Process for the photocatalytic synthesis of alpha-trifluoromethyl amines

Abstract

The application belongs to the technical field of organic synthesis, and particularly relates to a method for photocatalytically synthesizing alpha-trifluoromethyl amine compounds. In the presence of a photocatalyst, compound II and compound III are subjected to photocatalytic reaction in an organic solvent, compound IV is added after the first step reaction is completed, and compound I is obtained, and a reaction equation is as follows: The synthesis method provided by the application is simple in operation, high in yield, easy in product separation and purification, low in cost, and small in environmental pollution.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a method for photocatalytic synthesis of α-trifluoromethylamine compounds. Background Technology

[0002] Introducing fluorine-containing functional groups into organic compound molecules can, to some extent, alter the original compound's lipophilicity, solubility, molecular conformation, and metabolic activity. Therefore, fluorine-containing organic compounds play a crucial role in pesticide chemistry and pharmaceutical molecule design. To date, over 40% of commercially available drug molecules contain fluorine, and over 80% contain nitrogen. However, α-trifluoromethylamine compounds are extremely rare in drug molecules. This is primarily because efficient and mild methods for synthesizing α-trifluoromethylamine compounds are still lacking.

[0003] On the other hand, visible light is a green, pollution-free, and abundant clean energy source. Visible light-induced chemical conversion can efficiently convert light energy into chemical energy, thereby achieving the green and environmentally friendly synthesis of compounds. In the past decade or so, visible light-driven photocatalytic reactions have become an important means of molecular synthesis. Therefore, there is an urgent need to introduce photocatalysis into the synthesis of α-trifluoromethylamine compounds. Summary of the Invention

[0004] To address the problems in the prior art, this invention provides a method for photocatalytic synthesis of α-trifluoromethylamine compounds. This synthesis method has the advantages of simple operation, high yield, easy product separation and purification, low cost, and minimal environmental pollution.

[0005] To achieve the above technical objectives, the technical solution of the present invention is as follows: A method for photocatalytic synthesis of α-trifluoromethylamine compounds includes the following steps: In the presence of a photocatalyst, compound II and compound III undergo a photocatalytic reaction in an organic solvent; after the first step reaction is completed, compound IV is added to react and yield compound I. The reaction equation is as follows: Among them, R in compound III 1 for , , , , One of them; R 2 For H or ; The compound IV is used or , wherein R in 3 for , , , , , , , , One of H; R 4 It is H or CH3; The X in COX2 is Cl or Br; The R 1 Z in the equation represents O or S, and R represents... 1-1 It is one of H, 4-Me, 4-Cl, 4-MeO, 4-Ph, 4-AcO, 4-CN, 4-CO2Me, 3-Cl, and 2-Cl; R 1-2 It is one of PhO, BnO, and EtO; The R 3 R in 3-1 It is 4-Br or H; R 3-2 for , , One of them; R 3-3 For CH2CH3, CH2Br, OH, CN, NHBoc, One of them; R 3-4 It is either H or 4-OH.

[0006] The photocatalyst is one of the following: tri(2-phenylpyridine)iridium, (4,4'-di-tert-butyl-2,2'-bipyridine)bis[(2-pyridyl)phenyl]iridium(III) hexafluorophosphate, 2,4,5,6-tetra(9-carbazolyl)-isophthalonitrile, eosin Y, and tripyridine ruthenium chloride hexahydrate.

[0007] The photocatalytic reaction takes place in a nitrogen atmosphere at a temperature of 20-30°C, and the photocatalyst uses 3-10W blue light.

[0008] The organic solvent for the photocatalytic reaction is one of acetone, methanol, dichloromethane, and acetonitrile.

[0009] The post-processing of compound I includes rotary evaporation and column chromatography separation.

[0010] Furthermore, the rotary evaporation is performed in a rotary evaporator, and the column chromatography separation is performed using silica gel column chromatography.

[0011] The specific methods for the synthesis include: Step 1: Add cobalt halide, 1,2-bis(diphenylphosphino)benzene and 1 mL organic solvent to a 10 mL vial with a magnetic ball. Stir the mixture at room temperature for 0.5 h to allow the ligands to coordinate. Step 2: Take a 10 mL vial with a magnetic ferrule and add compound III and photocatalyst in sequence. Seal the vial with a rubber stopper and replace it with nitrogen to create an oxygen-free environment. Then, add the cobalt halide / 1,2-bis(diphenylphosphino)benzene solution from step 1 and compound II to obtain a mixture. Step 3: The mixture is irradiated and stirred in a blue LED photoreactor with an internal fan for 3-10 h, and the reaction is monitored by thin-layer chromatography. After the photoreaction is completed, triethylamine and compound IV are added, and the mixture is stirred at room temperature for 6 h. The reaction is detected by thin-layer chromatography to obtain crude compound I. Step 4: The crude compound I is subjected to column chromatography to obtain the product. The eluent is a petroleum ether-ethyl acetate system, and the volume ratio of petroleum ether to ethyl acetate is 10-50:1.

[0012] In the synthesis method, the molar ratio of compound II, compound III, amine compound IV, photocatalyst, cobalt halide, 1,2-bis(diphenylphosphine)benzene, and triethylamine is 2.5:1.25:1:0.01-0.03:0.05:0.05:1-2.

[0013] As can be seen from the above description, the present invention has the following advantages: 1. The synthesis method provided by this invention has the advantages of simple operation, high yield, easy product separation and purification, low cost and low environmental pollution.

[0014] 2. The synthesis method of the present invention has a wide range of applicable substrates and good functional group compatibility, and has good application prospects; that is, the present invention has great theoretical innovation value and implementation value. Attached Figure Description

[0015] Figure 1 3-(benzylamino)-4,4,4-trifluoro-1-phenyl-1-butanone prepared in Example 1 1 H NMR spectrum; Figure 2 3-(benzylamino)-4,4,4-trifluoro-1-phenyl-1-butanone prepared in Example 1 13 C NMR spectrum; Figure 3 3-(benzylamino)-4,4,4-trifluoro-1-phenyl-1-butanone prepared in Example 1 19 FNMR image. Detailed Implementation

[0016] Combination Figures 1 to 3 This description details a specific embodiment of the present invention, but does not limit the scope of the claims of the present invention in any way. Example

[0017] Cobalt bromide, 1,2-bis(diphenylphosphino)benzene, and 1 mL of solvent were added to a 10 mL dry vial equipped with a magnetic stopper. The mixture was stirred at room temperature for 0.5 h to allow ligand coordination. In another 10 mL vial equipped with a magnetic stopper, 2-bromoacetophenone and a photocatalyst were added sequentially. The vial was sealed with a rubber stopper and purged with nitrogen. The reaction should be carried out under anaerobic conditions. After nitrogen purging, the above cobalt bromide / 1,2-bis(diphenylphosphino)benzene solution and trifluorodiazoethane were added. The mixture was irradiated and stirred in a blue LED photoreactor with an internal fan for 1–24 h. The reaction was monitored by thin-layer chromatography (TLC). After the photoreaction was complete, Et3N and benzylamine reagent were added. The mixture was stirred at room temperature for 1–24 h. The reaction was monitored by TLC, and column chromatography was used for separation, eluting with a petroleum ether and ethyl acetate system (50:1 to 10:1). 58.3 mg of a yellow oily substance was obtained, with a yield of 96%. Product spectral analysis: such as Figure 1 As shown, 1 H NMR (600 MHz, CDCl3) δ 8.00 –7.95 (m, 2H), 7.66 – 7.60 (m, 1H), 7.54 – 7.49 (m, 2H), 7.34 – 7.23 (m, 5H), 4.10 – 3.88 (m, 3H), 3.33 (dd, J = 17.0, 3.5 Hz, 1H), 3.26 (dd, J = 17.0, 9.1Hz, 1H). For example... Figure 2 As shown, 13 C NMR (151 MHz, CDCl3) δ 196.1, 139.5, 136.4, 133.7,128.8, 128.4, 128.3, 128.2, 127.8, 126.9 (q, J = 283.4 Hz), 55.7 (q, J = 28.4Hz), 52.6, 38.5. For example Figure 3 As shown, 19 F NMR (376 MHz, CDCl3) δ -74.49 (d, J = 7.5 Hz).HRMS (ESI): Calcd for C 17 H 17F3NO [M+H] + : 308.1257; Found: 308.1258.

[0018] The reaction formula is as follows:

[0019] Example 2 Cobalt bromide, 1,2-bis(diphenylphosphino)benzene, and 1 mL of solvent were added to a 10 mL dry vial equipped with a magnetic swivel. The mixture was stirred at room temperature for 0.5 h to allow ligand coordination. In another 10 mL vial equipped with a magnetic swivel, 2-bromo-4'-methylacetophenone and a photocatalyst were added sequentially. The vial was sealed with a rubber stopper and purged with nitrogen. The reaction should be carried out under anaerobic conditions. After nitrogen purging, the above cobalt bromide / 1,2-bis(diphenylphosphino)benzene solution and trifluorodiazoethane were added. The mixture was irradiated and stirred in a blue LED photoreactor with an internal fan for 1–24 h. The reaction was monitored by thin-layer chromatography (TLC). After the photoreaction was complete, Et3N and benzylamine reagent were added. The mixture was stirred at room temperature for 1–24 h. The reaction was monitored by TLC, and column chromatography was used for separation, eluting with a petroleum ether and ethyl acetate system (50:1 to 10:1). 57.8 mg of a yellow oily substance was obtained, with a yield of 90%. Product spectral analysis 1 H NMR (400 MHz, CDCl3) δ 7.91 –7.84 (m, 2H), 7.35 – 7.20 (m, 7H), 4.07 – 3.88 (m, 3H), 3.35 – 3.17 (m, 2H), 2.46 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 195.7, 144.6, 139.5, 134.0, 129.5,128.4, 128.3, 128.3, 127.2, 126.9 (q, J = 283.8 Hz), 55.8 (q, J = 28.4 Hz), 52.6, 38.3, 21.7. 19 F NMR (376 MHz, CDCl3) δ -74.52 (d, J = 7.4 Hz). HRMS(ESI): Calcd for C 18 H 19 F3NO [M+H] + : 322.1413; Found: 322.1418.

[0020] The reaction formula is as follows:

[0021] Example 3 Cobalt bromide, 1,2-bis(diphenylphosphino)benzene, and 1 mL of solvent were added to a 10 mL dry vial equipped with a magnetic stopper. The mixture was stirred at room temperature for 0.5 h to allow ligand coordination. In another 10 mL vial equipped with a magnetic stopper, 4-(2-bromoacetic acid)phenylacetate and a photocatalyst were added sequentially. The vial was sealed with a rubber stopper and purged with nitrogen. The reaction should be carried out under anaerobic conditions. After nitrogen purging, the above cobalt bromide / 1,2-bis(diphenylphosphino)benzene solution and trifluorodiazoethane were added. The mixture was irradiated and stirred in a blue LED photoreactor with an internal fan for 1–24 h. The reaction was monitored by thin-layer chromatography (TLC). After the photoreaction was complete, Et3N and benzylamine reagent were added. The mixture was stirred at room temperature for 1–24 h. The reaction was monitored by TLC, and column chromatography was used for separation, eluting with a petroleum ether and ethyl acetate system (50:1 to 10:1). 59.2 mg of a yellow oily substance was obtained, with a yield of 81%. Product spectral analysis 1 H NMR (400 MHz, CDCl3) δ 8.03– 7.96 (m, 2H), 7.34 – 7.28 (m, 4H), 7.28 – 7.21 (m, 3H), 4.07 – 3.89 (m,3H), 3.34 – 3.17 (m, 2H), 2.36 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 194.8,168.8, 154.7, 139.4, 134.0, 129.8, 128.4, 128.3, 127.3, 126.8 (q, J = 283.4Hz), 122.0, 55.6 (q, J = 28.5 Hz), 52.5, 38.5, 21.2. 19 F NMR (376 MHz, CDCl3)δ -74.47 (d, J = 7.4 Hz). HRMS (ESI): Calcd for C 19 H 19 F3NO3 [M+H] + : 366.1312;Found: 366.1317.

[0022] The reaction formula is as follows:

[0023] Example 4 Cobalt bromide, 1,2-bis(diphenylphosphino)benzene, and 1 mL of solvent were added to a 10 mL dry vial equipped with a magnetic swivel. The mixture was stirred at room temperature for 0.5 h to allow ligand coordination. In another 10 mL vial equipped with a magnetic swivel, 3-methoxy-α-bromoacetophenone and a photocatalyst were added sequentially. The vial was sealed with a rubber stopper and purged with nitrogen. The reaction should be carried out under anaerobic conditions. After nitrogen purging, the above cobalt bromide / 1,2-bis(diphenylphosphino)benzene solution and trifluorodiazoethane were added. The mixture was irradiated and stirred in a blue LED photoreactor with an internal fan for 1–24 h. The reaction was monitored by thin-layer chromatography (TLC). After the photoreaction was complete, Et3N and benzylamine reagent were added. The mixture was stirred at room temperature for 1–24 h. The reaction was monitored by TLC, using column chromatography with elution in a petroleum ether and ethyl acetate system (50:1 to 10:1). 59.8 mg of a yellow oily substance was isolated, with a yield of 89%. Spectroscopic analysis of the product was performed. 1 H NMR (400 MHz, CDCl3) δ 7.58– 7.47 (m, 2H), 7.45 – 7.36 (m, 1H), 7.36 – 7.21 (m, 5H), 7.21 – 7.13 (m,1H), 4.08 – 3.92 (m, 3H), 3.89 (s, 3H), 3.48 – 3.07 (m, 2H). 13 C NMR (101 MHz, CDCl3) δ 196.0, 160.0, 139.5, 137.8, 129.8, 128.4, 128.3, 127.3, 126.8 (q, J = 282.9 Hz), 120.8, 120.1, 112.4, 55.8 (q, J = 28.4 Hz), 55.5, 52.5, 38.6,38.6, 38.6, 38.6. 19 F NMR (376 MHz, CDCl3) δ -74.47 (d, J = 7.2 Hz). HRMS(ESI): Calcd for C 18 H 19 F3NO2 [M+H] + : 338.1362; Found: 338.1368.

[0024] The reaction formula is as follows:

[0025] Example 5 Cobalt bromide, 1,2-bis(diphenylphosphino)benzene, and 1 mL of solvent were added to a 10 mL dry vial equipped with a magnetic swivel. The mixture was stirred at room temperature for 0.5 h to allow ligand coordination. In another 10 mL vial equipped with a magnetic swivel, 2-bromo-2'-chloroacetophenone and a photocatalyst were added sequentially. The vial was sealed with a rubber stopper and purged with nitrogen. The reaction should be carried out under anaerobic conditions. After nitrogen purging, the above cobalt bromide / 1,2-bis(diphenylphosphino)benzene solution and trifluorodiazoethane were added. The mixture was irradiated and stirred in a blue LED photoreactor with an internal fan for 1–24 h. The reaction was monitored by thin-layer chromatography (TLC). After the photoreaction was complete, Et3N and benzylamine reagent were added. The mixture was stirred at room temperature for 1–24 h. The reaction was monitored by TLC, and column chromatography was used for separation, eluting with a petroleum ether and ethyl acetate system (50:1 to 10:1). 57.1 mg of a yellow oily substance was obtained, with a yield of 84%. Product spectral analysis 1 H NMR (400 MHz, CDCl3) δ 7.54 – 7.48(m, 1H), 7.49 – 7.41 (m, 2H), 7.40 – 7.25 (m, 6H), 4.08 – 3.82 (m, 3H), 3.34(dd, J = 17.0, 3.8 Hz, 1H), 3.24 (dd, J = 17.0, 9.3 Hz, 1H). 13 C NMR (101 MHz, CDCl3) δ 199.1, 139.4, 138.6, 132.3, 131.0, 130.7, 129.4, 128.4, 128.3,127.3, 127.1, 126.7 (q, J = 284.4 Hz), 55.9 (q, J = 28.4 Hz), 52.3, 42.8. 19 FNMR (376 MHz, CDCl3) δ -74.28 (d, J = 7.4 Hz). HRMS (ESI): Calcd forC 17 H 16 ClF3NO [M+H] + : 342.0867; Found: 342.0870.

[0026] The reaction formula is as follows:

[0027] Example 6 Cobalt bromide, 1,2-bis(diphenylphosphino)benzene, and 1 mL of solvent were added to a 10 mL dry vial equipped with a magnetic swivel. The mixture was stirred at room temperature for 0.5 h to allow ligand coordination. In another 10 mL vial equipped with a magnetic swivel, 2-bromo-1-(2-furan)-1-ethylone and a photocatalyst were added sequentially. The vial was sealed with a rubber stopper and purged with nitrogen. The reaction should be carried out under anaerobic conditions. After nitrogen purging, the above cobalt bromide / 1,2-bis(diphenylphosphino)benzene solution and trifluorodiazoethane were added. The mixture was irradiated and stirred in a blue LED photoreactor with an internal fan for 1–24 h. The reaction was monitored by thin-layer chromatography (TLC). After the photoreaction was complete, Et3N and benzylamine reagent were added. The mixture was stirred at room temperature for 1–24 h. The reaction was monitored by TLC, using column chromatography with elution in a petroleum ether and ethyl acetate system (50:1 to 10:1). 30.3 mg of a yellow oily substance was isolated, with a yield of 51%. Spectroscopic analysis of the product was performed. 1 H NMR (400 MHz, CDCl3) δ7.64 – 7.57 (m, 1H), 7.33 – 7.21 (m, 6H), 6.61 – 6.55 (m, 1H), 4.13 – 3.69(m, 3H), 3.21 – 3.06 (m, 2H). 13 C NMR (101 MHz, CDCl3) δ 185.1, 152.4, 146.8,139.3, 128.4, 128.3, 127.3, 126.7 (q, J = 283.9 Hz), 117.7, 112.6, 55.5 (q, J = 28.5 Hz), 52.3, 38.3. 19 F NMR (376 MHz, CDCl3) δ -74.63 (d, J = 7.1 Hz).HRMS (ESI): Calcd for C 15 H 15 F3NO2 [M+H] + : 298.1049; Found: 298.1049.

[0028] The reaction formula is as follows:

[0029] Example 7 Add cobalt bromide, 1,2-bis(diphenylphosphino)benzene, and 1 mL of solvent to a 10 mL dry vial equipped with a magnetic button. Stir the mixture at room temperature for 0.5 h to allow ligand coordination. In another 10 mL vial equipped with a magnetic button, add 1-(1-benzothiophene-2-yl)-2-bromo-1-ethylone and a photocatalyst sequentially. Seal the vial with a rubber stopper and purge with nitrogen. The reaction should be carried out under anaerobic conditions. After nitrogen purging, add the aforementioned cobalt bromide / 1,2-bis(diphenylphosphino)benzene solution and trifluorodiazoethane. Irradiate the mixture in a blue LED photoreactor with an internal fan and stir for 1–24 h. The reaction can be monitored by thin-layer chromatography (TLC). After the photoreaction is complete, add Et3N and benzylamine reagent. Stir the mixture at room temperature for 1–24 h. Monitor the reaction by TLC, using column chromatography with elution in a petroleum ether and ethyl acetate system (50:1 to 10:1). 30.3 mg of a yellow oily substance was isolated, with a yield of 51%. Spectroscopic analysis of the product was performed. 1 H NMR (400 MHz, CDCl3) δ 7.99 – 7.88 (m, 3H), 7.56 – 7.41 (m, 2H), 7.34 – 7.17 (m, 5H), 4.24 – 3.70 (m, 3H), 3.39 – 3.23 (m, 2H). 13 C NMR (101 MHz, CDCl3) δ 190.5, 143.1,142.8, 139.3, 139.0, 129.7, 128.4, 128.3, 127.8, 127.3, 126.7 (q, J = 284.4Hz), 126.2, 125.2, 123.0, 55.9 (q, J = 28.5 Hz), 52.4, 39.0. 19 F NMR (376 MHz, CDCl3) δ -74.49 (d, J = 6.9 Hz). HRMS (ESI): Calcd for C 19 H 17 F3NOS [M+H] + :364.0977; Found: 364.0984.

[0030] The reaction formula is as follows:

[0031] Example 8 Cobalt bromide, 1,2-bis(diphenylphosphino)benzene, and 1 mL of solvent were added to a 10 mL dry vial equipped with a magnetic stopper. The mixture was stirred at room temperature for 0.5 h to allow ligand coordination. In another 10 mL vial equipped with a magnetic stopper, bromoacetone and a photocatalyst were added sequentially. The vial was sealed with a rubber stopper and purged with nitrogen. The reaction should be carried out under anaerobic conditions. After nitrogen purging, the above cobalt bromide / 1,2-bis(diphenylphosphino)benzene solution and trifluorodiazoethane were added. The mixture was irradiated and stirred in a blue LED photoreactor with an internal fan for 1–24 h. The reaction was monitored by thin-layer chromatography (TLC). After the photoreaction was complete, Et3N and benzylamine reagent were added. The mixture was stirred at room temperature for 1–24 h. The reaction was monitored by TLC, and column chromatography was used for separation, eluting with a petroleum ether and ethyl acetate system (50:1 to 10:1). 22.1 mg of a yellow oily substance was obtained, with a yield of 45%. Spectroscopic analysis of the product was performed. 1 H NMR (400 MHz, CDCl3) δ 7.41 – 7.23 (m, 5H), 4.01 (dd, J = 12.8, 1.2 Hz, 1H), 3.89 (d, J = 12.8 Hz, 1H), 3.80 – 3.67 (m,1H), 2.78 (dd, J = 17.0, 3.8 Hz, 1H), 2.67 (dd, J = 17.0, 9.1 Hz, 1H), 2.19(s, 3H). 13 C NMR (101 MHz, CDCl3) δ 204.5, 139.4, 128.5, 128.3, 127.4, 126.6(q, J = 283.9 Hz), 55.3 (q, J = 28.3 Hz), 52.3, 43.2, 30.5. 19 F NMR (376 MHz, CDCl3) δ -74.47 (d, J = 7.4 Hz). HRMS (ESI): Calcd for C 12 H 15 F3NO [M+H] + :246.1100; Found: 246.1114.

[0032] The reaction formula is as follows:

[0033] Example 9 Cobalt bromide, 1,2-bis(diphenylphosphino)benzene, and 1 mL of solvent were added to a 10 mL dry vial equipped with a magnetic stopper. The mixture was stirred at room temperature for 0.5 h to allow ligand coordination. In another 10 mL vial equipped with a magnetic stopper, phenyl bromoacetate and a photocatalyst were added sequentially. The vial was sealed with a rubber stopper and purged with nitrogen. The reaction should be carried out under anaerobic conditions. After nitrogen purging, the above cobalt bromide / 1,2-bis(diphenylphosphino)benzene solution and trifluorodiazoethane were added. The mixture was irradiated and stirred in a blue LED photoreactor with an internal fan for 1–24 h. The reaction was monitored by thin-layer chromatography (TLC). After the photoreaction was complete, Et3N and benzylamine reagent were added. The mixture was stirred at room temperature for 1–24 h. The reaction was monitored by TLC, and column chromatography was used for separation, eluting with a petroleum ether and ethyl acetate system (50:1 to 10:1). 33.6 mg of a yellow oily substance was obtained, with a yield of 52%. Spectroscopic analysis of the product was performed. 1 H NMR (400 MHz, CDCl3) δ 7.46 – 7.32 (m,6H), 7.32 – 7.24 (m, 2H), 7.14 – 7.06 (m, 2H), 4.12 (d, J = 13.0 Hz, 1H), 3.96 (d, J = 13.0 Hz, 1H), 3.90 – 3.77 (m, 1H), 2.99 (dd, J = 15.5, 4.2 Hz, 1H), 2.79 (dd, J = 15.5, 9.7 Hz, 1H). 13 C NMR (101 MHz, CDCl3) δ 168.7, 150.4,139.3, 129.5, 128.5, 128.3, 127.4, 126.3 (q, J = 284.7 Hz), 126.1, 121.4,56.4 (q, J = 28.5 Hz), 52.0, 35.3. 19 F NMR (376 MHz, CDCl3) δ -74.53 (d, J =6.9 Hz). HRMS (ESI): Calcd for C 17 H 17 F3NO2 [M+H] + : 324.1206; Found: 324.1210.

[0034] The reaction formula is as follows:

[0035] Example 10 Cobalt bromide, 1,2-bis(diphenylphosphino)benzene, and 1 mL of solvent were added to a 10 mL dry vial equipped with a magnetic stopper. The mixture was stirred at room temperature for 0.5 h to allow ligand coordination. In another 10 mL vial equipped with a magnetic stopper, diethyl bromide and a photocatalyst were added sequentially. The vial was sealed with a rubber stopper and purged with nitrogen. The reaction should be carried out under anaerobic conditions. After nitrogen purging, the above cobalt bromide / 1,2-bis(diphenylphosphino)benzene solution and trifluorodiazoethane were added. The mixture was irradiated and stirred in a blue LED photoreactor with an internal fan for 1–24 h. The reaction was monitored by thin-layer chromatography (TLC). After the photoreaction was complete, Et3N and benzylamine reagent were added. The mixture was stirred at room temperature for 1–24 h. The reaction was monitored by TLC, and column chromatography was used for separation, eluting with a petroleum ether and ethyl acetate system (50:1 to 10:1). 44.6 mg of a yellow oily substance was obtained, with a yield of 64%. Product spectral analysis 1 H NMR (400 MHz, CDCl3) δ 7.38 – 7.24(m, 5H), 4.43 – 4.15 (m, 4H), 4.11 – 4.02 (m, 1H), 4.02 – 3.86 (m, 2H), 3.77– 3.71 (m, 1H), 2.42 (s, 1H), 1.38 – 1.22 (m, 6H). 13 C NMR (101 MHz, CDCl3) δ166.7, 166.6, 139.3, 128.3, 128.2, 127.3, 126.9 (q, J = 285.9 Hz), 62.2,61.9, 58.8 (q, J = 28.4 Hz), 52.4, 52.1, 14.0, 13.9. 19 F NMR (376 MHz, CDCl3)δ -72.18 (d, J = 7.3 Hz). HRMS (ESI): Calcd for C 16 H 21 F3NO4 [M+H] + : 348.1417;Found: 348.1427.

[0036] The reaction formula is as follows:

[0037] Example 11 Cobalt bromide, 1,2-bis(diphenylphosphino)benzene, and 1 mL of solvent were added to a 10 mL dry vial equipped with a magnetic stopper. The mixture was stirred at room temperature for 0.5 h to allow ligand coordination. In another 10 mL vial equipped with a magnetic stopper, 2-bromoacetophenone and a photocatalyst were added sequentially. The vial was sealed with a rubber stopper and purged with nitrogen. The reaction should be carried out under anaerobic conditions. After nitrogen purging, the above cobalt bromide / 1,2-bis(diphenylphosphino)benzene solution and trifluorodiazoethane were added. The mixture was irradiated and stirred in a blue LED photoreactor with an internal fan for 1–24 h. The reaction was monitored by thin-layer chromatography (TLC). After the photoreaction was complete, Et3N and N-methylbenzylamine reagents were added. The mixture was stirred at room temperature for 1–24 h. The reaction was monitored by TLC, and column chromatography was used for separation, eluting with a petroleum ether and ethyl acetate system (50:1 to 10:1). 58 mg of a yellow oily substance was obtained, with a yield of 90%. Product spectral analysis 1 H NMR (400 MHz, CDCl3) δ 8.08 – 7.96(m, 2H), 7.73 – 7.44 (m, 3H), 7.27 – 7.14 (m, 5H), 4.19 (td, J = 8.8, 4.0 Hz, 1H), 3.86 (q, J = 13.7 Hz, 2H), 3.50 (dd, J = 16.7, 9.1 Hz, 1H), 3.17 (dd, J = 16.7, 4.0 Hz, 1H), 2.36 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 196.1, 139.0,136.7, 133.5, 128.8, 128.4, 128.3, 128.2, 127.3 (q, J = 289.7 Hz), 127.1,60.8 (q, J = 26.4 Hz), 37.0, 35.5. 19 F NMR (376 MHz, CDCl3) δ -69.32 (d, J =8.7 Hz). HRMS (ESI): Calcd for C 18 H 19 F3NO [M+H] +: 322.1413; Found: 322.1413.

[0038] The reaction formula is as follows:

[0039] Example 12 Cobalt bromide, 1,2-bis(diphenylphosphine)benzene, and 1 mL of solvent were added to a 10 mL dry vial equipped with a magnetic stopper. The mixture was stirred at room temperature for 0.5 h to allow ligand coordination. In another 10 mL vial equipped with a magnetic stopper, 2-bromoacetophenone and a photocatalyst were added sequentially. The vial was sealed with a rubber stopper and purged with nitrogen. The reaction should be carried out under anaerobic conditions. After nitrogen purging, the above cobalt bromide / 1,2-bis(diphenylphosphine)benzene solution and trifluorodiazoethane were added. The mixture was irradiated and stirred in a blue LED photoreactor with an internal fan for 1–24 h. The reaction was monitored by thin-layer chromatography (TLC). After the photoreaction was complete, Et3N and 2-thiophene methylamine reagent were added. The mixture was stirred at room temperature for 1–24 h. The reaction was monitored by TLC, and column chromatography was used for separation, eluting with a petroleum ether and ethyl acetate system (50:1 to 10:1). 62.7 mg of a yellow oily substance was obtained, with a yield of 99%. Product spectral analysis 1 H NMR (400 MHz, CDCl3) δ 8.01 – 7.93(m, 2H), 7.67 – 7.58 (m, 1H), 7.56 – 7.47 (m, 2H), 7.23 – 7.17 (m, 1H), 6.98– 6.89 (m, 2H), 4.23 (d, J = 13.8 Hz, 1H), 4.15 (d, J = 13.7 Hz, 1H), 4.06 –3.93 (m, 1H), 3.37 – 3.19 (m, 2H). 13 C NMR (101 MHz, CDCl3) δ 196.0, 143.0,136.4, 133.6, 128.8, 128.2, 126.8 (q, J = 284.6 Hz), 126.6, 125.3, 124.8,55.3 (q, J = 28.5 Hz), 47.1, 38.5. 19 F NMR (376 MHz, CDCl3) δ -74.47 (d, J =7.1 Hz). HRMS (ESI): Calcd for C15 H 15 F3NOS [M+H] + : 314.0821; Found: 314.0819.

[0040] The reaction formula is as follows:

[0041] Example 13 Cobalt bromide, 1,2-bis(diphenylphosphino)benzene, and 1 mL of solvent were added to a 10 mL dry vial equipped with a magnetic stopper. The mixture was stirred at room temperature for 0.5 h to allow ligand coordination. In another 10 mL vial equipped with a magnetic stopper, 2-bromoacetophenone and a photocatalyst were added sequentially. The vial was sealed with a rubber stopper and purged with nitrogen. The reaction should be carried out under anaerobic conditions. After nitrogen purging, the above cobalt bromide / 1,2-bis(diphenylphosphino)benzene solution and trifluorodiazoethane were added. The mixture was irradiated and stirred in a blue LED photoreactor with an internal fan for 1–24 h. The reaction was monitored by thin-layer chromatography (TLC). After the photoreaction was complete, Et3N and indole-3-propylamine reagent were added. The mixture was stirred at room temperature for 1–24 h. The reaction was monitored by TLC, and column chromatography was used for separation, eluting with a petroleum ether and ethyl acetate system (50:1 to 10:1). 51.1 mg of a yellow oily substance was obtained, with a yield of 70%. Product spectral analysis 1 H NMR (400 MHz, CDCl3) δ 8.02 –7.95 (m, 3H), 7.64 – 7.57 (m, 2H), 7.56 – 7.48 (m, 2H), 7.39 – 7.33 (m, 1H),7.27 – 7.09 (m, 2H), 6.99 – 6.94 (m, 1H), 3.91 (pd, J = 7.7, 4.0 Hz, 1H), 3.34 – 3.17 (m, 2H), 2.93 (dt, J = 13.1, 6.9 Hz, 1H), 2.82 (dt, J = 19.3, 7.2Hz, 3H), 1.88 (p, J = 7.1 Hz, 2H), 1.46 (s, 1H). 13 C NMR (101 MHz, CDCl3) δ196.4, 136.5, 136.4, 133.7, 128.8, 128.2, 127.5, 126.8 (q, J= 283.6 Hz),121.8, 121.4, 119.1, 118.9, 116.1, 111.1, 56.1 (q, J = 28.2 Hz), 48.0, 38.4,30.6, 22.4. 19 F NMR (376 MHz, CDCl3) δ -74.66 (d, J = 7.5 Hz). HRMS (ESI):Calcd for C 21 H 22 F3N2O [M+H] + : 375.1679; Found: 375.1692.

[0042] The reaction formula is as follows:

[0043] Example 14 Cobalt bromide, 1,2-bis(diphenylphosphino)benzene, and 1 mL of solvent were added to a 10 mL dry vial equipped with a magnetic stopper. The mixture was stirred at room temperature for 0.5 h to allow ligand coordination. In another 10 mL vial equipped with a magnetic stopper, 2-bromoacetophenone and a photocatalyst were added sequentially. The vial was sealed with a rubber stopper and purged with nitrogen. The reaction should be carried out under anaerobic conditions. After nitrogen purging, the above cobalt bromide / 1,2-bis(diphenylphosphino)benzene solution and trifluorodiazoethane were added. The mixture was irradiated and stirred in a blue LED photoreactor with an internal fan for 1–24 h. The reaction was monitored by thin-layer chromatography (TLC). After the photoreaction was complete, Et3N and aniline reagent were added. The mixture was stirred at room temperature for 1–24 h. The reaction was monitored by TLC, and column chromatography was used for separation, eluting with a petroleum ether and ethyl acetate system (50:1 to 10:1). 49.8 mg of a yellow oily substance was obtained, with a yield of 85%. Product spectral analysis 1 H NMR (400 MHz, CDCl3) δ 8.01 – 7.94 (m,2H), 7.67 – 7.59 (m, 1H), 7.55 – 7.47 (m, 2H), 7.29 – 7.18 (m, 3H), 6.87 –6.75 (m, 3H), 4.86 (m, 1H), 3.85 (d, J = 10.0 Hz, 1H), 3.44 (dd, J = 17.2, 4.5 Hz, 1H), 3.37 (dd, J = 17.2, 7.7 Hz, 1H).13 C NMR (101 MHz, CDCl3) δ195.2, 145.8, 136.3, 133.8, 129.4, 128.8, 128.2, 126.1 (q, J = 281.5 Hz),119.4, 114.0, 52.4 (q, J = 30.1 Hz), 38.4. 19 F NMR (376 MHz, CDCl3) δ -75.61(d, J = 7.2 Hz). HRMS (ESI): Calcd for C 16 H 15 F3NO [M+H] + : 294.1100; Found:294.1099.

[0044] The reaction formula is as follows:

[0045] Example 15 Add cobalt bromide, 1,2-bis(diphenylphosphino)benzene, and 1 mL of solvent to a 10 mL dry vial equipped with a magnetic swivel. Stir the mixture at room temperature for 0.5 h to allow ligand coordination. In another 10 mL vial equipped with a magnetic swivel, add 2-bromoacetophenone and the photocatalyst sequentially, seal with a rubber stopper, and purge with nitrogen. The reaction should be carried out under anaerobic conditions. After nitrogen purging, add the aforementioned cobalt bromide / 1,2-bis(diphenylphosphino)benzene solution and trifluorodiazoethane. Irradiate the mixture in a blue LED photoreactor with an internal fan and stir for 1–24 h. The reaction can be monitored by thin-layer chromatography (TLC). After the photoreaction is complete, add Et3N and 1,2,4-triazole reagent. Stir the mixture at room temperature for 1–24 h. Monitor the reaction by TLC, using column chromatography with elution in a petroleum ether and ethyl acetate system (50:1 to 10:1). 27.9 mg of a yellow oily substance was isolated, with a yield of 52%. 1 H NMR (400 MHz, CDCl3) δ 8.35 (s, 1H), 8.03 –7.93 (m, 3H), 7.68 – 7.59 (m, 1H), 7.57 – 7.45 (m, 2H), 5.66 (m, 1H), 4.42(dd, J = 18.1, 10.2 Hz, 1H), 3.57 (dd, J = 18.1, 2.6 Hz, 1H). 13C NMR (101MHz, CDCl3) δ 193.5, 152.5, 145.5, 135.3, 134.3, 128.9, 128.2, 123.5 (q, J =280.7 Hz), 56.3 (d, J = 32.7 Hz), 35.9. 19 F NMR (376 MHz, CDCl3) δ -74.03 (d, J = 7.4 Hz). HRMS (ESI): Calcd for C 12 H 11 F3N3O [M+H] + : 270.0849; Found:270.0848.

[0046] The reaction formula is as follows:

[0047] Example 16 Cobalt bromide, 1,2-bis(diphenylphosphino)benzene, and 1 mL of solvent were added to a 10 mL dry vial equipped with a magnetic stopper. The mixture was stirred at room temperature for 0.5 h to allow ligand coordination. In another 10 mL vial equipped with a magnetic stopper, 2-bromoacetophenone and a photocatalyst were added sequentially. The vial was sealed with a rubber stopper and purged with nitrogen. The reaction should be carried out under anaerobic conditions. After nitrogen purging, the above cobalt bromide / 1,2-bis(diphenylphosphino)benzene solution and trifluorodiazoethane were added. The mixture was irradiated and stirred in a blue LED photoreactor with an internal fan for 1–24 h. The reaction was monitored by thin-layer chromatography (TLC). After the photoreaction was complete, Et3N and ammonia were added. The mixture was stirred at room temperature for 1–24 h. The reaction was monitored by TLC, and column chromatography was used for separation, eluting with a petroleum ether and ethyl acetate system (50:1 to 10:1). 34.8 mg of a yellow oily substance was obtained, with a yield of 80%. 1 H NMR (400 MHz, CDCl3) δ 8.01 – 7.95 (m, 2H), 7.67 –7.58 (m, 1H), 7.55 – 7.47 (m, 2H), 4.09 – 3.97 (m, 1H), 3.34 (dd, J = 17.5, 2.7 Hz, 1H), 3.20 (dd, J = 17.5, 9.7 Hz, 1H), 1.66 (s, 2H). 13C NMR (101 MHz, CDCl3) δ 196.2, 136.4, 133.7, 128.8, 128.1, 126.5 (q, J = 279.3 Hz), 50.2 (q, J = 29.8 Hz), 39.3. 19 F NMR (376 MHz, CDCl3) δ -78.24 (d, J = 7.5 Hz). HRMS(ESI): Calcd for C 10 H 11 F3NO [M+H] + : 218.0787; Found: 218.0784.

[0048] The reaction formula is as follows:

[0049] Example 17 Add cobalt bromide, 1,2-bis(diphenylphosphine)benzene, and 1 mL of solvent to a 10 mL dry vial equipped with a magnetic stopper. Stir the mixture at room temperature for 0.5 h to allow ligand coordination. In another 10 mL vial equipped with a magnetic stopper, add 2-bromoacetophenone and the photocatalyst sequentially, seal with a rubber stopper, and purge with nitrogen. The reaction should be carried out under anaerobic conditions. After nitrogen purging, add the aforementioned cobalt bromide / 1,2-bis(diphenylphosphine)benzene solution and trifluorodiazoethane. Irradiate the mixture in a blue LED photoreactor with an internal fan and stir for 1–24 h. The reaction can be monitored by thin-layer chromatography (TLC). After the photoreaction is complete, add Et3N and tetrahydro-1,4-oxazine reagent. Stir the mixture at room temperature for 1–24 h. Monitor the reaction by TLC, using column chromatography with elution in a petroleum ether and ethyl acetate system (50:1 to 10:1). 56.6 mg of a yellow oily substance was isolated, with a yield of 98%. 1 H NMR (400 MHz, CDCl3) δ 8.01 – 7.94 (m,2H), 7.67 – 7.58 (m, 1H), 7.57 – 7.45 (m, 2H), 4.04 – 3.90 (m, 1H), 3.65 –3.50 (m, 4H), 3.43 (dd, J = 16.8, 9.0 Hz, 1H), 3.10 (dd, J= 16.8, 4.0 Hz,1H), 2.90 – 2.80 (m, 2H), 2.77 – 2.67 (m, 2H). 13 C NMR (101 MHz, CDCl3) δ196.0, 136.6, 133.5, 128.8, 128.0, 126.78 (q, J = 288.7 Hz), 61.5 (q, J =26.6 Hz), 67.5, 50.0, 34.8. 19 F NMR (376 MHz, CDCl3) δ -69.52 (d, J = 8.3 Hz).HRMS (ESI): Calcd for C 14 H 17 F3NO2 [M+H] + : 288.1206; Found: 288.1205.

[0050] The reaction formula is as follows:

[0051] In summary, the present invention has the following advantages: 1. The synthesis method provided by this invention has the advantages of simple operation, high yield, easy product separation and purification, low cost and low environmental pollution.

[0052] 2. The synthesis method of the present invention has a wide range of applicable substrates and good functional group compatibility, and has good application prospects; that is, the present invention has great theoretical innovation value and implementation value.

[0053] It is understood that the above detailed description of the present invention is for illustrative purposes only and is not intended to limit the technical solutions described in the embodiments of the present invention. Those skilled in the art should understand that modifications or equivalent substitutions can still be made to the present invention to achieve the same technical effects; as long as the usage requirements are met, they are all within the protection scope of the present invention.

Claims

1. A method for photocatalytic synthesis of α-trifluoromethylamine compounds, characterized in that: The reaction includes the following steps: In the presence of a photocatalyst, compound II and compound III undergo a photocatalytic reaction in an organic solvent. After the first step reaction is completed, compound IV is added to react and yield compound I. The reaction equation is as follows: Among them, R in compound III 1 for , , , , One of them; R 2 For H or ; The compound IV is used or , wherein R in 3 for , , , , , , , , One of H; R4 is H or CH3; The C O In X2, X is either Cl or Br; The R 1 Z in the equation represents O or S, and R represents... 1-1 It is one of H, 4-Me, 4-Cl, 4-MeO, 4-Ph, 4-AcO, 4-CN, 4-CO2Me, 3-Cl, and 2-Cl; R 1-2 It is one of PhO, BnO, and EtO; The R 3 R in 3-1 It is 4-Br or H; R 3-2 for , , One of them; R 3-3 For CH2CH3, CH2Br, OH, CN, NHBoc, One of them; R 3-4 It is either H or 4-OH.

2. The method for photocatalytic synthesis of α-trifluoromethylamine compounds according to claim 1, characterized in that: The photocatalyst is one of the following: tri(2-phenylpyridine)iridium, (4,4'-di-tert-butyl-2,2'-bipyridine)bis[(2-pyridyl)phenyl]iridium(III) hexafluorophosphate, 2,4,5,6-tetra(9-carbazolyl)-isophthalonitrile, eosin Y, and tripyridine ruthenium chloride hexahydrate.

3. The method for photocatalytic synthesis of α-trifluoromethylamine compounds according to claim 1, characterized in that: The photocatalytic reaction takes place in a nitrogen atmosphere at a temperature of 20-30°C, and the photocatalyst uses 3-10W blue light.

4. The method for photocatalytic synthesis of α-trifluoromethylamine compounds according to claim 1, characterized in that: The organic solvent for the photocatalytic reaction is one of acetone, methanol, dichloromethane, and acetonitrile.

5. The method for photocatalytic synthesis of α-trifluoromethylamine compounds according to claim 1, characterized in that: The post-processing of compound I includes rotary evaporation and column chromatography separation.

6. The method for photocatalytic synthesis of α-trifluoromethylamine compounds according to claim 5, characterized in that: The rotary evaporation was performed in a rotary evaporator, and the column chromatography separation was performed using silica gel column chromatography.

7. The method for photocatalytic synthesis of α-trifluoromethylamine compounds according to claim 1, characterized in that: The specific methods for the synthesis include: Step 1: Add cobalt halide, 1,2-bis(diphenylphosphino)benzene and 1 mL organic solvent to a 10 mL vial with a magnetic ball. Stir the mixture at room temperature for 0.5 h to allow the ligands to coordinate. Step 2: Take a 10 mL vial with a magnetic ferrule and add compound III and photocatalyst in sequence. Seal the vial with a rubber stopper and replace it with nitrogen to create an oxygen-free environment. Then, add the cobalt halide / 1,2-bis(diphenylphosphino)benzene solution from step 1 and compound II to obtain a mixture. Step 3: The mixture is irradiated and stirred in a blue LED photoreactor with an internal fan for 1-24 h, and the reaction is monitored by thin-layer chromatography. After the photoreaction is completed, triethylamine and compound IV are added, and the mixture is stirred at room temperature for 1-24 h. The reaction is detected by thin-layer chromatography to obtain crude compound I. Step 4: The crude compound I is subjected to column chromatography to obtain the product. The eluent in the column chromatography is a petroleum ether-ethyl acetate system, and the volume ratio of petroleum ether to ethyl acetate is 10-50:

1.

8. The method for photocatalytic synthesis of α-trifluoromethylamine compounds according to claim 7, characterized in that: In the synthesis method, the molar ratio of compound II, compound III, amine compound IV, photocatalyst, cobalt halide, 1,2-bis(diphenylphosphine)benzene, and triethylamine is 2.5:1.25:1:0.01-0.03:0.05:0.05:1-2.

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