acids and organic carboxylic acids; wherein, the organic sulfonic acid includes one or more of alkyl sulfonic acids and aryl sulfonic acids; and the organic carboxylic acid includes one or more of alkyl carboxylic acids and aryl carboxylic acids. The alkyl sulfonic acid includes C1 to C4 alkyl sulfonic acids; The aryl sulfonic acid includes substituted or unsubstituted benzenesulfonic acid, wherein the substituents are independently selected from C1-C3 alkyl, C1-C3 alkoxy, halogen, nitro, cyano, C1-C4 alkoxycarbonyl, trifluoromethyl, phenyl, or five- or six-membered heteroaryl. The alkyl carboxylic acids include C2-C6 alkyl carboxylic acids; The aryl carboxylic acid includes substituted or unsubstituted benzoic acid, wherein the substituents are independently selected from C1-C3 alkyl, C1-C3 alkoxy, halogen, nitro, cyano, C1-C4 alkoxycarbonyl, trifluoromethyl, phenyl, or five- or six-membered heteroaryl. The acid without non-active hydrogen includes perfluorinated substituted acids; the perfluorinated substituted acids include one or more of perfluorinated alkyl sulfonic acids and perfluorinated alkyl carboxylic acids; The perfluoroalkyl sulfonic acid includes C1 to C4 perfluoroalkyl sulfonic acids; The perfluoroalkyl carboxylic acids include C2-C8 perfluoroalkyl carboxylic acids.

3. The method for simultaneous detection of deuteration degree and mass fraction in deuterated acid solution according to claim 2, characterized in that, The alkyl sulfonic acid includes one or more of methanesulfonic acid, ethyl sulfonic acid, propyl sulfonic acid, isopropyl sulfonic acid, and butyl sulfonic acid; The aryl sulfonic acid includes one or more of benzenesulfonic acid, p-methylbenzenesulfonic acid, and 4-fluorobenzenesulfonic acid; The alkyl carboxylic acid includes one or more of acetic acid, propionic acid, isobutyric acid, and pivalic acid; The aryl carboxylic acid includes one or more of benzoic acid, p-fluorobenzoic acid, and p-methylbenzoic acid; The perfluoroalkyl sulfonic acid includes one or more of trifluoromethanesulfonic acid, perfluoroethanesulfonic acid, and perfluorobutyric acid. The perfluoroalkyl carboxylic acids include one or more of trifluoroacetic acid, perfluoropropionic acid, perfluorobutyric acid, and perfluorooctanoic acid.

4. The method for simultaneous detection of deuteration degree and mass fraction in deuterated acid solution according to claim 1 or 3, characterized in that, The internal standard includes one or more of dual-core or multi-core internal standards.

5. The method for simultaneous detection of deuteration degree and mass fraction in deuterated acid solution according to claim 4, characterized in that, The dual-core internal standard includes one or more of hydrogen-deuterium dual-core internal standards, fluorine-hydrogen dual-core internal standards, and fluorine-deuterium dual-core internal standards; the multi-core internal standard includes fluorine-hydrogen-deuterium tri-core internal standards. When the acid in the deuterated acid solution to be tested is an acid containing non-active hydrogen, the internal standard is a hydrogen-deuterium dual-core internal standard; When the acid in the deuterated acid solution to be tested is an acid without non-active hydrogen, the internal standard can be one or more of the following: a combination of a hydrogen-deuterium binuclear internal standard and a fluorine-hydrogen binuclear internal standard; a combination of a hydrogen-deuterium binuclear internal standard and a fluorine-deuterium binuclear internal standard; a combination of a fluorine-hydrogen binuclear internal standard and a fluorine-deuterium binuclear internal standard; or a fluorine-hydrogen-deuterium trinuclear internal standard.

6. The method for simultaneous detection of deuteration degree and mass fraction in deuterated acid solution according to claim 5, characterized in that, The deuterium-hydrogen binuclear internal standard is selected from one or more of the following: deuterated toluene-d5, ethyl(benzene-d5), deuterated mesitylene-d3, deuterated p-tert-butylbromobenzene-d4, deuterated 1,4-di-tert-butylbenzene-d4, deuterated p-xylene-d4, deuterated o-xylene-d4, deuterated m-xylene-d4, deuterated p-methoxytoluene-d4, deuterated anisole-d5, deuterated methyl tert-butyl ether-d9, deuterated ethanol-d5, deuterated hydroxymethanol-d1, and deuterated hydroxyethanol-d1. The fluorine-hydrogen dual-core internal standard is selected from one or more of methyl trifluoroacetate, ethyl trifluoroacetate, 4-methyltrifluorotoluene, 3-methyltrifluorotoluene, trifluorotoluene, and 1-(tert-butyl)-4-(trifluoromethyl)benzene; The fluorodeuterium binuclear internal standard is selected from one or more of deuterated fluorobenzene-d5, p-bromofluorobenzene-d4, and trifluorotoluene-d5; The trinuclear standard of fluorine hydrogen deuterium was selected from or .

7. The method for simultaneous detection of deuteration degree and mass fraction in deuterated acid solution according to any one of claims 4 to 6, characterized in that, The effective characteristic peak H content of the internal standard is 8-100 mmol / g; and / or, The effective characteristic peak D content of the internal standard is 8-100 mmol / g; and / or, The effective characteristic peak of the internal standard has an F content of 5-25 mmol / g.

8. The method for simultaneous detection of deuteration degree and mass fraction in deuterated acid solution according to any one of claims 4 to 6, characterized in that, The effective characteristic peak H content of the internal standard is 15-60 mmol / g; and / or, The effective characteristic peak D content of the internal standard is 15-50 mmol / g; and / or, The effective characteristic peak of the internal standard has an F content of 10-20 mmol / g.

9. The method for simultaneous detection of deuteration degree and mass fraction in a deuterated acid solution according to any one of claims 1 to 8, characterized in that, In step (3), data is collected. 1 For H NMR spectroscopy, the operating parameters of the NMR instrument are as follows: the field-locking reagent is any one of heavy water, deuterated benzene, or deuterated trifluoroacetic acid; the number of samples is no less than 16; the spectral width is 15 to 25 ppm; the center frequency is 5 to 8 ppm; the single sampling time is 3 to 6 s; the pulse tilt angle is 90°; and the relaxation delay time is 6 to 70 s; and / or, collection 2 For H NMR spectroscopy, the operating parameters of the NMR instrument are as follows: field-locking reagent is either heavy water or deuterated trifluoroacetic acid, or no field-locking; the number of samplings is no less than 32; the spectral width is 15 to 25 ppm; the center frequency is 2 to 6 ppm; the single sampling time is 3 to 6 s; the pulse tilt angle is 90°; and the relaxation delay time is 6 to 70 s; and / or, collection 19 For F NMR spectroscopy, the operating parameters of the NMR instrument are as follows: the field lock reagent is either heavy water or deuterated trifluoroacetic acid; the number of samplings is no less than 32; the spectral width is 200 to 300 ppm; the center frequency is -100 to -70 ppm; the single sampling time is 0.5 to 1.0 s; the pulse tilt angle is 90°; and the relaxation delay time is 1 to 15 s.

10. The method for simultaneous detection of deuteration degree and mass fraction in deuterated acid solution according to claim 9, characterized in that, In step (4), the formula for calculating the degree of deuteration of the deuterated acid solution sample is as shown in equation (1): ； Equation (1) Among them, S 样品D represent 2 The integral area of ​​the characteristic peak of active hydrogen in the H NMR spectrum of the sample to be tested; S 内标D represent 2 The integrated area of ​​the characteristic peak of the internal standard deuterium in the H NMR spectrum; S 样品H-1 represent 1 The integral area of ​​the characteristic peak of active hydrogen in the H NMR spectrum of the sample to be tested; S 内标H represent 1 The integral area of ​​the hydrogen characteristic peak of the internal standard in the 1H NMR spectrum; N D This represents the number of deuterium atoms corresponding to the deuterium characteristic peaks used for integration in the internal standard. N H This represents the number of hydrogen atoms corresponding to the hydrogen characteristic peaks used for integration in the internal standard. D 内标 It represents the degree of deuteration of the internal standard used.

11. The method for simultaneous detection of deuteration degree and mass fraction in deuterated acid solution according to claim 9, characterized in that, In step (4), when the acid in the deuterated acid solution to be tested is an acid containing non-active hydrogen, the formula for calculating the mass fraction of the deuterated acid solution sample is as shown in equation (2): ； Equation (2) Among them, S 内标H represent 1 The integral area of ​​the hydrogen characteristic peak of the internal standard in the 1H NMR spectrum; S 样品H-2 represent 1 The integral area of ​​the characteristic peak of non-active hydrogen in the H NMR spectrum of the sample to be tested. m 内标 The mass of the internal standard used in step (2), in g; M 内标 Represents the molar mass of the internal standard used in the labeled state, in g / mol; C 内标 This represents the purity of the internal standard used, % . N H This represents the number of hydrogen atoms in the internal standard used for integrating the hydrogen characteristic peak; M 酸 The molar mass of the acid in the deuterated acid solution of the test sample under the labeled state is represented in g / mol. m 酸溶液 The amount of the deuterated acid solution sample to be tested in step (2), in g; O H represent 1 The integral area S of the characteristic peak of non-active hydrogen in the H NMR spectrum of the sample to be tested 样品H-2 The corresponding number of hydrogen atoms; and / or, In step (4), when the acid in the deuterated acid solution to be tested is an acid without non-active hydrogen, the formula for calculating the mass fraction of the deuterated acid solution sample is as shown in equation (3): ； Equation (3) Among them, S 内标F represent 19 The area of ​​the fluorine characteristic peak of the internal standard in the integrated F NMR spectrum; S 样品F represent 19 The area of ​​the characteristic fluorine peak in the fluorine-containing acid sample to be tested in the F NMR spectrum; m 内标 The mass of the internal standard used in step (2), in g; C 内标 This represents the purity of the internal standard used, % . M 内标 The molar mass of the internal standard used in step (2) in the labeled state is expressed in g / mol. N F The integral area S of the fluorine characteristic peak of the internal standard used in step (2) 内标F The corresponding number of fluorine atoms; M 酸 The molar mass of the acid in the deuterated acid solution of the test sample under the labeled state is represented in g / mol. m 酸溶液 The amount of the deuterated acid solution sample to be tested in step (2), in g; P F represent 19 The integral area S of the fluorine characteristic peak in the fluorine sample in the F NMR spectrum 样品F The corresponding F numbers.

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