Method for synthesizing trifluoromethyl substituted aniline by using tetradentate platinum complex as photocatalyst

Abstract

The invention relates to a method for synthesizing a trifluoromethylaniline derivative by catalyzing direct trifluoromethylation of aniline compounds with visible light. According to the method, a tetradentate platinum (II) complex Pt (1-ptz) is used as a photocatalyst, a Umemoto reagent or a Langlois reagent (CF3SO2Na) is used as a trifluoromethyl source, direct trifluoromethylation of an aniline compound is realized under irradiation of visible light, the reaction does not need to use a redox reagent and does not need to protect an exposed amino group, and meanwhile, recovery and reuse of the photocatalyst are realized.

Description

Technical Field

[0001] The present invention relates to the field of photochemistry and pharmaceutical synthesis, and in particular to a method for preparing trifluoromethyl-substituted aniline derivatives by using a tetradentate platinum (II) complex Pt (1-ptz) as a photocatalyst and an Umemoto reagent or a Langlois reagent as a trifluoromethyl source to realize direct trifluoromethylation of aniline compounds under visible light irradiation. Background Art

[0002] Introducing a trifluoromethyl group with strong electron-withdrawing ability into a candidate drug molecule will significantly change the polarity, lipophilicity, metabolic stability and chemical stability of the molecule. Drugs containing trifluoromethyl groups have higher metabolic stability and are easily absorbed by the body, which greatly reduces the dosage of the drug. Therefore, drug molecules containing trifluoromethyl groups play a very important role in the pharmaceutical field. Trifluoromethyl-substituted aniline derivatives are an important class of pharmaceutical intermediates, such as 4-trifluoromethylaniline, an intermediate of the anti-rheumatic drug leflunomide, 4-trifluoromethylbenzylamine, an intermediate of the anti-angiogenic agent tasquinomod, 2-trifluoromethyl-6-chloroaniline, an intermediate of the antiasthmatic drug mabuterol, 4-chloro-3-trifluoromethylaniline, an intermediate of the anti-tumor drug sorafenib, and 4-chloro-2-trifluoromethylaniline, an intermediate of the fungicide triflumizole.

[0003]

[0004] How to effectively introduce trifluoromethyl groups into organic molecules has attracted extensive attention from organic chemists. Compared with the two synthetic methods of introducing trifluoromethyl groups into molecules, namely nucleophilic and electrophilic, the free radical trifluoromethylation synthesis based on photocatalysis has the advantages of being green and environmentally friendly, highly atom-economical, and not requiring additional redox reagents. Visible light catalytic organic synthesis will become one of the necessary strategies for organic synthesis. my country has abundant and renewable visible light resources, and the visible light catalytic reaction conditions are mild and highly efficient. Visible light photoredox catalysis has huge advantages over traditional synthetic methods in many aspects.

[0005] In 2014, the document Org. Lett. 2014, 16, 1768-1771 reported a method for introducing a trifluoromethyl group using photocatalytic tri(2-phenylpyridine)iridium complex to form trifluoromethyl aromatic amine; the patent with announcement number CN103553857B discloses a method for preparing o-trifluoromethyl aniline or its derivatives, which uses aromatic amine and trivalent iodine reagent compound as raw materials, tri(2-phenylpyridine)iridium complex as catalyst, and reacts under light conditions to obtain o-trifluoromethyl aniline or its derivatives.

[0006] Currently, the most widely used photocatalyst is cyclometallated iridium (III) complex molecules, but metallic iridium is expensive, and iridium (III) complexes are difficult to recycle after photocatalytic reactions, which greatly increases costs and is not conducive to 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 publication number CN103980322B discloses the use of tridentate platinum (II) complexes based on triplet-triplet annihilation upconversion luminescent materials for photocatalytic reactions; in 2015, Professor Zhi Zhiming reported the intramolecular dehalogenation cyclization reaction catalyzed by tridentate cyclometallate Pt(C^N^N)X complexes and the reductive self-coupling reaction of benzyl chloride and bromide (Angew. Chem. Int. Ed. 2015, 54, 2112–2117). Unlike the octahedral configuration of cyclometallated iridium (III) complexes, the central metal ion of the cyclometallated platinum (II) complex forms a planar quadrilateral configuration of the dsp2 hybrid orbital. Compared with bidentate and tridentate ligands, suitable tetradentate ligands can match well with platinum (II) ions to form complexes with planar or quasi-planar configurations, which can not only improve their chemical and thermal stability, so that their structure can remain unchanged after the photocatalytic reaction, which is conducive to recycling and application, but also greatly improve their quantum efficiency, even to 100%. In addition, the content of metallic platinum in the earth's crust and the annual output worldwide are both about ten times that of metallic iridium. The price of IrCl3.H2O (1,100 yuan / g) used to prepare iridium (III) complexes is also much higher than that of PtCl2 (210 yuan / g) used to prepare platinum (II) complexes. Summary of the invention

[0007] The purpose of the present invention is to provide a photocatalytic synthesis method of trifluoromethylation products with a simple system, mild reaction conditions, low cost and large-scale preparation, and to solve the high pollution and high cost problems of industrial trifluoromethylation reactions. The present invention has mild synthesis conditions, cheap and readily available raw materials, recyclable photocatalysts, low environmental pollution, and can be combined with continuous flow reactions for large-scale industrial production, with significant economic and social benefits.

[0008] In order to achieve the technical purpose of the present invention, the technical solution of the present invention is:

[0009] The present invention uses Umemoto reagent or Langlois reagent as a trifluoromethyl source and a tetradentate platinum (II) complex Pt (1-ptz) as a photocatalyst to achieve direct trifluoromethylation of aniline compounds under visible light irradiation. The reaction does not require additional redox reagents, and the reaction equation is expressed as follows:

[0010]

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

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

[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 the aniline compound 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 the present invention, the trifluoromethylation reagent is one of 2,8-difluoro-5-(trifluoromethyl)-5H-dibenzo[b,d]thiophene-5-trifluoromethanesulfonate (Umemoto reagent) and sodium trifluoromethanesulfinate (Langlois reagent).

[0015] In the visible light catalytic 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 400-760nm, preferably 400-500nm; the reaction temperature is 10-60°C, preferably 20-30°C; and the reaction time is 5-24 hours.

[0017] In the visible light catalytic trifluoromethylation process of the present invention, water having the same volume as the reaction solvent is added to precipitate the platinum (II) complex from the solvent, and the complex is filtered and purified to achieve the purpose of recovery and reuse.

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

[0019] In the visible light catalytic trifluoromethylation process of the present invention, the concentration is reduced pressure concentration. The separation and purification method used is column chromatography.

[0020] According to the different substituents in the raw materials of the aniline compounds, the trifluoromethyl substituted aniline derivatives shown below can be synthesized by referring to the above synthesis method:

[0021]

[0022] The process for preparing trifluoromethyl substituted aniline derivatives of the present invention has the following technical advantages: using a platinum (II) complex whose central metal price is about 1 / 5 of that of iridium as a visible light catalyst, the direct trifluoromethylation of aniline compounds is achieved, and there is no need to protect and deprotect the amino group. The trifluoromethyl group is directly introduced into the molecule in a green and environmentally friendly manner, and the yield is high (58% to 82%), avoiding the use of highly toxic and highly corrosive fluorine gas or hydrofluoric acid and redox reagents, and realizing the recycling of photocatalysts, greatly reducing the cost of photocatalytic reactions. Therefore, compared with the existing technical process, this project has the advantages of high efficiency and simplicity, green environmental protection, low cost, good industrial applicability, etc., and has obvious process reliability and technological advancement. DETAILED DESCRIPTION

[0023] In order to better understand the content of the present invention, the following is further described in conjunction with specific examples, but the specific implementation methods are not limitations of the content of the present invention. Among them, the tetradentate platinum (II) complex Pt (1-ptz) is synthesized according to the method of the literature (Chem. Mater. 2020, 32, 537), which is not 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 catalyst platinum (II) complex Pt(1-ptz) (30 mg, 0.05 mmol, 0.01 equiv) were weighed and added into a sealed tube, acetonitrile (20 mL) was added, nitrogen was replaced three times, and the reaction was stirred under 450 nm blue LED light. The reaction temperature was controlled at 20-30 ° C, the reaction time was 10-15 hours, and the reaction progress was detected by TLC (petroleum ether: ethyl acetate = 2:1). After the reaction, 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), and then dried over anhydrous sodium sulfate. After concentration, the crude product was separated by silica gel column chromatography using petroleum ether / ethyl acetate as eluent to obtain 484 mg of the target oily product 2-trifluoromethylaniline 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; 173mg of oily target product 4-trifluoromethylaniline was obtained 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 4-aminoacetanilide (751 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), replace with nitrogen three times, stir and react under 450 nm blue LED light, control the reaction temperature at 20-30 ° C, the reaction time is 10-15 hours, and monitor the reaction progress by TLC (petroleum ether: ethyl acetate = 2:1). After the reaction, 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 over 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 4-aminoacetanilide (751 mg, 5.00 mmol, 1.0 equiv), sodium trifluoromethanesulfinate (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), replace with nitrogen three times, stir and react under 450 nm blue LED light, control the reaction temperature at 40-50 ° C, the reaction time is 15-24 hours, and monitor the reaction progress by TLC (petroleum ether: ethyl acetate = 2:1). After the reaction, 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 over 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), replace with nitrogen three times, stir and react under 450 nm blue LED light, control the reaction temperature at 20-30 ° C, the reaction time is 10-15 hours, and monitor the reaction progress by TLC (petroleum ether: ethyl acetate = 2:1). After the reaction, 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 over 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), replace with nitrogen three times, stir and react under 450 nm blue LED light, control the reaction temperature at 20-30 ° C, the reaction time is 10-15 hours, and monitor the reaction progress by TLC (petroleum ether: ethyl acetate = 2:1). After the reaction, 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 over 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 trifluoromethanesulfinate (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), replace with nitrogen three times, stir and react under 450 nm blue LED light, control the reaction temperature at 40-50 ° C, the reaction time is 15-24 hours, and monitor the reaction progress by TLC (petroleum ether: ethyl acetate = 2:1). After the reaction, 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 over 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), replace with nitrogen three times, stir and react under 450 nm blue LED light, control the reaction temperature at 20-30 ° C, the reaction time is 10-15 hours, and monitor the reaction progress by TLC (petroleum ether: ethyl acetate = 2:1). After the reaction, 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 over 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] Weigh 4-aminobenzoic acid ethyl ester (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) into a sealed tube, add acetonitrile (20 mL), replace with nitrogen three times, stir and react under 450 nm blue LED light, control the reaction temperature at 20-30 ° C, the reaction time is 10-15 hours, and monitor the reaction progress by TLC (petroleum ether: ethyl acetate = 2:1). After the reaction, 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 over 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 4-amino-3-(trifluoromethyl)benzoic acid ethyl ester 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) into a sealed tube, add acetonitrile (20 mL), replace with nitrogen three times, stir and react under 450 nm blue LED light, control the reaction temperature at 20-30 ° C, the reaction time is 10-15 hours, and monitor the reaction progress by TLC (petroleum ether: ethyl acetate = 2:1). After the reaction, 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 over 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), replace with nitrogen three times, stir and react under 450 nm blue LED light, control the reaction temperature at 20-30 ° C, the reaction time is 10-15 hours, and monitor the reaction progress by TLC (petroleum ether: ethyl acetate = 2:1). After the reaction, 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 over 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), replace with nitrogen three times, stir and react under 450 nm blue LED light, control the reaction temperature at 20-30 ° C, the reaction time is 10-15 hours, and monitor the reaction progress by TLC (petroleum ether: ethyl acetate = 2:1). After the reaction, 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 over 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 present invention has been fully described in conjunction with specific embodiments, it should be noted that various changes and modifications are obvious to those skilled in the art. Such changes and modifications will be understood to be included within the scope of the present 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, aniline compounds are directly trifluoromethylated under visible light irradiation to prepare trifluoromethylaniline derivatives. The reaction formula is: wherein R1 is selected from hydrogen, alkyl, alkoxy, acyloxy, ester, keto, halogen, haloalkyl or cyano; R2 is selected from hydrogen, alkyl, halogen or amino, The trifluoromethyl source is Umemoto reagent or CF3SO2Na.

2. The preparation method according to claim 1, characterized in that: The aniline compound is aniline, 4-aminoacetanilide, 4-methylaniline, 4-chloroaniline, 4-cyanoaniline, 4-aminobenzoic acid ethyl ester, 1-(4-aminophenyl)ethyl-1-ketone, 2,6-dimethylaniline or 2-chloro-4-bromoaniline.

3. The preparation method according to claim 1, characterized in that: The photocatalyst is a tetradentate platinum (II) complex Pt (1-ptz) with the structural formula:

4. The preparation method according to claim 1, characterized in that: The trifluoromethylation reagent is one of 2,8-difluoro-5-(trifluoromethyl)-5H-dibenzo[b,d]thiophene-5-trifluoromethanesulfonate and sodium trifluoromethanesulfinate.

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

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

7. The preparation method according to claim 1, characterized in that: The molar amount of the trifluoromethylation agent is 1 to 4 times the molar amount of the aniline compound.

8. The preparation method according to claim 1, characterized in that: The wavelength of the visible light irradiation is 400-760 nm.

9. The preparation method according to claim 1, characterized in that: The reaction temperature is 10-60°C.

10. The preparation method according to claim 1, characterized in that: The reaction time is 5 to 24 hours.

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