Study on photo-mediated selective deuterium substitution at benzylic position of aromatic heterocycles

Abstract

The application discloses a method for researching light-mediated selective deuterium substitution reaction of benzyl position of aromatic heterocycle, and specifically, the method comprises the following steps: reacting a compound shown in a formula I with a deuterium source under light irradiation in an organic solvent in the presence of a photocatalyst and a hydrogen atom transfer catalyst to obtain a compound shown in a formula II. The method has the advantages of easy source of raw materials, mild and safe reaction conditions, easy synthesis of the photocatalyst, and suitability for green preparation of deuterium-substituted aromatic compounds, especially 2-deuterium-substituted methyl nitrogen heterocycle compounds. Therefore, the method has very important application prospect in the field of isotope labeling related to organic synthesis and medicinal chemistry.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, specifically to a method for studying light-mediated benzylic selective deuteration reactions of aromatic heterocyclic compounds. Background Technology

[0002] Deuterium, as a stable non-radioactive isotope of hydrogen, exhibits enormous application potential in medicinal chemistry due to its unique physicochemical properties. The carbon-deuterium bond possesses higher stability and lower vibrational frequency compared to the carbon-hydrogen bond, with significantly enhanced bond energy. This characteristic makes deuteration an effective strategy for optimizing drug metabolism. In 2017, the US FDA approved the world's first deuterated drug, deuterated benzodiazepine (Austedo), marking the formal entry of deuteration technology into the clinical application stage. This drug significantly improves pharmacokinetic characteristics and effectively reduces dosing frequency and toxic side effects by replacing the hydrogen atoms at the 9th and 10th methoxy groups in the benzodiazepine molecule with deuterium atoms. Nitrogen-containing heterocycles are the core skeleton of many bioactive molecules and are widely found in natural products and clinical drugs. Considering the significant methyl effect in clinical drugs, developing a highly selective deuteration method for the benzylic methyl group of nitrogen-containing aromatic heterocycles is of great significance.

[0003] Currently, the methods for synthesizing deuterated nitrogen-containing aromatic heterocyclic compounds are relatively limited. The general synthetic routes are: 1. Acid or base catalyzed hydrogen-deuterium exchange: This route has harsh reaction conditions, generally requiring high temperature, strong acid or strong base, etc.; 2. Transition metal catalyzed hydrogen-deuterium exchange: This method usually relies on precious metals such as iridium and rhodium. These metals are not only expensive but also scarce. The problem of metal residue is a major concern in drug development. It requires complex and expensive purification steps to ensure that the product meets drug specifications.

[0004] To address the shortcomings of the above methods, it is extremely important to develop a synthetic method for preparing deuterated nitrogen aromatic heterocyclic compounds with mild reaction conditions, low cost, high selectivity, and high deuteration rate. Summary of the Invention

[0005] The purpose of this invention is to overcome the shortcomings of the prior art and provide a light-mediated method for selective deuteration of aromatic heterocyclic compounds at the benzylic position.

[0006] In a first aspect of the present invention, a method for preparing an aromatic heterocyclic benign deuterated compound is provided, the method comprising: In an organic solvent, in the presence of a photocatalyst and a hydrogen atom transfer catalyst, the compound shown in Formula I is reacted with a deuterium source under light irradiation to obtain the compound of Formula II. Among the compounds of formula I and formula II, R aSelected from the following group: H, halogen, cyano, nitro, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, -C(O)-O-C1-C4 alkyl; m is selected from 0, 1, 2, 3 or 4; R or located on two ring atoms in the same, adjacent or interposition a The ring atoms attached to it together form a group selected from the group consisting of C6-C10 aromatic rings and 5-12 membered heteroaromatic rings; one or more hydrogen atoms on the above groups are optionally R b Replace, R a Selected from the following group: H, halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, phenyl; Where valence bonds permit, Z1, Z2, Z3, Z4, and Z5 are each independently CH or N; and when Z1, Z2, Z3, Z4, and Z5 are substituted by substituents on the ring, the CH becomes C; The photocatalyst is selected from the following group: bis(quaternary) phosphate (BPP), eosin Y, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), 9-mesinetrilyl-10-methylacridin-10-onium tetrafluoroborate ([Mes-Acr]). + BF4 - ), 2,4,5,6-tetra(9-carbazolyl)-isophthalonitrile (4CzIPN), preferably bis(quaternary) phosphate (BPP).

[0007] In another preferred embodiment, R a Selected from the following groups: H, Br, Cl, F, cyano, nitro, methyl, trifluoromethyl, -C(O)O-CH3, phenyl; m is selected from 0, 1, or 2; R or located on two ring atoms in the same, adjacent or interposition a The ring atoms attached to it together form a 6-membered heteroaromatic ring; one or more hydrogen atoms on the above groups are optionally R b Replace, R b Selected from the following groups: H, Br, Cl, F, cyano, nitro, methyl, trifluoromethyl, phenyl; Where valence bonds allow, Z1, Z2, Z3, Z4, and Z5 are each independently CH or N.

[0008] In another preferred embodiment, the 6-membered heteroaromatic ring is piperidinyl.

[0009] In another preferred embodiment, the 6-membered heteroaryl ring is .

[0010] In another preferred embodiment, the method includes: In an organic solvent, in the presence of a photocatalyst and a hydrogen atom transfer catalyst, the compound shown in Formula I is reacted with a deuterium source under light irradiation to obtain the compound of Formula II. R a The definitions of , m, Z1, Z2 and Z3 are as described above.

[0011] In another preferred embodiment, the Selected from the following group: .

[0012] In another preferred embodiment, the organic solvent is selected from the group consisting of N,N-dimethylformamide, ethyl acetate, acetone, acetonitrile, tetrahydrofuran, 1,4-dioxane, dichloromethane, toluene, trifluorotoluene, etc., with toluene, ethyl acetate, and tetrahydrofuran being more preferred, and toluene being even more preferred.

[0013] In another preferred embodiment, the organic solvent is ultra-dry toluene.

[0014] In another preferred embodiment, the photocatalyst is selected from the group consisting of: In another preferred embodiment, the hydrogen atom transfer catalyst is a disulfide.

[0015] In another preferred embodiment, the hydrogen atom transfer catalyst has the structure shown in formula V: Among them, R m R n Each is independently selected from the following group: H, halogen, OH, cyano, nitro, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy; x and y are each independently selected from 0, 1, 2, 3, 4 or 5.

[0016] In another preferred embodiment, the R m R n Each of the following groups is independently selected: H, F, Cl, Br, OH, cyano, methyl, ethyl, isopropyl, methoxy, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy; x and y are each independently selected from 1, 2, 3, 4 or 5.

[0017] In another preferred embodiment, the hydrogen atom transfer catalyst is selected from the group consisting of bis(4-methoxyphenyl) disulfide, bis(4-hydroxyphenyl) disulfide, bis(4-methylphenyl) disulfide, bis(2,4,6-triisopropylphenyl) disulfide, bis(4-bromophenyl) disulfide, bis(2,4,6-trichlorophenyl) disulfide, bis(2,3,4,5,6-pentafluorophenyl) disulfide, bis(4-cyanophenyl) disulfide, etc., among which bis(4-bromophenyl) disulfide, bis(2,4,6-trichlorophenyl) disulfide, bis(2,3,4,5,6-pentafluorophenyl) disulfide, and bis(4-cyanophenyl) disulfide have better reaction effects, and bis(2,4,6-trichlorophenyl) disulfide is preferred.

[0018] In another preferred embodiment, the hydrogen atom transfer catalyst is selected from the group consisting of: In another preferred embodiment, the hydrogen atom transfer catalyst is a bis(2,4,6-trichlorophenyl) disulfide having the following structure: .

[0019] In another preferred embodiment, the deuterium source is selected from MeOD, D2O, or a combination thereof, preferably D2O.

[0020] In another preferred embodiment, the illumination is provided by a light source with a wavelength of 365-500 nm, and more preferably, the light source is provided by a light source with a wavelength of 365-420 nm.

[0021] In another preferred embodiment, the compound of formula I is selected from the group consisting of: .

[0022] In another preferred embodiment, the compound of formula I is selected from 2-methyl nitrogen heterocyclic compounds such as those of formula Ia, Ib, Ic, Id or Ie; In equation Ia: R1 is selected from one of OCH3, CH3, H, Br, Cl, F, CF3, CN, CO2CH3, and NO2; In formula Ib: R2 is CH3; In formula Ic: R3 is H; In formula Id: R4 is H; In formula Ie: R5 represents H and Ph.

[0023] In another preferred embodiment, the compound of formula II is selected from the group consisting of: .

[0024] In another preferred embodiment, the compound of formula II is selected from aromatic heterocyclic benzylic selective deuterated compounds such as those of formula II-a, II-b, II-c, II-d, or II-e. ; In equation II-a: R1 is selected from one of OCH3, CH3, H, Br, Cl, F, CF3, CN, CO2CH3, and NO2; In formula II-b: R2 is CH3; In formula II-c: R3 is H; In formula II-d: R4 is H; In formula II-e: R5 represents H and Ph.

[0025] In another preferred embodiment, the reaction has one or more features selected from the group consisting of: (1) The molar ratio of compound I to photocatalyst in the reaction is 1:(0.001~0.2), preferably 1:(0.01~0.05); (2) The molar ratio of compound I to hydrogen atom transfer catalyst in the reaction is 1:(0.01~0.2), preferably 1:(0.05~0.15); (3) The molar ratio of compound I to deuterium source in the reaction is 1:(1~200); preferably 1:80~120. (4) The ratio of organic solvent to deuterium source in the reaction is (1~10):1; preferably (1~3):1.

[0026] (5) The amount of organic solvent added is 1 to 20 mL / mmol based on the amount of the substance of Formula I, preferably 5 to 10 mL / mmol; (6) The reaction temperature is 5~60℃, preferably 15~30℃; (7) The reaction time is 5 to 20 hours, preferably 10 to 15 hours.

[0027] In another preferred embodiment, the photocatalyst in the reaction is 1 to 5 mol% of the compound of formula I, preferably 2 mol%.

[0028] In another preferred embodiment, the hydrogen atom transfer catalyst in the reaction is 5 to 15 mol% of the compound of formula I, preferably 10 mol%.

[0029] In another preferred embodiment, the reaction is carried out under the protection of an inert gas.

[0030] In another preferred embodiment, the inert gas is nitrogen.

[0031] In another preferred embodiment, the reaction is: The compound shown in Formula I, the photocatalyst, and the hydrogen atom catalyst were added to a dry reaction flask. An organic solvent was added to a glove box, and the flask was tightened with a cap fitted with a polytetrafluoroethylene gasket. A nitrogen source was injected outside the glove box and sealed with a sealing film. The reaction was carried out under light for 10-12 hours to obtain the compound shown in Formula II.

[0032] In a second aspect, the invention provides a deuterated compound as shown in Formula II, wherein the compound is obtained by the preparation method described above. Among them, R a Selected from the following group: H, halogen, cyano, nitro, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, -C(O)-O-C1-C4 alkyl; m is selected from 0, 1, 2, 3 or 4; R or located on two ring atoms in the same, adjacent or interposition a The ring atoms attached to it together form a group selected from the group consisting of C6-C10 aromatic rings and 5-12 membered heteroaromatic rings; one or more hydrogen atoms on the above groups are optionally R b Replace, R a Selected from the following group: H, halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, phenyl; Where valence bonds allow, Z1, Z2, Z3, Z4, and Z5 are each independently CH or N.

[0033] In another preferred embodiment, the compound of formula II is selected from the group consisting of: .

[0034] It should be understood that, within the scope of this invention, the above-described technical features of this invention and the technical features specifically described below (such as in the embodiments) can be combined with each other to form new or preferred technical solutions. Due to space limitations, they will not be described in detail here. Attached Figure Description

[0035] Figure 1The proton and carbon NMR spectra of compound 6-methoxy-2-deuterated methylquinoline prepared in Example 1 are shown. Figure 2 The images show the 1H and 1C NMR spectra of the compound 6-methyl-2-deuterated methylquinoline prepared in Example 2.

[0036] Figure 3 The images show the 1H and 1C NMR spectra of the compound 2-deuterated methylquinoline prepared in Example 3.

[0037] Figure 4 The proton and carbon NMR spectra of the compound 4-deuterated methylquinoline prepared in step 4 are shown.

[0038] Figure 5 The images show the 1H and 1C NMR spectra of the compound 1-deuterated methyl isoquinoline prepared in Example 5.

[0039] Figure 6 The images show the 1H and 1C NMR spectra of the compound 6-bromo-2-deuterated methylquinoline prepared in Example 6.

[0040] Figure 7 The images show the 1H and 1C NMR spectra of the compound 6-chloro-2-deuterated methylquinoline prepared in Example 7.

[0041] Figure 8 The NMR spectra of the compound 6-fluoro-2-deuterated methylquinoline prepared in Example 8 are shown in the 1H and 1C NMR spectra.

[0042] Figure 9 The 1H and 1C NMR spectra of the compound 6-trifluoromethyl-2-deuterated methylquinoline prepared in Example 9 are shown.

[0043] Figure 10 The proton and carbon NMR spectra of the compound 6-cyano-2-deuterated methylquinoline prepared in Example 10 are shown.

[0044] Figure 11 The 1H and 1C NMR spectra of the compound methyl 6-formate-2-deuterated methylquinoline prepared in Example 11 are shown.

[0045] Figure 12 The 1H and 1C NMR spectra of the compound 6-nitro-2-deuterated methylquinoline prepared in Example 12 are shown.

[0046] Figure 13 The hydrogen and carbon NMR spectra of the compound 8-fluoro-2-deuterated methylquinoline prepared in Example 13 are shown.

[0047] Figure 14 The 1H and 1C NMR spectra of the compound 2,3-deuterated dimethylquinoxaline prepared in Example 14 are shown.

[0048] Figure 15 The hydrogen and carbon NMR spectra of the compound 2-deuterated methyl-[1,8]-naphthidine prepared in Example 15 are shown.

[0049] Figure 16 The 1H and 1C NMR spectra of the compound 2-deuterated methyl-1,5-naphthidine prepared in Example 16 are shown.

[0050] Figure 17 The 1H and 1C NMR spectra of compound 2,9-deuterated dimethyl-1,10-phenanthroline prepared in Example 17 are shown.

[0051] Figure 18 The 1H and 1C NMR spectra of compound 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline prepared in Example 18 are shown. Detailed Implementation

[0052] Through extensive and in-depth research, and through numerous screenings and tests, the inventors have provided a method for preparing deuterated aromatic ring compounds, particularly 2-deuterated methyl nitrogen heterocyclic compounds. This method utilizes readily available raw materials, employs mild and safe reaction conditions, and utilizes a unique photocatalyst, resulting in a green preparation method for 2-deuterated methyl nitrogen heterocyclic compounds without heavy metal residues. In particular, it employs a unique disulfide compound, unlike the noble metal catalysts used in existing technologies, to complete the catalytic reaction, achieving a green and harmless process with high yield. Purification treatment of the compound shown in Formula II In this invention, the reaction further includes: after the reaction is completed, the solvent is removed by concentration, and then the 2-deuterated methyl nitrogen heterocyclic compound shown in Formula II is obtained by column chromatography.

[0053] In another preferred embodiment, the column chromatography elution solvent is a mixture of n-pentane and diethyl ether.

[0054] In another preferred embodiment, the column chromatography elution solvent is a mixed solvent of n-pentane / diethyl ether in a volume ratio of (4~5):1.

[0055] The main advantages of this invention are: 1. Photocatalysis: Photocatalysis is advantageous in synthesizing complex molecules due to its mild conditions, high selectivity, and neutral reaction conditions. Traditional acid-base catalysis usually requires high temperatures, which not only increases energy consumption but may also cause decomposition or rearrangement of compounds containing acid-base sensitive functional groups, affecting the purity and yield of the final product.

[0056] 2. Non-metallic photocatalysts: Traditional hydrogen-deuterium exchange reactions typically rely on noble metal catalysts such as palladium and platinum. These metals are not only expensive but can also leave metal residues. In contrast, using non-metallic photocatalysts such as biquaternary phosphate (BPP) completely eliminates the need for these heavy metals. BPP is not only inexpensive but also leaves no metal residues after the reaction, ensuring the purity and safety of the product. This makes metal-free photocatalytic deuteration reactions a significant advantage in pharmaceutical synthesis and the production of other fine chemicals.

[0057] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Experimental methods in the following embodiments, unless otherwise specified, are generally performed under conventional conditions or as recommended by the manufacturer. Unless otherwise stated, percentages and parts are weight percentages and parts by weight.

[0058] Example 1: Selective deuteration of 6-methoxy-2-methylquinoline under light-mediated conditions The chemical reaction formula for preparing compound 6-methoxy-2-deuterated methylquinoline in this example is as follows: The specific process is as follows: Add the stir bar, 6-methoxy-2-methylquinoline (34.6 mg, 0.2 mmol), and BPP (3.7 mg, 4 mmol) sequentially to a dried 8 mL reaction flask. mol), (2,4,5-triClPhS)2 (8.5mg, 20 Inject organic solvent PhCH3 (0.67 mL, 0.2 M, including deuterium water as a solvent) into a glove box and tighten the cap with a polytetrafluoroethylene gasket. Inject D2O (0.34 mL, 17 mmol) outside the glove box and seal with sealing film. Irradiate with 400 nm LEDs for 12 h.

[0059] After the reaction was completed, the solvent was removed by vacuum distillation, and the solution was separated by column chromatography (n-pentane / diethyl ether = 2:1) to obtain a yellow liquid (26 mg, 75% yield).

[0060] The structural data characterization of the product prepared in this example are as follows: 1 H NMR (400 MHz, CDCl3) δ7.94 - 7.90 (m, 2H), 7.33 (dd, J = 9.2, 2.8Hz, 1H), 7.22 (d, J= 8.4 Hz, 1H), 7.03 (d, J = 2.8 Hz, 1H), 3.90 (s, 3H), 2.68-2.65 (m, 0.14H). 13 C NMR (125 MHz, CDCl3) δ157.2, 156.4, 143.9, 135.2,130.1, 127.4, 122.3, 122.0, 105.3, 55.6, 24.8-24.0 (m). Example 2: Selective deuteration of 6-methyl-2-methylquinoline under light-mediated conditions The chemical reaction formula for preparing compound 6-methyl-2-methylquinoline in this example is as follows: The specific process is as follows: Add the stir bar, 6-methyl-2-methylquinoline (31.4 mg, 0.2 mmol), and BPP (3.7 mg, 4 mmol) sequentially to a dried 8 mL reaction flask. mol), (2,4,5-triClPhS)2 (8.5mg, 20 Inject organic solvent PhCH3 (0.67 mL, 0.2 M) into a glove box and tighten the cap with a polytetrafluoroethylene gasket. Inject D2O (0.34 mL, 17 mmol) outside the glove box and seal with sealing film. Irradiate with 400 nm LEDs for 12 h.

[0061] After the reaction was completed, the solvent was removed by vacuum distillation, and the product was separated by column chromatography (n-pentane / diethyl ether = 5:1) to obtain a white powder (26.6 mg, 83% yield).

[0062] The structural data characterization of the product prepared in this example are as follows: 1 H NMR (400 MHz, CDCl3) δ7.95 (d, J = 8.4 Hz, 1H), 7.91 (d, J = 8.4Hz, 1H), 7.52-7.49 (m, 2H), 7.23 (d, J = 8.4 Hz, 1H), 2.70-2.68 (m, 0.09H), 2.51 (s, 3H). 13C NMR (125 MHz, CDCl3) δ158.0, 146.5, 135.7, 135.5, 131.8,128.3, 126.6, 126.5, 122.1, 24.9-24.3 (m), 21.6. Example 3: Selective deuterated 2-methylquinoline under light-mediated conditions The chemical reaction formula for preparing compound 2-deuterated methylquinoline in this example is as follows: The specific process is as follows: Add the stir bar, 2-methylquinoline (28.6 mg, 0.2 mmol), and BPP (3.7 mg, 4 mmol) sequentially to a dried 8 mL reaction flask. mol), (2,4,5-triClPhS)2 (8.5mg, 20 Inject organic solvent PhCH3 (0.67 mL, 0.2 M) into a glove box and tighten the cap with a polytetrafluoroethylene gasket. Inject D2O (0.34 mL, 17 mmol) outside the glove box and seal with sealing film. Irradiate with 400 nm LEDs for 12 h.

[0063] After the reaction was completed, the solvent was removed by vacuum distillation, and the solution was separated by column chromatography (n-pentane / diethyl ether = 5:1) to obtain a yellow oily liquid (25.4 mg, 87% yield).

[0064] The structural data characterization of the product prepared in this example are as follows: 1 H NMR (400 MHz, CDCl3) δ8.02 (d, J = 8.4 Hz, 2H), 7.75 (d, J = 8.0Hz, 1H), 7.69-7.65 (m, 1H), 7.46 (m, 1H), 7.27-7.25 (m, 1H), 2.71 - 2.70(m,0.10H). 13 C NMR (125 MHz, CDCl3) δ159.0, 147.9, 136.3, 129.6, 128.6, 127.6,126.6, 125.8, 122.1, 24.8-24.5 (m). Example 4: Selective deuterated 4-methylquinoline under light-mediated conditions The chemical reaction formula for preparing compound 4-methylquinoline in this example is as follows: The specific process is as follows: Add the stir bar, 4-methylquinoline (28.6 mg, 0.2 mmol), and BPP (3.7 mg, 4 mmol) sequentially to a dried 8 mL reaction flask. mol), (2,4,5-triClPhS)2 (8.5mg, 20 Inject organic solvent PhCH3 (0.67 mL, 0.2 M) into a glove box and tighten the cap with a polytetrafluoroethylene gasket. Inject D2O (0.34 mL, 17 mmol) outside the glove box and seal with sealing film. Irradiate with 400 nm LEDs for 12 h.

[0065] After the reaction was completed, the solvent was removed by vacuum distillation, and the solution was separated by column chromatography (n-pentane / diethyl ether = 2:1) to obtain a yellow liquid (24.9 mg, 85% yield).

[0066] The structural data characterization of the product prepared in this example are as follows: 1 H NMR (400 MHz, CDCl3) δ8.76 (d, J = 4.4 Hz, 1H), 8.11 (d, J = 8.4Hz, 1H), 7.98 (d, J = 8.4 Hz, 1H), 7.72-7.68 (m, 1H), 7.57-7.53 (m, 1H), 7.22(d, J = 4.4 Hz, 1H), 2.69-2.64 (m, 0.09H); 13 C NMR (125 MHz, CDCl3) δ150.2,147.9, 144.5, 129.9, 129.3, 128.4, 126.4, 123.9, 122.0, 18.1-17.8 (m). Example 5: Selective deuterated 1-methylisoquinoline under light-mediated conditions The chemical reaction formula for preparing compound 1-deuterated methyl isoquinoline in this example is as follows: The specific process is as follows: Add the stir bar, 1-methylisoquinoline (28.6 mg, 0.2 mmol), and BPP (3.7 mg, 4 mmol) sequentially to a dried 8 mL reaction flask. mol), (2,4,5-triClPhS)2 (8.5mg, 20 Inject 0.67 mL (0.2 M) of organic solvent PhCH3 into a glove box and tighten the cap with a polytetrafluoroethylene gasket. Inject 0.34 mL (17 mmol) of D2O into the outside of the glove box and seal it with a sealing film. Irradiate with 400 nm LEDs for 12 h.

[0067] After the reaction was completed, the solvent was removed by vacuum distillation, and the solution was separated by column chromatography (n-pentane / diethyl ether = 2:1) to obtain a yellow liquid (26.5 mg, 91% yield).

[0068] The structural data characterization of the product prepared in this example are as follows: 1 H NMR (400 MHz, CDCl3) δ8.4 (d, J = 6.0 Hz, 1H), 8.09 (d, J = 8.4 Hz, 1H), 7.78 (d, J = 8.0 Hz, 1H), 7.67 - 7.63 (m, 1H), 7.60 - 7.55 (m, 1H), 7.49(d, J = 6.0 Hz, 1H), 2.94-2.91 (m, 0.12H). 13 C NMR (125 MHz, CDCl3) δ158.6,141.8, 136.0, 130.1, 127.6, 127.3, 127.1, 125.7, 119.4, 22.3-21.8 (m). Example 6: Selective deuteration of 6-bromo-2-methylquinoline under light-mediated conditions The chemical reaction formula for preparing compound 6-bromo-2-deuterated methylquinoline in this example is as follows: The specific process is as follows: Add the stir bar, 6-bromo-2-methylquinoline (44.4 mg, 0.2 mmol), and BPP (3.7 mg, 4 mmol) sequentially to a dried 8 mL reaction flask. mol), (2,4,5-triClPhS)2 (8.5mg, 20 Inject the organic solvent PhCH3 (0.67 ml, 0.2 M) into the glove box, tighten the cap with a polytetrafluoroethylene gasket, inject D2O (0.34 ml, 17 mmol) outside the glove box, seal with sealing film, and irradiate with 400 nm LEDs for 12 h.

[0069] After the reaction was completed, the solvent was removed by vacuum distillation, and the product was separated by column chromatography (n-pentane / diethyl ether = 5:1) to obtain white crystals (32.9 mg, 73% yield).

[0070] The structural data characterization of the product prepared in this example are as follows: 1 H NMR (400 MHz, CDCl3) δ7.92 - 7.85 (m, 3H), 7.71 (dd, J =9.2, 2.0 Hz,1H), 7.26 (m, 1H), 2.69 - 2.66 (m, 0.08H). 13 C NMR (125 MHz, CDCl3) δ159.5,146.4, 135.3, 132.9, 130.4, 129.6, 127.7, 122.9, 119.5, 24.9-24.5 (m). Example 7: Selective deuteration of 6-chloro-2-methylquinoline under light-mediated conditions The chemical reaction formula for preparing compound 6-chloro-2-deuterated methylquinoline in this example is as follows: The specific process is as follows: Add the stir bar, 6-chloro-2-methylquinoline (35.5 mL, 0.2 mmol), and BPP (3.7 mg, 4 mmol) sequentially to a dried 8 mL reaction flask. mol), (2,4,5-triClPhS)2 (8.5mg, 20 Inject 0.67 mL (0.2 M) of organic solvent PhCH3 into a glove box and tighten the cap with a polytetrafluoroethylene gasket. Inject 0.34 mL (17 mmol) of D2O into the outside of the glove box and seal it with a sealing film. Irradiate with 400 nm LEDs for 12 h.

[0071] After the reaction was completed, the solvent was removed by vacuum distillation, and the product was separated by column chromatography (n-pentane / diethyl ether = 5:1) to obtain a white powder (25.5 mg, 71% yield).

[0072] The structural data characterization of the product prepared in this example are as follows: 1 H NMR (400 MHz, CDCl3) δ7.94 - 7.91 (m, 2H), 7.71(d, J= 1.6 Hz, 1H),7.60-7.57 (m, 1H), 7.27 (d, J = 8.4 Hz, 1H), 2.69 - 2.68 (m, 0.12H). 13 C NMR(125 MH, CDCl3) δ159.4, 146.2, 135.4, 131.4, 130.4, 130.3, 127.1, 126.3,123.0, 25.0-24.4 (m). Example 8: Selective deuterated 6-fluoro-2-methylquinoline under light-mediated conditions The chemical reaction formula for preparing compound 6-fluoro-2-deuterated methylquinoline in this example is as follows: The specific process is as follows: Add the stir bar, 6-fluoro-2-methylquinoline (32.2 mg, 0.2 mmol), and BPP (3.7 mg, 4 mmol) sequentially to a dried 8 mL reaction flask. mol), (2,4,5-triClPhS)2 (8.5m, 20 Inject organic solvent PhCH3 (0.67 mL, 0.2 M) into a glove box and tighten the cap with a polytetrafluoroethylene gasket. Inject D2O (0.34 mL, 17 mmol) outside the glove box and seal with sealing film. Irradiate with 400 nm LEDs for 12 h.

[0073] After the reaction was completed, the solvent was removed by vacuum distillation, and the product was separated by column chromatography (n-pentane / diethyl ether = 5:1) to obtain a white powder (23.8 mg, 72% yield).

[0074] The structural data characterization of the product prepared in this example are as follows: 1 H NMR (400 MHz, CDCl3) δ8.03 - 7.98 (m, 2H), 7.47 - 7.42 (m, 1H),7.39 - 7.36 (m, 1H), 7.29 (d, J = 8.4 Hz, 1H), 2.73 - 2.70 (m, 0.08H). 13 C NMR (125 MHz, CDCl3) δ160.1 (d, J F-C = 245 Hz), 158.3, 144.9, 135.8 (d, J F-C= 5.0Hz), 131.0 (d, J F-C = 8.8 Hz), 127.1 (d, J F-C = 10.0 Hz), 122.9, 119.7 (d, J F-C =25.0 Hz), 110.7 (d, J F-C = 21.2 Hz), 25.1-24.6 (m). Example 9: Selective deuteration of 6-trifluoromethyl-2-methylquinoline under light-mediated conditions The chemical reaction formula for preparing compound 6-trifluoromethyl-2-deuterated methylquinoline in this example is as follows: The specific process is as follows: Add the stir bar, 6-trifluoromethyl-2-deuterated methylquinoline (42.2 mg, 0.2 mmol), and BPP (3.7 mg, 4 mmol) sequentially to a dried 8 mL reaction flask. mol), (2,4,5-triClPhS)2 (8.5mg, 20 0.67 mL, 0.2 M of organic solvent PhCH3 was injected into the glove box and the cap with a polytetrafluoroethylene gasket was tightened. D2O (0.34 mL, 17 mmol) was injected outside the glove box and sealed with sealing film. The mixture was then irradiated with 400 nm LEDs for 12 h.

[0075] After the reaction was completed, the solvent was removed by vacuum distillation, and the product was separated into a white powder (32.1 mg, 75% yield) by column chromatography (n-pentane / diethyl ether = 5:1).

[0076] The structural data characterization of the product prepared in this example are as follows: 1 H NMR (400 MHz, CDCl3) δ8.12 - 8.07 (m, 3H), 7.85 - 7.83 (m, 1H),7.37 (d, J = 8.4 Hz, 1H), 2.75 - 2.73 (m, 0.09H). 13 C NMR (125 MHz, CDCl3) δ161.6, 148.9, 137.0, 129.9, 127.8 (q, J F-C = 32.5 Hz), 125.6 (q, JF-C = 3.8 Hz), 125.3 (q, J F-C = 2.5 Hz), 123.4, 123.1, 25.4-24.7 (m). Example 10: Selective deuteration of 6-cyano-2-methylquinoline under photomediated conditions The chemical reaction formula for preparing compound 6-cyano-2-deuterated methylquinoline in this example is as follows: The specific process is as follows: Add the stir bar, 6-cyano-2-methylquinoline (33.6 mg, 0.2 mmol), and BPP (3.7 mg, 4 mmol) sequentially to a dried 8 mL reaction flask. mol), (2,4,5-triClPhS)2 (8.5mg, 20 Inject the organic solvent PhCH3 (0.67 mL, 0.2 M) into the glove box, tighten the cap with a polytetrafluoroethylene gasket, inject D2O (0.34 mL, 17 mmol) outside the glove box, seal with sealing film, and irradiate with 400 nm LEDs for 12 h.

[0077] After the reaction was completed, the solvent was removed by vacuum distillation, and the product was separated by column chromatography (n-pentane / diethyl ether = 5:1) to obtain a white powder (27.9 mg, 82% yield).

[0078] The structural data characterization of the product prepared in this example are as follows: 1 H NMR (400 MHz, CDCl3) δ8.16 (s, 1H), 8.10 - 8.07 (m, 2H), 7.80 (d, J = 8.8 Hz, 1H), 7.41 (d, J = 8.4 Hz, 1H), 2.78-2.75 (m, 0.27H). 13 C NMR (125MHz, CDCl3) δ162.6, 148.9, 136.4, 133.8, 130.3, 130.2, 125.9, 123.8, 118.8,109.4, 25.4-24.6 (m). Example 11: Selective deuterated methyl 6-carboxylate-2-methylquinoline under light-mediated conditions The chemical reaction formula for preparing compound methyl 6-formate-2-deuterated methylquinoline in this example is as follows: The specific process is as follows: In a dried 8 mL reaction flask, add a stir bar, methyl 6-formate-2-methylquinoline (40.2 mL, 0.2 mmol), and BPP (3.7 mg, 4 mmol) sequentially. mol), (2,4,5-triClPhS)2 (8.5mg, 20 0.67 mL, 0.2 M organic solvent PhCH3 was injected into the glove box and the cap with a polytetrafluoroethylene gasket was tightened. D2O (0.34 m, 17 mmol) was injected outside the glove box and sealed with sealing film. The mixture was then irradiated with 400 nm LEDs for 12 h.

[0079] After the reaction was completed, the solvent was removed by vacuum distillation, and the product was separated by column chromatography (n-pentane / diethyl ether = 2:1) to obtain a white powder (38.7 mg, 95% yield).

[0080] The structural data characterization of the product prepared in this example are as follows: 1 H NMR (125 MHz, CDCl3) δ8.48 (d, J = 2.0 Hz, 1H), 8.22 (dd, J = 8.8, 2.0 Hz, 1H), 8.08 (d, J = 8.0 Hz, 1H), 8.00 (d, J = 8.8 Hz, 1H), 7.03 (d, J =8.8 Hz, 1H), 3.94 (s, 3H), 2.71-2.69 (m, 0.13H). 13 C NMR (125 MHz, CDCl3) δ166.8, 161.6, 149.8, 137.4, 130.8, 129.1, 129.0, 127.3, 125.7, 122.9,52.4,25.1-24.7 (m). Example 12: Selective deuteration of 6-nitro-2-methylquinoline under photomediated conditions The chemical reaction formula for preparing compound 6-nitro-2-methylquinoline in this example is as follows: The specific process is as follows: Add the stir bar, 4-methylquinoline (28.6 mg, 0.2 mmol), and BPP (3.7 mg, 4 mmol) sequentially to a dried 8 mL reaction flask. mol), (2,4,5-triClPhS)2 (8.5mg, 20 Organic solvent EA (0.67 mL, 0.2 M) was injected into a glove box and the cap with a PTFE gasket was tightened. D2O (0.34 mL, 17 mmol) was injected outside the glove box and sealed with a sealing film. The mixture was irradiated with 400 nm LEDs for 12 h. After the reaction was completed, the solvent was removed by vacuum distillation, and the mixture was separated into a white powder (30.4 mg, 80% yield) by column chromatography (n-pentane / diethyl ether = 2:1).

[0081] The structural data characterization of the product prepared in this example are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.70 (d, J = 2.4 Hz, 1H), 8.41-8.38 (m, 1H),8.19 (d, J = 8.8 Hz, 1H), 8.08 (d, J = 9.2 Hz, 1H), 7.43 (d, J = 8.4 Hz, 1H),2.76-2.74 (m, 0.10H). 13 C NMR (125 MHz, CDCl3) δ163.4, 150.0, 145.0, 137.8,130.4, 125.3, 124.4, 124.0, 123.0, 25.2-24.9 (m). Example 13: Selective deuterated 8-fluoro-2-methylquinoline under photomediated conditions The chemical reaction formula for preparing compound 8-fluoro-2-methylquinoline in this example is as follows: The specific process is as follows: In a dried 8 mL reaction flask, a stir bar, 8-fluoro-2-methylquinoline (32.2 mg, 0.2 mmol), and BPP (3.7 mg, 4 mmol) were added sequentially. mol), (2,4,5-triClPhS)2 (8.5mg, 20 0.67 mL (0.2 M) of organic solvent PhCH3 was injected into a glove box, and the box was sealed with a cap fitted with a PTFE gasket. D2O (0.34 mL, 17 mmol) was injected outside the glove box, and the box was sealed with a sealing film. The mixture was irradiated with 400 nm LEDs for 12 h. After the reaction was complete, the solvent was removed by vacuum distillation, and the mixture was separated into a white powder (25.5 mg, 79% yield) by column chromatography (n-pentane / diethyl ether = 2:1).

[0082] The structural data characterization of the product prepared in this example are as follows: 1 H NMR (400 MHz, CDCl3) δ) δ 8.08-8.05 (m, 1H), 7.57-7.54 (m, 1H), 7.42-7.33 (m, 3H), 2.78-2.75 (m, 0.13 H). 13 C NMR (125 MHz, CDCl3) 158.7,158.6, 156.6, 138.0 (d, J F-C = 11.3 Hz), 136.1 (d, J F-C = 2.5 Hz), 128.3 (d, J F-C = 2.5 Hz), 125.5 (d, J F-C = 8.8 Hz), 123.3 (d, J F-C =5.0 Hz), 123.2, 113.7 (d, J F-C = 18.8 Hz), 25.6-24.8 (m). Example 14: Selective deuteration of 2,3-dimethylquinoxaline under light-mediated conditions The chemical reaction formula for preparing compound 2,3-deuterated dimethylquinoxaline in this example is as follows: The specific process is as follows: Add the stir bar, 2,3-dimethylquinoxaline (31.6 mg, 0.2 mmol), and BPP (3.7 mg, 4 mmol) sequentially to a dried 8 mL reaction flask. mol), (2,4,5-triClPhS)2 (8.5mg, 20 Inject 0.67 mL, 0.2 M of organic solvent PhCH3 into a glove box, tighten the cap with a polytetrafluoroethylene gasket, inject D2O (0.34 mL, 17 mmol) outside the glove box, seal with sealing film, and irradiate with 400 nm LEDs for 12 h.

[0083] After the reaction was completed, the solvent was removed by vacuum distillation, and the product was separated into a white powder (25.9 mg, 80% yield) by column chromatography (n-pentane / diethyl ether = 2:1).

[0084] The structural data characterization of the product prepared in this example are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.98 - 7.94 (m, 2H), 7.66 - 7.62 (m, 2H), 2.70 - 2.66 (m, 0.31H). 13 C NMR (125 MHz, CDCl3) δ153.5, 141.3, 129.0, 128.4,23.2-22.4 (m). Example 15: Selective deuteration of 2-methyl-1,5-naphthidine under photomediated conditions The chemical reaction formula for preparing compound 2-deuterated methyl-1,5-naphthidine in this example is as follows: The specific process is as follows: Add the stir bar, 2-methyl-1,5-naphthidine (28.8 mg, 0.2 mmol), and BPP (3.7 mg, 4 mmol) sequentially to a dried 8 mL reaction flask. mol), (2,4,5-triClPhS)2 (8.5mg, 20 Inject the organic solvent PhCH3 (0.67 mL, 0.2 M) into the glove box, tighten the cap with a polytetrafluoroethylene gasket, inject D2O (0.34 mL, 17 mmol) outside the glove box, seal with sealing film, and irradiate with 400 nm LEDs for 12 h.

[0085] After the reaction was completed, the solvent was removed by vacuum distillation, and the product was separated into a white powder (23.2 mg, 79% yield) by column chromatography (n-pentane / diethyl ether = 1:2).

[0086] The structural data characterization of the product prepared in this example are as follows: 1H NMR (400 MHz, CDCl3) δ 8.89 - 8.87 (m, 1H), 8.30 - 8.25 (m, 2H), 7.59 - 7.56 (m, 2H), 7.49 (d, J = 8.8 Hz, 1H), 2.74 - 2.73 (m, 0.07H). 13 C NMR (125 MHz, CDCl3) δ 160.1, 150.3, 143.2, 142.7, 137.5, 136.6, 125.6, 124.4,24.9-24.4 (m). Example 16: Selective deuteration of 2-methyl-[1,8]-naphthidine under photomediated conditions The chemical reaction formula for preparing compound 2-deuterated methyl-[1,8]-naphthidine in this example is as follows: The specific process is as follows: Add the stir bar, 2-methyl-[1,8]-naphthidine (28.8 mg, 0.2 mmol), and BPP (3.7 mg, 4 mmol) sequentially to a dried 8 mL reaction flask. mol), (2,4,5-triClPhS)2 (8.5mg, 20 Inject the organic solvent PhCH3 (0.67 mL, 0.2 M) into the glove box, tighten the cap with a polytetrafluoroethylene gasket, inject D2O (0.34 mL, 17 mmol) outside the glove box, seal with sealing film, and irradiate with 400 nm LEDs for 12 h.

[0087] After the reaction was completed, the solvent was removed by vacuum distillation, and the solution was separated by column chromatography (n-pentane / diethyl ether = 2:1) to obtain a yellow liquid (28.4 mg, 99% yield).

[0088] The structural data characterization of the product prepared in this example are as follows: 1 H NMR (400 MHz, CDCl3) δ9.02 (d, J = 2.0 Hz, 1H), 8.11 - 8.08 (m,1H), 8.03 - 8.01 (m, 1H), 7.38 (dd, J = 8.0 Hz, J = 4.4 Hz, 1H), 7.33 (d, J =8.4 Hz, 1H), 2.74-2.73 (m, 0.09H).13 C NMR (125 MHz, CDCl3) δ163.0, 156.0,153.3, 136.9, 136.7, 123.1, 121.4, 120.8, 25.1-24.8 (m). Example 17: Selective deuteration of 2,9-dimethyl-1,10-phenanthroline under photomediated conditions The chemical reaction formula for preparing compound 2,9-deuterated dimethyl-1,10-phenanthroline in this example is as follows: The specific process is as follows: Add the stir bar, 2,9-dimethyl-1,10-phenanthroline (28.6 mg, 0.2 mmol), and BPP (3.7 mg, 4 mmol) sequentially to a dried 8 mL reaction flask. mol), (2,4,5-triClPhS)2 (8.5mg, 20 Inject the organic solvent PhCH3 (0.67 mL, 0.2 M) into the glove box, tighten the cap with a polytetrafluoroethylene gasket, inject D2O (0.34 mL, 17 mmol) outside the glove box, seal with sealing film, and irradiate with 400 nm LEDs for 12 h.

[0089] After the reaction was completed, the solvent was removed by vacuum distillation, and the white powder (36.6 mg, 88% yield) was obtained by column chromatography (DCM to DCM: MeOD = 100:1).

[0090] The structural data characterization of the product prepared in this example are as follows: 1 H NMR (400 MHz, CDCl3) δ8.10-8.08 (m, 2H), 7.67 (s, 2H), 7.46 (d, J =8.0 Hz, 2H), 2.92-2.88 (m, 0.77H). 13 C NMR (125 MHz, CDCl3) δ159.3, 145.2,136.4-136.3 (m), 126.9, 125.5, 123.6, 25.1-24.6 (m). Example 18: Selective deuterated 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline under photomediated conditions The chemical reaction formula for preparing compound 2,9-deuterated dimethyl-4,7-diphenyl-1,10-phenanthroline in this example is as follows: The specific process is as follows: In a dried 8 mL reaction flask, add a stir bar, 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline (28.6 mg, 0.2 mmol), and BPP (3.7 mg, 4 mmol) sequentially. mol), (2,4,5-triClPhS)2 (8.5mg, 20 0.67 mL, 0.2 M organic solvent PhCH3 was injected into the glove box, and the cap with a polytetrafluoroethylene gasket was tightened. D2O (0.34 mL, 17 mmol) was injected outside the glove box and sealed with sealing film. The mixture was then irradiated with 400 nm LEDs for 12 h.

[0091] After the reaction was completed, the solvent was removed by vacuum distillation, and the white powder (69 mg, 97% yield) was obtained by column chromatography (DCM to DCM: MeOD = 100:1).

[0092] The structural data characterization of the product prepared in this example are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.57 (s, 2H), 7.34 - 7.25 (m, 12H), 2.81 -2.77 (m, 0.58H). 13 C NMR (125 MHz, CDCl3) δ158.7, 148.6-148.5 (m), 146.0,138.2, 129.7, 128.5, 128.4, 124.7, 124.0, 123.0, 25.8-25.4 (m). Currently, patents have reported the application of supported Pd photocatalysts in the deuteration reaction of Csp2-H in nitrogen-containing aromatic hydrocarbons (CN119954729 A), and the application of 4CZIPN photocatalysts in the synthesis of deuterated acetamide compounds (CN 120349258A). However, neither of these photocatalytic systems has been used for the direct deuteration reaction of benzylic Csp3-H in aromatic heterocyclic compounds. Specifically, supported Pd photocatalysts use precious metals, which are not only costly but may also introduce metal residue problems; while the reaction catalyzed by 4CZIPN is essentially a dechlorination deuteration process, where Csp3-H needs to be pre-converted to Csp3-Cl before deuteration can occur, rather than directly deuterating unactivated Csp3-H. In contrast, this patent uses an organic photocatalyst, which has the advantages of being inexpensive, readily available, and free of metal residues. It can also directly deuterate unactivated benzylic Csp3-H in the raw material without the need for a prefunctionalization step, thus offering greater advantages in reaction efficiency and atom economy.

[0093] The embodiments described above merely illustrate specific implementation methods of this application, and while the descriptions are detailed and specific, they should not be construed as limiting the scope of protection of this application. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the technical solution of this application, and these modifications and improvements all fall within the scope of protection of this application.

[0094] All documents mentioned in this invention are incorporated herein by reference as if each document were individually incorporated by reference. Furthermore, it should be understood that after reading the foregoing teachings of this invention, those skilled in the art can make various alterations or modifications to this invention, and these equivalent forms also fall within the scope defined by the appended claims.

Claims

1. A method for preparing an aromatic heterocyclic benzylic selective deuterated compound, characterized in that, The method includes: In an organic solvent, in the presence of a photocatalyst and a hydrogen atom transfer catalyst, the compound shown in Formula I is reacted with a deuterium source under light irradiation to obtain the compound of Formula II. Among the compounds of formula I and formula II, R a Selected from the following group: H, halogen, cyano, nitro, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, -C(O)-O-C1-C4 alkyl; m is selected from 0, 1, 2, 3 or 4; R or located on two ring atoms in the same, adjacent or interposition a The ring atoms attached to it together form a group selected from the group consisting of C6-C10 aromatic rings and 5-12 membered heteroaromatic rings; one or more hydrogen atoms on the above groups are optionally R b Replace, R a Selected from the following group: H, halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, phenyl; Where valence bonds permit, Z1, Z2, Z3, Z4, and Z5 are each independently CH or N; and when Z1, Z2, Z3, Z4, and Z5 are substituted by substituents on the ring, the CH becomes C; The photocatalyst is selected from the following group: bis(quaternary) phosphate (BPP), eosin Y, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), 9-mesinetrilyl-10-methylacridin-10-onium tetrafluoroborate ([Mes-Acr]). + BF4 - ), 2,4,5,6-tetra(9-carbazolyl)-isophthalonitrile (4CzIPN), preferably bis(quaternary) phosphate (BPP).

2. The preparation method according to claim 1, characterized in that, The organic solvent is selected from the group consisting of N,N-dimethylformamide, ethyl acetate, acetone, acetonitrile, tetrahydrofuran, 1,4-dioxane, dichloromethane, toluene, trifluorotoluene, etc., with toluene, ethyl acetate, and tetrahydrofuran being preferred, and toluene being even more preferred.

3. The preparation method according to claim 1, characterized in that, The photocatalyst is selected from the group consisting of: 。 4. The preparation method according to claim 1, characterized in that, The hydrogen atom transfer catalyst has the structure shown in formula V: Among them, R m R n Each is independently selected from the following group: H, halogen, OH, cyano, nitro, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy; x and y are each independently selected from 0, 1, 2, 3, 4 or 5.

5. The preparation method according to claim 1, characterized in that, The hydrogen atom transfer catalyst is selected from the group consisting of: bis(4-methoxyphenyl) disulfide, bis(4-hydroxyphenyl) disulfide, bis(4-methylphenyl) disulfide, bis(2,4,6-triisopropylphenyl) disulfide, bis(4-bromophenyl) disulfide, bis(2,4,6-trichlorophenyl) disulfide, bis(2,3,4,5,6-pentafluorophenyl) disulfide, bis(4-cyanophenyl) disulfide, etc., among which bis(4-bromophenyl) disulfide, bis(2,4,6-trichlorophenyl) disulfide, bis(2,3,4,5,6-pentafluorophenyl) disulfide, and bis(4-cyanophenyl) disulfide have better reaction effects, and bis(2,4,6-trichlorophenyl) disulfide is preferred.

6. The preparation method according to claim 1, characterized in that, The deuterium source is selected from MeOD, D2O, or a combination thereof, preferably D2O.

7. The preparation method according to claim 1, characterized in that, The illumination is provided by a light source with a wavelength of 365-500 nm, preferably a light source with a wavelength of 365-420 nm.

8. The preparation method according to claim 1, characterized in that, The compound of formula I is selected from the following group: 。 9. The preparation method according to claim 1, characterized in that, The reaction has one or more characteristics selected from the group consisting of: (1) The molar ratio of compound I to photocatalyst in the reaction is 1:(0.001~0.2), preferably 1:(0.01~0.05); (2) The molar ratio of compound I to hydrogen atom transfer catalyst in the reaction is 1:(0.01~0.2), preferably 1:(0.05~0.15); (3) The molar ratio of compound I to deuterium source in the reaction is 1:(1~200); preferably 1:(80~120); (4) The volume ratio of the organic solvent to the deuterium source in the reaction is (1~10):1; preferably (1~3):1; (5) The amount of organic solvent added is 1 to 20 mL / mmol based on the amount of the substance of Formula I, preferably 5 to 10 mL / mmol; (6) The reaction temperature is 5~60℃, preferably 15~30℃; (7) The reaction time is 5 to 20 hours, preferably 10 to 15 hours.

10. A deuterated compound as shown in Formula II, characterized in that, The compound is obtained by the preparation method described in claim 1. Among them, R a Selected from the following group: H, halogen, cyano, nitro, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, -C(O)-O-C1-C4 alkyl; m is selected from 0, 1, 2, 3 or 4; R or located on two ring atoms in the same, adjacent or interposition a The ring atoms attached to it together form a group selected from the group consisting of C6-C10 aromatic rings and 5-12 membered heteroaromatic rings; one or more hydrogen atoms on the above groups are optionally R b Replace, R a Selected from the following group: H, halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, phenyl; Where valence bonds allow, Z1, Z2, Z3, Z4, and Z5 are each independently CH or N.

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