Method for preparing bromobenzene-d5

Abstract

The present invention provides a method for preparing bromobenzene-d5, comprising: in parts by mass, mixing 1 part of deuterated benzene, 0.61-1.08 parts of sodium bromide, 0.62-0.89 parts of sodium bromate, 0.007-0.07 parts of iron bromide, and 1.07-2.14 parts of water, and adding 2.8-7 parts of a sulfuric acid aqueous solution having a volume fraction of 20-25% for a reaction at a reaction temperature of 20-60°C for a reaction time of 12-48 h to obtain an initial product containing bromobenzene-d5; and purifying the initial product to obtain bromobenzene-d5. The present invention provides a safe method for preparing bromobenzene-d5. The method has a high yield and a maintained degree of deuteration and is suitable for industrial mass production.

Description

A preparation method of bromobenzene-d5 Technical Field

[0001] The present invention relates to the technical field of deuterated synthesis, and in particular to a method for preparing bromobenzene-d5. Background Art

[0002] In the current field of organic synthesis and isotope labeling, deuterated compounds, as an important type of compound, are widely used in many fields such as nuclear magnetic resonance detection, life sciences, food safety and materials science. Due to the introduction of the isotope deuterium atom, the relative molecular mass of deuterated compounds changes, which has a labeling effect. In addition, the C (carbon)-D (deuterium) bond is shorter and more stable than the CH (hydrogen) bond. The activation energy required to break the CD bond is higher, and its kinetic reaction rate is lower. This difference in kinetic reaction rate caused by deuteration is called the deuterium kinetic isotope effect. This effect contributes to the widespread application of deuterated compounds in the above-mentioned fields. For example, in the field of nuclear magnetic resonance detection, deuterated compounds can be used as nuclear magnetic solvents to dissolve and dilute the analyte to avoid the introduction of interfering hydrogen signals, while providing a nuclear magnetic lock field. In the life sciences, the labeling effect of deuterated compounds, combined with tandem mass spectrometry, allows for the study of the absorption, distribution, metabolism, and excretion (ADME) processes of drug molecules in vivo. The deuterated isotope effect brought about by the introduction of deuterium can alter the pharmacokinetics and metabolic pathways of drug molecules, thereby enabling the improvement and development of new drugs. Deuterated clenbuterol and deuterated Sudan red can be used as internal standards to detect the presence of illegal additives in food, thereby regulating food safety. Furthermore, due to the stability of CD bonds, optoelectronic materials synthesized based on deuterated compounds have longer luminescence lifetimes.

[0003] Among them, bromobenzene-d5 (C6D5Br) can be used as a specialty deuterated solvent and an important intermediate for the synthesis of fully deuterated compounds. It can also be used as an analytical reagent or in chemical and pharmaceutical research and development. However, the preparation of bromobenzene-d5 has some problems. The common preparation method uses deuterated benzene as the raw material and a bromination reagent. However, the reaction produces oxygen, which causes the raw material to be carried away by the gas and cause loss. It also poses a safety hazard. The reaction yield of existing preparation methods is low, which restricts the production efficiency and cost-effectiveness of bromobenzene-d5.

[0004] Summary of the Invention

[0005] The problem to be solved by the present invention is to provide a safe preparation method for bromobenzene-d5 which has high yield, maintains the degree of deuteration and is suitable for large-scale industrial production.

[0006] To address at least one aspect of the above problems, the present invention provides a method for preparing bromobenzene-d5, comprising: mixing, by mass, 1 part of deuterated benzene, 0.61-1.08 parts of sodium bromide, 0.62-0.89 parts of sodium bromate, 0.007-0.07 parts of ferric bromide, and 1.07-2.14 parts of water, and adding 2.8-7 parts of a 20%-25% aqueous sulfuric acid solution, and reacting at a reaction temperature of 20-60°C and a reaction time of 12-48 hours to obtain a primary product containing bromobenzene-d5, and purifying the primary product to obtain bromobenzene-d5.

[0007] Preferably, the ratio of the sum of the molar amounts of bromine in the sodium bromide, the sodium bromate and the ferric bromide to the molar amount of the deuterated benzene is greater than or equal to 1.

[0008] Preferably, the purification of the primary product includes: allowing the primary product to stand and separate into layers, taking the first organic phase, washing with dilute sulfuric acid, washing with an aqueous NaOH solution, washing with a saturated NaHSO3 aqueous solution, and washing with water, respectively, and obtaining a crude bromobenzene-d5 product after drying; and distilling the crude bromobenzene-d5 product to obtain the bromobenzene-d5.

[0009] Preferably, the steps of washing with dilute sulfuric acid, washing with an aqueous NaOH solution, washing with a saturated NaHSO 3 solution, and washing with water respectively comprise:

[0010] Add dilute sulfuric acid to the first organic phase and mix and disperse it, let it stand and separate, take the second organic phase, add NaOH aqueous solution to the second organic phase and mix and disperse it, let it stand and separate, take the third organic phase, add saturated NaHSO3 aqueous solution to the third organic phase and mix and disperse it, let it stand and separate, take the fourth organic phase, add water to the fourth organic phase and mix and disperse it, let it stand and disperse, take the fifth organic phase.

[0011] Preferably, the mass fraction of the dilute sulfuric acid is 10%.

[0012] Preferably, the mass fraction of the NaOH aqueous solution is 15%-25%.

[0013] Preferably, the crude bromobenzene-d5 product is distilled in a distillation tower, the bottom temperature of the distillation tower is 80-120° C., the top temperature is 70-85° C., and the vacuum degree is not higher than 200 mbar.

[0014] Preferably, the yield of the primary product is ≥80%.

[0015] Preferably, the purity of the bromobenzene-d5 is ≥99%.

[0016] Preferably, the difference between the degree of deuteration of the bromobenzene-d5 and the degree of deuteration of the deuterated benzene is less than or equal to 0.2%.

[0017] The present invention uses sodium bromate and sodium bromide as bromination reagents. Under an acidic environment, sodium bromate is activated, generating active oxygen while brominating benzene. The active oxygen reacts with sodium bromide to generate new active bromination reagents. By converting the active oxygen generated during the bromination process, a high yield of bromobenzene-D5 is achieved, with the yield being greater than or equal to 80%. Furthermore, since benzene vapor is highly flammable and oxygen is a combustion-supporting gas, the conversion of oxygen to generate new bromination reagents improves the safety of the reaction. Furthermore, the catalysis of a trace amount of ferric bromide avoids the need for adding a free radical initiator, thereby enabling the bromination reaction of deuterated benzene to be achieved using an electrophilic substitution reaction mechanism, reducing the probability of hydrogen-deuterium exchange reactions and thereby maintaining a high degree of deuteration.

[0018] In summary, the preparation method of bromobenzene-d5 of the present invention has the advantages of high product yield, maintained deuteration degree, suitability for large-scale industrial production, and safety. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] FIG1 is a nuclear magnetic resonance detection spectrum of bromobenzene-d5 prepared in Example 1 of the present invention. DETAILED DESCRIPTION

[0020] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, specific embodiments of the present invention are described in detail below with reference to the accompanying drawings.

[0021] Bromobenzene-d5 is typically prepared by bromination of deuterated benzene. Care must be taken during the preparation process to avoid hydrogen-deuterium exchange between the hydrogen in the reaction system and the deuterium on the benzene ring, which could reduce the isotopic abundance. Common bromination reagents include liquid bromine (Br2), bromates, and N-bromosuccinimide (NBS).

[0022] In the related art, concentrated sulfuric acid (11.89 g, 6.5 mL) was added to a reaction flask, diluted with 24 mL of water, cooled to 0°C, and deuterated benzene (3 g, 0.035 mol) was added dropwise. After the addition was complete, sodium bromate (5.92 g, 0.039 mol) was added in two portions at 0°C. The reaction was allowed to react at room temperature for 18 hours. 50 mL of ice water was added, and the mixture was extracted three times with n-hexane. The organic phases were combined, washed with saturated sodium bicarbonate and saturated sodium chloride, dried over anhydrous sodium sulfate, and concentrated below 30°C to obtain 2.38 g of bromobenzene-d5, with a yield of 41.8%. The overall reaction formula is: C6D6(benzene-d6)+NaBrO3+H2SO4→C6D5Br(bromobenzene-d5)+NaHSO4+HDO+O2↑;

[0023] In the above preparation method, sodium bromate is used as the bromination reagent to obtain bromobenzene-d5. However, the by-product of the reaction system is oxygen. The continuous generation of gas will carry away some of the raw materials, causing material loss and greatly reducing the reaction yield, which is only 41.8%. Secondly, oxygen is a combustion aid, and deuterated benzene is a volatile combustible reagent. Therefore, the above process also has great safety risks.

[0024] A method for preparing bromobenzene-d5 according to an embodiment of the present invention comprises: mixing, by weight, 1 part of deuterated benzene, 0.61-1.08 parts of sodium bromide, 0.62-0.89 parts of sodium bromate, 0.007-0.07 parts of ferric bromide, and 1.07-2.14 parts of water, adding 2.8-7 parts of a 20%-25% aqueous sulfuric acid solution, and reacting at a reaction temperature of 20-60° C. for 12-48 hours to obtain a primary product containing bromobenzene-d5, and purifying the primary product to obtain bromobenzene-d5.

[0025] The reaction technology route of the present embodiment is: adopt sodium bromate and sodium bromide as brominating reagent, under acidic (sulfuric acid solution) environment, sodium bromate is activated, produces active oxygen while benzene is brominated, active oxygen and sodium bromide react and generate new active brominating reagent, active bromination intermediate includes hypobromous acid, bromine element etc..Simultaneously, introduce ferric bromide, ferric iron is reaction catalyst, under ferric bromide effect, the hydrogen atom in aromatic ring is replaced by bromine atom, to introduce bromo group on aromatic ring.In addition, in the present embodiment, byproduct of reaction is sodium bisulfate and water, and the deuterium that wherein deuterated benzene is replaced in bromination process is transferred to water, and the overall reaction formula of the present embodiment is as follows:

[0026] Therefore, it can be seen that the preparation method of this embodiment has at least the following advantages:

[0027] (1) The amount of bromate used is reduced by 2 / 3 compared to the traditional process. Only 1 / 3 molecule of bromate is needed to brominate one molecule of benzene, and the remaining bromine element comes from sodium bromide, which is safer and cheaper.

[0028] (2) The reaction of this embodiment avoids the generation of oxygen. The active oxygen generated by the bromination of benzene reacts with sodium bromide to generate a new active bromination reagent. On the one hand, the amount of bromine source is reduced, and on the other hand, the raw material deuterated benzene is prevented from being carried away by the tail gas. This produces the following positive benefits:

[0029] ① The production process is more economical and has a high yield. The raw material, deuterated benzene, is valuable and volatile. Any gas released will be carried away. This embodiment greatly reduces raw material loss, avoids oxygen generation, and improves the reaction yield. In this embodiment, the yield of bromobenzene-d5 is ≥80%, and the degree of deuteration is maintained.

[0030] ② The production process is more environmentally friendly. The deuterated benzene content in the tail gas is significantly reduced, reducing the pressure on tail gas treatment during the production process. The byproducts of the reaction system in this embodiment are sodium bisulfate and water, making the treatment of the three wastes simple.

[0031] ③ The production process is safer. Benzene vapor is highly flammable, and oxygen is a combustion-supporting gas. Conventional processes pose significant safety risks of flammability and explosion. This embodiment effectively addresses this safety issue by converting oxygen.

[0032] In addition, what the present embodiment utilizes is the electrophilic substitution reaction mechanism of phenyl ring, compared to the situation that needs to improve the reactivity of saturated C-H bond by adding free radical initiator adopting such as free radical substitution reaction, For the direct bromination of non-activated aromatic ring, the present embodiment does not need to use free radical initiator, adopts trace Lewis acid such as ferric bromide to effectively catalyze the reaction.And the hydrogen-deuterium exchange reaction that CD bond rupture may be caused by free radical reaction, causes the deuteration degree of deuterated benzene to decline.And when bromobenzene-d5 is prepared by deuterated benzene bromination as described above, it is particularly important to avoid the hydrogen of reaction system and the deuterium on phenyl ring to undergo hydrogen-deuterium exchange reaction.

[0033] In summary, the present embodiment not only obtains a higher yield by converting the active oxygen generated during the bromination process, but also has a bromobenzene-d5 yield greater than or equal to 80%, and has higher safety. In addition, by the catalysis of a trace amount of ferric bromide, it is possible to avoid adding a free radical initiator, thereby enabling the bromination reaction of deuterated benzene to be realized by utilizing an electrophilic substitution reaction mechanism, reducing the probability of a hydrogen-deuterium exchange reaction, thereby being able to maintain a higher degree of deuteration. The preparation method of the bromobenzene-d5 of the present embodiment has the advantages that the product yield is high and the degree of deuteration is maintained, is suitable for industrialized large-scale production, and is safe.

[0034] In some embodiments, the ratio of the sum of the molar amounts of bromine in the sodium bromide, the sodium bromate, and the ferric bromide to the molar amount of the deuterated benzene is greater than or equal to 1.

[0035] That is, the sum of the molar amounts of bromine in sodium bromide, sodium bromate, and ferric bromide: deuterated benzene ≥ 1. This ratio ensures that the molar amount of deuterated benzene in the reaction is at least equal to or greater than the sum of the molar amounts of bromine in sodium bromide, sodium bromate, and ferric bromide. This is because deuterated benzene reacts with these compounds to form brominated products. If the molar amount of deuterated benzene is insufficient to react with the bromine in these compounds, there will be no guarantee that there will be sufficient brominated species in the final product. Therefore, ensuring that this ratio is greater than or equal to 1 ensures the formation of brominated products in the reaction and ultimately produces bromobenzene-d5.

[0036] In some embodiments, the purification of the primary product includes: allowing the primary product to stand and stratify to take the first organic phase, washing it with dilute sulfuric acid, washing it with an aqueous NaOH solution, washing it with a saturated NaHSO3 aqueous solution, and washing it with water, and drying it to obtain a crude bromobenzene-d5 product; and distilling the crude bromobenzene-d5 product to obtain the bromobenzene-d5.

[0037] In order to remove the impurities and residues that may be present in the primary product to ensure the purity and quality of the final product, the present embodiment purifies the primary product. First, the primary product is allowed to stand for stratification to obtain a first organic phase, which is washed once or multiple times to obtain a crude product, and then subjected to rectification and impurity removal. Wherein, multiple washings may include two or more of dilute sulfuric acid washing, NaOH aqueous solution washing, saturated NaHSO3 aqueous solution washing, and water washing. Wherein, dilute sulfuric acid can remove alkaline impurities and some organic matter, and can also neutralize alkaline substances at the same time to remove alkaline impurities that may be present and neutralize residual alkaline substances, thereby improving the purity of the product. Sodium hydroxide (NaOH) aqueous solution can remove acidic substances and some organic acids, and can also neutralize acidic substances at the same time to remove acidic impurities that may be present and neutralize residual acidic substances, thereby improving the purity of the product. Sodium bisulfite (NaHSO3) aqueous solution can reduce some organic matter, and can also neutralize some oxidizing substances at the same time to remove oxidizing impurities that may be present and neutralize residual oxidizing substances, thereby improving the purity of the product. The final water wash can remove residual salts and water-soluble impurities, ensuring the purity of the product. Through the above multiple washing steps, impurities and residues in the crude bromobenzene-d5 product can be effectively removed, which helps to obtain a high-purity bromobenzene-d5 product.

[0038] In at least one embodiment, the steps of washing with dilute sulfuric acid, washing with an aqueous NaOH solution, washing with a saturated NaHSO 3 solution, and washing with water respectively comprise:

[0039] Add dilute sulfuric acid to the first organic phase and mix and disperse it, let it stand and separate, take the second organic phase, add NaOH aqueous solution to the second organic phase and mix and disperse it, let it stand and separate, take the third organic phase, add saturated NaHSO3 aqueous solution to the third organic phase and mix and disperse it, let it stand and separate, take the fourth organic phase, add water to the fourth organic phase and mix and disperse it, let it stand and disperse, take the fifth organic phase.

[0040] In at least one embodiment, the mass fraction of the dilute sulfuric acid is 10%. The 10% concentration of dilute sulfuric acid can provide sufficient acidity to neutralize possible alkaline impurities and help remove some organic matter without introducing excessive water or other impurities during the washing process.

[0041] In at least one embodiment, the mass fraction of the NaOH aqueous solution is 15%-25%. This concentration range can effectively neutralize acidic substances during the washing process while avoiding the use of excessive sodium hydroxide solution.

[0042] In at least one embodiment, the crude bromobenzene-d5 product is rectified using a distillation tower having a bottom temperature of 80-120° C., a top temperature of 70-85° C., and a vacuum degree of no more than 200 mbar.

[0043] In the distillation process, the tower still refers to the part for heating and distilling liquid in the distillation tower, which is the bottom of the distillation tower. The temperature of the tower still can affect the temperature and vapor-liquid equilibrium of the distilled liquid, thereby affecting the fractionation effect. Since the boiling point of bromobenzene-d5 is about 85 DEG C, the tower still temperature is set between 80-120 DEG C in the present embodiment, ensuring that bromobenzene-d5 can be fully evaporated within this temperature range, but not too much above its boiling point, so as not to cause excessive decomposition or volatilization of other impurities. The tower top temperature of 70-85 DEG C is to ensure that highly purified bromobenzene-d5 is obtained during the distillation process. Within this temperature range, it is possible to ensure that bromobenzene-d5 is fully condensed in the overhead condenser without bringing excessive impurities into the final product. Thus, by the setting of the above-mentioned temperature range, bromobenzene-d5 can be effectively separated during the distillation process and a highly purified product can be obtained.

[0044] In some embodiments, the yield of the primary product is ≥80%.

[0045] In some embodiments, the purity of the bromobenzene-d5 is ≥99%.

[0046] In some embodiments, the difference between the degree of deuteration of the bromobenzene-d5 and the degree of deuteration of the deuterated benzene is less than or equal to 0.2%.

[0047] The present invention is described below by means of specific examples.

[0048] Example 1

[0049] Deuterated benzene (10 kg, 119 mol), sodium bromide (8.9 kg, 86.5 mol, 0.73 eq (equivalent)), sodium bromate (6.6 kg, 43.7 mol, 0.37 eq), ferric bromide (0.176 kg, 0.59 mol, 0.005 eq), and water (13.5 kg, 750 mol, 6.3 eq) were added to a kettle, and then a 25% volume fraction of sulfuric acid aqueous solution (25%, 45 kg, 115 mol, 0.96 eq) was added. The reaction temperature was 45 ° C. and the reaction time was 24 h to obtain a primary product containing bromobenzene-d5;

[0050] The primary product was allowed to stand, and the upper organic phase was taken, washed with a 20% by mass aqueous solution of NaOH, and the organic phase was taken after standing and stratification; then washed with a saturated aqueous solution of NaHSO3, and the organic phase was taken after standing and stratification; then washed with water, and the organic phase was taken after standing and stratification; finally dried with anhydrous magnesium sulfate, and filtered after drying to obtain a crude bromobenzene-d5 product;

[0051] The crude bromobenzene-d5 was distilled at a bottom temperature of 100°C, a top temperature of 75°C, and a vacuum degree of 200 mbar to obtain purified bromobenzene-d5.

[0052] Examples 2-15: The preparation process thereof is the same as that of Example 1, except that the addition amount of raw materials and process parameters are different. For details, see Table 1.

[0053] The difference between Comparative Example 1 and Example 1 is that no ferric bromide is added.

[0054] The difference between Comparative Example 2 and Example 1 is that no sodium bromide is added and the amount of sodium bromate is 1.11eq.

[0055] The difference between Comparative Example 3 and Example 1 is that the volume concentration of sulfuric acid is 15% and the reaction temperature is 80°C.

[0056] The following tests were performed on the obtained embodiments and comparative examples:

[0057] 1) Deuterium substitution detection: The deuterium substitution is detected by nuclear magnetic resonance hydrogen spectroscopy and calculated using the following formula:

[0058] Wherein, A is the hydrogen peak area of ​​the deuterated sample, D is the degree of deuteration, m1 is the added mass of the deuterated sample in g, n1 is the number of H atoms to be deuterated in the deuterated sample, M1 is the relative molecular mass of the sample before deuteration in g, m2 is the added mass of the internal standard in g, n2 is the number of H atoms in the deuterated sample, and M2 is the relative molecular mass of the internal standard.

[0059] 2) Purity detection: gas chromatography is used for detection.

[0060] 3) Yield detection: The calculation formula is: actual weight of bromobenzene-d5 / theoretical weight of bromobenzene-d5*%.

[0061] The specific test results are shown in Table 1.

[0062] Table 1

[0063] According to Table 1, the absence of ferric bromide in Comparative Example 1 and sodium bromide in Comparative Example 2 resulted in significantly lower product yields, with the yield in Comparative Example 1 being only 21.6%. This demonstrates that ferric bromide effectively catalyzes the reaction, significantly impacting yield even with a small amount. The addition of sodium bromide, on the other hand, can achieve higher yields by converting the active oxygen species generated during the bromination process. A comparison of Examples 1-15 with Comparative Example 3 reveals that higher yields can be achieved when the sulfuric acid concentration is selected between 20% and 25% by volume and the reaction temperature is maintained between 20° and 60°C.

[0064] In addition, the product (bromobenzene-d5) prepared in Example 1 was subjected to nuclear magnetic resonance (NMR) and gas chromatography (GC) detection, respectively. The NMR spectrum is shown in FIG1 . The deuteration degree of deuterated benzene is 99%, and the deuteration degree of bromobenzene-d5 is also 99%, indicating that the deuteration degree is maintained during the reaction.

[0065] The NMR data of bromobenzene-d5 are:

[0066] 1 HNMR (400MHz, C6D6) δ7.47(s,2H),7.19(s,1H),7.12(s,2H),1.26(s,1H).

[0067] The GC (FIDI A, front signal) detection data of the product of Example 1 is shown in Table 2, and the purity is 99.9%. Table 2:

[0068] Among them, RT (Retention Time) is the time when the peak of the compound appears when it is injected from the injection port to the detector, and is measured in minutes (min). The retention time depends on the residence time of the compound in the chromatographic column. According to Table 2, the retention time exceeds 5 minutes, and a longer retention time means that the compound is better separated in the column. Height refers to the maximum height of the chromatographic peak, that is, the maximum measured value of the peak. The peak height reflects the signal intensity of the compound in the detector, and a high peak indicates a higher concentration of the compound. Area refers to the area under the chromatographic peak, which indicates the amount of compound contained in the chromatographic peak. A larger area means a higher concentration of the compound. Area percent refers to the percentage of the area of ​​the chromatographic peak to the total area, which indicates the relative content of each compound in the sample and is used to compare the relative content of different compounds in the sample.

[0069] Although the present invention is disclosed as above, the protection scope of the present invention is not limited thereto. Those skilled in the art may make various changes and modifications without departing from the spirit and scope of the present invention, and these changes and modifications will fall within the protection scope of the present invention.

Claims

1. A method for preparing bromobenzene-d5, characterized in that, Comprising: By mass parts, 1 part of deuterated benzene, 0.61 - 1.08 parts of sodium bromide, 0.62 - 0.89 parts of sodium bromate, 0.007 - 0.07 parts of iron bromide, and 1.07 - 2.14 parts of water are mixed, and 2.8 - 7 parts of a sulfuric acid aqueous solution with a volume fraction of 20% - 25% is added, and a reaction is carried out. The reaction temperature is 20 - 60 °C, and the reaction time is 12 - 48 h to obtain a crude product containing bromobenzene-d5, and the crude product is purified to obtain bromobenzene-d5.

2. The preparation method of bromobenzene-d5 according to claim 1, characterized in that The ratio of the sum of the molar amounts of bromine in the sodium bromide, the sodium bromate, and the iron bromide to the molar amount of the deuterated benzene is greater than or equal to 1.

3. The preparation method of bromobenzene-d5 according to claim 1, characterized in that, The purification of the crude product includes: allowing the crude product to stand for layering to obtain a first organic phase, and performing at least one of washing with dilute sulfuric acid, washing with an aqueous NaOH solution, washing with a saturated aqueous NaHSO3 solution, and washing with water, and after drying, a crude product of bromobenzene-d5 is obtained; the crude product of bromobenzene-d5 is rectified to obtain the bromobenzene-d5.

4. The method for preparing bromobenzene-d5 according to claim 3, wherein Performing at least one of washing with dilute sulfuric acid, washing with an aqueous NaOH solution, washing with a saturated aqueous NaHSO3 solution, and washing with water respectively includes: Adding dilute sulfuric acid to the first organic phase and mixing and dispersing, standing for layering and then taking a second organic phase, adding an aqueous NaOH solution to the second organic phase and mixing and dispersing, standing for layering and then taking a third organic phase, adding a saturated aqueous NaHSO3 solution to the third organic phase and mixing and dispersing, standing for layering and then taking a fourth organic phase, adding water to the fourth organic phase and mixing and dispersing, and standing and dispersing and then taking a fifth organic phase.

5. The preparation method of bromobenzene-d5 according to claim 4, characterized in that, The mass fraction of the dilute sulfuric acid is 10%.

6. The preparation method of bromobenzene-d5 according to claim 4, wherein, The mass fraction of the aqueous NaOH solution is 15% - 25%.

7. The preparation method of bromobenzene-d5 according to claim 3, characterized in that, The crude product of bromobenzene-d5 is rectified using a rectification column. The bottom temperature of the rectification column is 80 - 120 °C, the top temperature is 70 - 85 °C, and the vacuum degree is not higher than 200 mbar.

8. The preparation method of bromobenzene-d5 according to claim 1, characterized in that, The yield of the crude product is ≥80%.

9. The preparation method of bromobenzene-d5 according to claim 1, wherein, The purity of the bromobenzene-d5 is ≥99%.

10. The preparation method of bromobenzene-d5 according to claim 1, characterized in that, The difference between the deuteration degree of the bromobenzene-d5 and the deuteration degree of the deuterated benzene is less than or equal to 0.2%.

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