Synthesis method and application of arylamine and indole compound containing hexafluoroisopropanol structural unit

Abstract

The invention provides a synthesis method and application of an arylamine and indole compound containing a hexafluoroisopropanol structural unit, and the synthesis method comprises the following steps: dissolving hexafluoroacetone trihydrate and an arylamine compound or an indole compound in an organic solvent to directly react for 6-48 hours at the reaction temperature of 10-100 DEG C; and after the reaction is finished, carrying out post-treatment to obtain the arylamine and indole compound containing the hexafluoroisopropanol structural unit. The method has the advantages of mild reaction conditions, simple operation, cheap and easily available raw materials, high atom economy, good functional group compatibility, wide substrate application range (can be directly used for later derivatization of some drug molecules), no waste generation, and suitableness for industrial production. The synthesized arylamine and indole compound containing the hexafluoroisopropanol structural unit can be used as an organic molecular catalyst to be applied to a hydroxydifluoroalkylation reaction of indole and difluoroacetaldehyde hemiethanol, and shows better reaction activity.

Description

Technical Field

[0001] The present invention relates to a method for synthesizing and applying an aromatic amine and an indole compound containing a hexafluoroisopropanol structural unit, and belongs to the technical field of the synthesis and application of fluorine-containing organic compounds. Background Art

[0002] Selectively introducing fluorine atoms or fluorine-containing groups into compounds can significantly regulate the physical, chemical, and physiological properties of target molecules, and has become an effective way to develop new compounds with important application prospects in the fields of biomedicine, pesticides, and functional materials. Among many fluorine-containing groups, the hexafluoroisopropanol group has a relatively special structure, which contains two trifluoromethyl groups and one alcohol hydroxyl group, and has a strong hydrogen bond donor ability. Compounds containing such structural units usually have special biological activities, such as anti-tumor, anti-inflammatory, treatment of hepatitis C and diabetes, etc., and have broad application prospects. The multiple fluorine atoms in the hexafluoroisopropanol structural unit enable the compounds containing this structure to provide strong 19 19F NMR signals and can be used as potential 19 FMRI contrast agents. This structure also has various applications in the design and development of ligands and catalysts as well as the modification of material properties. Therefore, continuously developing new synthesis methods for fluorine-containing organic compounds containing hexafluoroisopropanol structural units has important research significance and application space.

[0003] Aromatic amines and indoles are important nitrogen-containing organic compounds and have wide applications in many fields such as medicine, biochemistry, pharmacology, and material chemistry. At present, introducing hexafluoroisopropanol structural units into aromatic amine and indole skeletons can mainly be achieved through (1) the Friedel-Crafts alkylation reaction of hexafluoroacetone gas or hexafluoroacetone sesquihydrate with aromatic amines and indoles (J. Org. Chem. 1979, 44, 1779–1784; Eur. J. Org. Chem. 2003, 4286–4291); (2) the oxidative dehydrogenative coupling reaction of hexafluoroisopropanol with aromatic amines or indoles (Org. Lett. 2016, 18, 4662–4665; Org. Lett. 2019, 21, 218-222). In method (1), hexafluoroacetone gas has high reactivity but is highly toxic, and its acquisition and use operations are relatively difficult. Hexafluoroacetone sesquihydrate is expensive and difficult to obtain, and is mainly applicable to introducing hexafluoroisopropanol structural units into primary aromatic amines. In method (2), metal catalysts such as Cu and Co, peroxide oxidants, and equivalent bases are usually required, the reaction conditions are relatively harsh, the substrate scope and functional group compatibility are relatively limited, and it is difficult to scale up the reaction. Therefore, it is still of great significance to develop a new strategy for preparing aromatic amines and indole compounds containing hexafluoroisopropanol structural units that is simple, practical, sustainable, and easy to scale up. Summary of the Invention

[0004] The object of the present invention is to provide a synthesis method and application of an aromatic amine and an indole compound containing a hexafluoroisopropanol structural unit in view of the deficiencies of the prior art, providing a synthesis method with easily available raw materials, simple operation, mild reaction conditions, high safety, high reaction yield, good atom economy, and large-scale application prospects for the preparation of an aromatic amine and an indole compound containing a hexafluoroisopropanol structural unit. The obtained aromatic amine and indole compound containing a hexafluoroisopropanol structural unit can be used as an organic molecular catalyst for the reaction of indole and difluoroacetaldehyde semi-ethanol.

[0005] To achieve the above object, the technical solution adopted by the present invention is as follows:

[0006] The present invention provides a synthesis method of an aromatic amine and an indole compound containing a hexafluoroisopropanol structural unit, including:

[0007] Dissolve hexafluoroacetone trihydrate and an aromatic amine compound or an indole compound in an organic solvent and directly carry out a reaction. The reaction temperature is 10°C to 100°C, and the reaction time is 6 to 48 hours. After the reaction is completed, the obtained aromatic amine and indole compound containing a hexafluoroisopropanol structural unit is obtained through post-treatment; the organic solvent includes: 2,2-difluoroethanol, hexafluoroisopropanol, hexafluoro-2-methylisopropanol, hexafluoro-2-phenylisopropanol, trifluoroethanol, perfluoroalkyl ethanol, perfluorotert-butanol, ethylene glycol, tetrafluoropropanol, tetrafluorobutanediol, hexafluorobutanol, octafluoropentanol.

[0008] Preferably, the molar ratio of the aromatic amine compound or indole compound to hexafluoroacetone trihydrate is 1 to 6.2:1.

[0009] Preferably, the structural formula of the aromatic amine compound containing a hexafluoroisopropanol structural unit is shown in formula (I):

[0010]

[0011] In formula (I), n 1 represents an integer from 1 to 6, and R 1 independently selects from hydrogen, alkyl, alkoxy, cycloalkyl, arylmethyl, heteroarylmethyl, substituted arylmethyl, substituted heteroarylmethyl, aryl, heteroaryl, and substituted aryl, substituted heteroaryl. The aryl is phenyl, naphthalene, and the heteroaryl is pyridine, pyrimidine, furan, thiophene, benzofuran, benzothiophene, quinoline, isoquinoline, quinoxaline. The substituents of the substituted aryl and substituted heteroaryl are halogen, hydroxyl, alkoxy, R 2Independently selected from hydrogen, alkyl, alkoxy, cycloalkyl, arylmethyl, heteroarylmethyl, substituted arylmethyl, substituted heteroarylmethyl, aryl, heteroaryl and substituted aryl, substituted heteroaryl, wherein the aryl is phenyl, naphthalene, the heteroaryl is pyridine, pyrimidine, furan, thiophene, benzofuran, benzothiophene, quinoline, isoquinoline, quinoxaline, and the substituents of the substituted aryl, substituted heteroaryl are halogen, hydroxy, alkoxy, R 3 Independently selected from hydrogen, alkyl, alkoxy, cycloalkyl, aryl, propenyl, halogen, hydroxy, benzyl, thioalkyl, ester group.

[0012] Preferably, the structural formula of the indole compound containing a hexafluoroisopropanol structural unit is shown as formula (II) or formula (III):

[0013]

[0014] In formula (II), R 4 Independently selected from hydrogen, alkyl, aryl, R 5 Independently selected from hydrogen, alkyl, alkoxy, cycloalkyl, aryl, propenyl, halogen, hydroxy, benzyl, thioalkyl, ester group;

[0015] In formula (III), R 6 Independently selected from hydrogen, alkyl, aryl, acyl, R 7 Independently selected from hydrogen, alkyl, alkoxy, cycloalkyl, aryl, propenyl, halogen, hydroxy, benzyl, thioalkyl, ester group, R 8 Independently selected from hydrogen, alkyl, aryl.

[0016] Preferably, the arylamine compound includes various types (primary, secondary and tertiary) of ordinary arylamines or functionalized arylamines; the indole compound includes various types (monosubstituted, disubstituted, polysubstituted and unsubstituted) of ordinary indoles or functionalized indoles.

[0017] Preferably, the reaction temperature is 25 - 90 °C and the reaction time is 12 - 36 h.

[0018] Preferably, the post-treatment includes: after the reaction is completed, the solvent is removed under reduced pressure, and the concentrate is separated and purified by recrystallization or column chromatography to obtain an arylamine and an indole compound containing a hexafluoroisopropanol structural unit.

[0019] More preferably, the solvents used for recrystallization include ethanol, methanol, toluene, ethyl acetate, chloroform, petroleum ether.

[0020] More preferably, the organic solvent can be recovered by a simple distillation operation after the reaction is completed.

[0021] The present invention also provides the application of an aromatic amine and an indole compound containing a hexafluoroisopropanol structural unit synthesized by the above synthesis method as an organic molecular catalyst in the hydroxy-difluoroalkylation reaction of indole and difluoroacetaldehyde semi-ethyl acetal.

[0022] Preferably, the application includes: in carbon tetrachloride, using indole and difluoroacetaldehyde semi-ethyl acetal as raw materials, an aromatic amine and an indole compound containing a hexafluoroisopropanol structural unit synthesized as a catalyst, reacting at 25 °C for 48 h. After the reaction is complete, the solvent is removed by distillation under reduced pressure, and column chromatography separation is carried out to obtain the hydroxy-difluoroalkylation product of indole.

[0023] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0024] (1) The synthesis method of the present invention uses hexafluoroacetone trihydrate as the reagent source for introducing the hexafluoroisopropanol structural unit, and the reaction can be carried out only in an organic solvent without the need to additionally add a catalyst and an additive. The reaction conditions are mild, the operation is simple, the reaction reagents are safe, inexpensive and easily available, and the atom economy is good, having the prospect of large-scale application.

[0025] (2) The synthesis method of the present invention has excellent functional group compatibility, a wide range of substrate applicability (primary, secondary, and tertiary aromatic amines and indoles substituted at different sites can all participate in this chemical transformation well), the reaction is efficient, and one or more hexafluoroisopropanol structural units can be selectively introduced into aromatic amine compounds, and the hexafluoroisopropanol structural unit can be selectively introduced at the 2-position,

[0026] 3-position, 4-position, 5-position, 6-position, 7-position and unactivated C(sp 3 )-H sites of indole compounds respectively. At the same time, it can also be used for the introduction of hexafluoroisopropanol structural units in some complex molecules such as drug molecules containing hydroxyl and amino groups or related derivatives.

[0027] (3) The aromatic amine and indole compound containing a hexafluoroisopropanol structural unit synthesized by the present invention can efficiently realize the hydroxy-difluoroalkylation reaction of indole and difluoroacetaldehyde semi-ethyl acetal as an organic molecular catalyst and show good reaction activity. Specific Embodiments

[0028] The present invention will be described in detail below in conjunction with specific embodiments. The following specific examples are helpful for those skilled in the art to further understand the present invention, but do not limit the present invention in any form.

[0029] Example 1

[0030]

[0031] In a 100 mL reaction flask, N,N-dimethylaniline (1.21 g, 10.0 mmol), hexafluoroacetone hydrate (1.66 g, 10.0 mmol), and trifluoroethanol (30 mL) were added in sequence. The reaction was carried out at 50 °C, and the reaction was monitored by TLC plate. The reaction was completed after 12 h. After the reaction, the solvent was recovered by rotary evaporation, and the crude reaction product was recrystallized with petroleum ether and ethyl acetate to obtain 2.77 g of the product shown above in the form of a white powder, with a yield of 96%. The structural characterization data of the obtained target product are as follows: 1 H NMR(400MHz,CDCl 3 )δ7.53(d,J=8.9Hz,2H),6.74(d,J=9.1Hz,2H),3.38(s,1H),2.99(s,6H); 19 F NMR(376MHz,CDCl 3 )δ-75.84(s,6F); 13 C NMR(100MHz,CDCl 3 )δ151.3,127.3,122.9(q, 1 J C-F =286.7Hz),116.2,111.7,40.1;HRMS(ESI)m / z:[M+H] + Calcd for C 11 H 12 F 6 NO:288.0818,Found:288.0826.

[0032] Example 2

[0033]

[0034] In a 100 mL reaction flask, 1-methyl-1,2,3,4-tetrahydroquinoline (1.47 g, 10.0 mmol), hexafluoroacetone hydrate (1.66 g, 10.0 mmol), and perfluorotert-butanol (30 mL) were added in sequence. The reaction was carried out at 45 °C, and the reaction was monitored by TLC plate. The reaction was completed after 18 h. After the reaction, the solvent was recovered by rotary evaporation, and the crude reaction product was recrystallized with petroleum ether and ethyl acetate to obtain 2.82 g of the product shown above in the form of a white powder, with a yield of 89%. The structural characterization data of the obtained target product are as follows: 1 HNMR(400MHz,CDCl 3)δ 7.35 (d, J=8.7 Hz, 1H), 7.24 (d, J=12.6 Hz, 1H), 6.59 (d, J=8.8 Hz, 1H), 3.35 (s, 1H), 3.31–3.25 (m, 2H), 2.92 (s, 3H), 2.79 (t, J=6.3 Hz, 2H), 2.03–1.94 (m, 2H); 19 F NMR (376 MHz, CDCl 3 )δ -75.77 (s, 6F); 13 C NMR (100 MHz, CDCl 3 )δ 147.6, 126.6, 125.3, 122.9 (q, 1 J C-F =285.7 Hz), 122.4, 115.7, 110.1, 50.9, 38.8, 27.9, 21.9; HRMS (ESI) m / z: [M+H] + Calcd for C 13 H 14 F 6 NO: 314.0975, Found: 314.0976.

[0035] Example 3

[0036]

[0037] In a 100 mL reaction flask, N-phenylmorpholine (1.63 g, 10.0 mmol), hexafluoroacetone hydrate (1.66 g, 10.0 mmol), and perfluoroalkyl ethanol (30 mL) were successively added. The reaction was carried out at 40 °C, and the reaction was monitored by TLC plate spotting. The reaction was completed after 24 h. After the reaction, the solvent was recovered by rotary evaporation, and the crude reaction product was recrystallized from toluene to obtain 3.09 g of the white powdery product shown above, with a yield of 94%. The structure characterization data of the obtained target product are as follows: 1 H NMR (400 MHz, CDCl 3 )δ 7.58 (d, J=8.5 Hz, 2H), 6.93 (d, J=8.5 Hz, 2H), 4.05 (s, 1H), 3.90–3.82 (m, 4H), 3.25–3.18 (m, 4H); 19 F NMR (376 MHz, CDCl 3 )δ -75.70 (s, 6F); 13 C NMR (100 MHz, CDCl 3 )δ 152.0, 127.6, 122.8 (q, 1 J C-F= 288.0 Hz), 120.1, 114.7, 66.7, 48.2; HRMS(ESI) m / z: [M+H] + Calcd for C 13 H 14 F 6 NO 2 : 330.0924, Found: 330.0925.

[0038] Example 4

[0039]

[0040] In a 100 mL reaction flask, N-methyl-N-hydroxyethylaniline (1.51 g, 10.0 mmol), hexafluoroacetone hydrate (1.66 g, 10.0 mmol), and hexafluoroisopropanol (30 mL) were successively added. The reaction was carried out at 35 °C, and the reaction was monitored by TLC plate. The reaction was completed after 10 h. After the reaction, the solvent was recovered by rotary evaporation, and the crude reaction product was further separated and purified by column chromatography to obtain 2.82 g of the product shown in the above formula as a colorless liquid, with a yield of 89%. The structure characterization data of the obtained target product are as follows: 1 H NMR (400 MHz, CDCl 3 ) δ 7.35 (d, J = 8.7 Hz, 1H), 7.24 (d, J = 12.6 Hz, 1H), 6.59 (d, J = 8.8 Hz, 1H), 3.35 (s, 1H), 3.31–3.25 (m, 2H), 2.92 (s, 3H), 2.79 (t, J = 6.3 Hz, 2H), 2.03–1.94 (m, 2H); 19 F NMR (376 MHz, CDCl 3 ) δ -75.77 (s, 6F); 13 C NMR (100 MHz, CDCl 3 ) δ 147.6, 126.6, 125.3, 122.9 (q, 1 J C-F = 285.7 Hz), 122.4, 115.7, 110.1, 50.9, 38.8, 27.9, 21.9; HRMS(ESI) m / z: [M+H] + Calcd for C 13 H 14 F 6 NO: 314.0975, Found: 314.0976.

[0041] Example 5

[0042]

[0043] In a 100 mL reaction flask, N-methylaniline (1.07 g, 10.0 mmol), hexafluoroacetone hydrate (1.66 g, 10.0 mmol), and hexafluoroisopropanol (30 mL) were successively added. The reaction was carried out at 25 °C, and the reaction was monitored by TLC plate. The reaction was completed after 16 h. After the reaction, the solvent was recovered by rotary evaporation, and the crude reaction product was recrystallized with ethanol to obtain 2.68 g of the product shown above in the form of a white powder, with a yield of 98%. The structure characterization data of the obtained target product are as follows: 1 H NMR (400 MHz, CDCl 3 ) δ 7.49 (d, J = 8.8 Hz, 2H), 6.81–6.39 (m, 2H), 3.74 (s, 2H), 2.85 (s, 3H); 19 F NMR (376 MHz, CDCl 3 ) δ -75.84 (s, 6F); 13 C NMR (100 MHz, CDCl 3 ) δ 150.4, 127.5, 122.9 (q, 1 J C-F = 288.0 Hz), 117.4, 112.0, 30.4; HRMS (ESI) m / z: [M+H] + Calcd for C 10 H 10 F 6 NO: 274.0662, Found: 274.0661.

[0044] Example 6

[0045]

[0046] In a 100 mL reaction flask, indoline (1.19 g, 10.0 mmol), hexafluoroacetone hydrate (1.66 g, 10.0 mmol), and 2,2-difluoroethanol (30 mL) were successively added. The reaction was carried out at 30 °C, and the reaction was monitored by TLC plate. The reaction was completed after 18 h. After the reaction, the solvent was recovered by rotary evaporation, and the crude reaction product was further separated and purified by column chromatography to obtain 2.57 g of the product shown above in the form of a colorless liquid, with a yield of 90%. The structure characterization data of the obtained target product are as follows: 1 H NMR (400 MHz, CDCl 3 ) δ 7.31 (t, J = 6.9 Hz, 2H), 7.02 (t, J = 7.7 Hz, 1H), 3.60 (t, J = 8.1 Hz, 2H), 3.07 (t, J = 8.0 Hz, 2H); 19 F NMR (376 MHz, CDCl 3) δ -75.36 (s, 6F); 13 C NMR (100 MHz, DMSO-d 6 ) δ 153.4, 129.6, 126.4, 123.5 (q, 1 J C-F = 288.2 Hz), 122.8, 118.9, 108.1, 46.7, 29.2; HRMS (ESI) m / z: [M+H] + Calcd for C 11 H 10 F 6 NO: 286.0662, Found: 286.0666.

[0047] Example 7

[0048]

[0049] In a 100 mL reaction flask, aniline (0.93 g, 10.0 mmol), hexafluoroacetone hydrate (1.66 g, 10.0 mmol), and hexafluoroisopropanol (30 mL) were successively added. The reaction was carried out at 50 °C, and the reaction was monitored by TLC plate. The reaction was completed after 24 h. After the reaction, the solvent was recovered by rotary evaporation, and the crude reaction product was recrystallized with ethanol to obtain 2.09 g of the product shown in the above formula as a white powder, with a yield of 81%. The structure characterization data of the obtained target product are as follows: 1 H NMR (400 MHz, CDCl 3 ) δ 7.46 (d, J = 8.5 Hz, 2H), 6.71 (d, J = 8.8 Hz, 2H), 3.84 (s, 2H), 3.32 (s, 1H); 19 F NMR (376 MHz, CDCl 3 ) δ -75.86 (s, 6F); 13 C NMR (100 MHz, DMSO-d 6 ) δ 150.4, 127.8, 123.5 (q, 1 J C-F = 288.6 Hz), 116.9, 113.6; HRMS (ESI) m / z: [M+H] + Calcd for C 9 H 8 F 6 NO: 260.0505, Found: 260.0503.

[0050] Example 8

[0051]

[0052] In a 100 mL reaction flask, 4,4'-dimethyl diphenylamine (1.97 g, 10.0 mmol), hexafluoroacetone hydrate (1.66 g, 10.0 mmol), and tetrafluoropropanol (30 mL) were successively added. The reaction was carried out at 40 °C, and the reaction was monitored by TLC plate. The reaction was completed after 36 h. After the reaction, the solvent was recovered by rotary evaporation. The crude reaction product was recrystallized from toluene to obtain 3.34 g of the product shown above in the form of a white powder, with a yield of 92%. The structure characterization data of the obtained target product are as follows: 1 H NMR(400MHz,CDCl 3 )δ7.49(s,1H),7.23(d,J=8.1Hz,1H),7.12–7.04(m,3H),6.71(d,J=8.3Hz,2H),2.40(s,3H),2.29(s,3H); 19 F NMR(376MHz,CDCl 3 )δ-75.28(s,6F); 13 C NMR(100MHz,CDCl 3 )δ142.8,141.0,137.4,132.4,131.9,130.0,129.9,128.9,125.9(q, 1 J C-F =274.8Hz),125.9,118.9,21.3,20.6;HRMS(ESI)m / z:[M-H] - Calcd for C 17 H 14 F 6 NO:362.0985,Found:362.0983.

[0053] Example 9

[0054]

[0055] In a 100 mL reaction flask, N-(naphthalen-2-yl)-9-phenyl-9H-carbazol-2-amine (3.84 g, 10.0 mmol), hexafluoroacetone hydrate (1.66 g, 10.0 mmol), and hexafluoroisopropanol (30 mL) were successively added. The reaction was carried out at 80 °C, and the reaction was monitored by TLC plate. The reaction was completed after 36 h. After the reaction, the solvent was recovered by rotary evaporation. The crude reaction product was further separated and purified by column chromatography to obtain 3.13 g of the product shown above in the form of a white powder, with a yield of 57%. The structure characterization data of the obtained target product are as follows:

[0056] 1 H NMR(400MHz,CDCl 3)δ8.53(s,1H),8.29–8.19(m,1H),7.74(t,J=8.0Hz,2H),7.62(d,J=8.1Hz,1H),7.47(dt,J=6.7,4.3Hz,3H),7.44–7.33(m,7H),7.24(s,1H),7.11(d,J=1.9Hz,1H),7.05(dd,J=8.8,2.3Hz,1H),2.05(s,1H); 19 F NMR(376MHz,CDCl 3 )δ-75.23(s,6F); 13 C NMR(100MHz,CDCl 3 )δ143.3,142.3,141.6,140.8,136.6,135.2,134.1,130.1,129.9,129.6,128.1,127.7,127.3,126.8,126.8,126.7,125.0,124.5,123.5(q, 1 J C-F =288.4Hz),123.0,122.5,121.0,120.7,119.2,117.3,114.2,111.1,110.2;HRMS(ESI)m / z:[M+H] + Calcd for C 31 H 21 F 6 N 2 O:551.1553,Found:551.1562.

[0057] Example 10

[0058]

[0059] To a 100 mL reaction flask, N-methyldiphenylamine (1.83 g, 10.0 mmol), hexafluoroacetone hydrate (1.66 g, 10.0 mmol), and hexafluoroisopropanol (30 mL) were added successively. The reaction was carried out at 25 °C, and the reaction was monitored by TLC plate. The reaction was completed after 12 h. After the reaction was completed, the solvent was recovered by rotary evaporation, and the crude reaction product was further separated and purified by column chromatography to obtain 2.41 g of the product shown in the above formula as a colorless liquid, with a yield of 69%. The structural characterization data of the obtained target product are as follows: 1 H NMR(400MHz,CDCl 3)δ7.55(d, J = 8.8 Hz, 2H), 7.42–7.37(m, 2H), 7.22(d, J = 7.5 Hz, 2H), 7.18(dd, J = 11.6, 4.2 Hz, 1H), 6.95–6.90(m, 2H), 3.53(s, 1H), 3.37(s, 3H); 19 F NMR(376 MHz, CDCl 3 )δ -75.80(s, 6F); 13 C NMR(100 MHz, CDCl 3 )δ150.2, 147.9, 129.6, 127.3, 124.7, 124.4, 122.8(q, 1 J C-F = 287.6 Hz), 118.8, 115.5, 40.0; HRMS(ESI) m / z: [M + H] + Calcd for C 16 H 14 F 6 NO: 350.0975, Found: 350.0973.

[0060] Example 11

[0061]

[0062] In a 100 mL reaction flask, N - methyldiphenylamine (1.83 g, 10.0 mmol), hexafluoroacetone hydrate (3.32 g, 20.0 mmol), and hexafluoroisopropanol (30 mL) were successively added. The reaction was carried out at 40 °C, and the reaction was monitored by TLC plate. The reaction was completed after 18 h. After the reaction, the solvent was recovered by rotary evaporation, and the crude reaction product was further separated and purified by column chromatography to obtain 3.04 g of the product shown by the above formula in the form of a colorless liquid, with a yield of 59%. The structural characterization data of the obtained target product are as follows: 1 H NMR(400 MHz, CDCl 3 )δ7.61(d, J = 8.4 Hz, 4H), 7.12(d, J = 8.6 Hz, 4H), 3.63(s, 2H), 3.38(s, 3H); 19 F NMR(376 MHz, CDCl 3 )δ -75.68(s, 12F); 13 C NMR(100 MHz, CDCl 3 )δ149.5, 127.7, 122.7(q, 1 J C-F = 287.5 Hz), 122.1, 120.1, 39.9; HRMS(ESI) m / z: [M - H]- Calculated for C 19 H 12 F 12 NO 2 : 514.0681, Found: 514.0686.

[0063] Example 12

[0064]

[0065] Triphenylamine (2.45 g, 10.0 mmol), hexafluoroacetone hydrate (1.66 g, 10.0 mmol), and hexafluoroisopropanol (30 mL) were successively added to a 100 mL reaction flask, and the reaction was carried out at 25 °C. The reaction was monitored by TLC plate spotting, and the reaction was completed after 12 h. After the reaction, the solvent was recovered by rotary evaporation, and the crude reaction product was further separated and purified by column chromatography to obtain 2.96 g of the product shown by the above formula in the form of a colorless liquid, with a yield of 72%. The structural characterization data of the obtained target product are as follows: 1 H NMR (400 MHz, CDCl 3 ) δ 7.50 (d, J = 8.7 Hz, 2H), 7.33–7.27 (m, 4H), 7.16–7.12 (m, 4H), 7.12–7.04 (m, 4H), 3.52 (s, 1H); 19 F NMR (376 MHz, CDCl 3 ) δ -75.64 (s, 6F); 13 C NMR (100 MHz, CDCl 3 ) δ 149.5, 147.0, 129.5, 127.3, 125.4, 123.9, 122.7 (q, 1 J C-F = 288.2 Hz), 121.4, 121.2; HRMS (ESI) m / z: [M+H] + Calculated for C 21 H 16 F 6 NO: 412.1131, Found: 412,1130.

[0066] Example 13

[0067]

[0068] In a 100 mL reaction flask, N-methyl diphenylamine (1.83 g, 10.0 mmol), hexafluoroacetone hydrate (3.32 g, 20.0 mmol), and hexafluoroisopropanol (30 mL) were added in sequence. The reaction was carried out at 50 °C, and the reaction was monitored by TLC plate. The reaction was completed after 18 h. After the reaction, the solvent was recovered by rotary evaporation, and the crude reaction product was further separated and purified by column chromatography to obtain 3.23 g of the product shown above in the form of a white solid, with a yield of 56%. The structural characterization data of the obtained target product are as follows: 1 H NMR(400MHz,CDCl 3 )δ7.56(d,J=8.4Hz,4H),7.34(t,J=7.6Hz,2H),7.14(t,J=8.8Hz,7H),3.45(s,2H); 19 FNMR(376MHz,CDCl 3 )δ-75.64(s,12F); 13 C NMR(100MHz,CDCl 3 )δ148.8,146.4,129.8,127.6,126.2,124.8,122.9,122.8,122.7(q, 1 J C-F =287.8Hz);HRMS(ESI)m / z:[M-H] - Calcd forC 24 H 14 F 12 NO 2 :576.0838,Found:576.0841.

[0069] Example 14

[0070]

[0071] In a 100 mL reaction flask, N-methyl diphenylamine (1.83 g, 10.0 mmol), hexafluoroacetone hydrate (4.98 g, 30.0 mmol), and hexafluoroisopropanol (30 mL) were added in sequence. The reaction was carried out at 90 °C, and the reaction was monitored by TLC plate. The reaction was completed after 24 h. After the reaction, the solvent was recovered by rotary evaporation, and the crude reaction product was further separated and purified by column chromatography to obtain 3.19 g of the product shown above in the form of a white solid, with a yield of 43%. The structural characterization data of the obtained target product are as follows: 1 H NMR(400MHz,CDCl 3 )δ7.24(d,J=8.4Hz,6H),7.21(d,J=8.6Hz,6H),3.47(s,3H); 19 F NMR(376MHz,CDCl3 ) δ -75.24 (s, 18F); 13 13C NMR (100 MHz, CDCl 3 ) δ 144.3, 143.1, 130.7, 127.7, 124.3 (q, 1 J C-F = 288.3 Hz); HRMS (ESI) m / z: [M + H] + Calcd for C 27 H 16 F 18 NO 3 : 744.0837, Found: 744.0846.

[0072] Example 15

[0073]

[0074] In a 100 mL reaction flask, N,N'-diphenyl-m-phenylenediamine (2.60 g, 10.0 mmol), hexafluoroacetone hydrate (3.32 g, 20.0 mmol), and hexafluoroisopropanol (30 mL) were successively added. The reaction was carried out at 30 °C, and the reaction was monitored by TLC plate. The reaction was completed after 12 h. After the reaction, the solvent was recovered by rotary evaporation, and the crude reaction product was further separated and purified by column chromatography to obtain 3.73 g of the above-mentioned product in the form of a white solid, with a yield of 63%. The structural characterization data of the obtained target product are as follows: 1 1H NMR (400 MHz, CDCl 3 ) δ 7.81 (s, 1H), 7.22 (t, J = 7.9 Hz, 4H), 7.03–6.97 (m, 3H), 6.87 (d, J = 7.6 Hz, 4H), 2.96 (s, 1H), 2.88 (s, 1H); 19 19F NMR (376 MHz, CDCl 3 ) δ -76.95 (s, 6F); 13 13C NMR (100 MHz, CDCl 3 ) δ 146.8, 142.2, 129.5, 123.6, 122.9 (d, J = 287.8 Hz), 120.4, 117.6, 113.9; HRMS (ESI) m / z: [M - H] - Calcd for C 24 H 15 F 12 N 2 O 2 : 591.0947, Found: 591.0939.

[0075] Example 16

[0076]

[0077] In a 100 mL reaction flask, 2-(methyl(phenyl)amino)ethyl (R)-2-(6-methoxynaphthalen-2-yl)propionate, i.e., the naproxen derivative (3.63 g, 10.0 mmol), hexafluoroacetone hydrate (1.66 g, 10.0 mmol), and hexafluoroisopropanol (30 mL) were successively added. The reaction was carried out at 30 °C, and the reaction was monitored by TLC plate spotting. The reaction was completed after 24 h. After the reaction, the solvent was recovered by rotary evaporation, and the crude reaction product was further separated and purified by column chromatography to obtain 4.61 g of the white powdery product shown above, with a yield of 87%. The structural characterization data of the obtained target product are as follows: 1 H NMR(400MHz,CDCl 3 )δ7.68(d,J=1.9Hz,1H),7.66(s,1H),7.61(s,1H),7.47(d,J=8.8Hz,2H),7.32(dd,J=8.5,1.8Hz,1H),7.14(dd,J=8.9,2.5Hz,1H),7.11(d,J=2.4Hz,1H),6.66(d,J=9.1Hz,2H),4.31–4.17(m,2H),3.92(s,3H),3.76(q,J=7.2Hz,1H),3.54(t,J=5.8Hz,2H),3.44(s,1H),2.82(s,3H),1.51(d,J=7.2Hz,3H); 19 F NMR(376MHz,CDCl 3 )δ-75.80(s,6F); 13 C NMR(100MHz,CDCl 3 )δ174.9,157.6,149.8,135.3,133.7,129.2,128.9,127.5,127.2,126.1,125.9,122.9(q, 1 J C-F =287.6Hz),119.0,116.7,111.4,105.6,61.9,55.2,50.5,45.4,38.1,18.1;HRMS(ESI)m / z:[M+H] + Calcd for C 26 H 24 F 6 NO 4 :530.1761,Found:530.1752.

[0078] Example 17

[0079]

[0080] In a 100 mL reaction flask, indole (1.17 g, 10.0 mmol), hexafluoroacetone hydrate (1.66 g, 10.0 mmol), and hexafluoroisopropanol (30 mL) were added successively. The reaction was carried out at 25 °C, and the reaction was monitored by TLC plate. The reaction was completed after 18 h. After the reaction, the solvent was recovered by rotary evaporation, and the crude reaction product was further separated and purified by column chromatography to obtain 2.77 g of the product shown above in the form of a white solid, with a yield of 98%. The structure characterization data of the obtained target product are as follows: 1 H NMR (400 MHz, CDCl 3 ) δ 8.43 (s, 1H), 7.96 (d, J = 8.1 Hz, 1H), 7.47 (s, 1H), 7.43 (d, J = 8.1 Hz, 1H), 7.29 (d, J = 7.2 Hz, 1H), 7.21 (t, J = 7.6 Hz, 1H), 3.50 (s, 1H); 19 F NMR (376 MHz, CDCl 3 ) δ -76.25 (s, 6F); 13 C NMR (100 MHz, CDCl 3 ) δ 136.0, 125.2, 124.6, 123.1, 123.0 (q, 1 J C-F = 288.0 Hz), 121.2, 121.1, 111.5, 105.2; HRMS (ESI) m / z: [M - H] - Calcd for C 11 H 6 F 6 NO: 282.0359, Found: 282.0358.

[0081] Example 18

[0082]

[0083] In a 100 mL reaction flask, 3-methylindole (1.31 g, 10.0 mmol), hexafluoroacetone hydrate (1.66 g, 10.0 mmol), and hexafluorobutanol (30 mL) were added successively. The reaction was carried out at 35 °C, and the reaction was monitored by TLC plate. The reaction was completed after 15 h. After the reaction, the solvent was recovered by rotary evaporation, and the crude reaction product was further separated and purified by column chromatography to obtain 2.88 g of the product shown above in the form of a white solid, with a yield of 97%. The structure characterization data of the obtained target product are as follows: 1 H NMR (400 MHz, CDCl3 ) δ 8.42 (s, 1H), 7.65 (d, J = 8.0 Hz, 1H), 7.39 (d, J = 8.2 Hz, 1H), 7.30 (t, J = 7.5 Hz, 1H), 7.19 (t, J = 7.5 Hz, 1H), 3.81 (s, 1H), 2.48 (s, 3H); 19 F NMR (376 MHz, CDCl 3 ) δ -75.51 (s, 6F); 13 C NMR (100 MHz, CDCl 3 ) δ 135.1, 129.1, 123.9, 122.5 (q, 1 J C-F = 284.5 Hz), 119.9, 119.4, 113.6, 111.1, 9.1; HRMS (ESI) m / z: [M - H] - Calcd for C 12 H 8 F 6 NO: 296.0515, Found: 296.0509.

[0084] Example 19

[0085]

[0086] In a 100 mL reaction flask, 5-hydroxyindole (1.33 g, 10.0 mmol), hexafluoroacetone hydrate (1.66 g, 10.0 mmol), and hexafluoroisopropanol (30 mL) were successively added. The reaction was carried out at 45 °C, and the reaction was monitored by TLC plate. The reaction was completed after 18 h. After the reaction, the solvent was recovered by rotary evaporation, and the crude reaction product was further separated and purified by column chromatography to obtain 2.84 g of the above-mentioned product in the form of a white solid, with a yield of 95%. The structural characterization data of the obtained target product are as follows: 1 H NMR (400 MHz, CDCl 3 ) δ 8.40 (s, 1H), 7.42 (s, 1H), 7.35 (s, 1H), 7.26 (s, 1H), 6.84 (d, J = 8.4 Hz, 1H), 3.71 (d, J = 6.9 Hz, 2H); 19 F NMR (376 MHz, CDCl 3 ) δ -75.76 (s, 6F); 13 C NMR (100 MHz, DMSO-d6) δ 151.3, 131.0, 126.5, 125.8, 123.9 (q, 1 J C-F= 289.8 Hz), 112.5, 112.4, 105.4, 103.8; HRMS(ESI) m / z: [M-H] - Calcd for C 11 H 6 F 6 NO 2 : 298.00308, Found: 298.0307.

[0087] Example 20

[0088]

[0089] In a 100 mL reaction flask, 4-hydroxyindole (1.33 g, 10.0 mmol), hexafluoroacetone hydrate (1.66 g, 10.0 mmol), and hexafluoroisopropanol (30 mL) were successively added. The reaction was carried out at 45 °C, and the reaction was monitored by TLC plate. The reaction was completed after 18 h. After the reaction, the solvent was recovered by rotary evaporation, and the crude reaction product was further separated and purified by column chromatography to obtain 2.75 g of the above-mentioned product in the form of a white solid, with a yield of 92%. The structural characterization data of the obtained target product are as follows: 1 H NMR (400 MHz, CDCl 3 ) δ 8.52 (s, 1H), 7.74 (s, 1H), 7.41 (s, 1H), 7.14 (t, J = 7.9 Hz, 1H), 7.07 (dd, J = 8.2, 0.7 Hz, 1H), 6.66 (dd, J = 7.5, 0.7 Hz, 1H); 19 F NMR (376 MHz, CDCl 3 ) δ -76.42 (s, 6F); 13 C NMR (100 MHz, CDCl 3 ) δ 146.4, 138.1, 124.0, 123.7, 123.0 (q, 1 J C-F = 287.6 Hz), 114.9, 106.2, 105.2, 105.1; HRMS(ESI) m / z: [M-H] - Calcd for C 11 H 6 F 6 NO 2 : 298.00308, Found: 298.0313.

[0090] Example 21

[0091]

[0092] In a 100 mL reaction flask, 6-hydroxyindole (1.33 g, 10.0 mmol), hexafluoroacetone hydrate (1.66 g, 10.0 mmol), and hexafluoroisopropanol (30 mL) were successively added. The reaction was carried out at 50 °C, and the reaction was monitored by TLC plate. The reaction was completed after 24 h. After the reaction, the solvent was recovered by rotary evaporation, and the crude reaction product was further separated and purified by column chromatography to obtain 2.66 g of the above-mentioned product in the form of a white solid, with a yield of 89%. The structural characterization data of the obtained target product are as follows: 1 H NMR(400MHz,CDCl 3 )δ8.26(s,1H),7.77(d,J=8.8Hz,1H),7.35(s,1H),6.86(s,1H),6.80–6.68(m,1H),4.84(s,1H),3.46(s,1H); 19 F NMR(376MHz,CDCl 3 )δ-76.36(s,6F); 13 C NMR(100MHz,DMSO-d6)δ153.7,137.9,124.0,123.9(q, 1 J C-F =289.1Hz),121.9,119.1,110.9,104.8,96.9;HRMS(ESI)m / z:[M-H] - Calcd for C 11 H 6 F 6 NO 2 :298.00308,Found:298.0306.

[0093] Example 22

[0094]

[0095] In a 100 mL reaction flask, 2,3-diphenylindole (2.69 g, 10.0 mmol), hexafluoroacetone hydrate (1.66 g, 10.0 mmol), and hexafluoroisopropanol (30 mL) were successively added. The reaction was carried out at 80 °C, and the reaction was monitored by TLC plate. The reaction was completed after 24 h. After the reaction, the solvent was recovered by rotary evaporation, and the crude reaction product was further separated and purified by column chromatography to obtain 3.74 g of the above-mentioned product in the form of a white solid, with a yield of 86%. The structural characterization data of the obtained target product are as follows: 1 H NMR(400MHz,CDCl 3)δ8.41(s,1H),7.86(s,1H),7.74(d,J=8.6Hz,1H),7.45–7.38(m,6H),7.38–7.30(m,5H),3.61(s,1H); 19 F NMR(376MHz,CDCl 3 )δ-75.38(s,6F); 13 C NMR(100MHz,CDCl 3 )δ136.1,135.4,134.4,132.2,130.0,129.9,128.8,128.6,128.2,128.2,126.5,123.4,119.8,118.2,115.0,109.8;HRMS(ESI)m / z:[M-H] - Calcd for C 23 H 14 F 6 NO:434.0985,Found:434.0977.

[0096] Example 23

[0097]

[0098] In a 100 mL reaction flask, 2,3-dimethylindole (1.45 g, 10.0 mmol), hexafluoroacetone hydrate (1.66 g, 10.0 mmol), and hexafluoroisopropanol (30 mL) were successively added. The reaction was carried out at 30 °C, and the reaction was monitored by TLC plate. The reaction was completed after 12 h. After the reaction, the solvent was recovered by rotary evaporation, and the crude reaction product was further separated and purified by column chromatography to obtain 1.52 g of the above-mentioned product in the form of a colorless liquid, with a yield of 49%. The structure characterization data of the obtained target product are as follows: 1 H NMR(400MHz,CDCl 3 )δ8.07(s,1H),7.56(d,J=7.9Hz,1H),7.33(d,J=8.1Hz,1H),7.25–7.19(m,1H),7.17–7.11(m,1H),3.45(s,1H),3.44(s,2H),2.29(s,3H); 19 F NMR(376MHz,CDCl 3 )δ-77.07(s,6F); 13 C NMR(100MHz,CDCl 3 )δ136.2,128.5,123.4,122.9(q, 1 J C-F= 287.4 Hz), 122.8, 119.6, 118.9, 112.7, 110.77, 26.6, 8.5; HRMS(ESI) m / z: [M-H] - Calcd for C 13 H 10 F 6 NO: 310.0672, Found: 310.0679.

[0099] Example 24

[0100]

[0101] In a 100 mL reaction flask, 5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline (1.57 g, 10.0 mmol), hexafluoroacetone hydrate (1.66 g, 10.0 mmol), and hexafluoroisopropanol (30 mL) were added in sequence. The reaction was carried out at 30 °C, and the reaction was monitored by TLC plate. The reaction was completed after 18 h. After the reaction, the solvent was recovered by rotary evaporation, and the crude reaction product was further separated and purified by column chromatography to obtain 2.94 g of the above-mentioned product in the form of a white solid, with a yield of 91%. The structural characterization data of the obtained target product are as follows: 1 H NMR (400 MHz, CDCl 3 ) δ 7.68 (d, J = 8.2 Hz, 1H), 7.35 (s, 1H), 7.15–7.07 (m, 1H), 7.00 (d, J = 7.1 Hz, 1H), 4.30–4.12 (m, 2H), 3.43 (s, 1H), 3.02 (t, J = 6.1 Hz, 2H), 2.27 (dt, J = 11.8, 6.0 Hz, 2H); 19 F NMR (376 MHz, CDCl 3 ) δ -76.37 (s, 6F); 13 C NMR (100 MHz, CDCl 3 ) δ 134.3, 127.2, 123.5, 123.1 (q, 1 J C-F = 288.2 Hz), 120.4, 118.8, 103.4, 44.5, 24.5, 22.5; HRMS(ESI) m / z: [M+H] + Calcd for C 14 H 12 F 6 NO: 324.0818, Found: 324.0824.

[0102] Example 25

[0103]

[0104] In a 100 mL reaction flask, indolol (2.48 g, 10.0 mmol), hexafluoroacetone hydrate (1.66 g, 10.0 mmol), and hexafluoroisopropanol (30 mL) were successively added. The reaction was carried out at 25 °C, and the reaction was monitored by TLC plate. The reaction was completed after 24 h. After the reaction, the solvent was recovered by rotary evaporation, and the crude reaction product was further separated and purified by column chromatography to obtain 3.35 g of the product shown above in the form of a white solid, with a yield of 81%. The structural characterization data of the obtained target product are as follows: 1 H NMR (400 MHz, CDCl 3 ) δ 8.70 (s, 1H), 7.42 (s, 1H), 7.19 (t, J = 7.9 Hz, 1H), 7.13 (d, J = 8.1 Hz, 1H), 6.70 (d, J = 7.6 Hz, 1H), 4.25 (d, J = 5.0 Hz, 2H), 4.12 (td, J = 8.7, 4.8 Hz, 1H), 2.95 (dd, J = 12.3, 3.6 Hz, 1H), 2.84 (dt, J = 12.5, 6.2 Hz, 1H), 2.75 (dd, J = 12.2, 8.7 Hz, 1H), 2.04 (s, 1H), 1.26 (s, 1H), 1.10 (s, 3H), 1.08 (s, 3H); 19 F NMR (376 MHz, CDCl 3 ) δ -76.53 (s, 6F); 13 C NMR (100 MHz, DMSO-d6) δ 149.6, 138.1, 124.8, 123.5 (d, J = 289.5 Hz), 123.3, 115.2, 106.9, 103.9, 102.1, 71.9, 68.3, 49.8, 48.6, 22.9; HRMS (ESI) m / z: [M-H] - Calcd for C 17 H 19 F 6 N 2 O 3 : 413.1305, Found: 413.1302.

[0105] Example 26

[0106]

[0107] In a 100 mL reaction flask, indomethacin (3.58 g, 10.0 mmol), hexafluoroacetone hydrate (1.66 g, 10.0 mmol), and hexafluoroisopropanol (30 mL) were added in sequence. The reaction was carried out at 80 °C, and the reaction was monitored by TLC plate spotting. The reaction was completed after 24 h. After the reaction, the solvent was recovered by rotary evaporation, and the crude reaction product was further separated and purified by column chromatography to obtain 3.07 g of the above-mentioned product in the form of a white solid, with a yield of 64%. The structure characterization data of the obtained target product are as follows: 1 H NMR(400MHz,CDCl 3 )δ7.64(d,J=8.3Hz,2H),7.48(d,J=8.3Hz,2H),7.00(s,1H),6.87(d,J=9.0Hz,1H),6.71(d,J=9.0Hz,1H),3.83(s,3H),3.40(s,2H),3.14(s,1H),2.37(s,3H); 19 F NMR(376MHz,CDCl 3 )δ-76.86(s,6F); 13 CNMR(100MHz,CDCl 3 )δ168.3,156.2,139.8,138.4,133.4,131.3,130.9,130.8,129.3,123.1(q, 1 J C-F =288.1Hz),114.9,112.2,108.8,101.5,55.7,24.7,13.6;HRMS(ESI)m / z:[M-H] - Calcd for C 21 H 15 ClF 6 NO 3 :478.0650,Found:478.0648.

[0108] Example 27

[0109]

[0110] In a 100 mL reaction flask, indole (0.47 g, 4.0 mmol), difluoroacetaldehyde ethyl hemiacetal (0.25 g, 2.0 mmol), the arylamine and indole compound containing a hexafluoroisopropanol structural unit synthesized in Example 5 or 17 (0.2 mmol), and carbon tetrachloride (40 mL) were successively added, and the reaction was carried out at 25 °C for 48 h. After the reaction was completed, the solvent was removed by rotary evaporation, and the crude reaction product was further separated and purified by column chromatography to obtain 0.26 g and 0.23 g of the above-mentioned products in the form of light yellow liquids, with yields of 67% and 59%, respectively. The structural characterization data of the obtained target product are as follows: 1 H NMR(400MHz,CDCl 3 )δ8.26(s,1H),7.73(d,J=7.8Hz,1H),7.39(d,J=7.4Hz,1H),7.34–7.21(m,2H),7.21–7.08(m,1H),6.00(td,J=56.1,4.3Hz,1H),5.22–5.08(m,1H),2.40(d,J=4.1Hz,1H); 19 F NMR(376MHz,CDCl 3 )δ-125.98(ddd,J=281.6,55.6,9.7Hz,1F),-127.34(ddd,J=281.9,56.7,12.2Hz,1F); 13 C{ 1 H}NMR(100MHz,CDCl 3 )δ136.1,125.7,123.4,122.7,120.3,119.2,115.6(t, 1 J C-F =245.1Hz),111.5,111.1(dd, 3 J C-F =4.3,3.3Hz),68.2(dd, 2 J C-F =26.1,24.7Hz);HRMS(ESI)m / z:[M-H] - Calcd for C 10 H 8 F 2 NO:196.0579,Found:196.0583.

[0111] Obviously, the above-mentioned embodiments of the present invention are merely examples for more clearly illustrating the present invention, rather than limitations on the implementation manners of the present invention. For those of ordinary skill in the art, based on the above description, other different forms of changes or modifications can be made. It is impossible to enumerate all the implementation methods here. Any obvious changes or modifications derived from the technical solutions of the present invention still fall within the protection scope of the present invention.

Claims

1. A method for synthesizing aromatic amines and indole compounds containing hexafluoroisopropanol structural units, comprising: Hexafluoroacetone trihydrate and aromatic amine compounds or indole compounds are dissolved in an organic solvent and directly reacted at a reaction temperature of 10°C to 100°C and a reaction time of 6 to 48 hours. After the reaction is completed, the aromatic amine and indole compounds containing hexafluoroisopropanol structural units are obtained by post-treatment; the organic solvent includes: 2,2-difluoroethanol, hexafluoroisopropanol, hexafluoro-2-methylisopropanol, hexafluoro-2-phenylisopropanol, trifluoroethanol, perfluoroalkylethanol, perfluorotert-butyl alcohol, ethylene glycol, tetrafluoropropanol, tetrafluorobutanediol, hexafluorobutanol, and octafluoropentanol.

2. The synthesis method according to claim 1, characterized in that The molar ratio of the aromatic amine compound or indole compound to the hexafluoroacetone trihydrate is 1-6.2:

1.

3. The synthesis method according to claim 1, characterized in that The structural formula of the aromatic amine compound containing hexafluoroisopropanol structural units is shown in formula (I): In formula (I), n1 represents an integer of 1 to 6, R 1 R is independently selected from hydrogen, alkyl, alkoxy, cycloalkyl, arylmethyl, heteroarylmethyl, substituted arylmethyl, substituted heteroarylmethyl, aryl, heteroaryl and substituted aryl, substituted heteroaryl, the aryl is phenyl, naphthalene, the heteroaryl is pyridine, pyrimidine, furan, thiophene, benzofuran, benzothiophene, quinoline, isoquinoline, quinoxaline, the substituent of the substituted aryl, substituted heteroaryl is halogen, hydroxyl, alkoxy, R 2 R is independently selected from hydrogen, alkyl, alkoxy, cycloalkyl, arylmethyl, heteroarylmethyl, substituted arylmethyl, substituted heteroarylmethyl, aryl, heteroaryl and substituted aryl, substituted heteroaryl, the aryl is phenyl, naphthalene, the heteroaryl is pyridine, pyrimidine, furan, thiophene, benzofuran, benzothiophene, quinoline, isoquinoline, quinoxaline, the substituent of the substituted aryl, substituted heteroaryl is halogen, hydroxyl, alkoxy, R 3 Independently selected from hydrogen, alkyl, alkoxy, cycloalkyl, aryl, propenyl, halogen, hydroxyl, benzyl, sulfanyl, ester.

4. The synthesis method according to claim 1, characterized in that The structural formula of the indole compound containing the hexafluoroisopropanol structural unit is as shown in formula (II) or formula (III): In formula (II), R 4 are independently selected from hydrogen, alkyl, aryl, R 5 independently selected from hydrogen, alkyl, alkoxy, cycloalkyl, aryl, propenyl, halogen, hydroxyl, benzyl, sulfanyl, ester; In formula (III), R 6 are independently selected from hydrogen, alkyl, aryl, acyl, R 7 R is independently selected from hydrogen, alkyl, alkoxy, cycloalkyl, aryl, propenyl, halogen, hydroxyl, benzyl, sulfanyl, ester, 8 Independently selected from hydrogen, alkyl, aryl.

5. The synthesis method according to claim 1, characterized in that The aromatic amine compounds include primary, secondary and tertiary common aromatic amines or functionalized aromatic amines; the indole compounds include monosubstituted, disubstituted, multisubstituted and unsubstituted common indoles or functionalized indoles.

6. The synthesis method according to claim 1, characterized in that The post-treatment comprises: after the reaction is finished, removing the solvent under reduced pressure, and separating and purifying the concentrate by recrystallization or column chromatography to obtain aromatic amines and indole compounds containing hexafluoroisopropanol structural units.

7. The synthesis method according to claim 6, characterized in that The solvents used for recrystallization include ethanol, methanol, toluene, ethyl acetate, chloroform and petroleum ether.

8. The synthesis method according to claim 6, characterized in that After the reaction is completed, the organic solvent is recovered by distillation.

9. Use of aromatic amines containing hexafluoroisopropanol structural units and indole compounds synthesized by the synthesis method according to any one of claims 1 to 8 as organic molecular catalysts in the hydroxydifluoroalkylation reaction of indole and difluoroacetaldehyde hemiethanol acetal.

10. The use according to claim 9, characterized in that: The application includes: in carbon tetrachloride, using indole and difluoroacetaldehyde hemiethanol as raw materials, synthesized aromatic amine containing hexafluoroisopropanol structural units and indole compounds as catalysts, reacting at 25°C for 48 hours, and after the reaction is complete, removing the solvent by reduced pressure distillation, and separating by column chromatography to obtain the hydroxydifluoroalkylation product of indole.

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