Method for preparing deuterated phenol under catalysis of ETS-10 zeolite supported copper

Abstract

The invention relates to the field of heterogeneous catalysis organic synthesis, and discloses a method for preparing deuterated phenol through ETS-10 zeolite supported copper catalysis, which comprises the following steps: under the combined action of sodium sulfite and a Cu (at) ETS-10 catalyst, carrying out deuteration reaction by taking a halogenated phenol compound as a substrate to obtain a dehalogenated deuterated product. The invention provides a dehalogenation deuteration reaction which is simple and convenient and has no side reaction, the dehalogenation deuteration reaction is directly carried out under the reaction condition without participation of hydrogen or an oxidizing agent, and no by-product is generated. The reaction state is stable, products are easy to separate, post-treatment is simple, and the method is environment-friendly.

Description

Technical Field

[0001] The invention belongs to the technical field of dehalogenation deuteration chemistry, and specifically relates to a deuteration reaction using phenolic substances containing halogens as substrates under the combined action of sodium sulfite and a Cu@ETS-10 catalyst. Technical Background

[0002] The substitution of a hydrogen atom in a drug molecule with its isotope deuterium is a subtle structural change, a structural modification called deuteration, which can improve the pharmacokinetic and toxicity profiles of a drug and enhance drug stability. Initially, deuterated drugs were developed through a “deuterium switch” approach, such as deuterated tetrabenazine, which became the first deuterated drug approved by the FDA in 2017. Tetrabenazine is a vesicular monoamine transporter inhibitor approved in 2008 for the treatment of chorea associated with Huntington’s disease, significantly reducing the dose and frequency of dosing. The groundbreaking experience with deuterated tetrabenazine paved the way for other deuterium switches.

[0003] At present, various methods have been developed for selective deuteration of drugs, such as hydrogen-deuterium exchange (HIE), chemical building block method, and reductive deuteration method. Among them, the most common and effective method is hydrogen isotope exchange (HIE). However, the current HIE method cannot meet the requirements in terms of efficiency, selectivity and functional group tolerance, and the selectivity is poor in acid-deuteration and base-deuteration reactions, requiring an excess of deuterium source or multiple rounds of deuterium to achieve a high degree of deuteration. CH bond activation deuteration is a directional and direct deuterium incorporation strategy, however, noble metal catalysts are usually required to activate the inert CH bonds. In contrast, the dehalogenation deuteration of halides provides an alternative for diversified deuterated molecules due to the easier activation of CX (X is a halogen) bonds and their own selective deuteration characteristics. Although effective, typical metal-halogen exchange or transition metal-catalyzed dehalogenation processes generally require precious metal catalysts coordinated by complex organic ligands, as well as special deuterium donors and highly active alkyl metal reagents. Moreover, they can only be achieved under harsh anaerobic and low temperature conditions. Therefore, it is very necessary to develop a universal and mild method for efficient deuterium incorporation with a wide substrate range and excellent deuterium purity. Summary of the invention

[0004] The present invention aims at the shortcomings in the dehalogenation and deuteration synthesis process of deuterated aromatic compounds, and uses halogenated phenolic substances for dehalogenation and deuteration. The present invention uses Cu@ETS-10 as a catalyst and sodium sulfite (Na2SO3) as an additive. Under reaction conditions that do not require the participation of hydrogen or an oxidant, the dehalogenation and deuteration reaction of phenolic halogenated substances without the generation of byproducts is directly carried out. The method of the present invention is simple to operate, environmentally friendly, has a high deuteration rate, a high yield, and the catalyst is easy to separate and recover.

[0005] In order to achieve the above object, the technical solution adopted by the present invention is:

[0006] The dehalogenation and deuteration reaction steps involved in the present invention are as follows: a halogenated phenol compound substrate, a Na2SO3 additive and a Cu@ETS-10 catalyst are sequentially added into a reaction tube, deuterated water is then added, the tube is placed into a heater, and the reaction is stirred. After the reaction is completed, the tube is centrifuged and filtered, and the supernatant is collected to obtain a dehalogenated and deuterated product.

[0007] The reaction involved is:

[0008]

[0009] The halogenated position (CX) in halogenated phenol compounds and the CH at the ortho and para positions of phenol undergo deuteration reaction.

[0010] R is selected from one or two of hydrogen, alkyl, and alkoxy; R can be independently selected from the ortho, meta, or para position; R can be one substituent or multiple substituents, and the types of the substituents can be the same or different.

[0011] Furthermore, R is one of hydrogen, 3-methyl, 3,5-dimethyl, and 2-methoxy.

[0012] X is selected from halogen, such as I, Br; X can be independently selected in the ortho or para position; X can be one substituent or multiple substituents, and the substituents can be of the same type.

[0013] Furthermore, X is one of 4-iodo, 4-bromo, 2-iodo and 2-bromo.

[0014] The reaction temperature in the present invention is 130-150°C.

[0015] The reaction time in the present invention is 8 to 24 hours.

[0016] Furthermore, the molar ratio of the halogenated phenol compound to Na2SO3 is 1:1 to 1:5, preferably 1:2 to 1:3. The molar ratio of the halogenated phenol compound to the volume of deuterated water is 1:2 to 1:7 mol / L, preferably 1:5 mol / L.

[0017] Furthermore, the molar ratio of the halogenated phenol compound to the mass ratio of the Cu@ETS-10 zeolite is 1:100 to 1:200 mol / g, preferably 1:120 to 1:170 mol / g.

[0018] The preparation methods of Cu catalyst supported by ETS-10 zeolite include direct hydrothermal synthesis, ion exchange, and equal volume impregnation, and the preferred method is direct hydrothermal synthesis. The copper loading in Cu@ETS-10 zeolite is 1% to 10%, preferably 3%.

[0019] The preparation method of Cu@ETS-10 catalyst is as follows:

[0020] The ETS-10 zeolite used can be synthesized according to the method in CN 115536484 A. The mesopore volume of ETS-10 zeolite is 0.1-0.2 cm 3 / g, micropore volume is 0.1~0.12cm 3 / g, BET surface area 350~450m 2 / g.

[0021] Direct hydrothermal synthesis of Cu@ETS-10: Synthesis of transition metal-doped Cu@ETS-10 zeolite: For example, sodium hydroxide aqueous solution and potassium hydroxide aqueous solution are added to the water glass solution in sequence, and then polyhexamethylene biguanide is added. After stirring until clear, dilute nitric acid aqueous solution is added until the pH of the solution stabilizes to between 10.5 and 11.0. After stirring for 90 minutes, a certain amount of TiCl3 solution is taken, and Cu(NO3)2·3H2O is directly added to the TiCl3 solution and slowly added drop by drop to the previous solution. After all the additions are completed, stir for 120 minutes and then crystallize at 230°C for a certain period of time, crystallize for 48 to 72 hours, dry, and calcine. The molar ratio of the reaction gel is TiO2:SiO2:Na2O:K2O:Cu:H2O=1.00:6.1~6.8:4.7~6.3:1.2~1.8:X Cu :160~180(X Cu =0.012-0.271). The mass ratio of polyhexamethylene biguanide to silicon dioxide in water glass is 0.09-0.25.

[0022] Equivolumetric impregnation method: Using ETS-10 zeolite as a carrier, Cu(NO3)2·3H2O was dissolved in distilled water, and Cu was successfully loaded onto ETS-10 zeolite by the equivolumetric impregnation method. Subsequently, the sample was left to stand in an air atmosphere for 8 hours, dried at 120°C for 12 hours, and calcined in air at 450°C for 4 hours.

[0023] Ion exchange method: ETS-10 zeolite was used as a carrier, Cu(NO3)2·3H2O was dissolved in distilled water, placed in an 80°C water bath, stirred, and ion exchanged for 6 hours. After taking it out, it was filtered and washed, placed in a 100°C oven, dried overnight, and then calcined in air at 450°C for 4 hours.

[0024] Compared with the prior art, the technical advantages of the present invention are:

[0025] The invention provides a simple and convenient dehalogenation deuteration reaction without side reactions, the reaction state is stable, and it is a mild deuteration efficient incorporation method. The preparation process is simple, the conditions are mild, the product is easy to separate, the post-treatment is simple, and it is environmentally friendly. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 This is the magnetic resonance hydrogen spectrum of the deuterated phenol synthesized from 4-iodophenol (1a) in Example 1.

[0027] 1 HNMR (400MHz, DMSO-d6) δ6.76 (d, J = 8.4Hz, 0.47H), 7.15 (s, 2H), 9.35 (s, 1H).

[0028] Figure 2 This is the magnetic resonance hydrogen spectrum of the deuterated phenol synthesized from 4-iodo-3-methylphenol (1c) in Example 3.

[0029] 1 HNMR (400MHz, Chloroform-d) δ2.31 (d, J = 1.3Hz, 3H), 6.49-6.93 (m, 0.22H), 7.12 (s, 1H).

[0030] Figure 3 This is the magnetic resonance hydrogen spectrum of the deuterated phenol synthesized from 4-iodo-3,5-dimethylphenol (1d) in Example 4. 1 HNMR(400MHz,DMSO-d6)δ2.16(s,6H),6.61(s,0.06H),9.10(s,1H).

[0031] Figure 4 This is the magnetic resonance hydrogen spectrum of the deuterated phenol synthesized from 4-iodo-2-methoxyphenol (1e) in Example 5.

[0032] 1 HNMR (400MHz, Chloroform-d) δ6.97-6.84 (m, 2H), 5.68 (s, 1H), 3.89 (d, J = 1.8Hz, 3H).

[0033] Figure 5 This is the hydrogen magnetic resonance spectrum of the deuterated phenol synthesized from 4-bromophenol (1f) in Example 6.

[0034] 1 HNMR (400MHz, DMSO-d6) δ6.75(d,J=8.4Hz,0.11H),7.15(s,2H),9.33(d,J=2.1Hz,1H).

[0035] Figure 6 This is the hydrogen magnetic resonance spectrum of the deuterated phenol synthesized from 4-bromo-3-methylphenol (1 g) in Example 7.

[0036] 1 HNMR(400MHz,Chloroform-d)δ2.32(d,J=1.8Hz,3H),4.37(s,1H),6.58-

[0037] 6.75(m,0.08H),7.14(s,1H).

[0038] Figure 7 This is the hydrogen magnetic resonance spectrum of the deuterated phenol synthesized from 4-bromo-3,5-dimethylphenol (1h) in Example 8. 1 HNMR(400MHz,Chloroform-d)δ2.27(s,6H),5.01(s,1H),6.48(s,0.07H). Specific implementation plan

[0039] The following specific examples are used to describe the technical solution of the present invention in detail, but are not intended to limit the scope thereof. Unless otherwise specified, the reagents and instruments used in the following examples are all commercially available products.

[0040] The specific preparation process of Cu@ETS-10 is as follows: 23.75g of water glass was weighed into a 150mL beaker, 15mL of NaOH solution (23.5wt.%) and 10.0mL (21.2wt.%) of KOH solution were added dropwise into the above 150mL beaker and stirred. After the above system was stirred for 20min, 0.5g of polyhexamethylene biguanide was added and continued to stir for 60min. The pH was adjusted to 10.8 with 20wt.% dilute hydrochloric acid. After stirring for 90min, 13.155g of TiCl3 hydrochloric acid solution and 0.453g of Cu(NO3)2·3H2O was directly added to the TiCl3 solution and slowly added dropwise to the previous solution. After all the addition was completed, it was stirred for 120 minutes and then placed in a 50mL polytetrafluoroethylene-lined kettle for static crystallization at 230°C for 72 hours. The molar ratio of the reaction gel was TiO2:SiO2:Na2O:K2O:Cu:H2O=1.00:6.4:4.76:1.25:X Cu :177.03,X Cu =0.125; the mass ratio of polyhexamethylene biguanide to silicon dioxide in water glass is 0.095. Then wash and filter, dry the solid in an oven overnight, and calcine at 475°C to obtain 3% Cu@ETS-10. It is used as Cu@ETS-10 catalyst in the following examples.

[0041] Embodiment 1:

[0042]

[0043] 4-iodophenol (0.2mmol, 44mg), 3% Cu@ETS-10 (30mg), Na2SO3 (50.4mg), and D2O (1mL) were added to a 10mL glass tube in sequence. After the operation was completed, the reaction was placed in a reaction plate, the reaction temperature was controlled at 130°C, and the reaction was stirred for 12h. After the reaction was completed, it was cooled to room temperature, the reaction system was centrifuged, filtered, and the supernatant was collected to obtain deuterated phenol. The conversion rate was 100%, the selectivity was 100%, the yield of the product was 100%, the deuteration rate at the CI position was 100%, and the deuteration rate at the ortho position of the hydroxyl group was 76.5%.

[0044] Embodiment a

[0045] If the temperature of Example 1 is lowered to 120° C. and other conditions remain unchanged, the conversion rate is 87.6%, the selectivity is 100%, the product yield is 87.6%, the deuteration rate at the CI position is 100%, and the deuteration rate at the ortho position of the hydroxyl group is 78.6%.

[0046] Embodiment b

[0047] If the reaction time of Example 1 is reduced to 10 h and other conditions remain unchanged, the conversion rate is 94.8%, the selectivity is 100%, the product yield is 94.8%, the CI position deuteration rate is 100%, and the hydroxyl ortho position deuteration rate is 79.3%.

[0048] Example c

[0049] If the amount of catalyst used in Example 1 is reduced to 15 mg and other conditions remain unchanged, the conversion rate is 80.4%, the selectivity is 100%, the product yield is 80.4%, the deuteration rate at the CI position is 100%, and the deuteration rate at the ortho position of the hydroxyl group is 75%.

[0050] Embodiment d

[0051] If the Na2SO3 content of Example 1 is reduced to 25.2 mg, and other conditions remain unchanged, the conversion rate is 45.4% and the selectivity is 100% by GC-MS, the yield of the product is 45.4%, the deuteration rate at the CI position is 100%, and the deuteration rate at the ortho position of the hydroxyl group is 84.5%.

[0052] Embodiment e

[0053] The catalyst of Example 1 was changed to 3% Cu / ETS-10 (impregnation method): ETS-10 zeolite was used as a carrier, 0.23 g Cu(NO3)2·3H2O was dissolved in distilled water, and Cu was successfully loaded on ETS-10 zeolite by an equal volume impregnation method. Subsequently, the sample was allowed to stand for 8 hours in an air atmosphere, dried at 120°C for 12 hours, and calcined in air at 450°C for 4 hours.

[0054] The catalyst of Example 1 was changed to 3% Cu / ETS-10 (impregnation method), and other conditions remained unchanged. The conversion rate was 80.9%, the selectivity was 100%, the product yield was 80.9%, the CI position deuteration rate was 100%, and the hydroxyl ortho position deuteration rate was 82.3%.

[0055] Embodiment f

[0056] The catalyst of Example e was changed to 5% Cu / ETS-10 (impregnation), and other conditions remained unchanged. The conversion rate was 95.2%, the selectivity was 100%, the product yield was 95.2%, the CI position deuteration rate was 100%, and the hydroxyl ortho position deuteration rate was 79%.

[0057] Embodiment 2:

[0058]

[0059] 2-iodophenol (0.2mmol, 44mg), Cu@ETS-10 (30mg), Na2SO3 (50.4mg), and D2O (1mL) were added to a 10mL glass tube in sequence. After the operation was completed, the reaction was placed in a reaction plate, the reaction temperature was controlled at 130°C, and the reaction was stirred for 12h. After the reaction was completed, it was cooled to room temperature, the reaction system was centrifuged, filtered, and the supernatant was collected to obtain deuterated phenol. The conversion rate was 100%, the selectivity was 100%, the yield of the product was 100%, the deuteration rate at the CI position was 100%, the deuteration rate at the ortho position of the hydroxyl group was 80.5%, and the deuteration rate at the para position was 80.5%.

[0060] 1 HNMR (400MHz, Chloroform-d) δ2.31 (d, J = 1.3Hz, 3H), 6.49-6.93 (m, 0.22H), 7.12 (s, 1H).

[0061] Embodiment 3:

[0062]

[0063] 4-iodo-3-methylphenol (0.2mmol, 46.8mg), Cu@ETS-10 (30mg), Na2SO3 (50.4mg), and D2O (1mL) were added to a 10mL glass tube in sequence. After the operation was completed, the reaction was placed in a reaction plate, the reaction temperature was controlled at 130°C, and the reaction was stirred for 12h. After the reaction was completed, it was cooled to room temperature, the reaction system was centrifuged, filtered, and the supernatant was collected to obtain deuterated phenol. The conversion rate was 100%, the selectivity was 100%, the yield of the product was 100%, the deuteration rate at the CI position was 100%, and the deuteration rate at the ortho position of the hydroxyl group was 89%.

[0064] Embodiment 4:

[0065]

[0066] 4-iodo-3,5-dimethylphenol (0.2mmol, 49.6mg), Cu@ETS-10 (30mg), Na2SO3 (50.4mg), and D2O (1mL) were added to a 10mL glass tube in sequence. After the operation was completed, the mixture was placed in a reaction plate, the reaction temperature was controlled at 130°C, and the reaction was stirred for 12h. After the reaction was completed, the mixture was cooled to room temperature, the reaction system was centrifuged, filtered, and the supernatant was collected to obtain deuterated phenol. The conversion rate was 100%, the selectivity was 100%, the yield of the product was 100%, the deuteration rate at the CI position was 100%, and the deuteration rate at the ortho position of the hydroxyl group was 97%.

[0067] Embodiment 5:

[0068]

[0069] 4-iodo-2-methoxyphenol (0.2mmol, 50mg), Cu@ETS-10 (30mg), Na2SO3 (50.4mg), and D2O (1mL) were added to a 10mL glass tube in sequence. After the operation was completed, the mixture was placed in a reaction plate, the reaction temperature was controlled at 130°C, and the reaction was stirred for 12h. After the reaction was completed, the mixture was cooled to room temperature, the reaction system was centrifuged, filtered, and the supernatant was collected to obtain deuterated phenol. The conversion rate was 88%, the selectivity was 100%, the yield of the product was 88%, the deuteration rate at the CI position was 100%, and the deuteration rate at the ortho position of the hydroxyl group was 100%.

[0070] Embodiment 6:

[0071]

[0072] 4-bromophenol (0.2mmol, 34.6mg), Cu@ETS-10 (30mg), Na2SO3 (75.6mg), and D2O (1mL) were added to a 10mL glass tube in sequence. After the operation was completed, the reaction was placed in a reaction plate, the reaction temperature was controlled at 150°C, and the reaction was stirred for 24h. After the reaction was completed, it was cooled to room temperature, the reaction system was centrifuged, filtered, and the supernatant was collected to obtain deuterated phenol. The conversion rate was 100%, the selectivity was 100%, the yield of the product was 100%, the deuteration rate of the C-Br position was 100%, and the deuteration rate of the hydroxyl ortho position was 94.5%.

[0073] If the temperature of Example 6 is lowered to 130° C. and other conditions remain unchanged, the conversion rate is 97.4%, the selectivity is 100%, and the yield of the product is 97.4% as determined by GC-MS.

[0074] Embodiment 7:

[0075]

[0076] 4-Bromo-3-methylphenol (0.2mmol, 37.4mg), Cu@ETS-10 (30mg), Na2SO3 (75.6mg), and D2O (1mL) were added to a 10mL glass tube in sequence. After the operation was completed, the reaction was placed in a reaction plate, the reaction temperature was controlled at 150°C, and the reaction was stirred for 24h. After the reaction was completed, it was cooled to room temperature, the reaction system was centrifuged, filtered, and the supernatant was collected to obtain deuterated phenol. The conversion rate was 100%, the selectivity was 100%, the yield of the product was 100%, the deuteration rate of the C-Br position was 100%, and the deuteration rate of the hydroxyl ortho position was 96%.

[0077] If the temperature of Example 7 is lowered to 130°C and other conditions remain unchanged, the conversion rate is 50%, the selectivity is 100%, the product yield is 50%, the deuteration rate at the C-Br position is 100%, and the deuteration rate at the ortho-hydroxyl position is 95.3%.

[0078] Embodiment 8:

[0079]

[0080] 4-Bromo-3,5-dimethylphenol (0.2mmol, 40.2mg), Cu@ETS-10 (30mg), Na2SO3 (75.6mg), and D2O (1mL) were added to a 10mL glass tube in sequence. After the operation was completed, the mixture was placed in a reaction plate, the reaction temperature was controlled at 150°C, and the reaction was stirred for 24h. After the reaction was completed, the mixture was cooled to room temperature, the reaction system was centrifuged, filtered, and the supernatant was collected to obtain deuterated phenol. The conversion rate was 100%, the selectivity was 100%, the yield of the product was 100%, the deuteration rate at the C-Br position was 100%, and the deuteration rate at the ortho-hydroxyl position was 96.5%.

[0081] If the temperature of Example 8 is lowered to 130°C and other conditions remain unchanged, the conversion rate is 92%, the selectivity is 100%, the product yield is 92%, the deuteration rate at the C-Br position is 100%, and the deuteration rate at the ortho-hydroxyl position is 92%.

[0082] Embodiment 9:

[0083]

[0084] 2-bromophenol (0.2mmol, 34.6mg), Cu@ETS-10 (30mg), Na2SO3 (75.6mg), and D2O (1mL) were added to a 10mL glass tube in sequence. After the operation was completed, the reaction was placed in a reaction plate, the reaction temperature was controlled at 130°C, and the reaction was stirred for 24h. After the reaction was completed, it was cooled to room temperature, the reaction system was centrifuged, filtered, and the supernatant was collected to obtain deuterated phenol. The conversion rate was 100%, the selectivity was 100%, the yield of the product was 100%, the deuteration rate of the C-Br position was 100%, the deuteration rate of the hydroxyl ortho position was 81%, and the deuteration rate of the hydroxyl para position was 36%.

[0085] 1 H NMR (400MHz, DMSO-d6) δ6.69-6.78 (m, 0.64H), 6.92 (t, J = 13.9Hz, 0.19H), 7.15 (d, J = 3.3Hz, 2H), 9.34 (s, 1H).

[0086] If the temperature of Example 9 is lowered to 130°C and other conditions remain unchanged, the conversion rate is 50%, the selectivity is 100%, the product yield is 50%, the deuteration rate of the C-Br position is 100%, the deuteration rate of the ortho-hydroxyl position is 88.1%, and the deuteration rate of the para-hydroxyl position is 51.2%.

[0087] Comparative Example 1:

[0088] The preparation method of ETS-10 is the same as that of Example 1, except that no copper source is added.

[0089] 4-iodophenol (0.2mmol, 44mg), ETS-10 (30mg), Na2SO3 (50.4mg), and D2O (1mL) were added to a 10mL glass tube in sequence. After the operation was completed, the mixture was placed in a reaction plate, the reaction temperature was controlled at 130°C, and the reaction was stirred for 12h. After the reaction was completed, the mixture was cooled to room temperature, the reaction system was centrifuged, filtered, and the supernatant was collected to obtain deuterated phenol. The conversion rate was 42.2%, the selectivity was 100%, and the yield of the product was 42.2% as determined by GC-MS.

[0090] Comparative Example 2:

[0091] 4-iodophenol (0.2mmol, 44mg), Cu(NO)3·3H2O (30mg), Na2SO3 (50.4mg), and D2O (1mL) were added to a 10mL glass tube in sequence. After the operation was completed, the mixture was placed in a reaction plate, the reaction temperature was controlled at 130°C, and the reaction was stirred for 12h. After the reaction was completed, the mixture was cooled to room temperature, the reaction system was centrifuged, filtered, and the supernatant was collected to obtain deuterated phenol. The conversion rate was 40%, the selectivity was 28.3%, and the yield of the product was 11.3% as determined by GC-MS.

[0092] Comparative Example 3:

[0093] 4-iodophenol (0.2mmol, 44mg), CuI (30mg), Na2SO3 (50.4mg), and D2O (1mL) were added to a 10mL glass tube in sequence. After the operation was completed, the mixture was placed in a reaction plate, the reaction temperature was controlled at 130°C, and the reaction was stirred for 12h. After the reaction was completed, the mixture was cooled to room temperature, the reaction system was centrifuged, filtered, and the supernatant was collected to obtain deuterated phenol. The conversion rate was 49.1%, the selectivity was 39%, and the yield of the product was 19.2% as determined by GC-MS.

[0094] Comparative Example 4:

[0095] 4-iodophenol (0.2mmol, 44mg), Cu@ETS-10 (30mg), and D2O (1mL) were added to a 10mL glass tube in sequence. After the operation was completed, the reaction was placed in a reaction plate, the reaction temperature was controlled at 130°C, and the reaction was stirred for 12h. After the reaction was completed, it was cooled to room temperature, the reaction system was centrifuged, filtered, and the supernatant was collected to obtain deuterated phenol. The conversion rate was 23%, the selectivity was 100%, and the yield of the product was 23% using GC-MS.

[0096] Comparative Example 5:

[0097] 4-iodophenol (0.2mmol, 44mg), Cu@ETS-10 (30mg), NaOH (16mg), and D2O (1mL) were added to a 10mL glass tube in sequence. After the operation was completed, the reaction was placed in a reaction plate, the reaction temperature was controlled at 130°C, and the reaction was stirred for 12h. After the reaction was completed, it was cooled to room temperature, the reaction system was centrifuged, filtered, and the supernatant was collected to obtain deuterated phenol. The conversion rate was 10.7% and the selectivity was 100% using GC-MS. The yield of the product was 10.7%.

[0098] Comparative Example 6:

[0099] 4-iodophenol (0.2mmol, 44mg), X zeolite (commercially available, Tianjin Zhengyuan Haoye Chemical Technology Co., Ltd.) (30mg), Na2SO3 (50.4mg), D2O (1mL) were added to a 10mL glass tube in sequence, and the reaction was placed in a reaction plate after the operation was completed. The reaction temperature was controlled at 130°C and stirred for 12h. After the reaction was completed, it was cooled to room temperature, the reaction system was centrifuged, filtered, and the supernatant was collected to obtain deuterated phenol. The conversion rate was 33.1% and the selectivity was 100% using GC-MS. The yield of the product was 33.1%.

[0100] Comparative Example 7:

[0101] Cu / X zeolite was prepared by an equal volume impregnation method: 1 g of X zeolite was used as a carrier, 0.113 g of Cu(NO3)2·3H2O was dissolved in distilled water, and Cu was successfully loaded onto X zeolite by an equal volume impregnation method. Subsequently, the sample was allowed to stand in an air atmosphere for 8 hours, dried at 120°C for 12 hours, and calcined in air at 450°C for 4 hours.

[0102] 4-iodophenol (0.2mmol, 44mg), Cu / X zeolite (30mg), Na2SO3 (50.4mg), and D2O (1mL) were added to a 10mL glass tube in sequence. After the operation was completed, the mixture was placed in a reaction plate, the reaction temperature was controlled at 130°C, and the reaction was stirred for 12h. After the reaction was completed, the mixture was cooled to room temperature, the reaction system was centrifuged, filtered, and the supernatant was collected to obtain deuterated phenol. The conversion rate was 50.4%, the selectivity was 100%, and the yield of the product was 50.4% as determined by GC-MS.

[0103] The above describes the optional embodiments of the present invention to teach those skilled in the art how to implement and reproduce the present invention. The raw materials and equipment used in the present invention, unless otherwise specified, are all commonly used raw materials and equipment in the art; the methods used in the present invention, unless otherwise specified, are all conventional methods in the art. In order to teach the scheme of the present invention, some conventional technical aspects have been simplified and omitted. Those skilled in the art should understand that variations arising from this aspect are all within the scope of protection of the present invention.

Claims

1. A method for preparing deuterated phenol using ETS-10 zeolite-supported copper as catalyst, characterized in that: The halogenated phenol compound, sodium sulfite additive and Cu@ETS-10 catalyst shown in Formula 1 are sequentially added to the reaction device, and then deuterated water is added, and the reaction is stirred under heating conditions. After the reaction is completed, centrifugation and filtration are performed, and the supernatant is collected to obtain the dehalogenated deuterated product shown in Formula 2; the halogenated position CX in the halogenated phenol compound and the CH at the ortho and para positions of phenol undergo deuteration reaction; R is independently selected from one or two of hydrogen, alkyl, and alkoxy; R is independently selected from ortho, meta, and para positions; X is selected from halogen; X is independently selected from ortho and para positions.

2. The method for preparing deuterated phenol by catalysis of ETS-10 zeolite supported copper according to claim 1, characterized in that: The reaction temperature is 130-150°C.

3. The method for preparing deuterated phenol by catalysis of ETS-10 zeolite supported copper according to claim 1, characterized in that: The reaction time is 8 to 24 hours.

4. The method for preparing deuterated phenol by catalysis of ETS-10 zeolite supported copper according to claim 1, characterized in that: The Cu loading in Cu@ETS-10 catalyst is 1-10 wt.%.

5. The method for preparing deuterated phenol by catalysis of ETS-10 zeolite supported copper according to claim 1, characterized in that: The preparation method of Cu@ETS-10 catalyst is one of direct hydrothermal synthesis method, ion exchange method and equal volume impregnation method.

6. The method for preparing deuterated phenol by catalysis of ETS-10 zeolite supported copper according to claim 5, characterized in that: Cu@ETS-10 zeolite was synthesized by direct hydrothermal synthesis: sodium hydroxide aqueous solution and potassium hydroxide aqueous solution were added to water glass solution in sequence, and then polyhexamethylene biguanide was added. After stirring until clear, dilute nitric acid aqueous solution was added until the pH of the solution stabilized to 10.5-11.

0. Cu(NO3)2·3H2O was added to TiCl3 solution and slowly added dropwise to the above solution. After all the addition was completed, the solution was stirred evenly and then crystallization reaction was carried out. After the reaction, it was dried and calcined.

7. The method for preparing deuterated phenol by catalysis of ETS-10 zeolite supported copper according to claim 6, characterized in that: The molar ratio of the reaction gel is TiO2:SiO2:Na2O:K2O:Cu:H2O=1.00:6.1~6.8:4.7~6.3:1.2~1.8:X Cu :160~180, among which X Cu =0.012~0.271, the mass ratio of polyhexamethylene biguanide to silicon dioxide in water glass is 0.09~0.

25.

8. The method for preparing deuterated phenol by catalysis of ETS-10 zeolite supported copper according to claim 1, characterized in that: The molar ratio of the halogenated phenol compound to sodium sulfite is 1:1 to 1:

5.

9. The method for preparing deuterated phenol by catalysis of ETS-10 zeolite supported copper according to claim 1, characterized in that: The mass ratio of the halogenated phenol compound to the Cu@ETS-10 zeolite is 1:100 to 1:200 mol / g.

10. The method for preparing deuterated phenol by catalysis of ETS-10 zeolite supported copper according to claim 1, characterized in that: The ratio of the molar amount of the halogenated phenol compound to the volume of deuterated water is 1:2-1:7 mol / L.

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