2-fluoroalkyl quinoline derivative and synthesis method thereof

Abstract

The invention discloses a synthesis method of a 2-fluoroalkyl quinoline derivative, and relates to the technical field of organic synthesis, in particular to the synthesis method of the 2-fluoroalkyl quinoline derivative, which comprises the following steps: in the presence of an inert atmosphere and a catalyst, mixing and reacting o-alkenyl aryl isonitrile, perfluoroalkyl iodide and alkali in a solvent to obtain the 2-fluoroalkyl quinoline derivative. The 2-fluoroalkyl quinoline derivative is obtained; o-alkenyl aryl isonitrile and perfluoroalkyl iodide react under the promotion of ferric fluoride as a catalyst, cesium carbonate as alkali and N, N-dimethylformamide as a solvent to synthesize the 2-fluoroalkyl quinoline derivative, the technological process is simple, no special instrument or mode is needed, the method is very suitable for personnel in the field to operate, and the method has the advantages that operation is easy and convenient, and the product is easy to obtain.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthesis, and more specifically to a 2-fluoroalkylquinoline derivative and a synthesis method thereof. Background Art

[0002] Quinoline and its derivatives are key structural components of many natural products and drugs, and they have a wide range of biological activities (J. Org. Chem., 2008, 73, 4464–4475). Fluorinated compounds have attracted great attention from synthetic chemists and medicinal chemists due to their unique physical and biological properties, among which the substitution of aromatic hydrogen atoms by perfluoroalkyl groups has a great influence on the biological activity of quinoline. It has been found that 2-fluoroalkyl-substituted quinoline derivatives can enhance their biological properties, and these structures have been widely used in drug research (Chem. Pharm. Bull., 2001 49, 480–483). In particular, trifluoromethylated quinoline compounds have special biological properties. For example, 2-trifluoromethylquinoline has important pharmacological significance (J. Med. Chem., 1971, 14, 926–928) because they are used as effective antimalarial drugs (mefloquine), PDE4 inhibitors, DPP-IV inhibitors, and bactericides. Other 2-trifluoromethylquinolines also show strong anticancer effects and therapeutic properties for dementia and schizophrenia.

[0003] Given the importance of fluoroquinoline compounds, people have been committed to developing an effective method to synthesize trifluoromethylated quinoline derivatives. Traditional synthetic methods (Org. Lett., 2008, 10, 2657–2659; J. Fluor.Chem., 2012, 135, 195–199; Chem. Commun., 2010, 46, 2145–2147) mostly require the use of highly modified fluorinated substrates as starting materials, and these fluorinated substrates usually require multiple steps of reaction to pre-prepare or introduce fluorinated groups. Therefore, it is very necessary to develop a general and simple method to construct 2-fluoroalkylquinoline skeletons from readily available raw materials. Summary of the invention

[0004] The object of the present invention is to provide a 2-fluoroalkylquinoline derivative and a synthesis method thereof to solve the above-mentioned deficiencies. The synthesis method of the 2-fluoroalkylquinoline derivative provided by the present invention uses o-alkenyl aryl isonitrile and perfluoroalkyl iodide as reaction raw materials, has a simple technical process, high yield, low pollution, and is environmentally friendly and safe.

[0005] In order to achieve the above-mentioned purpose, the present invention specifically adopts the following technical solutions: The present invention provides a method for synthesizing a 2-fluoroalkylquinoline derivative, comprising: mixing an ortho-alkenyl aryl isonitrile, a perfluoroalkyl iodide and a base in a solvent in the presence of an inert atmosphere and a catalyst, and reacting the mixture to obtain a 2-fluoroalkylquinoline derivative; The structural formula of the ortho-alkenyl aryl isonitrile is shown in Formula I: Formula I; In Formula I, Ar is one of phenyl, 4-methylphenyl, 4-tert-butylphenyl, 6-methoxyphenyl, 3,5-dimethylphenyl, 5-fluorophenyl, 5-chlorophenyl, 5-bromophenyl, and naphthyl; R is one of methyl, phenyl, 4-methylphenyl, 4-fluorophenyl, and 4-chlorophenyl; The structural formula of the perfluoroalkyl iodide is shown in Formula II: R f IForm II; In Formula II, R f It is one of trifluoromethyl, pentafluoropropyl, perfluorobutyl, perfluorohexyl, perfluorooctyl and perfluorodecyl.

[0006] In the synthesis method of the 2-fluoroalkylquinoline derivatives of the present invention, the chemical reaction formula is as follows: .

[0007] The mechanism of the present invention is as follows: Taking perfluorobutyl iodide as an example, first, perfluorobutyl iodide is homolytically cleaved in the presence of Cs2CO3 to generate perfluoroalkyl A. Subsequently, perfluoroalkyl A undergoes free radical addition with the isonitrile moiety to generate imine B, which undergoes a six-membered cyclization reaction to generate a more stable free radical C. Free radical C is further deprotonated under alkaline conditions to generate free radical anion D. Finally, free radical anion D reacts with perfluorobutyl iodide through a single electron transfer process to generate the desired product and perfluoroalkyl A. The possible reaction mechanism chemical reaction formula is as follows: .

[0008] Further, the ortho-alkenyl aromatic isonitrile is selected from 1-isocyano-2-(1-phenylvinyl)benzene, 1-isocyano-4-methyl-2-(1-phenylvinyl)benzene, 1-isocyano-4-tert-butyl-2-(1-phenylvinyl)benzene, 1-isocyano-6-methoxy-2-(1-phenylvinyl)benzene, 1-isocyano-3,5-dimethyl-2-(1-phenylvinyl)benzene, 5-fluoro-1-isocyano-2-(1-phenylvinyl)benzene, 5-chloro-1-isocyano-2- At least one of (1-phenylvinyl)benzene, 5-bromo-1-isonitiy-2-(1-phenylvinyl)benzene, 1-isonitiy-2-(1-phenylvinyl)naphthalene, 1-isonitiy-2-(1-(p-tolyl)vinyl)benzene, 2-(1-(4-fluorophenyl)vinyl)-1-isonitiy-benzene, 2-(1-(4-chlorophenyl)vinyl)-1-isonitiy-benzene, 2-(1-methylvinyl)-1-isonitiy-benzene and 1-isonitiy-2-(1-methylvinyl)benzene.

[0009] Furthermore, the perfluoroalkyl iodide is at least one selected from perfluorobutyl iodide, trifluoromethyl iodide, pentafluoropropyl iodide, perfluorohexyl iodide, perfluorooctyl iodide and perfluorodecyl iodide.

[0010] Furthermore, the inert atmosphere is selected from at least one of nitrogen and argon.

[0011] Furthermore, the catalyst is selected from at least one of ferric fluoride, nickel chloride, cobalt chloride and ferrous fluoride.

[0012] Furthermore, the base is selected from at least one of cesium carbonate, potassium carbonate, potassium phosphate, sodium carbonate and triethylamine.

[0013] Furthermore, the solvent is selected from at least one of N,N-dimethylformamide, toluene, N,N-dimethylacetamide, 1,4-dioxane, and N-methylpyrrolidone.

[0014] Furthermore, the reaction conditions include: temperature of 100° C. to 120° C. and time of 12 hours.

[0015] Furthermore, the dosage ratio of the ortho-alkenyl aryl isonitrile, perfluoroalkyl iodide, catalyst, base and solvent is 0.2 mmol: 0.6 mmol: 0.02 mmol: 0.6 mmol: 2 mL.

[0016] Furthermore, after the reaction is completed, the product is filtered, the filtrate is washed with a saturated sodium chloride solution, extracted with ethyl acetate and dried with anhydrous sodium sulfate, the combined organic layer is evaporated using a rotary evaporator, the solvent is removed to obtain a residue, the residue is eluted through a silica gel column with an eluent prepared by ethyl acetate and petroleum ether in a volume ratio of (1:100), the effluent is collected according to the actual gradient, detected by TLC, the effluent containing the target product is combined, the combined effluent is rotated on a rotary evaporator to remove the solvent, and finally the target product is obtained by vacuum drying.

[0017] Beneficial effects: The method for synthesizing the 2-fluoroalkylquinoline derivative provided by the present invention is to synthesize the 2-fluoroalkylquinoline derivative by reacting an ortho-alkenyl aryl isonitrile and a perfluoroalkyl iodide under the promotion of ferric fluoride as a catalyst, cesium carbonate as a base, and N,N-dimethylformamide as a solvent. The process is simple, no special instruments or methods are required, and the method is very suitable for operation by personnel in the field. The method has the advantages of simple operation, easy product acquisition, etc.

[0018] The synthesis method provided by the present invention can directly synthesize the target product without separating the intermediate product. The target product can be obtained by a simple separation method, and the yield can reach up to 81%, which greatly simplifies the process engineering, reduces energy consumption, and has excellent yield. In addition, less waste solution is produced during the reaction, and no other polluting gas and liquid are discharged. Therefore, the present invention reduces the discharge of waste solution, has the advantages of protecting the environment and ensuring the health of operators. In addition, the synthesis method can prepare a series of 2-fluoroalkylquinoline derivatives, and the method has good substrate universality.

[0019] Thus, the present invention fills the gap in the current method for preparing 2-fluoroalkylquinoline derivatives and promotes the development of 2-fluoroalkylquinoline derivatives. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0021] Figure 1 The hydrogen spectrum of the product of Example 1 of the present invention is shown 1 H NMR (400 MHz, CDCl3); Figure 2 The carbon spectrum of the product of Example 1 of the present invention is shown 13 C NMR (125 MHz, CDCl3); Figure 3 The fluorine spectrum of the product of Example 1 of the present invention is shown 19 F NMR (470 MHz, CDCl3); Figure 4 The hydrogen spectrum of the product of Example 2 of the present invention is shown 1 H NMR (400 MHz, CDCl3); Figure 5 The carbon spectrum of the product of Example 2 of the present invention is shown 13 C NMR (125 MHz, CDCl3); Figure 6 The fluorine spectrum of the product of Example 2 of the present invention is shown 19 F NMR (470 MHz, CDCl3); Figure 7 The hydrogen spectrum of the product of Example 3 of the present invention is shown 1 H NMR (400 MHz, CDCl3); Figure 8 The carbon spectrum of the product of Example 3 of the present invention is shown 13 C NMR (125 MHz, CDCl3); Fig. 9 The fluorine spectrum of the product of Example 3 of the present invention is shown 19 F NMR (470 MHz, CDCl3); Fig.10 The hydrogen spectrum of the product of Example 4 of the present invention is shown 1 H NMR (400 MHz, CDCl3); Fig.11 The carbon spectrum of the product of Example 4 of the present invention is shown 13 C NMR (125 MHz, CDCl3); Fig.12 The fluorine spectrum of the product of Example 4 of the present invention is shown 19 F NMR (470 MHz, CDCl3); Fig.13 The hydrogen spectrum of the product of Example 5 of the present invention is shown 1 H NMR (400 MHz, CDCl3); Fig.14 The carbon spectrum of the product of Example 5 of the present invention is shown 13 C NMR (125 MHz, CDCl3); Fig.15 The fluorine spectrum of the product of Example 5 of the present invention is shown 19F NMR (470 MHz, CDCl3); Fig.16 The hydrogen spectrum of the product of Example 6 of the present invention is shown 1 H NMR (400 MHz, CDCl3); Fig.17 The carbon spectrum of the product of Example 6 of the present invention is shown 13 C NMR (125 MHz, CDCl3); Fig.18 The fluorine spectrum of the product of Example 6 of the present invention is shown 19 F NMR (470 MHz, CDCl3); Fig.19 The hydrogen spectrum of the product of Example 7 of the present invention is shown 1 H NMR (400 MHz, CDCl3); Fig. 20 The carbon spectrum of the product of Example 7 of the present invention is shown 13 C NMR (125 MHz, CDCl3); Fig.21 The fluorine spectrum of the product of Example 7 of the present invention is shown 19 F NMR (470 MHz, CDCl3); Fig. 22 The hydrogen spectrum of the product of Example 8 of the present invention is shown 1 H NMR (400 MHz, CDCl3); Fig.23 The carbon spectrum of the product of Example 8 of the present invention is shown 13 C NMR (125 MHz, CDCl3); Fig.24 The fluorine spectrum of the product of Example 8 of the present invention is shown 19 F NMR (470 MHz, CDCl3); Fig.25 The hydrogen spectrum of the product of Example 9 of the present invention is shown 1 H NMR (400 MHz, CDCl3); Fig.26 The carbon spectrum of the product of Example 9 of the present invention is shown 13 C NMR (125 MHz, CDCl3); Fig. 27 The fluorine spectrum of the product of Example 9 of the present invention is shown 19 F NMR (470 MHz, CDCl3); Fig.28The hydrogen spectrum of the product of Example 10 of the present invention is shown 1 H NMR (400 MHz, CDCl3); Fig.29 The carbon spectrum of the product of Example 10 of the present invention is shown 13 C NMR (125 MHz, CDCl3); Fig.30 The fluorine spectrum of the product of Example 10 of the present invention is shown 19 F NMR (470 MHz, CDCl3); Fig.31 The hydrogen spectrum of the product of Example 11 of the present invention is shown 1 H NMR (400 MHz, CDCl3); Fig.32 The carbon spectrum of the product of Example 11 of the present invention is shown 13 C NMR (125 MHz, CDCl3); Fig.33 The fluorine spectrum of the product of Example 11 of the present invention is shown 19 F NMR (470 MHz, CDCl3); Fig.34 The hydrogen spectrum of the product of Example 12 of the present invention is shown 1 H NMR (400 MHz, CDCl3); Fig.35 The carbon spectrum of the product of Example 12 of the present invention is shown 13 C NMR (125 MHz, CDCl3); Fig.36 The fluorine spectrum of the product of Example 12 of the present invention is shown 19 F NMR (470 MHz, CDCl3); Fig.37 The hydrogen spectrum of the product of Example 13 of the present invention is shown 1 H NMR (400 MHz, CDCl3); Fig.38 The carbon spectrum of the product of Example 13 of the present invention is shown 13 C NMR (125 MHz, CDCl3); Fig.39 The fluorine spectrum of the product of Example 13 of the present invention is shown 19 F NMR (470 MHz, CDCl3); Fig.40 The hydrogen spectrum of the product of Example 14 of the present invention is shown 1H NMR (400 MHz, CDCl3); Fig.41 The carbon spectrum of the product of Example 14 of the present invention is shown 13 C NMR (125 MHz, CDCl3); Fig.42 The fluorine spectrum of the product of Example 14 of the present invention is shown 19 F NMR (470 MHz, CDCl3); Fig.43 The hydrogen spectrum of the product of Example 15 of the present invention is shown 1 H NMR (400 MHz, CDCl3); Fig.44 The carbon spectrum of the product of Example 15 of the present invention is shown 13 C NMR (125 MHz, CDCl3); Fig.45 The fluorine spectrum of the product of Example 15 of the present invention is shown 19 F NMR (470 MHz, CDCl3); Fig.46 The hydrogen spectrum of the product of Example 16 of the present invention is shown 1 H NMR (400 MHz, CDCl3); Fig.47 The carbon spectrum of the product of Example 16 of the present invention is shown 13 C NMR (125 MHz, CDCl3); Fig.48 The fluorine spectrum of the product of Example 16 of the present invention is shown 19 F NMR (470 MHz, CDCl3); Fig.49 The hydrogen spectrum of the product of Example 17 of the present invention is shown 1 H NMR (400 MHz, CDCl3); Fig.50 The carbon spectrum of the product of Example 17 of the present invention is shown 13 C NMR (125 MHz, CDCl3); Fig.51 The fluorine spectrum of the product of Example 17 of the present invention is shown 19 F NMR (470 MHz, CDCl3); Fig.52 The hydrogen spectrum of the product of Example 18 of the present invention is shown 1 H NMR (400 MHz, CDCl3); Fig.53 The carbon spectrum of the product of Example 18 of the present invention is shown 13 C NMR (125 MHz, CDCl3); Fig.54 The fluorine spectrum of the product of Example 18 of the present invention is shown 19 F NMR (470 MHz, CDCl3). DETAILED DESCRIPTION

[0022] The present invention will be further explained below in conjunction with the embodiments.

[0023] The raw materials and reagents used in the present invention are all commonly available on the market.

[0024] Example 1 This embodiment provides a method for synthesizing a 2-fluoroalkylquinoline derivative 1-Isononitrile-2-(1-phenylvinyl)benzene (0.2 mmol), perfluorobutyl iodide (0.6 mmol), iron trifluoride (2.0 mg), and cesium carbonate (195.5 mg) were added to N,N-dimethylformamide (2 mL) and stirred at 110 °C. o C and stirred in a nitrogen atmosphere for 12 hours. The reaction solution was filtered to obtain a filtrate and washed with a saturated sodium chloride solution, extracted with ethyl acetate and dried with anhydrous sodium sulfate, and the filtrate was removed by a rotary evaporator to obtain a residue. The residue was eluted with an eluent prepared by ethyl acetate and petroleum ether in a volume ratio of 1:100 through a silica gel column, and the effluent was collected according to the actual gradient. After TLC detection, the effluent containing the target product was combined, and the combined effluent was rotated to remove the solvent by a rotary evaporator, and vacuum dried to obtain 64.3 mg of white solid 2-(perfluorobutyl)-4-phenylquinoline, with a yield of 76%. (The theoretical amount of the product obtained by 100% conversion of 0.2 mmol of raw material is 84.6 mg, and the yield is the actual amount separated divided by the theoretical amount, that is, 64.3 / 84.6=76%) 1 H NMR (400 MHz, CDCl3) δ 8.32 (d, J = 8.4 Hz, 1H), 8.01 (d, J = 8.4 Hz,1H), 7.85 – 7.81 (m, 1H), 7.68 (s, 1H), 7.66 – 7.62 (m, 1H), 7.56 – 7.53 (m,5H). 13 C NMR (125 MHz, CDCl3) δ 150.5, 148.0, 147.2 (t, J= 22.5 Hz), 137.1,130.7, 130.5, 129.6, 129.0, 128.8, 128.7, 127.2, 125.9, 118.4. 19 F NMR (470 MHz, CDCl3) δ -80.87 – -80.92 (m, 3F), -113.61 – -113.67 (m, 2F), -122.19 – -122.21 (m, 2F), -125.46 – -125.52 (m, 2F).

[0025] Example 2 This embodiment provides a method for synthesizing a 2-fluoroalkylquinoline derivative 1-Isononitrile-4-methyl-2-(1-phenylvinyl)benzene (0.2 mmol), perfluorobutyl iodide (0.6 mmol), iron trifluoride (2.0 mg) and cesium carbonate (195.5 mg) were added to N,N-dimethylformamide (2 mL) and stirred at 110 °C. o C and stirred in a nitrogen atmosphere for 12 hours. The reaction solution was filtered to obtain a filtrate, which was washed with a saturated sodium chloride solution, extracted with ethyl acetate and dried with anhydrous sodium sulfate, and the filtrate was subjected to a rotary evaporator to remove the solvent to obtain a residue, which was eluted through a silica gel column with an eluent prepared by ethyl acetate and petroleum ether in a volume ratio of 1:100, and the effluent was collected according to the actual gradient, detected by TLC, and the effluent containing the target product was combined, and the combined effluent was subjected to a rotary evaporator to remove the solvent, and vacuum dried to obtain 65.5 mg of white solid 6-methyl-2-perfluorobutyl-4-phenylquinoline with a yield of 75%.

[0026] 1 H NMR (400 MHz, CDCl3) δ 8.21 (d, J = 8.4 Hz, 1H), 7.74 (s, 1H), 7.70 –7.63 (m, 2H), 7.56 – 7.54 (m, 5H), 2.52 (s, 3H). 13 C NMR (125 MHz, CDCl3) δ 149.6, 146.6, 146.2 (t, J = 24.8 Hz), 139.1,137.3, 132.8, 130.4, 129.5, 128.9, 128.8, 127.2, 124.5, 118.6, 22.0. 19F NMR (470 MHz, CDCl3) δ -80.89 – -80.93 (m, 3F), -113.57 – -113.63 (m, 2F), -122.24– -122.26 (m, 2F), -125.49 – -125.55 (m, 2F).

[0027] Example 3 This embodiment provides a method for synthesizing a 2-fluoroalkylquinoline derivative 1-Isononitrile-4-tert-butyl-2-(1-phenylethylene)benzene (0.2 mmol), perfluorobutyl iodide (0.6 mmol), iron trifluoride (2.0 mg) and cesium carbonate (195.5 mg) were added to N,N-dimethylformamide (2 mL) and stirred at 110 °C. o C and stirred in a nitrogen atmosphere for 12 hours. The reaction solution was filtered to obtain a filtrate, which was washed with a saturated sodium chloride solution, extracted with ethyl acetate and dried with anhydrous sodium sulfate, and the filtrate was subjected to a rotary evaporator to remove the solvent to obtain a residue, which was eluted through a silica gel column with an eluent prepared by ethyl acetate and petroleum ether in a volume ratio of 1:100, and the effluent was collected according to the actual gradient. After TLC detection, the effluent containing the target product was combined, and the combined effluent was subjected to a rotary evaporator to remove the solvent, and vacuum dried to obtain 75.0 mg of 6-tert-butyl-2-perfluorobutyl-4-phenylquinoline as a yellow oily liquid with a yield of 78%.

[0028] 1 H NMR (400 MHz, CDCl3) δ 8.19 (d, J = 8.4 Hz, 1H), 7.88 – 7.86 (m, 2H), 7.58 (s, 1H), 7.53 – 7.46 (m, 5H), 1.29 (s, 9H). 13 C NMR (125 MHz, CDCl3) δ 151.9, 150.1, 146.6, 146.4 (t, J = 25.3 Hz),137.4, 130.2, 129.6, 129.5, 128.9, 128.8, 126.8, 120.6, 118.5, 35.3, 31.0. 19F NMR (470 MHz, CDCl3) δ -80.89 – -80.93 (m, 3F), -113.56 – -113.65 (m, 2F), -122.24 – -122.27 (m, 2F), -125.46 – -125.52 (m, 2F).

[0029] Example 4 This embodiment provides a method for synthesizing a 2-fluoroalkylquinoline derivative 1-Isocyano-6-methoxy-2-(1-phenylvinyl)benzene (0.2 mmol), perfluorobutyl iodide (0.6 mmol), iron trifluoride (2.0 mg) and cesium carbonate (195.5 mg) were added to N,N-dimethylformamide (2 mL) and stirred at 110 °C. o C and stirred in a nitrogen atmosphere for 12 hours. The reaction solution was filtered to obtain a filtrate, which was washed with a saturated sodium chloride solution, extracted with ethyl acetate and dried with anhydrous sodium sulfate, and the filtrate was subjected to a rotary evaporator to remove the solvent to obtain a residue, which was eluted through a silica gel column with an eluent prepared by ethyl acetate and petroleum ether in a volume ratio of 1:100, and the effluent was collected according to the actual gradient. After TLC detection, the effluent containing the target product was combined, and the combined effluent was subjected to a rotary evaporator to remove the solvent, and vacuum dried to obtain 61.6 mg of white solid 8-methoxy-2-perfluorobutyl-4-phenylquinoline with a yield of 68%.

[0030] 1 H NMR (400 MHz, CDCl3) δ 7.69 (s, 1H), 7.54 – 7.52 (m, 7H), 7.17 –7.14 (m, 1H), 4.12 (s, 3H). 13 C NMR (125 MHz, CDCl3) δ 156.3, 150.2, 145.63 (t, J = 22.9 Hz), 140.2,137.5, 129.5, 129.0, 128.9, 128.7, 128.5, 119.6, 117.4, 108.9, 56.6. 19 F NMR (470 MHz, CDCl3) δ -80.85 – -80.90 (m, 3F), -113.29 – -113.35 (m, 2F), -121.92– -121.94 (m, 2F), -125.42 – -125.49 (m, 2F).

[0031] Example 5 This embodiment provides a method for synthesizing a 2-fluoroalkylquinoline derivative 1-Isononitrile-3,5-dimethyl-2-(1-phenylvinyl)benzene (0.2 mmol), perfluorobutyl iodide (0.6 mmol), iron trifluoride (2.0 mg) and cesium carbonate (195.5 mg) were added to N,N-dimethylformamide (2 mL) and stirred at 110 °C. o C and stirred in a nitrogen atmosphere for 12 hours. The reaction solution was filtered to obtain a filtrate, which was washed with a saturated sodium chloride solution, extracted with ethyl acetate and dried with anhydrous sodium sulfate, and the filtrate was subjected to a rotary evaporator to remove the solvent to obtain a residue, which was eluted through a silica gel column with an eluent prepared by ethyl acetate and petroleum ether in a volume ratio of 1:100, and the effluent was collected according to the actual gradient. After TLC detection, the effluent containing the target product was combined, and the combined effluent was subjected to a rotary evaporator to remove the solvent, and vacuum dried to obtain 65.8 mg of 5,7-dimethyl-2-(perfluorobutyl)-4-phenylquinoline as a yellow oily liquid with a yield of 73%.

[0032] 1 H NMR (400 MHz, CDCl3) δ 7.98 (s, 1H), 7.47 – 7.46 (m, 4H), 7.34 –7.33 (m, 2H), 7.26 (s, 1H), 2.53 (s, 3H), 2.01 (s, 3H). 13 C NMR (125 MHz, CDCl3) δ 150.6, 149.4, 145.8 (t, J = 24.1 Hz), 141.6,140.5, 135.3, 134.3, 128.7, 128.4, 128.2, 128.1, 124.9, 119.7, 24.3, 21.4. 19 F NMR (470 MHz, CDCl3) δ -80.90 – -80.95 (m, 3F), -113.78 – -113.84 (m, 2F), -122.28 – -122.30 (m, 2F), -125.50 – -125.56 (m, 2F).

[0033] Example 6 This embodiment provides a method for synthesizing a 2-fluoroalkylquinoline derivative 5-Fluoro-1-isonitro-2-(1-phenylvinyl)benzene (0.2 mmol), perfluorobutyl iodide (0.6 mmol), iron trifluoride (2.0 mg) and cesium carbonate (195.5 mg) were added to N,N-dimethylformamide (2 mL) and stirred at 110 °C. o C and stirred in a nitrogen atmosphere for 12 hours. The reaction solution was filtered to obtain a filtrate, which was washed with a saturated sodium chloride solution, extracted with ethyl acetate and dried with anhydrous sodium sulfate, and the filtrate was subjected to a rotary evaporator to remove the solvent to obtain a residue, which was eluted through a silica gel column with an eluent prepared by ethyl acetate and petroleum ether in a volume ratio of 1:100, and the effluent was collected according to the actual gradient, detected by TLC, and the effluent containing the target product was combined, and the combined effluent was subjected to a rotary evaporator to remove the solvent, and vacuum dried to obtain 62.6 mg of 7-fluoro-2-(perfluorobutyl)-4-phenylquinoline as a yellow oily liquid with a yield of 71%.

[0034] 1 H NMR (400 MHz, CDCl3) δ 8.08 (d, J = 8.4 Hz, 1H), 7.73 – 7.68 (m, 1H), 7.54 (s, 1H), 7.42 – 7.37 (m, 5H), 7.22 – 7.18 (m, 1H). 13 C NMR (125 MHz, CDCl3) δ 158.1 (d, J = 258.7 Hz), 149.1, 148.6, 147.8(t, J = 25.2 Hz), 139.4, 130.3, 128.5, 128.46, 128.0, 1271, 120.6, 118.0, 113.8(d, J = 21.3 Hz). 19 F NMR (470 MHz, CDCl3) δ -80.88 – -80.93 (m, 3F), -104.89 (s, 1F), -113.79 – -113.85 (m, 2F), -122.18 – -122.20 (m, 2F), -125.46 – -125.52 (m,2F).

[0035] Example 7 This embodiment provides a method for synthesizing a 2-fluoroalkylquinoline derivative 5-Chloro-1-isocyanato-2-(1-phenylvinyl)benzene (0.2 mmol), perfluorobutyl iodide (0.6 mmol), iron trifluoride (2.0 mg) and cesium carbonate (195.5 mg) were added to N,N-dimethylformamide (2 mL) and stirred at 110 °C. o C and stirred in a nitrogen atmosphere for 12 hours. The reaction solution was filtered to obtain a filtrate, which was washed with a saturated sodium chloride solution, extracted with ethyl acetate and dried with anhydrous sodium sulfate, and the filtrate was subjected to a rotary evaporator to remove the solvent to obtain a residue, which was eluted through a silica gel column with an eluent prepared by ethyl acetate and petroleum ether in a volume ratio of 1:100, and the effluent was collected according to the actual gradient. After TLC detection, the effluent containing the target product was combined, and the combined effluent was subjected to a rotary evaporator to remove the solvent, and vacuum dried to obtain 65.8 mg of 7-chloro-2-(perfluorobutyl)-4-phenylquinoline as a yellow oily liquid with a yield of 72%.

[0036] 1 H NMR (400 MHz, CDCl3) δ 8.29 – 8.26 (m, 1H), 7.75 – 7.69 (m, 2H), 7.64 (s, 1H), 7.47 – 7.46 (m, 3H), 7.37 – 7.34 (m, 2H). 13 C NMR (125 MHz, CDCl3) δ 150.6, 149.4, 147.0 (t, J = 25.9 Hz), 139.9,131.6, 131.1, 130.6, 130.1, 128.9, 128.3, 127.9, 125.1, 121.8. 19 F NMR (470 MHz, CDCl3) δ -80.87 – -80.92 (m, 3F), -113.67 – -113.73 (m, 2F), -122.21– -122.23 (m, 2F), -125.47 – -125.53 (m, 2F).

[0037] Example 8 This embodiment provides a method for synthesizing a 2-fluoroalkylquinoline derivative 5-Bromo-1-isonitro-2-(1-phenylvinyl)benzene (0.2 mmol), perfluorobutyl iodide (0.6 mmol), iron trifluoride (2.0 mg) and cesium carbonate (195.5 mg) were added to N,N-dimethylformamide (2 mL) and stirred at 110 °C. oC and stirred in a nitrogen atmosphere for 12 hours. The reaction solution was filtered to obtain a filtrate, which was washed with a saturated sodium chloride solution, extracted with ethyl acetate and dried with anhydrous sodium sulfate, and the filtrate was subjected to a rotary evaporator to remove the solvent to obtain a residue, which was eluted through a silica gel column with an eluent prepared by ethyl acetate and petroleum ether in a volume ratio of 1:100, and the effluent was collected according to the actual gradient, detected by TLC, and the effluent containing the target product was combined, and the combined effluent was subjected to a rotary evaporator to remove the solvent, and vacuum dried to obtain 69.4 mg of 7-bromo-2-(perfluorobutyl)-4-phenylquinoline as a yellow oily liquid with a yield of 69%.

[0038] 1 H NMR (400 MHz, CDCl3) δ 8.31 (d, J = 8.4 Hz, 1H), 7.94 (d, J = 7.6 Hz,1H), 7.67 – 7.61 (m, 2H), 7.47 – 7.46 (m, 3H), 7.36 – 7.34 (m, 2H). 13 C NMR (125 MHz, CDCl3) δ 151.4, 149.4, 146.78 (t, J = 25.7 Hz), 139.3,136.0, 131.3, 130.5, 129.4, 128.5, 128.0, 126.1, 121.8, 119.2. 19 F NMR (470 MHz, CDCl3) δ -80.91 – -80.95 (m, 3F), -113.85 – -113.91 (m, 2F), -122.21 – -122.23 (m, 2F), -125.51 – -125.57 (m, 2F).

[0039] Example 9 This embodiment provides a method for synthesizing a 2-fluoroalkylquinoline derivative 1-Isononitrile-2-(1-phenylvinyl)naphthalene (0.2 mmol), perfluorobutyl iodide (0.6 mmol), iron trifluoride (2.0 mg) and cesium carbonate (195.5 mg) were added to N,N-dimethylformamide (2 mL) and stirred at 110 °C. oC and stirred in a nitrogen atmosphere for 12 hours. The reaction solution was filtered to obtain a filtrate, which was washed with a saturated sodium chloride solution, extracted with ethyl acetate and dried with anhydrous sodium sulfate, and the filtrate was subjected to a rotary evaporator to remove the solvent to obtain a residue, which was eluted through a silica gel column with an eluent prepared by ethyl acetate and petroleum ether in a volume ratio of 1:100, and the effluent was collected according to the actual gradient, detected by TLC, and the effluent containing the target product was combined, and the combined effluent was subjected to a rotary evaporator to remove the solvent, and vacuum dried to obtain 60.4 mg of 2-(perfluorobutyl)-4-phenylbenzo[h]quinoline as a yellow oily liquid with a yield of 64%. 1 H NMR (400 MHz, CDCl3) δ 9.42 (d, J = 8.4 Hz, 1H), 7.92 (d, J = 8.4 Hz,1H), 7.89 – 7.75 (m, 5H), 7.59 – 7.57 (m, 5H). 13 C NMR (125 MHz, CDCl3) δ 149.9, 146.6, 145.6 (t, J = 25.9 Hz), 137.6,133.5, 131.5, 130.0, 129.7, 129.1, 128.9, 128.8, 127.8, 127.6, 125.5, 125.4,122.4, 119.5. 19 F NMR (470 MHz, CDCl3) δ -80.84 – -80.89 (m, 3F), -113.69 – -113.75 (m, 2F), -122.16 – -122.18 (m, 2F), -125.32– -125.38 (m, 2F).

[0040] Example 10 This embodiment provides a method for synthesizing a 2-fluoroalkylquinoline derivative 1-Isononitrile-2-(1-(p-tolyl)vinyl)benzene (0.2 mmol), perfluorobutyl iodide (0.6 mmol), iron trifluoride (2.0 mg) and cesium carbonate (195.5 mg) were added to N,N-dimethylformamide (2 mL) and stirred at 110 °C. oC and stirred in a nitrogen atmosphere for 12 hours. The reaction solution was filtered to obtain a filtrate, which was washed with a saturated sodium chloride solution, extracted with ethyl acetate and dried with anhydrous sodium sulfate, and the filtrate was subjected to a rotary evaporator to remove the solvent to obtain a residue, which was eluted through a silica gel column with an eluent prepared by ethyl acetate and petroleum ether in a volume ratio of 1:100, and the effluent was collected according to the actual gradient, detected by TLC, and the effluent containing the target product was combined, and the combined effluent was subjected to a rotary evaporator to remove the solvent, and vacuum dried to obtain 68.2 mg of a yellow-brown solid 2-(perfluorobutyl)-4-(p-tolyl)quinoline with a yield of 78%.

[0041] 1 H NMR (400 MHz, CDCl3) δ 8.31 (d, J = 8.4 Hz, 1H), 8.04 (d, J = 8.4 Hz,1H), 7.85 – 7.81 (m, 1H), 7.67 – 7.61 (m, 2H), 7.44 (d, J = 8.0 Hz, 2H), 7.38(d, J = 8.0 Hz, 2H), 2.49 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 150.6, 148.0, 147.2 (t, J = 23.3 Hz), 139.1,134.2, 130.7, 130.4, 129.5, 128.6, 127.3, 125.9, 118.4, 113.5, 21.3. 19 F NMR (470 MHz, CDCl3) δ -80.89 – -80.94 (m, 3F), -113.61 – -113.67 (m, 2F), -122.20 – -122.22 (m, 2F), -125.46 – -125.52 (m, 2F).

[0042] Embodiment 11 This embodiment provides a method for synthesizing a 2-fluoroalkylquinoline derivative 2-(1-(4-Fluorophenyl)vinyl)-1-isonitrilebenzene (0.2 mmol), perfluorobutyl iodide (0.6 mmol), iron trifluoride (2.0 mg) and cesium carbonate (195.5 mg) were added to N,N-dimethylformamide (2 mL) and stirred at 110 °C. oC and stirred in a nitrogen atmosphere for 12 hours. The reaction solution was filtered to obtain a filtrate, which was washed with a saturated sodium chloride solution, extracted with ethyl acetate and dried with anhydrous sodium sulfate, and the filtrate was subjected to a rotary evaporator to remove the solvent to obtain a residue, which was eluted through a silica gel column with an eluent prepared by ethyl acetate and petroleum ether in a volume ratio of 1:100, and the effluent was collected according to the actual gradient, detected by TLC, and the effluent containing the target product was combined, and the combined effluent was subjected to a rotary evaporator to remove the solvent, and vacuum dried to obtain 70.5 mg of yellow solid 4-(4-fluorophenyl)-2-(perfluorobutyl)quinoline with a yield of 80%.

[0043] 1 H NMR (400 MHz, CDCl3) δ 8.24 (d, J = 8.4 Hz, 1H), 7.88 (d, J = 8.4 Hz,1H), 7.78 – 7.75 (m, 1H), 7.59 – 7.56 (m, 2H), 7.46 – 7.42 (m, 2H), 7.21 –7.17 (m, 2H). 13 C NMR (100 MHz, CDCl3) δ 163.3 (d, J = 248 Hz), 149.4, 148.0, 147.2(t, J = 23.6 Hz), 133.1, 131.4, 130.8, 130.6, 128.9, 127.2, 125.6, 118.5, 116.0(d, J = 21.8 Hz). 19 F NMR (470 MHz, CDCl3) δ -80.89 – -80.94 (m, 3F), -112.16 (s, 1F), -113.58 – -113.64 (m, 2F), -122.17 – -122.19 (m, 2F), -125.45 – -125.51 (m,2F).

[0044] Example 12 This embodiment provides a method for synthesizing a 2-fluoroalkylquinoline derivative 2-(1-(4-chlorophenyl)vinyl)-1-isonitrilebenzene (0.2 mmol), perfluorobutyl iodide (0.6 mmol), iron trifluoride (2.0 mg) and cesium carbonate (195.5 mg) were added to N,N-dimethylformamide (2 mL) and stirred at 110 °C.o C and stirred in a nitrogen atmosphere for 12 hours. The reaction solution was filtered to obtain a filtrate, which was washed with a saturated sodium chloride solution, extracted with ethyl acetate and dried with anhydrous sodium sulfate, and the filtrate was subjected to a rotary evaporator to remove the solvent to obtain a residue, which was eluted through a silica gel column with an eluent prepared by ethyl acetate and petroleum ether in a volume ratio of 1:100, and the effluent was collected according to the actual gradient, detected by TLC, and the effluent containing the target product was combined, and the combined effluent was subjected to a rotary evaporator to remove the solvent, and vacuum dried to obtain 74.0 mg of yellow solid 4-(4-chlorophenyl)-2-(perfluorobutyl)quinoline with a yield of 81%.

[0045] 1 H NMR (400 MHz, CDCl3) δ 8.25 (d, J = 8.4 Hz, 1H), 7.88 (d, J = 8.4 Hz,1H), 7.80 – 7.76 (m, 1H), 7.60 – 7.58 (m, 2H), 7.49 – 7.40 (m, 4H). 13 C NMR (125 MHz, CDCl3) δ 163.3 (d, J = 248 Hz), 149.2, 147.9, 147.2(t, J = 25.3 Hz), 135.5, 135.4, 130.8, 130.7, 129.1, 129.0, 127.0, 125.5,118.3, 115.2. 19 F NMR (470 MHz, CDCl3) δ -80.89 – -80.93 (m, 3F), -113.56 – -113.63 (m, 2F), -122.16 – -122.19 (m, 2F), -125.44 – -125.50 (m, 2F).

[0046] Embodiment 13 This embodiment provides a method for synthesizing a 2-fluoroalkylquinoline derivative 2-(1-Methylvinyl)-1-isonitrile benzene (0.2 mmol), perfluorobutyl iodide (0.6 mmol), iron trifluoride (2.0 mg) and cesium carbonate (195.5 mg) were added to N,N-dimethylformamide (2 mL) and stirred at 110 °C. oC and stirred in a nitrogen atmosphere for 12 hours. The reaction solution was filtered to obtain a filtrate, which was washed with a saturated sodium chloride solution, extracted with ethyl acetate and dried with anhydrous sodium sulfate, and the filtrate was subjected to a rotary evaporator to remove the solvent to obtain a residue, which was eluted through a silica gel column with an eluent prepared by ethyl acetate and petroleum ether in a volume ratio of 1:100, and the effluent was collected according to the actual gradient, detected by TLC, and the effluent containing the target product was combined, and the combined effluent was subjected to a rotary evaporator to remove the solvent, and vacuum dried to obtain 43.3 mg of yellow solid 4-methyl-2-(perfluorobutyl)quinoline with a yield of 60%. 1 H NMR (400 MHz, CDCl3) δ 8.24 (d, J = 8.4 Hz, 1H), 8.07 (d, J = 8.4Hz, 1H), 7.81 (t, J = 7.6 Hz, 1H), 7.69 (t, J = 7.6 Hz, 1H), 7.57 (s, 1H),2.80 (s, 3H). 13 C NMR (125 MHz, CDCl3) δ 147.2 (t, J = 25.1 Hz), 147.1, 146.6,130.9, 130.3, 128.6, 128.4, 123.8, 118.8, 19.1. 19 F NMR (470 MHz, CDCl3) δ -80.90 – -80.95 (m, 3F), -113.84 – -113.90 (m, 2F), -122.34 – -122.37 (m, 2F), -125.52 – -125.58 (m, 2F).

[0047] Embodiment 14 This embodiment provides a method for synthesizing a 2-fluoroalkylquinoline derivative 1-Isononitrile-2-(1-phenylvinyl)benzene (0.2 mmol), trifluoromethyl iodide (0.6 mmol), iron trifluoride (2.0 mg) and cesium carbonate (195.5 mg) were added to N,N-dimethylformamide (2 mL) and stirred at 110 °C. oC and stirred in a nitrogen atmosphere for 12 hours. The reaction solution was filtered to obtain a filtrate, which was washed with a saturated sodium chloride solution, extracted with ethyl acetate and dried with anhydrous sodium sulfate, and the filtrate was subjected to a rotary evaporator to remove the solvent to obtain a residue, which was eluted through a silica gel column with an eluent prepared by ethyl acetate and petroleum ether in a volume ratio of 1:100, and the effluent was collected according to the actual gradient, detected by TLC, and the effluent containing the target product was combined, and the combined effluent was subjected to a rotary evaporator to remove the solvent, and vacuum dried to obtain 23.8 mg of 4-phenyl-2-(trifluoromethyl)quinoline as a yellow oily liquid with a yield of 52%. 1 H NMR (400 MHz, CDCl3) δ 8.21 (d, J = 8.4 Hz, 1H), 7.91 (d, J = 8.4 Hz,1H), 7.76 – 7.72 (m, 1H), 7.60 (s, 1H), 7.56 – 7.52 (m, 1H), 7.47 – 7.45 (m,5H). 13 C NMR (125 MHz, CDCl3) δ 150.9, 147.8, 147.5 (q, J = 34.3 Hz), 137.1,130.54, 130.50 129.5, 129.0, 128.8, 128.6, 127.4, 125.9, 121.6 (q, J = 275.1Hz), 117.0. 19 F NMR (470 MHz, CDCl3) δ -67.46.

[0048] Embodiment 15 This embodiment provides a method for synthesizing a 2-fluoroalkylquinoline derivative 1-Isononitrile-2-(1-phenylvinyl)benzene (0.2 mmol), pentafluoropropyl iodide (0.6 mmol), iron trifluoride (2.0 mg) and cesium carbonate (195.5 mg) were added to N,N-dimethylformamide (2 mL) and stirred at 110 °C. oC and stirred in a nitrogen atmosphere for 12 hours. The reaction solution was filtered to obtain a filtrate, which was washed with a saturated sodium chloride solution, extracted with ethyl acetate and dried with anhydrous sodium sulfate, and the filtrate was subjected to a rotary evaporator to remove the solvent to obtain a residue, which was eluted through a silica gel column with an eluent prepared by ethyl acetate and petroleum ether in a volume ratio of 1:100, and the effluent was collected according to the actual gradient, detected by TLC, and the effluent containing the target product was combined, and the combined effluent was subjected to a rotary evaporator to remove the solvent, and vacuum dried to obtain 56.6 mg of 4-phenyl-2-(pentafluoropropyl)quinoline as a yellow oily liquid with a yield of 76%.

[0049] 1 H NMR (400 MHz, CDCl3) δ 8.32 (d, J = 8.4 Hz, 1H), 8.01 (d, J = 8.4 Hz,1H), 7.85-7.82 (m, 1H), 7.67-7.62 (m, 2H), 7.56-7.54 (m, 5H). 13 C NMR (100 MHz, CDCl3) δ 150.5, 147.9, 147.0 (t, J = 24.4 Hz), 137.1,130.7, 130.5, 129.5, 129.0, 128.8, 128.7, 127.2, 125.9, 118.4. 19 F NMR (470 MHz, CDCl3) δ -80.04 – -80.08 (m, 3F), -114.35 – -114.41 (m, 2F), -125.86 – -125.8.93 (m, 2F).

[0050] Example 16 This embodiment provides a method for synthesizing a 2-fluoroalkylquinoline derivative 1-Isononitrile-2-(1-phenylvinyl)benzene (0.2 mmol), perfluorohexyl iodide (0.6 mmol), iron trifluoride (2.0 mg), and cesium carbonate (195.5 mg) were added to N,N-dimethylformamide (2 mL) and stirred at 110 °C. oC and stirred in a nitrogen atmosphere for 12 hours. The reaction solution was filtered to obtain a filtrate, which was washed with a saturated sodium chloride solution, extracted with ethyl acetate and dried with anhydrous sodium sulfate, and the filtrate was subjected to a rotary evaporator to remove the solvent to obtain a residue, which was eluted through a silica gel column with an eluent prepared by ethyl acetate and petroleum ether in a volume ratio of 1:100, and the effluent was collected according to the actual gradient, detected by TLC, and the effluent containing the target product was combined, and the combined effluent was subjected to a rotary evaporator to remove the solvent, and vacuum dried to obtain 80.5 mg of 4-phenyl-2-(perfluorohexyl)quinoline as a yellow oily liquid with a yield of 77%.

[0051] 1 H NMR (400 MHz, CDCl3) δ 8.32 (d, J = 8.4 Hz, 1H), 8.01 (d, J = 8.4 Hz,1H), 7.87 – 7.82 (m, 1H), 7.68 – 7.62 (m, 2H), 7.56 – 7.55 (m, 5H). 13 C NMR (100 MHz, CDCl3) δ 150.5, 147.9, 147.2 (t, J = 25.0 Hz), 137.1,130.7, 130.5, 129.6, 129.0, 128.8, 128.7, 127.2, 125.9, 118.5. 19 F NMR (470 MHz, CDCl3) δ -80.76 – -80.80 (m, 3F), -113.39 – -113.45 (m, 2F), -121.24 – -121.36 (m, 4F), -122.57 – -122.88 (m, 2F), -126.09 – -126.10 (m, 2F).

[0052] Embodiment 17 This embodiment provides a method for synthesizing a 2-fluoroalkylquinoline derivative 1-Isononitrile-2-(1-phenylvinyl)benzene (0.2 mmol), perfluorooctyl iodide (0.6 mmol), iron trifluoride (2.0 mg) and cesium carbonate (195.5 mg) were added to N,N-dimethylformamide (2 mL) and stirred at 110 °C. oC and stirred in a nitrogen atmosphere for 12 hours. The reaction solution was filtered to obtain a filtrate, which was washed with a saturated sodium chloride solution, extracted with ethyl acetate and dried with anhydrous sodium sulfate, and the filtrate was subjected to a rotary evaporator to remove the solvent to obtain a residue, which was eluted through a silica gel column with an eluent prepared by ethyl acetate and petroleum ether in a volume ratio of 1:100, and the effluent was collected according to the actual gradient, detected by TLC, and the effluent containing the target product was combined, and the combined effluent was subjected to a rotary evaporator to remove the solvent, and vacuum dried to obtain 93.4 mg of yellow oily liquid 4-phenyl-2-(perfluorooctyl)quinoline with a yield of 75%. 1 H NMR (400 MHz, CDCl3) δ 8.32 (d, J = 8.4 Hz, 1H), 8.01 (d, J = 8.4 Hz,1H), 7.85 – 7.82 (m, 1H), 7.68 – 7.62 (m, 2H), 7.56 – 7.54 (m, 5H). 13 C NMR (100 MHz, CDCl3) δ 150.5, 147.9, 147.2 (t, J = 22.8 Hz), 137.1,130.7, 130.5, 129.6, 129.0, 128.8, 128.7, 127.2, 125.9, 118.5, 19 F NMR (470 MHz, CDCl3) δ -80.73 – -80.77 (m, 3F), -113.40 – -113.45 (m, 2F), -121.16 – -121.18 (m, 4F), -121.75 – -121.88 (m, 4F), -122.55 – -122.81 (m, 2F), -126.02 – -126.18 (m, 2F).

[0053] Embodiment 18 This embodiment provides a method for synthesizing a 2-fluoroalkylquinoline derivative 1-Isononitrile-2-(1-phenylvinyl)benzene (0.2 mmol), perfluorodecyl iodide (0.6 mmol), iron trifluoride (2.0 mg) and cesium carbonate (195.5 mg) were added to N,N-dimethylformamide (2 mL) and stirred at 110 °C. oC and stirred in a nitrogen atmosphere for 12 hours. The reaction solution was filtered to obtain a filtrate, which was washed with a saturated sodium chloride solution, extracted with ethyl acetate and dried with anhydrous sodium sulfate, and the filtrate was subjected to a rotary evaporator to remove the solvent to obtain a residue, which was eluted through a silica gel column with an eluent prepared by ethyl acetate and petroleum ether in a volume ratio of 1:100, and the effluent was collected according to the actual gradient, detected by TLC, and the effluent containing the target product was combined, and the combined effluent was subjected to a rotary evaporator to remove the solvent, and vacuum dried to obtain 104.1 mg of 4-phenyl-2-(perfluorodecyl)quinoline as a yellow oily liquid with a yield of 72%.

[0054] 1 H NMR (400 MHz, CDCl3) δ 8.25 (d, J = 8.4 Hz, 1H), 7.93 (d, J = 8.4 Hz,1H), 7.78 – 7.74 (m, 1H), 7.60 – 7.54 (m, 2H), 7.48 – 7.47 (m, 5H). 13 C NMR (125 MHz, CDCl3) δ 150.5, 148.0, 147.3 (d, J = 24.8 Hz), 137.2,130.7, 130.5, 129.6, 129.0, 128.8, 128.7, 127.2, 125.9, 118.5. 19 F NMR (470 MHz, CDCl3) δ -80.77 – -80.80 (m, 3F), -113.38 – -113.43(m, 2F), -121.94 – -121.32 (m, 4F), -121.70 – -121.89 (m, 8F), -122.57 – -122.87 (m, 2F), -125.98 – -126.27 (m, 2F).

[0055] In the embodiment of the present invention, ortho-alkenyl aryl isonitrile and perfluoroalkyl iodide are used as reaction substrates, ferric fluoride is used as catalyst, cesium carbonate is used as base, N,N-dimethylformamide is used as solvent, and the reaction mixture is heated to 110 °C. o C was stirred in a nitrogen atmosphere for 12 hours. In Examples 1 to 9, Ar in the o-alkenyl aryl isonitrile was replaced by different substituents as a variable, in Examples 10 to 13, R in the o-alkenyl aryl isonitrile was replaced by different substituents as a variable, and in Examples 14 to 18, R of the perfluoroalkyl iodide was replaced by f is a variable.

[0056] The present invention does not need to separate the intermediate product, and can directly synthesize the target product through simple raw materials, simplifying the process, low energy consumption, reducing the discharge of waste solution, reducing environmental pollution, and the yield is as high as 81%; the above embodiment uses ortho-alkenyl aryl isonitriles containing different substituents and different perfluoroalkyl iodides as reactants to prepare 2-fluoroalkyl quinoline derivatives, and the method has certain substrate adaptability and ease of operation. The present invention is not limited to the above specific embodiments, and those skilled in the art can use other various specific embodiments to implement the present invention according to the content disclosed in the present invention, or all those who use the design structure and ideas of the present invention and make simple changes or modifications fall into the protection scope of the present invention.

[0057] The above embodiments are preferred implementation modes of the present invention, but the implementation modes of the present invention are not limited by the description of the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications that do not deviate from the spirit and principles of the present invention should be equivalent replacement methods and are included in the protection scope of the present invention.

[0058] The above are only preferred embodiments of the present invention and are not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A method for synthesizing a 2-fluoroalkylquinoline derivative, characterized in that: The synthesis method comprises mixing an ortho-alkenyl aryl isonitrile, a perfluoroalkyl iodide and a base in a solvent in the presence of an inert atmosphere and a catalyst, and reacting the mixture to obtain a 2-fluoroalkyl quinoline derivative; The structural formula of the ortho-alkenyl aryl isonitrile is shown in Formula I: Formula I; In Formula I, Ar is one of phenyl, 4-methylphenyl, 4-tert-butylphenyl, 6-methoxyphenyl, 3,5-dimethylphenyl, 5-fluorophenyl, 5-chlorophenyl, 5-bromophenyl, and naphthyl; R is one of methyl, phenyl, 4-methylphenyl, 4-fluorophenyl, and 4-chlorophenyl; The structural formula of the perfluoroalkyl iodide is shown in Formula II: R f Formula III; In Formula II, R f It is one of trifluoromethyl, pentafluoropropyl, perfluorobutyl, perfluorohexyl, perfluorooctyl and perfluorodecyl.

2. The synthesis method according to claim 1, characterized in that The ortho-alkenyl aryl isonitrile is selected from 1-isocyano-2-(1-phenylvinyl)benzene, 1-isocyano-4-methyl-2-(1-phenylvinyl)benzene, 1-isocyano-4-tert-butyl-2-(1-phenylvinyl)benzene, 1-isocyano-6-methoxy-2-(1-phenylvinyl)benzene, 1-isocyano-3,5-dimethyl-2-(1-phenylvinyl)benzene, 5-fluoro-1-isocyano-2-(1-phenylvinyl)benzene, 5-chloro-1-isocyano-2-(1 at least one of 1-(p-tolyl)vinyl)benzene, 2-(1-(4-fluorophenyl)vinyl)-1-isocyanobenzene, 2-(1-(4-chlorophenyl)vinyl)-1-isocyanobenzene, 2-(1-methylvinyl)-1-isocyanobenzene and 1-isocyanobenzene-2-(1-methylvinyl)benzene.

3. The synthesis method according to claim 1, characterized in that The perfluoroalkyl iodide is at least one selected from perfluorobutyl iodide, trifluoromethyl iodide, pentafluoropropyl iodide, perfluorohexyl iodide, perfluorooctyl iodide and perfluorodecyl iodide.

4. The synthesis method according to claim 1, characterized in that The inert atmosphere is selected from at least one of nitrogen and argon.

5. The synthesis method according to claim 1, characterized in that The catalyst is selected from at least one of ferric fluoride, nickel chloride, cobalt chloride and ferrous fluoride.

6. The synthesis method according to claim 1, characterized in that The base is selected from at least one of cesium carbonate, potassium carbonate, potassium phosphate, sodium carbonate and triethylamine.

7. The synthesis method according to claim 1, characterized in that The solvent is selected from at least one of N,N-dimethylformamide, toluene, N,N-dimethylacetamide, 1,4-dioxane, and N-methylpyrrolidone.

8. The synthesis method according to claim 1, characterized in that The reaction conditions include: temperature of 100° C. to 120° C., and time of 10 hours to 14 hours.

9. The synthesis method according to claim 1, characterized in that The dosage ratio of the ortho-alkenyl aromatic isonitrile, perfluoroalkyl iodide, catalyst, base and solvent is 0.2 mmol: 0.6 mmol: 0.02 mmol: 0.6 mmol: 2 mL.

10. A 2-fluoroalkylquinoline derivative, characterized in that: The method is prepared by the synthesis method described in any one of claims 1 to 9.

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