A method for synthesizing trifluoromethyl-substituted aniline using a tetradentate platinum complex as a photocatalyst

Abstract

The application relates to a method for directly trifluoromethylating aniline compounds to synthesize trifluoromethylaniline derivatives by using visible light catalysis. A tetradentate platinum (II) complex Pt (1-ptz) is used as a photocatalyst, Umemoto reagent or Langlois reagent (CF3SO2Na) is used as a trifluoromethyl source, and direct trifluoromethylation of aniline compounds is realized under visible light irradiation. The reaction does not need to use an oxidation-reduction reagent, and naked amino groups are not needed to be protected, and meanwhile, photocatalyst recycling and reuse are realized.

Description

Technical Field

[0001] This invention relates to the fields of photochemistry and pharmaceutical synthesis, specifically to a method for directly trifluoromethylating aniline compounds under visible light irradiation using a tetradentate platinum(II) complex Pt(1-ptz) as a photocatalyst and Umemoto reagent or Langlois reagent as a trifluoromethyl source, thereby preparing trifluoromethyl-substituted aniline derivatives. Background Technology

[0002] Introducing a trifluoromethyl group with strong electron-withdrawing ability into candidate drug molecules significantly alters the molecule's polarity, lipophilicity, metabolic stability, and chemical stability. Drugs containing trifluoromethyl groups exhibit higher metabolic stability and are more easily absorbed by the body, thus requiring significantly lower dosages. Therefore, trifluoromethyl-containing drug molecules play a crucial role in the pharmaceutical industry. Trifluoromethyl-substituted aniline derivatives are an important class of pharmaceutical intermediates, such as 4-trifluoromethylaniline (an intermediate in the antirheumatic drug leflunomide), 4-trifluoromethylaniline (an intermediate in the antiangiogenic agent taquimod), 2-trifluoromethyl-6-chloroaniline (an intermediate in the bronchodilator mabuterol), 4-chloro-3-trifluoromethylaniline (an intermediate in the antitumor drug sorafenib), and 4-chloro-2-trifluoromethylaniline (an intermediate in the fungicide fluocinolone acetonide).

[0003]

[0004] The effective introduction of trifluoromethyl groups into organic molecules has attracted widespread attention from organic chemists. Compared to nucleophilic and electrophilic methods for introducing trifluoromethyl groups into molecules, photocatalytic radical trifluoromethylation synthesis offers advantages such as being environmentally friendly, having high atom economy, and requiring no additional redox reagents. Visible light photocatalysis is becoming one of the essential strategies for organic synthesis. my country has abundant and renewable visible light resources, and visible light photocatalysis offers mild reaction conditions and high efficiency. Visible light photoredox catalysis has significant advantages over traditional synthetic methods in many aspects.

[0005] In 2014, the literature Org. Lett. 2014, 16, 1768–1771 reported a method for introducing trifluoromethyl groups into trifluoromethyl aromatic amines using photocatalysis of tri(2-phenylpyridine)iridium; the patent with publication number CN103553857B disclosed a method for preparing o-trifluoromethylaniline or its derivatives, which uses aromatic amines and trivalent iodine reagent compounds as raw materials, tri(2-phenylpyridine)iridium as catalyst, and reacts under light conditions to obtain o-trifluoromethylaniline or its derivatives.

[0006] Currently, the most widely used photocatalysts are cyclic iridium(III) complexes. However, iridium is expensive, and iridium(III) complexes are difficult to recycle after photocatalytic reactions, which greatly increases costs and hinders large-scale industrial production. Tetradentate platinum(II) complexes have been widely used in OLED luminescent materials due to their excellent performance (Adv. Mater., 2020, DIO:10.1002 / adma.202004873), but there are few reports on their use as efficient photocatalysts in photochemical reactions. Patent CN103980322B discloses the use of tridentate platinum(II) complexes, which are triplet-triplet annihilation upconversion luminescent materials, for photocatalytic reactions. In 2015, Professor Zhiming Zhi reported intramolecular dehalogenation cyclization reactions catalyzed by tridentate cyclic metal Pt(C^N^N)X complexes and the reductive self-coupling reactions of benzyl chloride and hexane (Angew. Chem. Int. Ed. 2015, 54, 2112–2117). Unlike octahedral iridium(III) cyclic metal complexes, the central metal ion of cyclic platinum(II) cyclic metal complexes forms a planar quadrilateral configuration with dsp2 hybrid orbitals. Compared to bidentate and tridentate ligands, suitable tetradentate ligands can match well with platinum(II) ions to form complexes with planar or near-planar configurations. This not only improves their chemical and thermal stability, allowing them to maintain their structure after photocatalytic reactions, which is beneficial for recycling, but also significantly increases their quantum efficiency, even reaching 100%. In addition, the content of platinum in the Earth's crust and the annual production worldwide are about ten times that of iridium. The price of IrCl3.H2O (1100 yuan / gram) used to prepare iridium(III) complexes is also much higher than that of PtCl2 (210 yuan / gram) used to prepare platinum(II) complexes. Summary of the Invention

[0007] The purpose of this invention is to provide a photocatalytic synthesis method for trifluoromethylation products that is simple in system, mild in reaction conditions, low in cost, and can be prepared in large quantities, aiming to solve the problems of high pollution and high cost in industrial trifluoromethylation reactions. This invention features mild synthesis conditions, inexpensive and readily available raw materials, recyclable and reusable photocatalysts, and low environmental pollution. Combined with a continuous flow reaction, it allows for large-scale industrial production and has significant economic and social benefits.

[0008] To achieve the technical objective of this invention, the technical solution of this invention is as follows:

[0009] This invention utilizes Umemoto or Langlois reagents as trifluoromethyl sources and the tetradentate platinum(II) complex Pt(1-ptz) as a photocatalyst to achieve direct trifluoromethylation of aniline compounds under visible light irradiation. This reaction requires no additional redox reagents, and the reaction equation is as follows:

[0010]

[0011] In the visible light catalytic trifluoromethylation process of this invention, R1 is selected from hydrogen, alkyl, alkoxy, acyloxy, ester, ketone, halogen, haloalkyl, cyano, etc., and R2 is selected from hydrogen, alkyl, halogen, amino, etc.

[0012] In the visible light catalytic trifluoromethylation process of this invention, the molar ratio of the raw material aniline compound, the trifluoromethylation reagent, and the photocatalyst is 1:1 to 4:0.005 to 0.05.

[0013] In the visible light catalytic trifluoromethylation process of the present invention, the solvent is one of acetonitrile, dimethyl sulfoxide, N,N-dimethylformamide, 1,4-dioxane, and dichloromethane, preferably acetonitrile; the concentration of aniline compounds in the solvent is 0.1-1 mol / L, preferably 0.2-0.3 mol / L.

[0014] In the visible light catalytic trifluoromethylation process of this invention, the trifluoromethylating reagent is one of 2,8-difluoro-5-(trifluoromethyl)-5H-dibenzo[b,d]thiophene-5-trifluoromethanesulfonate (Umemoto reagent) or sodium trifluoromethylsulfinate (Langlois reagent).

[0015] In the visible light photocatalytic trifluoromethylation process of the present invention, the photocatalyst is a tetradentate platinum(II) complex, preferably Pt(1-ptz).

[0016] In the visible light catalytic trifluoromethylation process of the present invention, the wavelength of the visible light irradiation is 400-760 nm, preferably 400-500 nm; the reaction temperature is 10-60℃, preferably 20-30℃; and the reaction time is 5-24 hours.

[0017] In the visible light catalytic trifluoromethylation process of this invention, by adding water of the same volume as the reaction solvent, the platinum(II) complex is precipitated from the solvent, and then filtered and purified to achieve the purpose of recycling.

[0018] In the visible light catalytic trifluoromethylation process of this invention, the extraction solvent is ethyl acetate, and the drying agent is anhydrous sodium sulfate.

[0019] In the visible light photocatalytic trifluoromethylation process of this invention, the concentration is carried out under reduced pressure. The separation and purification method used is column chromatography.

[0020] Based on the different substituents in the aniline compound raw materials, and referring to the above synthesis method, the following trifluoromethyl substituted aniline derivatives can be synthesized:

[0021]

[0022] The process for preparing trifluoromethyl-substituted aniline derivatives in this invention has the following technical advantages: Using a platinum(II) complex with a central metal price approximately 1 / 5 that of iridium as a visible light photocatalyst, direct trifluoromethylation of aniline compounds is achieved without the need for amino group protection and deprotection. This green and environmentally friendly method directly introduces the trifluoromethyl group into the molecule, achieving a high yield (58%–82%). It avoids the use of highly toxic and corrosive fluorine gas or hydrofluoric acid, as well as redox reagents. Furthermore, it enables the recycling and reuse of the photocatalyst, significantly reducing the cost of the photocatalytic reaction. Therefore, compared with existing technologies, this project has advantages such as high efficiency and simplicity, environmental friendliness, low cost, and good industrial applicability, demonstrating significant process reliability and technological advancement. Detailed Implementation

[0023] To better understand the content of this invention, further explanation is provided below with reference to specific embodiments. However, the specific embodiments are not intended to limit the scope of this invention. The tetradentate platinum(II) complex Pt(1-ptz) was synthesized according to the method described in the literature (Chem. Mater. 2020, 32, 537), and will not be described in detail here.

[0024] Example 1: Preparation of 2-trifluoromethylaniline and 4-trifluoromethylaniline

[0025] Aniline (466 mg, 5.00 mmol, 1.0 equiv), 2,8-difluoro-5-(trifluoromethyl)-5H-dibenzo[b,d]thiophene-5-trifluoromethanesulfonate (4383 mg, 10.00 mmol, 2.0 equiv), and the platinum(II) complex Pt(1-ptz) (30 mg, 0.05 mmol, 0.01 equiv) were weighed and added to a sealed tube. Acetonitrile (20 mL) was added, and the mixture was purged with nitrogen three times. The reaction was stirred under a 450 nm blue LED lamp, with the reaction temperature controlled at 20–30 °C and the reaction time at 10–15 hours. The reaction progress was monitored by TLC (petroleum ether: ethyl acetate = 2:1). After the reaction was complete, water (20 mL) was added, the catalyst was recovered by filtration, and the filtrate was extracted with ethyl acetate (20 mL × 2). The organic phases were combined, washed with 10% brine (20 mL × 2), dried over anhydrous sodium sulfate, and concentrated. The crude product was separated by silica gel column chromatography using petroleum ether / ethyl acetate as eluent to give 484 mg of the target product 2-trifluoromethylaniline in oil, with a yield of 60.0%. 1 H-NMR (400MHz, CDCl3): δ7.44(d,J=7.8Hz,1H), 7.30(t,J=7.7Hz,1H), 6.79(t,J=7.7Hz,1H), 6.74(d,J=8.2Hz,1H), 4.16(s,2H).19 F-NMR (400MHz, CDCl3): δ-62.7ppm; 173 mg of the target product 4-trifluoromethylaniline was also obtained in oil, with a yield of 21.5%. 1 H-NMR (400MHz, CDCl3): δ9.73 (s, 1H), 7.40 (d, J = 8.4Hz, 2H), 6.68 (d, J = 4.2Hz, 2H), 3.95 (s, 2H). 19 F-NMR (400MHz, CDCl3): δ-61.1ppm.

[0026] Example 2: Preparation of 4-amino-3-trifluoromethylacetanilide

[0027] Weigh 751 mg of 4-aminoacetanilide (5.00 mmol, 1.0 equiv), 2,8-difluoro-5-(trifluoromethyl)-5H-dibenzo[b,d]thiophene-5-trifluoromethanesulfonate (4383 mg, 10.00 mmol, 2.0 equiv), and Pt(1-ptz) (30 mg, 0.05 mmol, 0.01 equiv) into a sealed tube, add 20 mL of acetonitrile, purge with nitrogen three times, stir under a 450 nm blue LED lamp, maintain the reaction temperature at 20–30 °C, and react for 10–15 hours. Monitor the reaction progress by TLC (petroleum ether: ethyl acetate = 2:1). After the reaction was completed, water (20 mL) was added, the catalyst was recovered by filtration, the filtrate was extracted with ethyl acetate (20 mL × 2), the organic phases were combined, the organic phases were washed with 10% brine (20 mL × 2), and then dried with anhydrous sodium sulfate. After concentration, the crude product was separated by silica gel column chromatography using petroleum ether / ethyl acetate as eluent to obtain 795 mg of the target product 4-amino-3-trifluoromethylacetanilide, with a yield of 73.2%. 1 H-NMR (400MHz, DMSO-d6): δ9.73(s,1H),7.66(d,J=2.4Hz,1H),7.38(dd,J=8.8,2.4Hz,1H),6.77(d,J=8.8Hz,1H),5.32(s,2H),1.97(s,3H). 19 F-NMR (400MHz, DMSO-d6): δ-61.5ppm.

[0028] Example 3: Preparation of 4-amino-3-trifluoromethylacetanilide

[0029] Weigh 751 mg of 4-aminoacetanilide (5.00 mmol, 1.0 equiv), sodium trifluoromethyl sulfinate (1561 mg, 10.00 mmol, 2.0 equiv), and Pt(1-ptz) (30 mg, 0.05 mmol, 0.01 equiv) into a sealed tube, add 20 mL of acetonitrile, purge with nitrogen three times, stir under a 450 nm blue LED lamp, maintain the reaction temperature at 40–50 °C, and react for 15–24 hours. Monitor the reaction progress by TLC (petroleum ether: ethyl acetate = 2:1). After the reaction was completed, water (20 mL) was added, the catalyst was recovered by filtration, the filtrate was extracted with ethyl acetate (20 mL × 2), the organic phases were combined, the organic phases were washed with 10% brine (20 mL × 2), and then dried with anhydrous sodium sulfate. After concentration, the crude product was separated by silica gel column chromatography using petroleum ether / ethyl acetate as eluent to obtain 673 mg of the target product 4-amino-3-trifluoromethylacetanilide, with a yield of 62.0%.

[0030] Example 4: Preparation of 4-methyl-2-trifluoromethylaniline

[0031] Weigh 4-methylaniline (536 mg, 5.00 mmol, 1.0 equiv), 2,8-difluoro-5-(trifluoromethyl)-5H-dibenzo[b,d]thiophene-5-trifluoromethanesulfonate (4383 mg, 10.00 mmol, 2.0 equiv), and Pt(1-ptz) (30 mg, 0.05 mmol, 0.01 equiv) into a sealed tube, add acetonitrile (20 mL), purge with nitrogen three times, stir under a 450 nm blue LED lamp, maintain the reaction temperature at 20–30 °C, and react for 10–15 hours. Monitor the reaction progress by TLC (petroleum ether: ethyl acetate = 2:1). After the reaction was completed, water (20 mL) was added, the catalyst was recovered by filtration, the filtrate was extracted with ethyl acetate (20 mL × 2), the organic phases were combined, the organic phases were washed with 10% brine (20 mL × 2), and then dried with anhydrous sodium sulfate. After concentration, the crude product was separated by silica gel column chromatography using petroleum ether / ethyl acetate as eluent to obtain 714 mg of the target product 4-methyl-2-trifluoromethylacetanilide, with a yield of 81.5%. 1 H-NMR (400MHz, CDCl3): δ7.23 (s, 1H), 7.10 (d, J = 5.7Hz, 1H), 6.66 (d, J = 8.2Hz, 1H), 4.01 (s, 2H), 2.26 (s, 3H). 19 F-NMR (400MHz, CDCl3): δ-62.5ppm.

[0032] Example 5: Preparation of 4-chloro-2-trifluoromethylaniline

[0033] Weigh 4-chloroaniline (638 mg, 5.00 mmol, 1.0 equiv), 2,8-difluoro-5-(trifluoromethyl)-5H-dibenzo[b,d]thiophene-5-trifluoromethanesulfonate (4383 mg, 10.00 mmol, 2.0 equiv), and Pt(1-ptz) (30 mg, 0.05 mmol, 0.01 equiv) into a sealed tube, add acetonitrile (20 mL), purge with nitrogen three times, stir under a 450 nm blue LED lamp, maintain the reaction temperature at 20–30 °C, and react for 10–15 hours. Monitor the reaction progress by TLC (petroleum ether: ethyl acetate = 2:1). After the reaction was completed, water (20 mL) was added, the catalyst was recovered by filtration, the filtrate was extracted with ethyl acetate (20 mL × 2), the organic phases were combined, the organic phases were washed with 10% brine (20 mL × 2), and then dried with anhydrous sodium sulfate. After concentration, the crude product was separated by silica gel column chromatography using petroleum ether / ethyl acetate as eluent to obtain 652 mg of the target product 4-chloro-2-trifluoromethylacetanilide, with a yield of 66.7%. 1 H-NMR (400MHz, CDCl3): δ7.39 (d, J = 2.4Hz, 1H), 7.23 (d, J = 8.7Hz, 1H), 6.67 (d, J = 8.7Hz, 1H), 4.17 (s, 2H). 19 F-NMR (400MHz, CDCl3): δ-63.2ppm.

[0034] Example 6: Preparation of 4-chloro-2-trifluoromethylaniline

[0035] Weigh 4-chloroaniline (638 mg, 5.00 mmol, 1.0 equiv), sodium trifluoromethyl sulfinate (1561 mg, 10.00 mmol, 2.0 equiv), and Pt(1-ptz) (30 mg, 0.05 mmol, 0.01 equiv) into a sealed tube, add acetonitrile (20 mL), purge with nitrogen three times, stir under a 450 nm blue LED lamp, maintain the reaction temperature at 40–50 °C, and react for 15–24 hours. Monitor the reaction progress by TLC (petroleum ether: ethyl acetate = 2:1). After the reaction was completed, water (20 mL) was added, the catalyst was recovered by filtration, the filtrate was extracted with ethyl acetate (20 mL × 2), the organic phases were combined, the organic phases were washed with 10% brine (20 mL × 2), and then dried with anhydrous sodium sulfate. After concentration, the crude product was separated by silica gel column chromatography using petroleum ether / ethyl acetate as eluent to obtain 566 mg of the target product 4-chloro-2-trifluoromethylacetanilide, with a yield of 57.9%.

[0036] Example 7: Preparation of 4-cyano-2-trifluoromethylaniline

[0037] Weigh 4-cyanoaniline (591 mg, 5.00 mmol, 1.0 equiv), 2,8-difluoro-5-(trifluoromethyl)-5H-dibenzo[b,d]thiophene-5-trifluoromethanesulfonate (4383 mg, 10.00 mmol, 2.0 equiv), and Pt(1-ptz) (30 mg, 0.05 mmol, 0.01 equiv) into a sealed tube, add acetonitrile (20 mL), purge with nitrogen three times, stir under a 450 nm blue LED lamp, maintain the reaction temperature at 20–30 °C, and react for 10–15 hours. Monitor the reaction progress by TLC (petroleum ether: ethyl acetate = 2:1). After the reaction was completed, water (20 mL) was added, the catalyst was recovered by filtration, the filtrate was extracted with ethyl acetate (20 mL × 2), the organic phases were combined, the organic phases were washed with 10% brine (20 mL × 2), and then dried with anhydrous sodium sulfate. After concentration, the crude product was separated by silica gel column chromatography using petroleum ether / ethyl acetate as eluent to obtain 611 mg of the target product 4-cyano-2-trifluoromethylacetanilide, with a yield of 65.7%. 1 H-NMR (400MHz, CDCl3): δ7.72(s,1H),7.53(dd,J=8.6,1.6Hz,1H),6.77(d,J=8.4Hz,1H),4.75(s,2H). 19 F-NMR (400MHz, CDCl3): δ-63.6ppm.

[0038] Example 8: Preparation of ethyl 4-amino-3-(trifluoromethyl)benzoate

[0039] Ethyl 4-aminobenzoate (826 mg, 5.00 mmol, 1.0 equiv), 2,8-difluoro-5-(trifluoromethyl)-5H-dibenzo[b,d]thiophene-5-trifluoromethanesulfonate (4383 mg, 10.00 mmol, 2.0 equiv), and Pt(1-ptz) (30 mg, 0.05 mmol, 0.01 equiv) were weighed and added to a sealed tube. Acetonitrile (20 mL) was added, and the mixture was purged with nitrogen three times. The reaction was stirred under a 450 nm blue LED lamp, with the reaction temperature controlled at 20–30 °C and the reaction time at 10–15 hours. The reaction progress was monitored by TLC (petroleum ether: ethyl acetate = 2:1). After the reaction was completed, water (20 mL) was added, the catalyst was recovered by filtration, the filtrate was extracted with ethyl acetate (20 mL × 2), the organic phases were combined, the organic phases were washed with 10% brine (20 mL × 2), and then dried with anhydrous sodium sulfate. After concentration, the crude product was separated by silica gel column chromatography using petroleum ether / ethyl acetate as eluent to obtain 807 mg of the target product ethyl 4-amino-3-(trifluoromethyl)benzoate, with a yield of 69.2%. 1H-NMR (400MHz, CDCl3): δ8.15 (d, J=1.4Hz, 1H), 7.96 (dd, J=8.6, 1.8Hz, 1H), 6. 72(d,J=6.2Hz,1H),4.60(s,2H),4.34(q,J=7.1Hz,2H),1.38(t,J=7.1Hz,3H). 19 F-NMR (400MHz, CDCl3): δ-63.0ppm.

[0040] Example 9: Preparation of 1-(4-amino-3-(trifluoromethyl)phenyl)ethyl-1-one

[0041] Weigh 1-(4-aminophenyl)ethyl-1-one (676 mg, 5.00 mmol, 1.0 equiv), 2,8-difluoro-5-(trifluoromethyl)-5H-dibenzo[b,d]thiophene-5-trifluoromethanesulfonate (4383 mg, 10.00 mmol, 2.0 equiv) and Pt(1-ptz) (30 mg, 0.05 mmol, 0.01 equiv) and add them to a sealed tube. Add acetonitrile (20 mL), purge with nitrogen three times, and stir the reaction under a 450 nm blue LED lamp. The reaction temperature is controlled at 20–30 °C, and the reaction time is 10–15 hours. The reaction progress is monitored by TLC (petroleum ether: ethyl acetate = 2:1). After the reaction was completed, water (20 mL) was added, the catalyst was recovered by filtration, the filtrate was extracted with ethyl acetate (20 mL × 2), the organic phases were combined, the organic phases were washed with 10% brine (20 mL × 2), and then dried with anhydrous sodium sulfate. After concentration, the crude product was separated by silica gel column chromatography using petroleum ether / ethyl acetate as eluent to obtain 683 mg of the target product 1-(4-amino-3-(trifluoromethyl)phenyl)ethyl-1-one, with a yield of 67.2%. 1 H-NMR (400MHz, CDCl3): δ8.07(d,J=1.5Hz,1H),7.91(dd,J=8.6,1.9Hz,1H),6.75(d,J=8.6Hz,1H),4.74(s,2H),2.53(s,3H). 19 F-NMR (400MHz, CDCl3): δ-63.1ppm.

[0042] Example 10: Preparation of 2,6-dimethyl-4-trifluoromethylaniline

[0043] Weigh 2,6-dimethylaniline (606 mg, 5.00 mmol, 1.0 equiv), 2,8-difluoro-5-(trifluoromethyl)-5H-dibenzo[b,d]thiophene-5-trifluoromethanesulfonate (4383 mg, 10.00 mmol, 2.0 equiv), and Pt(1-ptz) (30 mg, 0.05 mmol, 0.01 equiv) into a sealed tube, add acetonitrile (20 mL), purge with nitrogen three times, stir under a 450 nm blue LED lamp, maintain the reaction temperature at 20–30 °C, and react for 10–15 hours. Monitor the reaction progress by TLC (petroleum ether: ethyl acetate = 2:1). After the reaction was completed, water (20 mL) was added, the catalyst was recovered by filtration, the filtrate was extracted with ethyl acetate (20 mL × 2), the organic phases were combined, the organic phases were washed with 10% brine (20 mL × 2), and then dried with anhydrous sodium sulfate. After concentration, the crude product was separated by silica gel column chromatography using petroleum ether / ethyl acetate as eluent to obtain 687 mg of the target product 2,6-dimethyl-4-trifluoromethylaniline, with a yield of 72.6%. 1 H-NMR (400MHz, CDCl3): δ7.19(s,2H),3.84(s,2H),2.20(s,6H). 19 F-NMR (400MHz, CDCl3): δ-60.5ppm.

[0044] Example 11: Preparation of 6-chloro-4-bromo-2-trifluoromethylaniline

[0045] Weigh 2-chloro-4-bromoaniline (1032 mg, 5.00 mmol, 1.0 equiv), 2,8-difluoro-5-(trifluoromethyl)-5H-dibenzo[b,d]thiophene-5-trifluoromethanesulfonate (4383 mg, 10.00 mmol, 2.0 equiv), and Pt(1-ptz) (30 mg, 0.05 mmol, 0.01 equiv) into a sealed tube, add acetonitrile (20 mL), purge with nitrogen three times, stir under a 450 nm blue LED lamp, maintain the reaction temperature at 20–30 °C, and react for 10–15 hours. Monitor the reaction progress by TLC (petroleum ether: ethyl acetate = 2:1). After the reaction was completed, water (20 mL) was added, the catalyst was recovered by filtration, the filtrate was extracted with ethyl acetate (20 mL × 2), the organic phases were combined, the organic phases were washed with 10% brine (20 mL × 2), and then dried with anhydrous sodium sulfate. After concentration, the crude product was separated by silica gel column chromatography using petroleum ether / ethyl acetate as eluent to obtain 836 mg of the target product 6-chloro-4-bromo-2-trifluoromethylaniline, with a yield of 60.9%. 1H-NMR (400MHz, CDCl3): δ7.56 (d, J = 2.0 Hz, 1H), 7.48 (d, J = 2.0 Hz, 1H). 19 F-NMR (400MHz, CDCl3): δ-63.5ppm.

[0046] Although the invention has been fully described in conjunction with specific embodiments, it should be noted that various changes and modifications will be apparent to those skilled in the art. Such changes and modifications are to be understood to be included within the scope of the invention as defined by the appended claims.

Claims

1. A method for preparing a trifluoromethylaniline derivative, characterized in that, Using a tetradentate platinum(II) complex as a photocatalyst, trifluoromethylaniline derivatives were prepared by direct trifluoromethylation of aniline compounds under visible light irradiation. The reaction formula is as follows: Wherein, R1 is selected from hydrogen, halogen, or cyano; R2 is selected from hydrogen, halogen, or amino. The trifluoromethyl source is a trifluoromethylating agent, which is one of 2,8-difluoro-5-(trifluoromethyl)-5H-dibenzo[b,d]thiophene-5-trifluoromethanesulfonate or sodium trifluoromethylsulfinate. The photocatalyst tetradentate platinum(II) complex is Pt(1-ptz), and its structural formula is:

2. A method for preparing a trifluoromethylaniline derivative, characterized in that, Using a tetradentate platinum(II) complex as a photocatalyst, trifluoromethylaniline derivatives were prepared by direct trifluoromethylation of aniline compounds under visible light irradiation. The reaction formula is as follows: The aniline compounds are aniline, 4-aminoacetaniline, 4-methylaniline, 4-chloroaniline, 4-cyanoaniline, ethyl 4-aminobenzoate, 1-(4-aminophenyl)ethyl-1-one, 2,6-dimethylaniline, or 2-chloro-4-bromoaniline. The trifluoromethyl source is a trifluoromethylating agent, which is one of 2,8-difluoro-5-(trifluoromethyl)-5H-dibenzo[b,d]thiophene-5-trifluoromethanesulfonate or sodium trifluoromethylsulfinate. The photocatalyst tetradentate platinum(II) complex is Pt(1-ptz), and its structural formula is:

3. The preparation method according to claim 1 or 2, characterized in that, The reaction is carried out in the presence of a solvent selected from acetonitrile, dimethyl sulfoxide, N,N-dimethylformamide, 1,4-dioxane, and dichloromethane.

4. The preparation method according to claim 1 or 2, characterized in that, The molar amount of the tetradentate platinum(II) complex is 0.5% to 5% of the molar amount of the aniline compound.

5. The preparation method according to claim 1 or 2, characterized in that, The molar amount of the trifluoromethylating agent is 1 to 4 times the molar amount of the aniline compound.

6. The preparation method according to claim 1 or 2, characterized in that, The wavelength of the visible light irradiation is 400–760 nm.

7. The preparation method according to claim 1 or 2, characterized in that, The reaction temperature is 10–60°C.

8. The preparation method according to claim 1 or 2, characterized in that, The reaction time is 5 to 24 hours.

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