Beta-aryl-gamma-perfluoroalkyl amide derivative and synthesis method thereof

Abstract

The invention discloses a synthesis method for para-acylation / migration of aromatic hydrocarbon under catalysis of carbene, which is characterized by comprising the following steps: reacting aldehyde, acrylamide, a fluorine source, a carbene catalyst, alkali and a solvent in N2 atmosphere under heating and stirring conditions, then adding water for quenching, extracting with ethyl acetate, removing the solvent in vacuum to obtain a coarse material, purifying the coarse material by silica gel column chromatography, and finally obtaining the para-acylation / migration of aromatic hydrocarbon under catalysis of carbene. The target compound beta-aryl-gamma-perfluoroalkyl amide derivative is obtained. The reaction is carried out under extremely mild conditions, the substrate range is wide, and the tolerance of functional groups is good. The method provided by the invention has selectivity on aromatic acylation positions, and is not influenced by electron and space effects of aromatic substrates. In addition, the research activity of the derivatives shows that the derivatives have the potential to be developed into effective fungicides for crop protection. The compound can be used as a potential candidate drug for inhibiting phytopathogen bacteria, and has good research and development values.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and particularly relates to a method for synthesizing a β-aryl-γ-perfluoroalkylamide derivative by carbene-catalyzed para-acylation / migration of aromatic hydrocarbons to quickly obtain the derivative. Background Art

[0002] Aromatic hydrocarbons are among the most important building blocks in pharmaceuticals, agrochemicals, and materials. Direct C-H functionalization of aromatic hydrocarbons offers the most efficient route to construct complex molecules from simple starting materials, without the need for pre-activation of the aromatics. Selective control of C-H bonds has been a challenge in this field. However, achieving selective distal C-H functionalization is difficult due to the relative distance and spatial orientation between the para- and directing groups. Summary of the Invention

[0003] The present invention aims to address the technical problems of existing technologies, such as harsh reaction conditions, the use of transition metal catalysts, difficult substrate pre-preparation, limited structural diversity, and poor product selectivity. The present invention provides a synthetic method for the para-acylation / migration of aromatic hydrocarbons that overcomes these limitations. Through mild reaction conditions and simple post-treatment, the para-acylation / migration products of aromatic hydrocarbons are obtained concisely and efficiently from readily available starting materials.

[0004] The technical solution of the present invention is: the derivative structural formula of the β-aryl-γ-perfluoroalkylamide derivative is as follows: Wherein, R1 is hydrogen or methyl; R2 is methyl, isopropyl, cyclohexyl, benzyl or heterocyclic methylene; R3 is hydrogen, methyl or halogen; n is 1, 4, 6, 8 or 10.

[0005] The Ar is an ortho-substituted benzene ring, a para-substituted benzene ring, a disubstituted benzene ring, a nitrogen-containing heterocycle or a substituted furan ring, the substituent of the substituted benzene ring is cyano, phenyl, halogen, formyl, nitro, methyl, trifluoromethyl or methoxy, and the substituent of the substituted furan ring is cyano.

[0006] A method for synthesizing the β-aryl-γ-perfluoroalkylamide derivative by carbene-catalyzed para-acylation / migration of aromatic hydrocarbons comprises placing an aldehyde, an eneamide, a fluorine source, a carbene catalyst, a base, and a solvent in an N2 atmosphere, reacting under heating and stirring conditions, then adding water to quench the reaction, extracting with ethyl acetate, and removing the solvent under vacuum to obtain a crude material. The crude material is purified by silica gel column chromatography to obtain the target compound, the β-aryl-γ-perfluoroalkylamide derivative.

[0007] The method described, the reaction equation is as follows:

[0008]

[0009] The molar ratio of the aldehyde, eneamide, fluorine source, carbene catalyst and base is 1:2:2:0.02:0.02.

[0010] The solvent is dimethyl sulfoxide, acetonitrile or ethyl acetate.

[0011] The carbene catalyst is NHC-1, NHC-2, NHC-3, NHC-4, NHC-5, NHC-6, NHC-7, NHC-8, NHC-9 or NHC-10.

[0012] The base is rubidium carbonate, cesium carbonate, tetramethylguanidine, potassium phosphate, sodium benzoate or sodium ethanol.

[0013] The heating temperature is 10-70°C.

[0014] The derivative is used in the preparation of drugs for resisting plant pathogenic bacteria and diseases.

[0015] The present invention provides a highly versatile method for synthesizing para-acylated β-aryl-γ-perfluoroalkylamide derivatives of aromatic hydrocarbons, using aldehydes, olefinic acids, and fluorine sources as starting materials—all of which are readily available, structurally diverse, and inexpensive. The method provides a highly versatile method for synthesizing para-acylated aromatic hydrocarbon derivatives with multifunctional structures, diverse structures, and potentially reactive sites. Traditionally, the synthesis of para-acylated aromatic hydrocarbon derivatives requires multiple steps, but the inventive method allows for rapid, one-step synthesis. The present invention facilitates the preparation of various β-aryl-γ-perfluoroalkylamide derivatives that are difficult to obtain using other methods.

[0016] At the same time, this method can also be successfully applied to the synthesis and structural modification of drug molecules and natural products, demonstrating its potential practicality.

[0017] Furthermore, at 50 μg / mL, many of the tested products exhibited significant inhibitory activity against Xac. Some exhibited excellent inhibitory activity, outperforming or comparable to the commercial fungicides BT and TC. Impressive results were obtained against Xoo at 100 μg / mL. Some compounds, such as 4d, 4l, 4m, and 4s, exhibited inhibition rates of around 80% against Xoo, demonstrating their potential for development as effective fungicides for crop protection. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 This is the single crystal structure diagram of compound 4x. DETAILED DESCRIPTION

[0019] In order to more clearly understand the above-mentioned objects, features and advantages of the present invention, the present invention is further described in detail below with reference to the accompanying drawings and specific embodiments. In the following description, many specific details are set forth to facilitate a full understanding of the present invention. However, the present invention may also be implemented in other ways different from those described herein. Therefore, the present invention is not limited to the specific embodiments disclosed below.

[0020] To a reaction tube equipped with a stirrer, aldehyde 1 (0.2 mmol), eneamide 2 (0.1 mmol), a fluorine source (0.2 mmol), a carbene catalyst (0.02 mmol), and a base (0.02 mmol) were added. Dimethyl sulfoxide (3 mL) was used as the solvent and the mixture was stirred at 40°C under a nitrogen atmosphere for 12 hours. Water was then added and extracted with ethyl acetate. The organic solvent was removed under vacuum to obtain a crude material, which was purified by column chromatography (silica gel, ethyl acetate / n-hexane) to obtain the target compound β-aryl-γ-perfluoroalkylamide derivative 4. The product structure was confirmed by nuclear magnetic resonance, high-resolution mass spectrometry, and single crystal diffraction analysis of representative products. The general reaction formula is as follows:

[0021]

[0022] Example 1

[0023] Preparation of 3-(4-(4-acetylbenzoyl)phenyl)-5,5,5-trifluoro-N-isopropylvaleramide (4a):

[0024] To a reaction tube equipped with a stirrer, 4-acetylbenzaldehyde (0.2 mmol), N-isopropyl-N-phenyl-3-butenamide (0.1 mmol), Togni I (0.2 mmol), NHC-1 (0.02 mmol), and cesium carbonate (0.02 mmol) were added. Dimethyl sulfoxide (3 mL) was used as the solvent and the mixture was stirred at 40°C under a nitrogen atmosphere for 12 hours. Water was then added and extracted with ethyl acetate. The organic solvent was removed under vacuum to obtain a crude material. The crude material was purified by column chromatography (silica gel, ethyl acetate / n-hexane) to obtain the target compound β-aryl-γ-perfluoroalkylamide derivative 4a as a colorless liquid in a 66% yield.

[0025]

[0026] The structural characterization of the compound represented by Formula 4a is as follows:

[0027] 1H NMR (400MHz, CDCl3) δ8.04(d,J=8.4,2H),7.82(d,J=8.4,2H),7.75(d,J=8.3,2H),7.35(d,J=8.3,2H),5.22(d,J=8.0,1H),4.01–3 .90(m,1H),3.68–3.61(m,1H),2.66(s,3H),2.64–2.48(m,3H),2.43(dd,J=14.4,8.2,1H),1.06(d,J=6.6,3H),0.93(d,J=6.5,3H).

[0028] 13 C NMR (101MHz, CDCl3) δ197.52,195.38,168.63,147.46,141.20,139.56,135.72,130.54,129.91,128 .15,127.54,126.15(q,J=277.9),43.03,41.34,38.92(q,J=27.9),36.74(q,J=2.7),26.84,22.51.

[0029] 19 F NMR (377MHz, CDCl3) δ-63.46 (t, J=10.5).

[0030] HRMS(ESI-TOF,m / z):Mass calcd.for C 23 H 24 F3NO3Na + [M+Na] + ,442.1600;found:442.1600.

[0031] Example 2

[0032] Preparation of 5,5,5-trifluoro-N-isopropyl-3-(4-(4-(methylsulfonyl)benzoyl)phenyl)pentanamide (4b):

[0033] To a reaction tube equipped with a stirrer, p-methylsulfonylbenzaldehyde (0.2 mmol), N-isopropyl-N-phenyl-3-butenamide (0.1 mmol), Toogni I (0.2 mmol), NHC-1 (0.02 mmol), and cesium carbonate (0.02 mmol) were added. Dimethyl sulfoxide (3 mL) was used as the solvent and the mixture was stirred at 40°C under a nitrogen atmosphere for 12 hours. Water was then added and extracted with ethyl acetate. The organic solvent was removed under vacuum to obtain a crude material. The crude material was purified by column chromatography (silica gel, ethyl acetate / n-hexane) to obtain the target compound β-aryl-γ-perfluoroalkylamide derivative 4b as a colorless liquid in a 63% yield.

[0034]

[0035] The structural characterization of the compound shown in Formula 4b is as follows:

[0036] 1 H NMR (400MHz, CDCl3) δ8.06(d,J=8.4,2H),7.91(d,J=8.3,2H),7.75(d,J=8.2,2H),7.37(d,J=8.2,2H),5.22(d,J=8.0,1H),4.01–3 .90(m,1H),3.70–3.61(m,1H),3.11(s,3H),2.69–2.49(m,3H),2.43(dd,J=14.5,8.2,1H),1.06(d,J=6.5,3H),0.94(d,J=6.5,3H).

[0037] 13 C NMR (101MHz, CDCl3) δ194.53,168.57,147.96,143.42,142.25,135.14,130.57,130.43,127.72 ,127.44,127.45(q,J=277.8),44.32,42.91,41.36,38.90(q,J=27.7),36.72(q,J=2.8),22.52.

[0038] 19 F NMR (377MHz, CDCl3) δ-63.43 (t, J=10.4).

[0039] HRMS(ESI-TOF,m / z):Mass calcd.for C 22 H 24 F3NO4SNa + [M+Na] + ,478.1270;found:478.1272.

[0040] Example 3

[0041] Preparation method of 5,5,5-trifluoro-N-isopropyl-3-(4-(4-nitrobenzoyl)phenyl)pentanamide (4c):

[0042] The method is the same as Example 1, except that the aldehyde is p-nitrobenzaldehyde. Yellow liquid, yield 77%.

[0043]

[0044] The structural characterization of the compound represented by Formula 4c is as follows:

[0045] 1 H NMR (400MHz, CDCl3) δ8.32(d,J=8.8,2H),7.89(d,J=8.7,2H),7.75(d,J=8.2,2H),7.38(d,J=8.2,2H),5.23(d,J=8.0,1H),4 .02–3.90(m,1H),3.69–3.62(m,1H),2.66–2.50(m,3H),2.44(dd,J=14.5,8.1,1H),1.06(d,J=6.6,3H),0.94(d,J=6.6,3H).

[0046] 13 C NMR (101MHz, CDCl3) δ194.20,168.55,149.79,148.04,142.78,135.09,130.57,130.53,127 .75,126.10(q,J=277.7),123.53,42.90,41.38,38.90(q,J=27.9),36.72(q,J=2.8),22.51. 19 F NMR (377MHz, CDCl3) δ-63.45 (t, J=10.9).

[0047] HRMS(ESI-TOF,m / z):Mass calcd.for C 21 H 21 F3N2O4Na + [M+Na] + ,445.1346;found:445.1339.

[0048] Example 4

[0049] Preparation method of 5,5,5-trifluoro-N-isopropyl-3-(4-(4-(trifluoromethyl)benzoyl)phenyl)pentanamide (4d):

[0050] The method is the same as Example 1, except that the aldehyde is p-trifluoromethylbenzaldehyde. Colorless liquid, yield 55%.

[0051]

[0052] The structural characterization of the compound shown in Formula 4d is as follows:

[0053] 1 H NMR(400MHz, CDCl3) δ7.85(d,J=8.0,2H),7.80–7.69(m,4H),7.41–7.31(m,2H),5.20(d,J=8.0,1H),4.02–3.90( m,1H),3.69–3.62(m,1H),2.70–2.48(m,3H),2.43(dd,J=14.4,8.2,1H),1.06(d,J=6.6,3H),0.93(d,J=6.5,3H).

[0054] 13 C NMR (101MHz, CDCl3) δ194.98,168.60,147.58,140.60,135.56,133.76(q,J=32.7),130.56,130.02,127.59,126.2 4(q,J=257.6),125.36(q,J=3.7),123.50(q,J=252.5),43.02,41.37,38.93(q,J=27.9),36.74(q,J=2.9),22.52.

[0055] 19 F NMR (377MHz, CDCl3) δ-63.24 (d, J=172.2).

[0056] HRMS(ESI-TOF,m / z):Mass calcd.for C 22 H 21 F6NO2Na + [M+Na] + ,468.1369;found:468.1379.

[0057] Example 5

[0058] Preparation method of 3-(4-(4-bromobenzoyl)phenyl)-5,5,5-trifluoro-N-isopropylvaleramide (4e):

[0059] The method is the same as Example 1, except that the aldehyde is p-bromobenzaldehyde. The product is a colorless liquid with a yield of 51%.

[0060]

[0061] The structural characterization of the compound represented by Formula 4e is as follows:

[0062] 1 H NMR (400MHz, CDCl3) δ7.78–7.69(m,2H),7.69–7.51(m,4H),7.34(d,J=8.2,2H),5.29(d,J=8.1,1H),3.99–3.90( m,1H),3.67–3.60(m,1H),2.68–2.48(m,3H),2.42(dd,J=14.4,8.2,1H),1.05(d,J=6.6,3H),0.92(d,J=6.5,3H).

[0063] 13 C NMR (101MHz, CDCl3) δ195.09,168.66,147.13,136.15,135.95,131.61,131.41,130.38,127 .56,127.45,126.13(q,J=278.8),43.03,41.31,38.92(q,J=27.8),36.71(d,J=3.0),22.48.

[0064] 19 F NMR (377 MHz, CDCl3) δ-63.45.

[0065] HRMS(ESI-TOF,m / z):Mass calcd.for C 21 H 21 BrF3NO2Na + [M+Na] + ,478.0600;found:478.0590.

[0066] Example 6

[0067] Preparation method of 3-(4-(4-cyanobenzoyl)phenyl)-5,5,5-trifluoro-N-isopropylvaleramide (4f):

[0068] The method is the same as Example 1, except that the aldehyde is p-cyanobenzaldehyde. The product is a colorless liquid with a yield of 75%.

[0069]

[0070] The structural characterization of the compound shown in Formula 4f is as follows:

[0071] 1 H NMR (400MHz, CDCl3) δ7.84(d,J=8.3,2H),7.78(d,J=8.4,2H),7.74(d,J=8.2,2H),7.37(d,J=8.3,2H),5.18(d,J=8.0,1H),4 .01–3.91(m,1H),3.70–3.633(m,1H),2.68–2.49(m,3H),2.43(dd,J=14.5,8.1,1H),1.06(d,J=6.6,3H),0.94(d,J=6.5,3H).

[0072] 13 C NMR (101MHz, CDCl3) δ194.44,168.56,147.86,141.11,135.11,132.14,130.48,130.09,127.69, 126.09(q,J=277.9),117.92,115.61,42.89,41.34,38.89(q,J=27.7),36.70(q,J=3.6),22.49.

[0073] 19 F NMR (377MHz, CDCl3) δ-63.44 (t, J=10.5).

[0074] HRMS(ESI-TOF,m / z):Mass calcd.for C 22 H 21 F3N2O2Na + [M+Na] + ,425.1447;found:425.1458.

[0075] Example 7

[0076] Preparation method of 5,5,5-trifluoro-N-isopropyl-3-(4-(4-(morpholine-4-carbonyl)benzoyl)phenyl)pentanamide (4g):

[0077] The method is the same as Example 1, except that the aldehyde is 4-(morpholine-4-carbonyl)benzaldehyde. Colorless liquid, yield 63%.

[0078]

[0079] The structural characterization of the compound shown in Formula 4g is as follows:

[0080] 1H NMR (400MHz, CDCl3) δ7.79(d,J=8.3,2H),7.74(d,J=8.3,2H),7.50(d,J=8.3,2H),7.34(d,J=8.3,2H),5.30(d,J=8.0,1H),3.98–3.88(m, 1H),3.79(s,4H),3.67–3.60(m,3H),3.43(s,2H),2.66–2.47(m,3H),2.41(dd,J=14.4,8.2,1H),1.04(d,J=6.5,3H),0.91(d,J=6.5,3H).

[0081] 13 C NMR (101MHz, CDCl3) δ195.28,169.29,168.64,147.31,138.97,138.66,135.78,130.49,130.07,127.49 ,126.96,126.13(q,J=276.7),77.20,66.75,42.97,41.29,38.91(q,J=27.7),36.70(q,J=2.9),22.48.

[0082] 19 F NMR (377MHz, CDCl3) δ-63.44 (t, J=10.4).

[0083] HRMS(ESI-TOF,m / z):Mass calcd.for C 26 H 29 F3N2O4Na + [M+Na] + ,513.1972;found:513.1972.

[0084] Example 8

[0085] Preparation method of 3-(4-([1,1'-biphenyl]-4-carbonyl)phenyl)-5,5,5-trifluoro-N-isopropylvaleramide (4h):

[0086] The method is the same as Example 1, except that the aldehyde is 4-phenylbenzaldehyde. Yellow liquid, yield 46%.

[0087]

[0088] The structural characterization of the compound represented by formula 4h is as follows:

[0089] 1H NMR (400MHz, CDCl3) δ7.88–7.82(m,2H),7.81–7.76(m,2H),7.72–7.67(m,2H),7.67–7.61(m,2H),7.51–7.44(m,2H),7.44–7.33(m,3H),5.32 (d,J=8.0,1H),4.03–3.91(m,1H),3.69–3.62(m,1H),2.71–2.50(m,3H ), 2.44 (dd, J = 14.3, 8.2, 1H), 1.06 (d, J = 6.6, 3H), 0.93 (d, J = 6.6, 3H).

[0090] 13 C NMR (101MHz, CDCl3) δ195.86 (d, J = 2.2), 168.80 (d, J = 2.8), 146.79 (d, J = 3.4), 145.31, 139.81, 136.53, 136.05, 130.60, 130. 45,128.94,128.20,127.36,127.24,126.95,126.18(q,J=278.8),43.13,41.31,38.94(q,J=27.8),36.76(q,J=2.8),22.49.

[0091] 19 F NMR (377MHz, CDCl3) δ-63.42 (d, J=4.1).

[0092] HRMS(ESI-TOF,m / z):Mass calcd.for C 27 H 26 F3NO2Na + [M+Na] + ,476.1808;found:476.1816.

[0093] Example 9

[0094] Preparation method of 3-(4-(2-cyanobenzoyl)phenyl)-5,5,5-trifluoro-N-isopropylvaleramide (4i):

[0095] The method is the same as Example 1, except that the aldehyde is 2-cyanobenzaldehyde. Yellow liquid, yield 61%.

[0096]

[0097] The structural characterization of the compound represented by formula 4i is as follows:

[0098] 1H NMR (400MHz, CDCl3) δ7.84 (dd, J=6.7, 2.2, 1H), 7.80–7.71 (m, 2H), 7.70 -7.66(m,J=6.6,1.7,2H),7.65–7.60(m,1H),7.42–7.33(m,2H),5.38(d,J=7.9,1H),3.98–3.90(m,1H),3.6 8–3.61(m,6.0,1H),2.69–2.49(m,3H),2.44(dd,J=14.4,8.0,1H),1.04(d,J=6.6,3H),0.92(d,J=6.5,3H).

[0099] 13 C NMR (101MHz, CDCl3) δ193.26,168.65,148.60,141.33,134.76,134.26,132.12,131.42,130.76,129.97,127. 83,126.14(q,J=277.6),117.03,111.82,43.01,41.36,38.75(q,J=27.7),36.82(d,J=2.9),22.42(d,J=2.8).

[0100] 19 F NMR (377 MHz, CDCl3) δ-63.48.

[0101] HRMS(ESI-TOF,m / z):Mass calcd.for C 22 H 21 F3N2O2Na + [M+Na] + ,425.1447;found:425.1456.

[0102] Example 10

[0103] Preparation method of 3-(4-(4-cyano-3-methoxybenzoyl)phenyl)-5,5,5-trifluoro-N-isopropylvaleramide (4j):

[0104] The method is the same as Example 1, except that the aldehyde is 4-cyano-3-methoxybenzaldehyde. The product is a colorless liquid with a yield of 73%.

[0105]

[0106] The structural characterization of the compound shown in Formula 4j is as follows:

[0107] 1H NMR (400MHz, CDCl3) δ7.74(d,J=8.2,2H),7.65(d,J=7.9,1H),7.41–7.34(m,3H),7.28(dd,J=7.8,1.4,1H),5.22(d,J=8.0,1H) ,4.00–3.91(m,4H),3.69–3.62(m,1H),2.67–2.48(m,3H),2.43(dd,J=14.4,8.1,1H),1.06(d,J=6.6,3H),0.93(d,J=6.5,3H).

[0108] 13 C NMR (101MHz, CDCl3) δ194.48,168.55,161.25,147.85,142.82,135.22,133.51,130.49,127.67,126.10(q,J =277.6),122.04,115.62,111.80,105.18,56.33,42.91,41.36,38.93(q,J=27.9),36.71(d,J=2.7),22.51.

[0109] 19 F NMR (377 MHz, CDCl3) δ-63.45.

[0110] HRMS(ESI-TOF,m / z):Mass calcd.for C 23 H 23 F3N2O3Na + [M+Na] + ,455.1553;found:455.1556.

[0111] Example 11

[0112] Preparation method of 3-(4-(4-chloro-3-methoxybenzoyl)phenyl)-5,5,5-trifluoro-N-isopropylvaleramide (4k):

[0113] The method is the same as Example 1, except that the aldehyde is 4-chloro-3-methylbenzaldehyde. The product is a colorless liquid with a yield of 59%.

[0114]

[0115] The structural characterization of the compound represented by Formula 4k is as follows:

[0116] 1H NMR (400MHz, CDCl3) δ7.77–7.69(m,2H),7.65(d,J=2.1,1H),7.51(dd,J=8.2,2.1,1H),7.43(d,J=8.2,1H),7.37–7.31(m,2H),5. 18(d,J=8.0,1H),4.00–3.90(m,1H),3.68–3.60(m,1H),2.67–2.49(m,3H),2.43(m,4H),1.05(d,J=6.6,3H),0.92(d,J=6.6,3H).

[0117] 13 C NMR (101MHz, CDCl3) δ195.24,168.67,146.95,139.10,136.45,136.23,135.86,132.22,130.41,129.00,128. 72,127.41,126.18(q,J=273.7),43.14,41.34,38.96(q,J=27.8),36.75(d,J=2.9),22.53(d,J=2.3),20.06.

[0118] 19 F NMR (377MHz,CDCl3)δ-63.47.

[0119] HRMS(ESI-TOF,m / z):Mass calcd.for C 22 H 23 ClF3NO2Na + [M+Na] + ,448.1262;found:448.1259.

[0120] Example 12

[0121] Preparation method of 5,5,5-trifluoro-N-isopropyl-3-(4-pyridylphenyl)pentanamide (4l):

[0122] The method is the same as Example 1, except that the aldehyde is 2-pyridinecarboxaldehyde. The product is a colorless liquid with a yield of 69%.

[0123]

[0124] The structural characterization of the compound shown in Formula 41 is as follows:

[0125] 1H NMR(400MHz, CDCl3)δ8.70(d,J=4.6,1H),8.09–8.02(m,2H),8.02–7.98( m,1H),7.89(td,J=7.7,1.8,1H),7.50–7.46(m,1H),7.33(d,J=8.3,2H), 5.24(d,J=8.0,1H),3.99–3.90(m,1H),3.65–3.58(m,1H),2.68–2.46(m, 3H), 2.41 (dd, J = 14.4, 7.8, 1H), 1.04 (d, J = 6.5, 3H), 0.93 (d, J = 6.5, 3H).

[0126] 13 C NMR (101MHz, CDCl3) δ193.15,168.78,154.96,148.48,147.33,137.07,135.09,131.55,127.15,126. 20,126.18(q,J=278.8),124.56,43.11,41.34,38.75(q,J=27.7),36.73(q,J=2.9),22.46(d,J=5.8).

[0127] 19 F NMR (377MHz, CDCl3) δ-63.48 (d, J=10.9).

[0128] HRMS(ESI-TOF,m / z):Mass calcd.for C 20 H 21 F3N2O2Na + [M+Na] + ,401.1447;found:401.1445.

[0129] Example 13

[0130] Preparation of 5,5,5-trifluoro-N-isopropyl-3-(4-(pyrimidine-5-carbonyl)phenyl)pentanamide (4m):

[0131] The method is the same as Example 1, except that the aldehyde is pyrimidine-5-carboxaldehyde. The product is a colorless liquid with a yield of 75%.

[0132]

[0133] The structural characterization of the compound shown in Formula 4m is as follows:

[0134] 1H NMR (400MHz, CDCl3) δ9.39 (s, 1H), 9.08 (s, 2H), 7.78 (d, J = 8.3, 2H), 7.41 (d, J = 8.3, 2H), 5.14 (d, J = 8.0, 1H), 4.02–3. 92(m,1H),3.71–3.64(m,1H),2.70–2.49(m,3H),2.43(dd,J=14.5,8.1,1H),1.06(d,J=6.6,3H),0.94(d,J=6.6,3H).

[0135] 13 C NMR (101MHz, CDCl3) δ191.97,168.43,160.78,157.59,148.52,134.77,130.90,130.40, 128.04,126.07(q,J=277.8),42.90,41.42,38.90(q,J=28.1),36.74,22.56(d,J=2.5).

[0136] 19 F NMR(377MHz, CDCl3)δ-63.41–-63.50(m).

[0137] HRMS(ESI-TOF,m / z):Mass calcd.for C 19 H 20 F3N3O2Na + [M+Na] + ,402.1400;found:402.1395.

[0138] Example 14

[0139] Preparation method of 3-(4-(4-chloropyrimidine-2-carbonyl)phenyl)-5,5,5-trifluoro-N-isopropylvaleramide (4n):

[0140] The method is the same as Example 1, except that the aldehyde is 4-chloropyrimidine-2-carboxaldehyde. The product is a colorless liquid with a yield of 57%.

[0141]

[0142] The structural characterization of the compound represented by formula 4n is as follows:

[0143] 1H NMR (400MHz, CDCl3) δ8.80(d,J=5.3,1H),7.99(d,J=8.3,2H),7.53(d,J=5.3,1H),7.36(d,J=8.1,2H),5.14(d,J=8.0,1H),3 .99–3.87(m,1H),3.69–3.58(m,1H),2.71–2.47(m,3H),2.40(dd,J=14.3,8.0,1H),1.04(d,J=6.6,3H),0.92(d,J=6.5,3H).

[0144] 13 C NMR (101MHz, CDCl3) δ188.99,168.59,162.91,162.10,158.30,148.57,133.44,131.38,127 .57,126.12(q,J=179.8),122.93,43.10,41.40,38.75(q,J=28.0),36.83,22.51(d,J=2.3). 19 F NMR (377MHz, CDCl3) δ-63.51 (t, J=10.4).

[0145] HRMS(ESI-TOF,m / z):Mass calcd.for C 19 H 19 ClF3N3O2Na + [M+Na] + ,436.1010;found:436.1007.

[0146] Example 15

[0147] Preparation method of 5,5,5-trifluoro-N-isopropyl-3-(4-(pyrazine-2-carbonyl)phenyl)pentanamide (4o):

[0148] The method is the same as Example 1, except that the aldehyde is 2-pyrazinecarboxaldehyde. Yellow liquid, yield 74%.

[0149]

[0150] The structural characterization of the compound represented by formula 4o is as follows:

[0151] 1H NMR (400MHz, CDCl3) δ9.23(d,J=1.5,1H),8.77(d,J=2.5,1H),8.67–8.66(m,1H),8.07(d,J=8.3,2H),7.37(d,J=8.4,2H),5.12(d,J=8 .0,1H),3.99–3.91(m,1H),3.68–3.61(m,1H),2.71–2.47(m,3H),2.41(dd,J=14.4,8.0,1H),1.05(d,J=6.5,3H),0.93(d,J=6.5,3H).

[0152] 13 C NMR (101MHz, CDCl3) δ191.49,168.63,149.85,148.01,146.83,146.08,142.85,134.42,131.45,1 27.41, 126.14 (q, J = 278.8), 43.11, 41.40, 38.80 ( q, J = 27.9), 36.79 ( q, J = 2.9), 22.52 ( d, J = 4.4).

[0153] 19 F NMR (377MHz, CDCl3) δ-63.49 (t, J=10.5).

[0154] HRMS(ESI-TOF,m / z):Mass calcd.for C 19 H 20 F3N3O2Na + [M+Na] + ,402.1400;found:402.1401.

[0155] Example 16

[0156] Preparation method of 5,5,5-trifluoro-N-isopropyl-3-(4-(pyridazine-3-carbonyl)phenyl)pentanamide (4p):

[0157] The method is the same as Example 1, except that the aldehyde is pyridazine-3-carboxaldehyde. Colorless liquid, yield 60%.

[0158]

[0159] The structural characterization of the compound represented by formula 4p is as follows:

[0160] 1H NMR (400MHz, CDCl3) δ9.35(dd,J=5.1,1.8,1H),8.21–8.13(m,3H),7.72(dd,J=8.4,5.0,1H),7.37(d,J=8.3,2H),5.21(d,J=8.0, 1H),3.99–3.91(m,1H),3.67–3.60(m,1H),2.71–2.48(m,3H),2.42(dd,J=14.4,7.9,1H),1.05(d,J=6.6,3H),0.93(d,J=6.5,3H).

[0161] 13 C NMR (101MHz, CDCl3) δ191.16,168.68,157.87,152.42,148.23,134.21,131.95,127.50,127. 43,126.14(q,J=275.7),43.10,41.39,38.78(q,J=27.7),36.82(d,J=3.0),22.51(d,J=4.4).

[0162] 19 F NMR (376MHz, CDCl3) δ-63.48 (t, J=10.8).

[0163] HRMS(ESI-TOF,m / z):Mass calcd.for C 19 H 20 F3N3O2Na + [M+Na] + ,402.1400;found:402.1399.

[0164] Example 17

[0165] Preparation of 5,5,5-trifluoro-N-isopropyl-3-(4-(quinoline-6-carbonyl)phenyl)pentanamide (4q):

[0166] The method is the same as Example 1, except that the aldehyde is quinoline-6-carboxaldehyde. Yellow liquid, yield 59%.

[0167]

[0168] The structural characterization of the compound represented by formula 4q is as follows:

[0169] 1H NMR(400MHz, CDCl3)δ9.03(dd,J=4.3,1.7,1H),8.28–8.17(m,3H),8.12(dd, J=8.7,1.9,1H),7.82(d,J=8.3,2H),7.50(dd,J=8.3,4.3,1H),7.38(d,J=8. 3,2H),5.19(d,J=8.0,1H),4.02–3.94(m,1H),3.72–3.63(m,1H),2.72–2.50 (m,3H),2.44(dd,J=14.4,8.2,1H),1.07(d,J=6.6,3H),0.95(d,J=6.5,3H).

[0170] 13 C NMR (101MHz, CDCl3) δ195.48,168.71,152.47,149.68,147.14,137.42,136.26,135.40,131.21,130.59,12 9.80,129.45,127.53,127.28,122.04,43.13,41.39,38.98(q,J=27.3),36.77(d,J=3.1),22.57(d,J=3.6).

[0171] 19 F NMR (377MHz, CDCl3) δ-63.44 (t, J=10.4).

[0172] HRMS(ESI-TOF,m / z):Mass calcd.for C 24 H 23 F3N2O2Na + [M+Na] + ,451.1604;found:451.1607.

[0173] Example 18

[0174] Preparation method of 5,5,5-trifluoro-N-isopropyl-3-(4-(isoquinoline-3-carbonyl)phenyl)pentanamide (4r):

[0175] The method is the same as Example 1, except that the aldehyde is 3-isoquinolinecarboxaldehyde. Yellow liquid, yield 55%.

[0176]

[0177] The structural characterization of the compound shown in Formula 4r is as follows:

[0178] 1H NMR (400MHz, CDCl3) δ9.33(s,1H),8.45(s,1H),8.07(dd,J=8.6,7.0Hz,3H),8.01(d,J=7.9Hz,1H),7.83–7.75(m,2H),7.36(d,J=8.0Hz,2H),5.22(d ,J=7.9Hz,1H),4.06–3.91(m,1H),3.68–3.61(m,1H),2.69–2.51(m,3H),2 .43(dd,J=14.3,7.9Hz,1H),1.06(d,J=6.6Hz,3H),0.95(d,J=6.6Hz,3H).

[0179] 13 C NMR (101MHz, CDCl3) δ193.46,168.83,151.54,148.58,147.11,135.81,135.64,131.49,131.24,129.57,129.54, 128.20,127.70,127.18,126.23(q,J=278.8),123.54,43.22,41.38,38.81(q,J=27.8),36.79,22.52(d,J=4.2).

[0180] 19 F NMR (377MHz, CDCl3) δ-63.47 (t, J=10.4).

[0181] HRMS(ESI-TOF,m / z):Mass calcd.for C 24 H 23 F3N2O2Na + [M+Na] + ,451.1604;found:451.1600.

[0182] Example 19

[0183] Preparation method of 3-(4-(5-cyanofuran-2-carbonyl)phenyl)-5,5,5-trifluoro-N-isopropylvaleramide (4s):

[0184] The method is the same as Example 1, except that the aldehyde is 5-cyano-2-furfural. The product is a colorless liquid with a yield of 66%.

[0185]

[0186] The structural characterization of the compound represented by Formula 4s is as follows:

[0187] 1H NMR (400MHz, CDCl3) δ7.99–7.96(m,2H),7.41–7.39(m,2H),7.30(d,J=3.8Hz,1H),7.24(d,J=3.8Hz,1H),5.17(d,J=8.0Hz,1H),3. 99–3.90(m,1H),3.69–3.62(m,1H),2.68–2.49(m,3H),2.42(dd,J=14.4,8.1Hz,1H),1.05(d,J=6.6Hz,3H),0.92(d,J=6.6Hz,3H).

[0188] 13 C NMR (101MHz, CDCl3) δ180.65,168.53,154.98,148.27,134.51,130.05,128.43,127.83,126.10( q,J=277.6),122.81,118.96,110.50,43.02,41.38,38.86(q,J=27.8),36.78(q,J=2.9),22.51.

[0189] 19 F NMR (377MHz, CDCl3) δ-63.47 (t, J=10.5).

[0190] HRMS(ESI-TOF,m / z):Mass calcd.for C 20 H 19 F3N2O3Na + [M+Na] + ,415.1240;found:415.1244.

[0191] Example 20

[0192] Preparation method of 3-(4-(4-cyanobenzoyl)-3-methylphenyl)-5,5,5-trifluoro-N-isopropylvaleramide (4t):

[0193] The method is the same as Example 1, except that the enamide is N-isopropyl-N-(3-methylphenyl)-3-butenamide. Colorless liquid, yield 45%.

[0194]

[0195] The structural characterization of the compound shown in Formula 4t is as follows:

[0196] 1H NMR (400MHz, CDCl3) δ7.83(d,J=8.4Hz,2H),7.75(d,J=8.4Hz,2H),7.24(s,1H),7.18(s,1H),7.12(dd,J=7.9,1.8Hz,1H),5.10(d,J=8.0Hz,1H), 4.02–3.94(m,1H),3.62–3.55(m,1H),2.66–2.49(m,3H),2.41(dd,J=14. 4,8.1Hz,1H),2.35(s,3H),1.08(d,J=6.5Hz,3H),0.97(d,J=6.5Hz,3H).

[0197] 13 C NMR (101MHz, CDCl3) δ196.37,168.72,145.54,141.18,138.36,135.76,132.30,130.65,130.28,129.7 0,126.20(q,J=278.1),124.27,117.93,116.22,43.15,41.39,38.94(q,J=27.7),36.61,22.59,20.31.

[0198] 19 F NMR (377MHz,CDCl3)δ-63.47.

[0199] HRMS(ESI-TOF,m / z):Mass calcd.for C 23 H 23 F3N2O2Na + [M+Na] + ,439.1604;found:439.1609.

[0200] Example 21

[0201] Preparation method of N-benzyl-3-(4-(4-cyanobenzoyl)phenyl)-5,5,5-trifluoropentanamide (4u):

[0202] The method is the same as Example 1, except that the enamide is N-benzyl-N-phenyl-3-butenamide. Colorless liquid, yield 64%.

[0203]

[0204] The structural characterization of the compound represented by formula 4u is as follows:

[0205] 1H NMR (400MHz, CDCl3) δ7.83(d,J=8.4Hz,2H),7.77(d,J=8.4Hz,2H),7.73(d,J=8.3Hz,2H),7.37(d,J=8.4Hz,2H),7.24–7.20(m,3H),7.0 1(dd,J=7.3,2.2Hz,2H),5.73(t,J=5.8Hz,1H),4.41–4.21(m,2H),3.75–3.68(m,1H),2.70(dd,J=14.6,6.3Hz,1H),2.69–2.49(m,3H).

[0206] 13 C NMR (101MHz, CDCl3) δ194.41,137.71,132.17,130.61,130.12,128.64,127.73,127.54,126.12(q,J=279.8),117.95,115.66 43.47, 42.75, 39.05 (q, J = 27.7), 36.65 (d, J = 2.7).

[0207] 19 F NMR (377MHz,CDCl3)δ-63.43.

[0208] HRMS(ESI-TOF,m / z):Mass calcd.for C 26 H 21 F3N2O2Na + [M+Na] + ,473.1447;found:473.1450.

[0209] Example 22

[0210] Preparation method of 3-(4-(4-cyanobenzoyl)phenyl)-N-cyclohexyl-5,5,5-trifluoropentanamide (4v):

[0211] The method is the same as Example 1, except that the enamide is N-cyclohexyl-N-phenyl-3-butenamide. Colorless liquid, yield 62%.

[0212]

[0213] The structural characterization of the compound shown in Formula 4v is as follows:

[0214] 1H NMR (400MHz, CDCl3) δ7.84(d,J=8.4Hz,2H),7.78(d,J=8.4Hz,2H),7.75–7. 72(m,2H),7.38–7.36(m,2H),5.23(d,J=8.2Hz,1H),3.69–3.60(m,2H),2.6 7–2.48(m,3H),2.44(dd,J=14.4,8.2Hz,1H),1.82(dd,J=12.4,4.1Hz,1H), 1.66–1.54(m,4H),1.35–1.22(m,2H),1.12–0.96(m,2H),0.92–0.83(m,1H).

[0215] 13 C NMR (101MHz, CDCl3) δ194.43,168.44,147.85,141.13,135.13,132.15,130.51,130.11,127.70,126.10(q,J =277.6),117.94,115.65,48.15,42.99,38.92(q,J=27.7),36.75(q,J=2.7),32.93,25.32,24.66(d,J=4.3).

[0216] 19 F NMR (377MHz,CDCl3)δ-63.44.

[0217] HRMS(ESI-TOF,m / z):Mass calcd.for C 25 H 25 F3N2O2Na + [M+Na] + ,465.1760;found:465.1748.

[0218] Example 23

[0219] Preparation method of 3-(4-(4-cyanobenzoyl)phenyl)-5,5,5-s trifluoro-N-methylpentanamide (4w):

[0220] The method is the same as Example 1, except that the enamide is N-methyl-N-phenyl-3-butenamide. Yellow liquid, yield 62%.

[0221]

[0222] The structural characterization of the compound shown in Formula 4w is as follows:

[0223] 1H NMR (400MHz, CDCl3) δ7.85(d,J=8.2Hz,2H),7.79(d,J=8.3Hz,2H),7.76–7.74(m,2H),7.37(d,J=8.2 Hz,2H),5.36(s,1H),3.72–3.65(m,1H),2.71(d,J=4.8Hz,3H),2.68–2.60(m,2H),2.57–2.47(m,2H).

[0224] 13 C NMR (101MHz, CDCl3) δ194.48,170.08,147.95,141.13,135.19,132.18,130.60,130.15,127. 65,126.11(d,J=277.4),117.97,115.68,42.54,38.96(q,J=28.0),36.52(q,J=2.9),26.30.

[0225] 19 F NMR (377MHz,CDCl3)δ-63.44.

[0226] HRMS(ESI-TOF,m / z):Mass calcd.for C 20 H 17 F3N2O2Na + [M+Na] + ,397.1134;found:397.1125.

[0227] Example 24

[0228] Preparation of (2S,3R)-3-(4-(4-cyanobenzoyl)phenyl)-5,5,5-trifluoro-N-isopropyl-2-methylpentanamide (4x):

[0229] The method is the same as Example 1, except that the enamide is N-isopropyl-2-methyl-N-phenyl-3-butenamide. Yellow solid, yield 66%.

[0230]

[0231] The structural characterization of the compound represented by formula 4x is as follows:

[0232] 1H NMR (400MHz, CDCl3) δ7.83(d,J=8.4Hz,2H),7.77(d,J=8.4Hz,2H),7.72(d,J=8.1Hz,2H),7.35(d,J=8.1Hz,2H),5.00(d,J=8.1Hz,1H),3.86–3.78(m, 1H),3.32–3.26(m,1H),2.78–2.66(m,1H),2.59–2.48(m,1H),2.42–2.35( m,1H),1.26(d,J=6.8Hz,3H),0.99(d,J=6.6Hz,3H),0.71(d,J=6.5Hz,3H).

[0233] 13 C NMR (101MHz, CDCl3) δ172.21,147.10,135.05,132.16,130.20,130.09,128.48,126.41(q,J=277 .5),117.95,115.64,47.10,43.17(q,J=2.9),40.96,36.34(q,J=27.7),22.34(d,J=3.4),15.70.

[0234] 19 F NMR (377MHz,CDCl3)δ-63.39.

[0235] HRMS(ESI-TOF,m / z):Mass calcd.for C 23 H 23 F3N2O2Na + [M+Na] + ,439.1604;found:439.1599.

[0236] Example 25

[0237] Preparation method of 3-(4-(4-cyanobenzoyl)phenyl)-5,5,6,6,7,7,8,8,8-nonafluoro-N-isopropyloctanamide (4y):

[0238] The method is the same as Example 1, except that the fluorine source is perfluoroiodobutane. Yellow liquid, yield

[0239] The structural characterization of the compound represented by Formula 4y is as follows:

[0240] 1H NMR (400MHz, CDCl3) δ7.86–7.84(m,2H),7.80–7.74(m,4H),7.41–7.38(m,2H),5.13(d,J=8.0Hz,1H), 4.03–3.89(m,1H),3.81–3.74(m,1H),2.71–2.43(m,4H),1.07(d,J=6.6Hz,3H),0.95(d,J=6.5Hz,3H).

[0241] 13 C NMR (101MHz, CDCl3) δ194.41,168.46,148.27,141.13,135.17,132.18,130.5 9,130.13,127.67,117.95,115.70,43.52,41.42,35.56,35.40,35.20,22.53.

[0242] 19 F NMR(377MHz, CDCl3)δ-81.05(d,J=9.7Hz),-111.47,-112.19,-112.19(d,J=27.4Hz),-113.0 5(d,J=27.0Hz),-113.05,-113.77,-124.42(q,J=9.5,8.8Hz),-125.89(td,J=12.6,4.2Hz).

[0243] HRMS(ESI-TOF,m / z):Mass calcd.for C 25 H 21 F9N2O2Na + [M+Na] + ,575.1352;found:575.1351.

[0244] Example 26

[0245] Preparation method of 3-(4-(4-cyanobenzoyl)phenyl)-5,5,6,6,7,7,8,8,9,9,10,10,10-tridecafluoro-N-isopropyldecaneamide (4z):

[0246] The method is the same as Example 1, except that the fluorine source is perfluoroiodohexane. Colorless liquid, yield 53%.

[0247]

[0248] The structural characterization of the compound shown in Formula 4z is as follows:

[0249] 1 H NMR(400MHz, CDCl3) δ7.85(d,J=8.4Hz,2H),7.80–7.74(m,4H),7.41–7.39(m,2H),5.12(d,J=8.0Hz,1H) ,4.01–3.93(m,1H),3.82–3.74(m,1H),2.71–2.43(m,4H),1.07(d,J=6.5Hz,3H),0.95(d,J=6.5Hz,3H).

[0250] 13 C NMR (101MHz, CDCl3) δ194.42,168.47,148.28,141.13,135.18,132.19,130.59,130.14,1 27.68,127.47,127.22,117.96,115.70,43.53,41.42,35.72,35.60,35.51,35.30,22.54.

[0251] 19 F NMR(377MHz, CDCl3)δ-80.79(t,J=9.9Hz),-111.21(d,J=14.4Hz),-111.95(t,J=14.8Hz),-112.81(t,J=14.7Hz),-113.51(d ,J=13.0Hz),-121.77(p,J=12.5,11.6Hz),-122.85(t,J=14.8Hz),-123.19–-123.64(m),-126.13(td,J=14.7,14.2,5.3Hz).

[0252] HRMS(ESI-TOF,m / z):Mass calcd.for C 27 H 21 F 13 N2O2Na + [M+Na] + ,675.1288;found:675.1283.

[0253] Example 27

[0254] Preparation method of 3-(4-(4-cyanobenzoyl)phenyl)-5,5,6,6,7,7,8,8,9,9,10,10,11,11,12,12,12-heptadecafluoro-N-isopropyldodecanoamide (4aa):

[0255] The method is the same as Example 1, except that the fluorine source is perfluoroiodooctane. Yellow solid, yield 57%.

[0256]

[0257] The structural characterization of the compound represented by formula 4aa is as follows:

[0258] 1 H NMR (400MHz, CDCl3) δ7.85(d,J=8.1Hz,2H),7.80–7.74(m,4H),7.40(d,J=8.0Hz,2H),5.09(d,J=8.0Hz,1H),4.03–3.93( m,1H),3.82–3.75(m,1H),2.70–2.52(m,3H),2.46(dd,J=14.4,8.0Hz,1H),1.07(d,J=6.6Hz,3H),0.95(d,J=6.5Hz,3H).

[0259] 13 C NMR (101MHz, CDCl3) δ194.41,168.45,148.29,141.15,135.20,132.19,130.60,130.14,127.68,117.95,115.73,43.56,41.44,35.61,22.55.

[0260] 19 F NMR(377MHz, CDCl3)δ-80.74(t,J=9.9Hz),-111.21(t,J=14.7Hz),-111.93(t,J=14.6Hz),-112.78(t,J=14.2Hz),-1 21.73(ddt,J=120.4,24.7,14.7Hz),-122.68,-122.74(d,J=9.1Hz),-123.41(d,J=15.0Hz),-126.08(t,J=13.4Hz).

[0261] HRMS(ESI-TOF,m / z):Mass calcd.for C 29 H 21 F 17 N2O2Na + [M+Na] + ,775.1224;found:775.1222.

[0262] Example 28

[0263] Preparation method of 3-(4-(4-cyanobenzoyl)phenyl)-5,5,6,6,7,7,8,8,9,9,10,10,11,11,12,12,13,13,14,14,14-heneicosafuoro-N-isopropyltetradecanoamide (4ab):

[0264] The method is the same as Example 1, except that the fluorine source is perfluoroiododecane. White solid, yield 53%.

[0265]

[0266] The structural characterization of the compound shown in Formula 4ab is as follows:

[0267] 1 H NMR(400MHz, CDCl3) δ7.85(d,J=8.2Hz,2H),7.80–7.74(m,4H),7.40(d,J=8.2Hz,2H),5.10(d,J=8.0Hz,1H),4.01–3.93( m,1H),3.82–3.75(m,1H),2.70–2.50(m,3H),2.46(dd,J=14.4,8.0Hz,1H),1.07(d,J=6.5Hz,3H),0.95(d,J=6.5Hz,3H).

[0268] 13 C NMR (101MHz, CDCl3) δ194.42,168.45,148.28,141.14,135.20,132.19,130.60,130.15,127.69,115.73,43.56,41.44,35.60,22.56.

[0269] 19 F NMR(377MHz, CDCl3)δ-80.72(t,J=10.0Hz),-111.93(t,J=14.0Hz),-112.78(t ,J=13.9Hz),-121.76(t,J=34.3Hz),-122.41–-122.93(m),-123.42,-126.07.

[0270] HRMS(ESI-TOF,m / z):Mass calcd.for C 31 H 21 F 21 N2O2Na + [M+Na] + ,875.1160;found:875.1177.

[0271] Pharmacological Example 1:

[0272] Plant pathogen resistance testing.

[0273] Test method: Turbidimetric method. β-Aryl-γ-perfluoroalkylamide derivatives were tested for their inhibitory effects on plant pathogens Xanthophyllotoxin (Xoo) and Xanthophyllotoxin (Xac). DMSO was used as a blank control, and chlorothalonil and thiophanate-methyl were used as positive controls.

[0274] Test steps: The constant temperature shaker is controlled at 28℃ and 180rpm. Xoo and Xac pathogens are inoculated into NB medium respectively and cultured to the logarithmic phase. Different concentrations of the test compound and the positive control drug are prepared into toxic NB liquid medium. 40μL of NB medium containing plant pathogens in the logarithmic phase is added to each medium. The mixture is shaken in a constant temperature shaker at 28℃ / 180rpm. The rice bacterial blight pathogen is cultured for about 36 hours and the citrus canker pathogen is cultured for about 48 hours. The OD value of the blank control group in the shaker is 0. 595 When the cells were in the logarithmic growth phase, the OD values of the blank control group, positive control drug and compound were measured at 595 nm by a microplate reader.

[0275] The calculation formulas for corrected OD value and inhibition rate are as follows:

[0276] Corrected OD value = OD value of bacteria-containing culture medium - OD value of sterile culture medium.

[0277] Inhibition rate (%) = [(corrected OD value of the bacterial solution in the control culture medium - corrected OD value of the toxic culture medium) / corrected OD value of the bacterial solution in the control culture medium] × 100.

[0278] The examples of the present invention are used to illustrate the technical solutions of the present invention, but the contents of the examples are not limited thereto. The plant pathogenic bacteria inhibitory activities of the target compounds are shown in Tables 1 and 2.

[0279] Table 1 Inhibitory activity of target compounds against plant pathogenic bacteria XAC

[0280]

[0281]

[0282] Table 2 Inhibitory activity of target compounds against plant pathogenic bacteria XOO

[0283] serial number XOO inhibition rate (%) (100 μg / mL) Inhibition rate 4c 57.88 57.88±0.45 4d 81.22 81.22±1.45 4e 14.57 14.57±1.25 4l 80.30 80.30±1.77 4m 78.25 78.25±1.4 4o 36.28 36.28±1.74 4p 13.80 13.80±1.31 4s 79.32 79.32±1.45 4t 35.97 35.97±5.43 4u 13.75 13.75±3.8 4v 18.73 18.73±4.85 4ab 50.13 50.13±2.23 BT 82.35 82.35±1.8 TC 48.18 48.18±2.95 CK 0 0

[0284] The experimental activity data above demonstrate that the tested derivatives exhibited good antibacterial activity against plant pathogens. At 50 μg / mL, many tested products exhibited significant inhibitory activity against Xac. Some products demonstrated excellent inhibitory activity, superior to or equivalent to the commercial fungicides BT and TC. The antibacterial activity results for Xoo measured at 100 μg / mL were impressive. Some compounds, such as 4d, 4l, 4m, and 4s, exhibited inhibition rates of around 80% against Xoo, indicating their potential for development as effective fungicides for crop protection. These compounds may serve as potential drug candidates for inhibiting plant pathogens and possess considerable research and development value.

Claims

1. β-aryl-γ-perfluoroalkylamide derivatives, characterized in that: The structural formula of the derivative is as follows: Wherein, R1 is hydrogen or methyl; R2 is methyl, isopropyl, cyclohexyl, benzyl or heterocyclic methylene; R3 is hydrogen, methyl or halogen; n is 1, 4, 6, 8 or 10.

2. The derivative according to claim 1, characterized in that: Ar is an ortho-substituted benzene ring, a para-substituted benzene ring, a disubstituted benzene ring, a nitrogen-containing heterocycle or a substituted furan ring.

3. A method for synthesizing the β-aryl-γ-perfluoroalkylamide derivative according to any one of claims 1 to 2 by carbene-catalyzed para-acylation / migration of aromatic hydrocarbons, characterized in that: Aldehyde, ene amide, fluorine source, carbene catalyst, base and solvent are placed in N2 atmosphere and reacted under heating and stirring conditions, then water is added to quench, extracted with ethyl acetate, and the solvent is removed under vacuum to obtain a crude material. The crude material is purified by silica gel column chromatography to obtain the target compound β-aryl-γ-perfluoroalkylamide derivative.

4. The method according to claim 3, wherein: The reaction equation is as follows:

5. The method according to claim 3, wherein: The molar ratio of the aldehyde, eneamide, fluorine source, carbene catalyst and base is 1:2:2:0.02:0.

02.

6. The method according to claim 3, wherein: The solvent is dimethyl sulfoxide, acetonitrile or ethyl acetate.

7. The method according to claim 3, wherein: The carbene catalyst is NHC-1, NHC-2, NHC-3, NHC-4, NHC-5, NHC-6, NHC-7, NHC-8, NHC-9 or NHC-10.

8. The method according to claim 3, wherein: The base is rubidium carbonate, cesium carbonate, tetramethylguanidine, potassium phosphate, sodium benzoate or sodium ethanol.

9. The method according to claim 3, wherein: The heating temperature is 10-70°C.

10. Use of the derivative according to any one of claims 1 to 2 in the preparation of drugs for resisting plant pathogens and bacterial diseases.

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