Quinolinyl ketone compound as well as preparation method and application thereof

Abstract

The invention provides a quinolinyl ketone compound as well as a preparation method and application thereof, and belongs to the technical field of compounds containing two or more heterocyclic rings. The quinolinyl ketone compound can be obtained by taking enaminone, a perfluoroalkane compound and aminobenzene as raw materials, adding an organic solvent and alkali and stirring and reacting in an argon atmosphere and under blue light irradiation. The prepared product has good antibacterial activity, the preparation condition is mild, and the yield is basically kept at 80% or above and can reach 90% to the maximum.

Description

Technical Field

[0001] The present application relates to a quinoline alkyl ketone compound, a preparation method thereof and an application thereof, belonging to the technical field of compounds containing two or more heterocycles. Background Art

[0002] Quinoline and its derivatives are a class of organic compounds with wide application values, especially in the fields of medicine, pesticides, dyes and polymer materials. Due to their unique structures and properties, compounds containing quinoline structures often exhibit excellent biological activities and physicochemical properties. Therefore, the synthesis methods and technologies of such compounds have always been a research hotspot in the chemical field. In the early stage, the synthesis of compounds containing quinoline structures mainly relied on natural extraction or simple chemical synthesis methods. However, these methods often have problems such as limited raw material sources, harsh reaction conditions, and low product purity, which limit the large-scale production and application of such compounds.

[0003] With the progress of science and technology, especially the rapid development of fields such as molecular biology, materials science and computer science, the demand for compounds containing quinoline structures is increasing day by day. To meet this demand, scientific research personnel have begun to explore and develop more efficient and environmentally friendly synthesis methods. In addition, with the development of technologies such as computer-aided drug design and molecular simulation, scientific research personnel can more accurately predict and optimize the biological activities of compounds containing quinoline structures, providing strong support for new drug research and development. Summary of the Invention

[0004] In view of this, the first aspect objective of the present application is to provide the following series of quinoline alkyl ketone compounds.

[0005] Specifically, the present application is implemented through the following solutions:

[0006] A quinoline alkyl ketone compound satisfying the general formula: wherein, R is any one of methyl, dimethyl, trifluoromethyl, methoxy, ethoxycarbonyl, fluorine, chlorine, bromine, iodine, phenyl, biphenyl, ethyl, isopropyl, tert-butyl, pentafluorothio.

[0007] Specifically, the quinoline alkyl ketone compound of the above general formula is any one of the following structural formulas:

[0008]

[0009] A quinoline alkyl ketone compound satisfying the general formula: R f is any one of pentafluoroethyl, nonafluorobutyl, undecafluoropentyl, pentadecafluoroheptyl.

[0010] Specifically, the quinoline alkyl ketone compound of the above general formula is any one of the following structural formulas:

[0011]

[0012] A quinoline alkyl ketone compound, satisfying the structural general formula: R is any one of p-fluorophenyl, p-chlorophenyl, p-bromophenyl, p-methoxyphenyl, cyclopropyl, furan, and thiophene.

[0013] Specifically, the quinoline alkyl ketone compound of the above general formula is any one of the following structural formulas:

[0014]

[0015] The novel quinoline alkyl ketone compound provided by this application has excellent antibacterial, anti-tumor, anti-fungal, blood pressure lowering, and anti-HIV and other properties.

[0016] The second aspect of the purpose of this application is to provide a preparation method of the above quinoline alkyl ketone compound: using enaminone, perfluoroalkane compounds, and aminobenzene as raw materials, adding an organic solvent and a base, and stirring and reacting under an argon atmosphere and blue light irradiation to obtain the quinoline alkyl ketone compound satisfying the above general formula.

[0017] Further, as a preference:

[0018] The enaminone is any one of 3-(dimethylamino)-1-(2-phenyl)-2-propen-1-one, (2E)-3-(dimethylamino)-1-(4-fluorophenyl)prop-2-en-1-one, (2E)-1-(4-chlorophenyl)-3-(dimethylamino)-2-propen-1-one, 1-(4-bromophenyl)-3-(dimethylamino)-2-propen-1-one, (2Z)-3-(dimethylamino)-1-(4-methoxyphenyl)prop-2-en-1-one, (E)-1-cyclopropyl-3-(dimethylamino)prop-2-en-1-one, 3-(dimethylamino)-1-(furan-2-yl)prop-2-en-1-one, and 3-dimethylamino-1-(2-thienyl)-2-propen-1-one.

[0019] The perfluoroalkane compounds are any one of perfluorobutyl iodide, perfluoropropyl iodide, 1-iodoperfluoropentane, 1-iodoperfluorohexane, and 1-iodoperfluorooctane.

[0020] The aminobenzene is any one of p - toluidine, 2,5 - dimethylaniline, p - trifluoromethylaniline, p - methoxyaniline, p - fluoroaniline, p - chloroaniline, p - bromoaniline, p - iodoaniline, 4 - aminobiphenyl, 4 - aminop - terphenyl, p - isopropylaniline, 4 - (tert - butyl)aniline, 2 - fluoroaniline, 2 - chloroaniline, 2 - bromoaniline, 2 - iodoaniline, 4 - ethylaniline, pentafluoro(4 - aminophenyl)sulfide, ethyl 4 - aminobenzoate, 2,4 - dimethylaniline, 1 - amino - 3,5 - xylene.

[0021] When the enaminone is any one of 3 - (dimethylamino)-1-(2 - phenyl)prop - 2 - en - 1 - one, (2Z)-3 - (dimethylamino)-1-(4 - methoxyphenyl)prop - 2 - en - 1 - one, 3 - dimethylamino - 1-(2 - thienyl)prop - 2 - en - 1 - one, and the aminobenzene is any one of p - toluidine, 4 - aminop - terphenyl, p - isopropylaniline, 4 - aminobiphenyl, 2,4 - dimethylaniline, the synthesis yield of the quinolinealkyl methyl ketone compound can reach over 80%.

[0022] The organic solvent is any one of acetonitrile (MeCN), dimethyl sulfoxide (DMSO), tetrahydrofuran (THF), ethanol (EtOH), N,N - dimethylformamide (DMF), acetone (Acetone), dichloromethane (DCM), toluene (Toluene), ethyl acetate (EA), N - methylpyrrolidone (NMP), isopropanol (IPA), 1,4 - dioxane (1,4 - Dioxane).

[0023] The base is any one of 1,8 - diazabicyclo[5.4.0]undec - 7 - ene (DBU), potassium carbonate (K2CO3), 1,4 - diazabicyclo[2.2.2]octane (DABCO), sodium bicarbonate (NaHCO3), N,N,N',N'-tetramethylethylenediamine (TMEDA), N,N - diisopropylethylamine (DIPEA), triethylamine (Et3N).

[0024] The molar ratio of the enaminone, perfluoroalkane compound, and p - toluidine is 2 - 6:2 - 6:1, preferably 4 - 6:2 - 4:1, and optimally 5:3:1.

[0025] The above - mentioned preparation method synthesizes the quinolinealkyl methyl ketone compound described in this case through visible - light - mediated dehalogenation and radical cyclization addition. It has the following beneficial effects:

[0026] (1) Through the given reaction conditions, this preparation method can achieve the high - yield synthesis of the quinolinealkyl methyl ketone compound. This can not only improve production efficiency but also reduce production costs, thereby enhancing the market competitiveness of the product.

[0027] (2) The reaction conditions of this preparation method are mild. Compared with traditional preparation methods, the preparation method provided in this patent has milder reaction conditions. This can not only reduce energy consumption and waste generation, but also lower equipment requirements, thus facilitating industrial production.

[0028] (3) This preparation method has good environmental friendliness. The preparation method provided in this patent generates less waste during the reaction process and is easy to handle. At the same time, this method does not use photocatalysts, thus greatly reducing production costs.

[0029] (4) This preparation method has a simple process and does not require a photocatalyst. It is a typical EDA reaction. The preparation method provided in this patent has simple steps, convenient operation, and is easy to realize industrial production. This can not only reduce production costs, but also improve production efficiency, thus meeting market demands.

[0030] The third aspect of this application aims to provide the application of the above-mentioned quinoline alkyl ketone compound in the preparation of drugs, such as the preparation of antibacterial, anti-tumor, anti-fungal, antihypertensive, and anti-HIV drugs, which has outstanding application value. Description of the Drawings

[0031] In order to more clearly illustrate the technical solutions in the embodiments of this application, the following will briefly introduce the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings in the following description are only some embodiments of this application. For those of ordinary skill in the art, without creative efforts, other drawings can also be obtained based on these drawings.

[0032] Figure 1 It is the ultraviolet absorption diagram of the reaction involved in this application. Detailed Embodiments

[0033] In order to make the technical problems, technical solutions, and beneficial effects to be solved by this application clearer, the following will further elaborate on the technical solutions in the embodiments of this application in combination with the drawings in the embodiments of this application. It should be understood that the specific embodiments described here are only used to explain this application and are not used to limit the technical solutions of this application. Based on the embodiments in this application, all other embodiments obtained by those of ordinary skill in the art without creative efforts belong to the scope of protection of this application.

[0034] Example 1

[0035]

[0036] In a glass reaction flask, 3-(dimethylamino)-1-(2-phenyl)-2-propen-1-one (1a in the above reaction formula, 0.0876 g, 0.5 mmol), p-toluidine (3a in the above reaction formula, 0.0107 g, 0.1 mmol), perfluoroiodobutane (2a in the above reaction formula, IC4F9, 0.1040 g, 0.3 mmol), triethylenediamine (DABCO, 0.0449 g, 0.4 mmol) and the solvent acetonitrile (MeCN, 2 ml) were added in sequence and mixed evenly. After adding a magnetic stir bar, the reaction flask was placed under argon and purged for 8 minutes, and then reacted for 36 hours under irradiation with a 3 W blue light-emitting LED tube. After the reaction was completed, the reaction solution was washed with ethyl acetate and concentrated, and the product was separated using a developing agent of petroleum ether:ethyl acetate = 10:1. Finally, the separated product 4a was dried, and the product yield was 90%.

[0037] Product confirmation:

[0038] 1 H NMR(400MHz,CDCl3)δ8.18(d,J=8.7Hz,1H),8.12(s,1H),7.80(d,J=7.9Hz,2H),7.73(d,J=8.7Hz,1H),7.67-7.60(m,2H),7.47(t,J=6.8Hz,2H),2.59(s,3H).

[0039] 13 C NMR(101MHz,CDCl3)δ193.6,145.6,143.9,143.6,143.3,140.4,136.7,136.1,134.3,134.1,132.1,130.2,129.9,128.7,127.1,126.5,21.9;

[0040] 19 F NMR(376MHz,CDCl3)δ-79.4,-79.4,-79.4,-105.9,-105.9,-105.9,-106.0,-123.5.HRMS(ESI-TOF)m / z:[M+H] + Calcd for C 20 H 13 F7NO + 416.0880;Found 416.0880.

[0041] Replacement Example 1

[0042] This replacement example has the same preparation method as Example 1, except that: the type of catalyst was adjusted, and its influence on the reaction was tested respectively, as shown in Table 1.

[0043] Table 1: Influence of Catalysts on the Reaction

[0044] Entry Photocatalyst 4a Yield(%) 1 Eosin Y 39 2 Eosin B 35 3 Rose bengal 45 4 <![CDATA[Eosin Y-Na + > 45 5 <![CDATA[Ir(ppy)3]]> 46 6 <![CDATA[Ru(bpy)3Cl2]]> 53 7 \ 90

[0045] As can be seen from Table 1: Under the same preparation conditions, when using eosin Y, Eosin B, Rose bengal, Eosin Y-Na + , Ir(ppy)3, and Ru(bpy)3Cl2 as photocatalysts to participate in the reaction, the yields are all lower than those obtained without a photocatalyst. Thus, it can be known that: the reaction yield is the highest without a catalyst. From this, it is inferred that this reaction belongs to an EDA reaction. And combined with Figure 1 the ultraviolet absorption spectrum, it can be seen that: there will be a certain ultraviolet absorption during the reaction process, proving that an EDA intermediate is generated during the reaction process. The catalyst structure is as follows:

[0046]

[0047] Replacement Example 2

[0048] This replacement example has the same preparation method as Example 1, except that: the types of solvents are adjusted, and their influences on the reaction are respectively tested, as shown in Table 2.

[0049] Table 2: Influence of Solvents on the Reaction

[0050] Entry Solvent 4a Yield(%) 1 MeCN 90 2 DMSO 31 3 THF 6 4 EtOH 15 5 DMF 41 6 DCM 25 7 Acetone 59 8 Toluene 20 9 EA 19 10 NMP 11 11 IPA 12 12 1,4-Dioxane 20

[0051] As can be seen from Table 2: Under the same preparation conditions, when using DMSO (dimethyl sulfoxide), THF (tetrahydrofuran), EtOH (ethanol), DMF (N,N-dimethylformamide), DCM (dichloromethane), Acetone (acetone), and Toluene (toluene), the yields are lower than those obtained with MeCN (acetonitrile) in Example 1.

[0052] Replacement Example 3

[0053] This replacement example has the same preparation method as Example 1, except that: the types of bases are adjusted, and their influences on the reaction are respectively tested, as shown in Table 3.

[0054] Table 3: Influence of Bases on the Reaction

[0055] Entry Base 4a Yield(%) 1 <![CDATA[Et3N]]> 8 2 DIPEA 5 3 DBU 8 4 TMEDA 9 5 <![CDATA[Potassium carbonate]]> 9 6 <![CDATA[NaHCO3]]> 16 7 DABCO 90 10 \ 23

[0056] As can be seen from Table 3: Under the same preparation conditions, when using Et3N (triethylamine), DIPEA (N,N-diisopropylethylamine), DBU (1,8-diazabicyclo[5.4.0]undec-7-ene), TMEDA (tetramethylethylenediamine), K2CO3 (potassium carbonate), and NaHCO3 (sodium bicarbonate) as bases to participate in the reaction, the yield of the reaction is much lower than that when using DABCO (1,4-diazabicyclo[2.2.2]octane) as the base to participate in the reaction.

[0057] Replacement Example 4

[0058] This replacement example has the same preparation method as Example 1, except that: the molar ratios of the raw materials are different, and their effects on the reaction are tested respectively, as shown in Table 4.

[0059] Table 4: Influence of Molar Ratio on the Reaction

[0060]

[0061]

[0062] As can be seen from Table 4: Under the same preparation conditions, when 3-(dimethylamino)-1-(2-phenyl)-2-propen-1-one: perfluoroiodobutane: p-toluidine = 5:3:1, the yield of quinolinealkyl methyl ketone is the highest, and the corresponding yield can reach 90% when the reaction time is 36 h. In summary: During the synthesis of quinolinealkyl methyl ketone, when the solvent is acetonitrile, the base is 1,4-diazabicyclo[2.2.2]octane, 3-(dimethylamino)-1-(2-phenyl)-2-propen-1-one: perfluoroiodobutane: p-toluidine = 5:3:1, and the reaction time is 36 h, the yield of quinolinealkyl methyl ketone is the highest, reaching 90%.

[0063] Example 2

[0064]

[0065] This example has the same settings as Example 1, except that: when adding the raw materials, 2,5-dimethylaniline (3b in the above reaction formula, 0.0121 g, 0.1 mmol) is used instead of p-toluidine (0.0107 g, 0.1 mmol) to obtain quinolinealkyl methyl ketone with the structure of 4b in the above reaction formula, and the yield of product 4b is 78%.

[0066] Product confirmation:

[0067] 1 H NMR (400 MHz, CDCl3) δ8.33 (s, 1H), 7.84 - 7.79 (m, 2H), 7.65 - 7.60 (m, 2H), 7.50 - 7.43 (m, 3H), 2.80 (s, 3H), 2.62 (s, 3H).

[0068] 13 13C NMR (101 MHz, CDCl3) δ 194.1, 146.3, 143.0, 142.8, 142.5, 136.9, 136.6, 134.1, 133.7, 132.5, 131.4, 131.2, 130.3, 129.9, 128.7, 126.7, 18.3, 17.4.

[0069] 19 19F NMR (376 MHz, CDCl3) δ -79.3, -79.3, -79.3, -105.3, -105.4, -105.4, -123.6. HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 21 H 15 F7NO + 430.1037; Found 430.1045.

[0070] Example 3

[0071]

[0072] This example was set up the same as Example 1, except that: when adding raw materials, p-trifluoromethylaniline (3c in the above reaction formula, 0.0161 g, 0.1 mmol) was used instead of p-toluidine (0.0107 g, 0.1 mmol) to obtain quinolinealkyl methyl ketone with the structure of 4c in the above reaction formula, and the yield of product 4c was 57%.

[0073] Product confirmation:

[0074] 1 1H NMR (400 MHz, Chloroform-d) δ 8.43 (d, J = 8.9 Hz, 1H), 8.35 (s, 1H), 8.25 (s, 1H), 8.08 (dd, J = 8.9, 2.0 Hz, 1H), 7.80 (d, J = 7.4 Hz, 2H), 7.66 (t, J = 7.4 Hz, 1H), 7.50 (t, J = 7.7 Hz, 2H).

[0075] 1313C NMR (101 MHz, CDCl3) δ 192.6, 147.6, 147.3, 147.0, 146.7, 137.9, 136.2, 134.4, 133.3, 132.1, 131.8, 131.7, 131.5, 131.1, 130.2, 128.9, 127.5, 127.5, 127.4, 126.1, 125.9, 125.8, 125.8, 124.8, 122.1.

[0076] 19 19F NMR (376 MHz, CDCl3) δ -62.5, -79.4, -79.5, -79.5, -106.1, -106.1, -106.1, -106.1,

[0077] -106.2, -106.2, -123.4. HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 20 H 10 F 10 NO + 470.0598; Found 470.0595.

[0078] Example 4

[0079]

[0080] This example was set up the same as Example 1, except that: when adding the raw materials, p-methoxyaniline (3d in the above reaction formula, 0.0123 g, 0.1 mmol) was used instead of p-toluidine (0.0107 g, 0.1 mmol) to obtain quinolinealkyl methyl ketone with the structure of 4d in the above reaction formula, and the yield of product 4d was 72%.

[0081] Product confirmation:

[0082] 1 1H NMR (400 MHz, Chloroform-d) δ 8.16 (d, J = 9.3 Hz, 1H), 8.07 (s, 1H), 7.80 (d, J = 6.9 Hz, 2H), 7.63 (t, J = 7.4 Hz, 1H), 7.53 (dd, J = 9.3, 2.7 Hz, 1H), 7.47 (t, J = 7.8 Hz, 2H), 7.10 (d, J = 2.7 Hz, 1H), 3.95 (s, 3H).

[0083] 1313C NMR (101 MHz, CDCl3) δ 193.7, 160.3, 143.2, 141.8, 136.7, 135.2, 134.1, 132.4, 131.7, 130.2, 128.7, 128.6, 125.2, 104.6, 55.8.

[0084] 19 19F NMR (376 MHz, CDCl3) δ -79.4, -79.4, -79.5, -105.8, -105.9, -105.9, -105.9, -123.6,

[0085] -123.6. HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 20 H 13 F7NO2 + 432.0830; Found 432.0833.

[0086] Example 5

[0087]

[0088] This example is the same as that of Example 1, except that: when adding raw materials, p-fluoroaniline (3e in the above reaction formula, 0.0111 g, 0.1 mmol) is used instead of p-toluidine (0.0107 g, 0.1 mmol) to obtain quinolinealkyl methyl ketone with the structure of 4e in the above reaction formula, and the yield of product 4e is 62%.

[0089] Product confirmation:

[0090] 1 1H NMR (400 MHz, Chloroform-d) δ 8.31 (dd, J = 9.4, 5.2 Hz, 1H), 8.18 (s, 1H), 7.80 (d, J = 7.7 Hz, 2H), 7.66 (dt, J = 14.3, 7.3 Hz, 2H), 7.50 (q, J = 9.2, 7.6 Hz, 3H).

[0091] 13 13C NMR (101 MHz, CDCl3) δ 193.1, 163.6, 161.1, 144.0, 136.4, 136.2, 136.2, 134.3, 133.2, 133.1, 132.9, 130.2, 128.8, 128.5, 128.1, 128.0, 122.6, 122.4, 111.0, 110.8.

[0092] 1919F NMR (376 MHz, CDCl3) δ -79.4, -79.4, -79.5, -105.9, -106.0, -106.0, -106.0, -106.7, -106.8, -106.8, -106.8, -123.5. HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 19 H 10 F8NO + 420.0630; Found 420.0628.

[0093] Example 6

[0094]

[0095] This example was set up the same as Example 1, except that: when adding raw materials, p-chloroaniline (3f in the above reaction formula, 0.0128 g, 0.1 mmol) was used instead of p-toluidine (0.0107 g, 0.1 mmol) to obtain quinolinealkyl methyl ketone with the structure of 4f in the above reaction formula, and the yield of product 4f was 73%.

[0096] Product confirmation:

[0097] 1 1H NMR (400 MHz, Chloroform-d) δ 8.24 (d, J = 9.0 Hz, 1H), 8.15 (s, 1H), 7.90 (s, 1H), 7.84 (d, J = 9.1 Hz, 1H), 7.80 (d, J = 8.1 Hz, 2H), 7.68 - 7.61 (m, 1H), 7.49 (t, J = 7.2 Hz, 2H).

[0098] 13 13C NMR (101 MHz, CDCl3) δ 192.9, 145.2, 144.9, 144.7, 136.3, 136.1, 135.9, 134.3, 133.0, 132.9, 131.9, 130.2, 128.8, 127.7, 126.4.

[0099] 19 19F NMR (376 MHz, CDCl3) δ -79.4, -79.4, -79.5, -106.0, -106.0, -106.0, -106.1, -123.5. HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 19 H 10 ClF7NO +436.0334; Found 436.0331.

[0100] Example 7

[0101]

[0102] This example has the same settings as Example 1, except that: when adding raw materials, p-bromoaniline (3 g, 0.0172 g, 0.1 mmol in the above reaction formula) is used instead of p-toluidine (0.0107 g, 0.1 mmol), and quinolinealkyl methyl ketone with a structure of 4 g in the above reaction formula is obtained. The yield of the product 4 g is 72%.

[0103] Product confirmation:

[0104] 1 H NMR(400MHz,Chloroform-d)δ8.16(d,J=10.2Hz,2H),8.08(s,1H),7.97(d,J=8.9Hz,1H),7.79(d,J=7.4Hz,2H),7.64(t,J=7.5Hz,1H),7.50(d,J=7.3Hz,2H).

[0105] 13 C NMR(101MHz,CDCl3)δ192.9,145.4,145.1,144.8,136.3,135.8,135.5,134.3,133.0,131.9,130.2,129.8,128.8,128.1,124.4.

[0106] 19 F NMR(376MHz,CDCl3)δ-79.4,-79.4,-79.4,-79.5,-106.0,-106.1,-106.1,-106.1,-123.5.HRMS(ESI-TOF)m / z:[M+H] + Calcd for C 19 H 10 BrF7NO + 479.9829; Found479.9829.

[0107] Example 8

[0108]

[0109] This example is the same as that of Example 1, except that: when adding raw materials, 4-iodoaniline (3h in the above reaction formula, 0.0219 g, 0.1 mmol) is used instead of p-toluidine (0.0107 g, 0.1 mmol) to obtain quinoline alkyl ketone with the structure of 4h in the above reaction formula, and the yield of product 4h is 75%.

[0110] Product confirmation:

[0111] 1 H NMR(400MHz,Chloroform-d)δ8.32(s,1H),8.14(d,J=9.0Hz,1H),8.11(s,1H),8.00(d,J=8.9Hz,1H),7.79(d,J=7.4Hz,2H),7.64(t,J=7.4Hz,1H),7.49(t,J=7.7Hz,2H).

[0112] 13 C NMR(101MHz,CDCl3)δ192.9,145.7,145.4,145.2,144.9,140.7,136.6,136.3,135.6,134.3,132.8,131.6,130.2,128.8,128.4,96.4.

[0113] 19 F NMR(376MHz,CDCl3)δ-79.8,-79.8,-79.9,-106.5,-106.5,-106.5,-106.5,-106.6,-123.9.HRMS(ESI-TOF)m / z:[M+H] + Calcd for C 19 H 10 IF7NO + 527.9690;Found527.9700.

[0114] Example 9

[0115]

[0116] This example is the same as that of Example 1, except that: when adding raw materials, 4-aminobiphenyl (3i in the above reaction formula, 0.0169 g, 0.1 mmol) is used instead of p-toluidine (0.0107 g, 0.1 mmol) to obtain quinoline alkyl ketone with the structure of 4i in the above reaction formula, and the yield of product 4i is 80%.

[0117] Product confirmation:

[0118] 11H NMR (400 MHz, Chloroform-d) δ 8.35 (d, J = 8.8 Hz, 1H), 8.25 (s, 1H), 8.16 (dd, J = 8.9, 2.0 Hz, 1H), 8.05 (s, 1H), 7.83 (d, J = 7.5 Hz, 2H), 7.71 (d, J = 7.1 Hz, 2H), 7.63 (t, J = 7.4 Hz, 1H), 7.53 - 7.42 (m, 5H).

[0119] 13 13C NMR (101 MHz, CDCl3) δ 193.5, 146.2, 144.7, 144.4, 144.1, 142.7, 139.4, 137.0, 136.6, 134.2, 132.5, 131.7, 130.7, 130.3, 129.3, 128.8, 128.6, 127.6, 127.3, 125.2.

[0120] 19 19F NMR (376 MHz, CDCl3) δ -79.4, -79.4, -79.5, -105.9, -106.0, -106.0, -123.4. HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 25 H 14 F7NO + 478.1037;Found 478.1047.

[0121] Example 10

[0122]

[0123] This example is set up the same as Example 1, except that: when adding raw materials, 4-aminop-terphenyl (3j in the above reaction formula, 0.0245 g, 0.1 mmol) is used instead of p-toluidine (0.0107 g, 0.1 mmol) to obtain quinolinealkyl methyl ketone with the structure of 4j in the above reaction formula, and the yield of product 4j is 86%.

[0124] Product confirmation:

[0125] 11H NMR (400 MHz, Chloroform-d) δ 8.35 (d, J = 8.9 Hz, 1H), 8.24 (s, 1H), 8.19 (dd, J = 8.9, 2.0 Hz, 1H), 8.08 (d, J = 2.0 Hz, 1H), 7.85 - 7.82 (m, 2H), 7.81 - 7.72 (m, 4H), 7.67 - 7.61 (m, 3H), 7.47 (q, J = 8.0 Hz, 4H), 7.37 (t, J = 7.4 Hz, 1H).

[0126] 13 13C NMR (101 MHz, CDCl3) δ 193.5, 146.3, 144.7, 144.4, 142.1, 141.5, 140.3, 138.1, 137.0, 136.6, 134.2, 132.5, 131.6, 130.8, 130.3, 129.0, 128.8, 128.0, 128.0, 127.8, 127.4, 127.1, 125.0.

[0127] 19 19F NMR (376 MHz, CDCl3) δ -79.4, -79.4, -79.4, -105.9, -105.9, -106.0, -123.4. HRMS (ESI-TOF) m / z: [M + H] + Calcd for C 31 H 19 F7NO + 554.1350; Found 554.1352.

[0128] Example 11

[0129]

[0130] This example is set up the same as Example 1, except that: when adding raw materials, p-isopropylaniline (3k in the above reaction formula, 0.0135 g, 0.1 mmol) is used instead of p-toluidine (0.0107 g, 0.1 mmol) to obtain quinolinealkyl methyl ketone with the structure of 4k in the above reaction formula, and the yield of product 4k is 81%.

[0131] Product confirmation:

[0132] 11H NMR (400 MHz, Chloroform-d) δ 8.22 (d, J = 8.8 Hz, 1H), 8.17 (s, 1H), 7.81 (ddd, J = 8.4, 4.0, 1.7 Hz, 3H), 7.69 (d, J = 2.0 Hz, 1H), 7.62 (t, J = 7.4 Hz, 1H), 7.47 (t, J = 7.8 Hz, 2H), 3.15 (p, J = 6.9 Hz, 1H), 1.36 (d, J = 6.9 Hz, 6H).

[0133] 13 13C NMR (101 MHz, CDCl3) δ 193.6, 151.0, 145.9, 144.0, 143.7, 143.4, 136.7, 136.5, 134.1, 132.0, 130.2, 130.1, 128.7, 127.2, 123.8, 34.4, 23.6.

[0134] 19 19F NMR (376 MHz, CDCl3) δ -79.4, -79.4, -79.4, -105.9, -105.9, -106.0, -106.0, -123.5. HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 22 H 17 F7NO + 444.1193; Found 444.1194.

[0135] Example 12

[0136]

[0137] This example is set up the same as Example 1, except that: when adding the raw materials, 4-(tert-butyl)aniline (3l in the above reaction formula, 0.0149 g, 0.1 mmol) is used instead of p-toluidine (0.0107 g, 0.1 mmol) to obtain quinolinealkyl methyl ketone with the structure of 4l in the above reaction formula, and the yield of product 4l is 74%.

[0138] Product confirmation:

[0139] 1 1H NMR (400 MHz, Chloroform-d) δ 8.23 (d, J = 9.0 Hz, 1H), 8.19 (s, 1H), 8.01 (dd, J = 9.0, 2.2 Hz, 1H), 7.84 - 7.78 (m, 3H), 7.62 (t, J = 7.4 Hz, 1H), 7.47 (t, J = 7.7 Hz, 2H), 1.44 (s, 9H).

[0140] 13 13C NMR(101MHz,CDCl3)δ193.6,153.2,145.6,144.1,143.9,143.6,136.8,136.7,134.1,132.0,131.1,130.2,129.8,128.7,126.9,122.7,35.4,31.0.

[0141] 19 19F NMR(376MHz,CDCl3)δ-79.8,-79.8,-79.9,-79.9,-106.4,-106.4,-106.4,-106.5,-123.9,-123.9,-123.9.HRMS(ESI-TOF)m / z:[M+H] + Calcd for C 23 H 19 F7NO + 458.1350;Found458.1338.

[0142] Example 13

[0143]

[0144] This example has the same settings as Example 1, except that: when adding raw materials, 2-fluoroaniline (3m in the above reaction formula, 0.0111 g, 0.1 mmol) is used instead of p-toluidine (0.0107 g, 0.1 mmol) to obtain quinolinealkyl methanone with the structure of 4m in the above reaction formula, and the yield of product 4m is 49%.

[0145] Product confirmation:

[0146] 1 1H NMR(400MHz,Chloroform-d)δ8.27(s,1H),7.80(d,J=6.9Hz,2H),7.70(t,J=3.1Hz,2H),7.64(t,J=7.4Hz,1H),7.61-7.55(m,1H),7.49(t,J=7.7Hz,2H).

[0147] 1313C NMR (101 MHz, CDCl3) δ 193.0, 159.5, 156.8, 145.1, 144.9, 144.6, 137.3, 137.2, 136.8, 136.7, 136.3, 134.4, 133.1, 130.2, 130.1, 130.0, 128.8, 128.5, 123.5, 123.4, 116.0, 115.8.

[0148] 19 19F NMR (376 MHz, CDCl3) δ -79.8, -79.8, -79.8, -106.2, -106.2, -106.3, -106.3, -106.3, -106.3, -106.3, -122.0, -122.1, -123.9, -123.9, -123.9. HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 19 H 10 F8NO + 420.0630; Found 420.0631.

[0149] Example 14

[0150]

[0151] This example is the same as that of Example 1, except that: during the addition of raw materials, 2-chloroaniline (3n in the above reaction formula, 0.0128 g, 0.1 mmol) is used instead of p-toluidine (0.0107 g, 0.1 mmol) to obtain quinolinealkyl methyl ketone with the structure of 4n in the above reaction formula, and the yield of product 4n is 36%.

[0152] Product confirmation:

[0153] 1 1H NMR (400 MHz, Chloroform-d) δ 8.26 (s, 1H), 8.01 (d, J = 7.5 Hz, 1H), 7.85 - 7.77 (m, 3H), 7.66 (q, J = 7.5 Hz, 2H), 7.49 (t, J = 7.8 Hz, 2H).

[0154] 13 13C NMR (101 MHz, CDCl3) δ 193.0, 145.5, 145.2, 144.9, 143.2, 137.4, 136.4, 135.1, 134.3, 133.0, 131.8, 130.2, 129.8, 128.8, 128.4, 126.7.

[0155] 19 19F NMR (376 MHz, CDCl3) δ -79.2, -79.3, -79.3, -105.5, -105.5, -105.6, -105.6, -123.5. HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 19 H 10 ClF7NO + 436.0334; Found 436.0341.

[0156] Example 15

[0157]

[0158] This example has the same settings as Example 1, except that: when adding raw materials, 2-bromoaniline (3o in the above reaction formula, 0.0172 g, 0.1 mmol) is used instead of p-toluidine (0.0107 g, 0.1 mmol) to obtain quinolinealkyl methyl ketone with the structure of 4o in the above reaction formula, and the yield of product 4o is 43%.

[0159] Product confirmation:

[0160] 1 1H NMR (400 MHz, Chloroform-d) δ 8.24 (s, 1H), 8.22 (d, J = 7.8 Hz, 1H), 7.87 (d, J = 8.2 Hz, 1H), 7.79 (d, J = 7.1 Hz, 2H), 7.64 (t, J = 7.5 Hz, 1H), 7.59 (t, J = 7.8 Hz, 1H), 7.49 (t, J = 7.8 Hz, 2H).

[0161] 13 13C NMR (101 MHz, CDCl3) δ 193.0, 145.6, 145.4, 144.1, 137.6, 136.4, 135.4, 134.4, 132.9, 130.2, 128.8, 128.4, 127.5, 126.1.

[0162] 19 19F NMR (376 MHz, CDCl3) δ -79.7, -79.7, -79.8, -105.9, -105.9, -105.9, -106.0, -123.9. HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 19 H 10 BrF7NO +479.9829; Found 479.9837.

[0163] Example 16

[0164]

[0165] This example has the same settings as Example 1, except that: when adding raw materials, 2-iodoaniline (3p in the above reaction formula, 0.0219 g, 0.1 mmol) is used instead of p-toluidine (0.0107 g, 0.1 mmol) to obtain quinolinealkyl methanone with the structure of 4p in the above reaction formula, and the yield of product 4p is 45%.

[0166] Product confirmation:

[0167] 1 H NMR (400 MHz, Chloroform-d) δ 8.51 (dd, J = 7.4, 1.2 Hz, 1H), 8.19 (s, 1H), 7.88 (d, J = 8.2 Hz, 1H), 7.79 (d, J = 6.9 Hz, 2H), 7.64 (t, J = 7.4 Hz, 1H), 7.47 (dt, J = 12.8, 7.8 Hz, 3H).

[0168] 13 C NMR (101 MHz, CDCl3) δ 193.0, 146.0, 145.6, 145.3, 142.4, 137.9, 136.4, 134.3, 133.0, 130.8, 130.2, 130.2, 128.8, 128.7, 128.4, 127.7, 103.9.

[0169] 19 F NMR (376 MHz, CDCl3) δ -79.7, -79.8, -79.8, -79.8, -79.8, -105.8, -105.8, -105.8, -105.9, -105.9, -123.8, -123.8, -123.8. HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 19 H 10 IF7NO + 527.9690; Found 527.9694.

[0170] Example 17

[0171]

[0172] This example is the same as Example 1, except that: when adding raw materials, 4-ethylaniline (3q in the above reaction formula, 0.0121 g, 0.1 mmol) is used instead of p-toluidine (0.0107 g, 0.1 mmol) to obtain quinoline alkyl ketone with the structure of 4q in the above reaction formula, and the yield of product 4q is 71%.

[0173] Product confirmation:

[0174] 1 H NMR(400MHz,Chloroform-d)δ8.20(d,J=8.8Hz,1H),8.15(s,1H),7.83-7.79(m,2H),7.77(dd,J=8.8,2.0Hz,1H),7.67(s,1H),7.62(t,J=7.5Hz,1H),7.47(t,J=7.8Hz,2H),2.89(q,J=7.6Hz,2H),1.35(t,J=7.6Hz,3H).

[0175] 13 C NMR(101MHz,CDCl3)δ193.7,146.5,145.8,143.9,143.6,143.4,136.7,136.3,134.1,133.3,132.0,130.2,130.0,128.7,127.2,125.2,29.1,15.1.

[0176] 19 F NMR(376MHz,CDCl3)δ-79.4,-79.4,-79.4,-105.9,-105.9,-106.0,-106.0,-123.5.HRMS(ESI-TOF)m / z:[M+H] + Calcd for C 21 H 15 F7NO + 430.1037;Found 430.1038.

[0177] Example 18

[0178]

[0179] This example is the same as Example 1, except that: when adding raw materials, sulfur pentafluoride(4-aminophenyl)(3r in the above reaction formula, 0.0219 g, 0.1 mmol) is used instead of p-toluidine (0.0107 g, 0.1 mmol) to obtain quinoline alkyl ketone with the structure of 4r in the above reaction formula, and the yield of product 4r is 50%.

[0180] Product confirmation:

[0181] 1 H NMR(400MHz,Chloroform-d)δ8.43 - 8.35(m,3H),8.23(dd,J=9.3,2.4Hz,1H),7.80(d,J=7.0Hz,2H),7.66(t,J=7.4Hz,1H),7.50(t,J=7.8Hz,2H).

[0182] 13 C NMR(101MHz,CDCl3)δ192.3,154.0,153.8,153.7,147.9,147.6,147.4,146.8,138.3,136.1,134.5,133.6,131.4,130.2,128.9,128.3,126.6,126.0.

[0183] 19 F NMR(376MHz,CDCl3)δ - 79.9,-79.9,-79.9,-79.9,-79.9,-106.6,-106.6,-106.6,-106.6,-106.7,-106.7,-123.8.HRMS(ESI-TOF)m / z:[M + H] + Calcd for C 19 H 10 F 12 NOS + 528.0286;Found 528.0292.

[0184] Example 19

[0185]

[0186] This example has the same settings as Example 1, except that: when adding raw materials, ethyl 4 - aminobenzoate (3s in the above reaction formula, 0.0165 g, 0.1 mmol) is used instead of p - toluidine (0.0107 g, 0.1 mmol) to obtain quinolinealkyl methanone with the structure of 4s in the above reaction formula, and the yield of product 4s is 54%.

[0187] Product confirmation:

[0188] 11H NMR (400 MHz, Chloroform-d) δ 8.68 (d, J = 1.8 Hz, 1H), 8.49 (dd, J = 8.9, 1.9 Hz, 1H), 8.38 - 8.31 (m, 2H), 7.81 (d, J = 7.0 Hz, 2H), 7.65 (t, J = 7.4 Hz, 1H), 7.50 (t, J = 7.8 Hz, 2H), 4.48 (q, J = 7.1 Hz, 2H), 1.45 (t, J = 7.1 Hz, 3H).

[0189] 13 13C NMR (101 MHz, CDCl3) δ 192.9, 165.3, 148.3, 147.0, 146.7, 146.4, 138.3, 136.4, 134.3, 132.8, 131.5, 131.2, 130.6, 130.5, 130.2, 128.8, 126.3, 61.9, 14.3.

[0190] 19 19F NMR (376 MHz, CDCl3) δ -79.4, -79.4, -79.5, -106.0, -106.0, -106.1, -106.1, -123.4. HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 22 H 15 F7NO3 + 474.0935; Found 474.0946.

[0191] Example 20

[0192]

[0193] This example is the same as that of Example 1, except that: when adding raw materials, 2,4-dimethylaniline (3t in the above reaction formula, 0.0121 g, 0.1 mmol) is used instead of p-toluidine (0.0107 g, 0.1 mmol) to obtain quinolinealkyl methyl ketone with the structure of 4t in the above reaction formula, and the yield of product 4t is 80%.

[0194] Product confirmation:

[0195] 1 1H NMR (400 MHz, Chloroform-d) δ 8.07 (s, 1H), 7.82 - 7.78 (m, 2H), 7.61 (t, J = 7.4 Hz, 1H), 7.57 (s, 1H), 7.49 - 7.43 (m, 3H), 2.80 (s, 3H), 2.53 (s, 3H).

[0196] 13 C NMR (101 MHz, CDCl3) δ 194.0, 144.6, 142.7, 142.4, 142.1, 140.1, 138.3, 136.8, 136.3, 134.2, 134.0, 131.7, 130.2, 128.7, 127.2, 124.3, 21.8, 17.3.

[0197] 19 F NMR (376 MHz, CDCl3) δ -79.3, -79.3, -79.3, -105.1, -105.1, -105.1, -105.2, -123.6. HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 21 H 15 F7NO + 430.1037; Found 430.1041.

[0198] Example 21

[0199]

[0200] This example has the same setup as Example 1, except that: when adding the raw materials, 1-amino-3,5-dimethylbenzene (3u in the above reaction formula, 0.0121 g, 0.1 mmol) is used instead of p-toluidine (0.0107 g, 0.1 mmol) to obtain quinolinealkyl methanone with the structure of 4u in the above reaction formula, and the yield of product 4u is 63%.

[0201] Product confirmation:

[0202] 1 H NMR (400 MHz, Chloroform-d) δ 8.29 (s, 1H), 7.92 (s, 1H), 7.84 - 7.78 (m, 2H), 7.63 (t, J = 7.4 Hz, 1H), 7.48 (t, J = 7.8 Hz, 2H), 7.41 (s, 1H), 2.63 (s, 3H), 2.58 (s, 3H).

[0203] 13 C NMR (101 MHz, CDCl3) δ 194.0, 147.7, 144.3, 144.0, 143.7, 142.4, 136.9, 134.6, 134.1, 133.3, 132.6, 130.8, 130.3, 128.7, 127.3, 124.8, 21.9, 18.4.

[0204] 19 F NMR (376 MHz, CDCl3) δ -80.4, -80.4, -80.5, -107.1, -107.2, -107.2, -107.2, -107.2, -124.5, -124.5, -124.6, -124.6. HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 21 H 15 F7NO + 430.1037; Found 430.1038.

[0205] Comparing Examples 1 to 21, it can be seen that:

[0206] When anilines with different substituents are used for the reaction, the synthetic effects are in the following order: p-toluidine > 4-aminop-terphenyl > p-isopropylaniline > 4-aminobiphenyl > 2,4-dimethylaniline > 2,5-dimethylaniline > p-iodoaniline > 4-(tert-butyl)aniline > p-chloroaniline > p-bromoaniline > p-methoxyaniline > 4-ethylaniline > 1-amino-3,5-dimethylbenzene > p-fluoroaniline > p-trifluoromethylaniline > ethyl 4-aminobenzoate > pentafluoro(4-aminophenyl)sulfide > 2-fluoroaniline > 2-iodoaniline > 2-bromoaniline > 2-chloroaniline.

[0207] Example 22

[0208]

[0209] This example is the same as that of Example 1, except that: when adding raw materials, perfluoropropionyl iodide (2b in the above reaction formula, 0.0888 g, 0.3 mmol) is used instead of perfluorobutyl iodide (0.104 g, 0.3 mmol) to obtain quinolinyl methyl ketone with the structure of 5a in the above reaction formula, and the yield of product 5a is 71%.

[0210] Product confirmation:

[0211] 1 H NMR (400 MHz, Chloroform-d) δ 8.17 (d, J = 8.7 Hz, 1H), 8.12 (s, 1H), 7.80 (d, J = 6.8 Hz, 2H), 7.73 (dd, J = 8.7, 1.9 Hz, 1H), 7.67 - 7.60 (m, 2H), 7.48 (t, J = 7.7 Hz, 2H), 2.60 (s, 3H).

[0212] 1313C NMR (101 MHz, CDCl3) δ 193.7, 145.6, 143.8, 140.4, 136.7, 136.1, 134.3, 134.1, 132.1, 130.2, 129.9, 128.7, 127.1, 126.5, 21.9.

[0213] 19 19F NMR (376 MHz, CDCl3) δ -80.6, -107.9. HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 19 H 13 F5NO + 366.0912; Found 366.0918.

[0214] Example 23

[0215]

[0216] This example was set up the same as Example 1, except that: when adding the raw materials, 1-iodoperfluoropentane (2c in the above reaction formula, 0.1188 g, 0.3 mmol) was used instead of perfluoroiodobutane (0.104 g, 0.3 mmol) to obtain quinolinyl methyl ketone with the structure of 5b in the above reaction formula, and the yield of product 5b was 71%.

[0217] Product confirmation:

[0218] 1 1H NMR (400 MHz, Chloroform-d) δ 8.18 (d, J = 8.7 Hz, 1H), 8.11 (s, 1H), 7.80 (d, J = 6.9 Hz, 2H), 7.73 (dd, J = 8.7, 1.9 Hz, 1H), 7.67 - 7.60 (m, 2H), 7.47 (t, J = 7.7 Hz, 2H), 2.59 (s, 3H).

[0219] 13 13C NMR (101 MHz, CDCl3) δ 193.7, 145.6, 144.1, 143.8, 143.5, 140.4, 136.7, 136.1, 134.3, 134.1, 132.1, 130.2, 129.9, 128.7, 127.1, 126.5, 21.9.

[0220] 1919F NMR (376 MHz, CDCl3) δ -80.4, -80.5, -80.5, -105.2, -105.3, -105.3, -105.3, -119.7, -119.8, -124.6, -124.6, -124.7. HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 21 H 13 F9NO + 466.0848; Found 466.0852.

[0221] Example 24

[0222]

[0223] This example is the same as that of Example 1, except that: when adding raw materials, 1-iodoperfluorohexane (2d in the above reaction formula, 0.1338 g, 0.3 mmol) is used instead of perfluorobutyl iodide (0.104 g, 0.3 mmol) to obtain quinolinyl methyl ketone with the structure of 5c in the above reaction formula, and the yield of product 5c is 79%.

[0224] Product confirmation:

[0225] 1 1H NMR (400 MHz, Chloroform-d) δ 8.18 (d, J = 8.7 Hz, 1H), 8.11 (s, 1H), 7.80 (d, J = 6.9 Hz, 2H), 7.74 (dd, J = 8.7, 1.9 Hz, 1H), 7.66 - 7.60 (m, 2H), 7.48 (t, J = 7.8 Hz, 2H), 2.60 (s, 3H).

[0226] 13 13C NMR (101 MHz, CDCl3) δ 193.7, 145.6, 143.8, 140.4, 136.7, 136.1, 134.2, 134.1, 132.1, 130.2, 129.9, 128.7, 127.1, 126.5, 21.9.

[0227] 19 19F NMR (376 MHz, CDCl3) δ -80.3, -80.3, -80.3, -105.2, -105.2, -105.3, -119.1, -121.4, -125.6, -125.7, -125.7. HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 22 H 13F 11 NO + 516.0816; Found 516.0816.

[0228] Example 25

[0229]

[0230] This example is set the same as Example 1, the difference is that: when adding raw materials, 1-iodoperfluorooctane (2e in the above reaction formula, 0.1638 g, 0.3 mmol) is used instead of perfluorobutyl iodide (0.104 g, 0.3 mmol) to obtain quinolinyl methyl ketone with the structure of 5d in the above reaction formula, and the yield of product 5d is 77%.

[0231] Product confirmation:

[0232] 1 H NMR(400 MHz, Chloroform-d) δ 8.18(d, J = 8.7 Hz, 1H), 8.11(s, 1H), 7.80(d, J = 6.9 Hz, 2H), 7.74(dd, J = 8.7, 1.9 Hz, 1H), 7.67 - 7.60(m, 2H), 7.47(t, J = 7.7 Hz, 2H), 2.60(s, 3H).

[0233] 13 C NMR(101 MHz, CDCl3) δ 193.6, 145.6, 143.8, 140.4, 136.7, 136.1, 134.2, 134.1, 132.1, 130.2, 129.9, 128.7, 127.1, 126.5, 21.9.

[0234] 19 F NMR(376 MHz, CDCl3) δ -80.3, -80.4, -80.4, -105.1, -105.2, -105.2, -118.8, -118.8, -118.9, -120.4, -121.5, -122.2, -125.7, -125.7, -125.7. HRMS(ESI-TOF) m / z: [M+H] + Calcd for C 24 H 13 F 15 NO + 616.0753; Found 616.0765.

[0235] Comparing Comparative Examples 22 to 25, it can be seen that:

[0236] When using different perfluoroiodoalkanes for the reaction, the synthesis effects are in the following order: 1-iodoperfluorohexane > 1-iodoperfluorooctane > 1-iodoperfluoropentane ≈ perfluoroiodopropane. However, the yields of the synthesized quinolinyl methyl ketone compounds are all lower than that of perfluoroiodobutane in Example 1.

[0237] Example 26

[0238]

[0239] This example is set the same as Example 1, except that when adding the raw materials, (2E)-3-(dimethylamino)-1-(4-fluorophenyl)prop-2-en-1-one (1b in the above reaction formula, 0.0966 g, 0.5 mmol) is used instead of 3-(dimethylamino)-1-(2-phenyl)-2-propen-1-one (0.0876 g, 0.5 mmol) to obtain quinolinyl methyl ketone with the structure of 6a in the above reaction formula, and the yield of product 6a is 72%.

[0240] Product confirmation:

[0241] 1 H NMR(400MHz,Chloroform-d)δ8.18(d,J=8.7Hz,1H),8.11(s,1H),7.86-7.81(m,2H),7.75(d,J=8.7Hz,1H),7.66(s,1H),7.15(t,J=8.5Hz,2H),2.60(s,3H).

[0242] 13 C NMR(101MHz,CDCl3)δ192.1,167.6,165.1,145.6,143.7,143.4,140.5,136.0,134.4,133.2,132.9,132.8,131.7,130.7,130.6,129.9,127.1,126.5,116.1,115.9,21.9.

[0243] 19 F NMR(376MHz,CDCl3)δ-79.4,-79.4,-79.5,-102.6,-102.6,-102.6,-102.7,-102.7,-105.9,-106.0,-106.0,-123.5.HRMS(ESI-TOF)m / z:[M+H] + Calcd for C 20 H 12 F8NO + 434.0786;Found 434.0785.

[0244] Example 27

[0245]

[0246] This example has the same setup as Example 1, with the difference being that when adding the raw materials, (2E)-1-(4-chlorophenyl)-3-(dimethylamino)-2-propen-1-one (1c in the above reaction formula, 0.1048 g, 0.5 mmol) is used instead of 3-(dimethylamino)-1-(2-phenyl)-2-propen-1-one (0.0876 g, 0.5 mmol) to obtain quinolinealkyl methanone with the structure of 6b in the above reaction formula, and the yield of product 6b is 75%.

[0247] Product confirmation:

[0248] 1 H NMR(400MHz,Chloroform-d)δ8.18(d,J=8.6Hz,1H),8.10(s,1H),7.74(d,J=8.6Hz,3H),7.66(s,1H),7.45(d,J=8.6Hz,2H),2.60(s,3H).

[0249] 13 C NMR(101MHz,CDCl3)δ192.4,145.6,143.4,140.8,140.6,136.0,135.1,134.4,131.5,131.5,129.9,129.1,127.1,126.5,21.9.

[0250] 19 F NMR(376MHz,CDCl3)δ-79.7,-79.8,-79.9,-79.9,-106.3,-106.4,-106.4,-123.9,-124.0,-124.0.HRMS(ESI-TOF)m / z:[M+H] + Calcd for C 20 H 12 ClF7NO + 450.0491;Found 450.0493.

[0251] Example 28

[0252]

[0253] This example has the same setup as Example 1, with the difference that: when adding the raw materials, 1-(4-bromophenyl)-3-(dimethylamino)-2-propen-1-one (1d in the above reaction formula, 0.1271 g, 0.5 mmol) is used instead of 3-(dimethylamino)-1-(2-phenyl)-2-propen-1-one (0.0876 g, 0.5 mmol) to obtain quinolinyl methyl ketone with the structure of 6c in the above reaction formula, and the yield of product 6c is 69%.

[0254] Product confirmation:

[0255] 1 H NMR(400MHz,Chloroform-d)δ8.17(d,J=8.7Hz,1H),8.10(s,1H),7.77-7.72(m,1H),7.68-7.61(m,5H),2.60(s,3H).

[0256] 13 C NMR(101MHz,CDCl3)δ192.6,145.6,143.4,143.2,140.6,136.1,135.5,134.4,132.3,132.1,131.5,131.5,129.9,129.6,127.1,126.5,21.9.

[0257] 19 F NMR(376MHz,CDCl3)δ-79.8,-79.8,-79.9,-106.3,-106.3,-106.4,-106.4,-123.9,-124.0.HRMS(ESI-TOF)m / z:[M+H] + Calcd for C 20 H 12 BrF7NO + 493.9985;Found493.9984.

[0258] Example 29

[0259]

[0260] This example has the same setup as Example 1, with the difference that: when adding the raw materials, (2Z)-3-(dimethylamino)-1-(4-methoxyphenyl)prop-2-en-1-one (1e in the above reaction formula, 0.1026 g, 0.5 mmol) is used instead of 3-(dimethylamino)-1-(2-phenyl)-2-propen-1-one (0.0876 g, 0.5 mmol) to obtain quinolinyl methyl ketone with the structure of 6d in the above reaction formula, and the yield of product 6d is 88%.

[0261] Product confirmation:

[0262] 1 H NMR (400 MHz, Chloroform-d) δ 8.16 (d, J = 8.7 Hz, 1H), 8.10 (s, 1H), 7.77 (d, J = 8.8 Hz, 2H), 7.72 (dd, J = 8.7, 1.9 Hz, 1H), 7.64 (s, 1H), 6.94 (d, J = 9.0 Hz, 2H), 3.87 (s, 3H), 2.59 (s, 3H).

[0263] 13 C NMR (101 MHz, CDCl3) δ 192.2, 164.4, 145.5, 143.8, 143.6, 143.3, 140.3, 136.0, 134.1, 132.6, 132.4, 130.4, 129.9, 129.8, 127.2, 126.4, 114.0, 113.7, 55.6, 21.9.

[0264] 19 F NMR (376 MHz, CDCl3) δ -79.4, -79.4, -79.4, -106.1, -106.1, -106.1, -106.2, -123.5. HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 21 H 15 ClF7NO2 + 446.0986; Found 446.0987.

[0265] Example 30

[0266]

[0267] This example is the same as that of Example 1, except that: when adding raw materials, (E)-1-cyclopropyl-3-(dimethylamino)prop-2-en-1-one (1f in the above reaction formula, 0.0696 g, 0.5 mmol) is used instead of 3-(dimethylamino)-1-(2-phenyl)prop-2-en-1-one (0.0876 g, 0.5 mmol) to obtain quinolinealkyl methyl ketone with the structure of 6e in the above reaction formula, and the yield of product 6e is 63%.

[0268] Product confirmation:

[0269] 11H NMR (400 MHz, Chloroform-d) δ 8.19 (s, 1H), 8.11 (d, J = 8.5 Hz, 1H), 7.70 (dd, J = 11.0, 2.1 Hz, 2H), 2.59 (s, 3H), 2.33 (tt, J = 8.1, 4.5 Hz, 1H), 1.40 (p, J = 4.0 Hz, 2H), 1.19 (dq, J = 7.7, 3.8 Hz, 2H).

[0270] 13 13C NMR (101 MHz, CDCl3) δ 203.5, 145.4, 142.5, 140.2, 135.4, 135.0, 134.2, 129.8, 127.5, 126.5, 21.9, 13.5.

[0271] 19 19F NMR (376 MHz, CDCl3) δ -79.7, -79.7, -79.7, -79.8, -79.8, -106.2, -106.2, -106.2, -106.2, -123.6, -123.6. HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 17 H 13 F7NO + 380.0880; Found 380.0887.

[0272] Example 31

[0273]

[0274] This example is set up the same as Example 1, with the difference that: when adding the raw materials, 3-(dimethylamino)-1-(furan-2-yl)prop-2-en-1-one (1 g, 0.0826 g, 0.5 mmol in the above reaction formula) is used instead of 3-(dimethylamino)-1-(2-phenyl)prop-2-en-1-one (0.0876 g, 0.5 mmol) to obtain quinolinealkyl methyl ketone with the structure of 6f in the above reaction formula, and the yield of product 6f is 48%.

[0275] Product confirmation:

[0276] 11H NMR (400 MHz, Chloroform-d) δ 8.22 (s, 1H), 8.16 (d, J = 8.6 Hz, 1H), 7.74 (dd, J = 8.8, 1.9 Hz, 1H), 7.69 (s, 2H), 7.06 (d, J = 3.6 Hz, 1H), 6.60 (dd, J = 3.6, 1.7 Hz, 1H), 2.60 (s, 3H).

[0277] 13 13C NMR (101 MHz, CDCl3) δ 180.8, 152.4, 148.3, 145.6, 143.4, 140.4, 136.6, 134.4, 130.9, 129.9, 127.0, 126.6, 121.3, 112.8, 21.9.

[0278] 19 19F NMR (376 MHz, CDCl3) δ -79.2, -79.4, -79.4, -79.4, -79.4, -106.4, -106.5, -123.4. HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 18 H 11 F7NO2 + 406.0673; Found 406.0670.

[0279] Example 32

[0280]

[0281] This example is the same as that of Example 1, except that: when adding raw materials, 3-dimethylamino-1-(2-thienyl)-2-propen-1-one (0.0906 g, 0.5 mmol) is used instead of 3-(dimethylamino)-1-(2-phenyl)-2-propen-1-one (1h in the above reaction formula, 0.0876 g, 0.5 mmol), and quinoline alkyl methyl ketone as shown in 6g in the above reaction formula is obtained, and the yield of product 6g is 80%.

[0282] Product confirmation:

[0283] 11H NMR (400 MHz, Chloroform-d) δ 8.23 (s, 1H), 8.17 (d, J = 8.7 Hz, 1H), 7.81 (dd, J = 4.9, 1.2 Hz, 1H), 7.74 (dd, J = 8.7, 1.9 Hz, 1H), 7.68 (s, 1H), 7.33 (dd, J = 3.8, 1.2 Hz, 1H), 7.13 (dd, J = 5.0, 3.8 Hz, 1H), 2.60 (s, 3H).

[0284] 13 13C NMR (101 MHz, CDCl3) δ 185.7, 145.6, 144.2, 143.4, 140.5, 136.3, 136.1, 136.0, 134.4, 131.5, 129.9, 128.4, 127.0, 126.6, 21.9.

[0285] 19 19F NMR (376 MHz, CDCl3) δ -79.4, -79.4, -79.4, -79.4, -106.0, -106.1, -106.1, -106.1, -123.5, -123.5. HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 18 H 11 F7NOS + 422.0445; Found 422.0444.

[0286] It can be seen from Comparative Examples 26 to 32 that:

[0287] When different enaminones are used for the reaction, the synthetic effects are in the order of: (2Z)-3-(dimethylamino)-1-(4-methoxyphenyl)prop-2-en-1-one > 3-dimethylamino-1-(2-thienyl)-2-propen-1-one > (2E)-1-(4-chlorophenyl)-3-(dimethylamino)-2-propen-1-one > (2E)-3-(dimethylamino)-1-(4-fluorophenyl)prop-2-en-1-one > 1-(4-bromophenyl)-3-(dimethylamino)-2-propen-1-one > (E)-1-cyclopropyl-3-(dimethylamino)prop-2-en-1-one > 3-(dimethylamino)-1-(furan-2-yl)prop-2-en-1-one, but the yields of the synthesized quinolinyl methyl ketone compounds are all lower than that of 3-(dimethylamino)-1-(2-phenyl)-2-propen-1-one in Example 1.

[0288] In this case, enaminones, perfluoroalkane compounds and p-toluidine were used as raw materials, and quinoline alkyl ketone compounds were synthesized through visible light-mediated dehalogenation and radical cyclization addition. The reaction conditions were green and mild, the reaction time was short, and the operation process was simple. When 3-(dimethylamino)-1-(2-phenyl)prop-2-en-1-one, perfluoroiodobutane and p-toluidine were used as raw materials, the highest yield of quinoline alkyl ketone was obtained when the solvent was acetonitrile and the base was 1,4-diazabicyclo[2.2.2]octane (DABCO). And under this condition, the substrate adaptability was explored. It can be seen from Examples 2 to 21 that the substrate adaptability was good, and quite good yields could be obtained. In particular, 4-aminoterphenyl, 1-iodoperfluorodecane and 3-(dimethylamino)-1-(furan-2-yl)prop-2-en-1-one could all obtain yields above 85%.

[0289] Application Example: Antibacterial Performance Evaluation

[0290] Weigh 60 mg of the product obtained in Example 1, dissolve it in DMSO, and dilute it with water to the solution concentrations of 60 mg / ml, 30 mg / ml, 15 mg / ml, 5 mg / ml, and 1 mg / ml respectively. The inhibitory effects of the reagent solutions on Staphylococcus aureus were tested by the inhibition zone method respectively.

[0291] Experimental Method:

[0292] Activate Staphylococcus aureus in advance to make its OD 600 = 0.6 - 0.8, and then dilute the bacterial solution to OD 600 = 0.08, and evenly smear the bacterial solution on the broth medium with a cotton swab. Then soak the blank drug sensitivity test paper in the reagent solutions and solvents with different concentration gradients for one hour to fully immerse the drug in the paper. Finally, stick the paper soaked with the reagent solution to the broth medium coated with the bacterial solution in sections, and incubate it overnight in a constant temperature and humidity incubator at 37°C. After incubation, take it out to observe the results and record the antibacterial situation, as shown in Table 5.

[0293] Table 5: Antibacterial Performance Table

[0294] Serial number Reagent concentration (mg / ml) Inhibition zone diameter (mm) 1 60 10.0 2 30 8.5 3 15 6.0 4 5 5.0 5 1 0.5 6 0 0.0

[0295] According to Table 5, it can be seen that the products with different concentrations have different antibacterial effects on Staphylococcus aureus, and the higher the concentration, the stronger the bactericidal effect. It is proved that the quinoline alkyl ketone compound in this case has good antibacterial effects and can be used to prepare antibacterial drugs.

[0296] The above-described embodiments merely represent several feasible implementation manners of the present invention. The description is relatively specific and detailed, but it should not be construed as a limitation on the scope of the patent for the present invention. The embodiments are not intended to limit the scope of protection in the claims of the present invention. For those of ordinary skill in the art, without departing from the concept of the present invention, several modifications and improvements can be made. Any equivalent implementation or change made without departing from the present invention shall be included in the technology of the present invention.

Claims

1. A quinoline alkyl ketone compound, characterized in that Satisfy the general structure: Here, R is any one of methyl, dimethyl, trifluoromethyl, methoxy, ethoxycarbonyl, fluorine, chlorine, bromine, iodine, phenyl, biphenyl, ethyl, isopropyl, tert-butyl, and pentafluorothio.

2. A quinoline alkyl ketone compound according to claim 1, characterized in that: The quinoline alkyl ketone compound is any one of the following structural formulas:

3. A quinoline alkyl ketone compound, characterized in that Satisfy the general structure: R f It is any one of pentafluoroethyl, nonafluorobutyl, undecafluoropentyl and pentafluoroheptyl.

4. A quinoline alkyl ketone compound according to claim 3, characterized in that: The quinoline alkyl ketone compound is any one of the following structural formulas:

5. A quinoline alkyl ketone compound, characterized in that Satisfy the general structure: R is any one of p-fluorophenyl, p-chlorophenyl, p-bromophenyl, p-methoxyphenyl, cyclopropyl, furan, and thiophene.

6. A quinoline alkyl ketone compound according to claim 1, characterized in that: The quinoline alkyl ketone compound is any one of the following structural formulas:

7. A method for preparing the quinoline alkyl ketone compound according to any one of claims 1 to 6, characterized in that: With enaminone, perfluoroalkane compounds and aminobenzene as raw materials, an organic solvent and a base are added, and the mixture is stirred and reacted under an argon atmosphere and blue light irradiation to obtain a quinoline alkyl ketone compound.

8. The method for preparing a quinoline alkyl ketone compound according to claim 7, characterized in that: The enaminone is any one of 3-(dimethylamino)-1-(2-phenyl)-2-propene-1-one, (2E)-3-(dimethylamino)-1-(4-fluorophenyl)prop-2-ene-1-one, (2E)-1-(4-chlorophenyl)-3-(dimethylamino)-2-propene-1-one, 1-(4-bromophenyl)-3-(dimethylamino)-2-propene-1-one, (2Z)-3-(dimethylamino)-1-(4-methoxyphenyl)prop-2-ene-1-one, (E)-1-cyclopropyl-3-(dimethylamino)prop-2-ene-1-one, 3-(dimethylamino)-1-(furan-2-yl)prop-2-ene-1-one and 3-dimethylamino-1-(2-thienyl)-2-propene-1-one; The perfluoroalkane compound is any one of perfluoroiodobutane, perfluoroiodopropane, 1-iodoperfluoropentane, 1-iodoperfluorohexane and 1-iodoperfluorooctane; The aminobenzene is any one of p-toluidine, 2,5-dimethylaniline, p-trifluoromethylaniline, p-methoxyaniline, p-fluoroaniline, p-chloroaniline, p-bromoaniline, p-iodoaniline, 4-aminobiphenyl, 4-amino-p-terphenyl, p-isopropylaniline, 4-(tert-butyl)aniline, 2-fluoroaniline, 2-chloroaniline, 2-bromoaniline, 2-iodoaniline, 4-ethylaniline, (4-aminophenyl) sulfide pentafluoride, ethyl 4-aminobenzoate, 2,4-dimethylaniline, and 1-amino-3,5-xylene.

9. The method for preparing a quinoline alkyl ketone compound according to claim 7, characterized in that: The molar ratio of the enaminone, the perfluoroalkane compound and p-toluidine is 2-6:2-6:

1.

10. Use of the quinoline alkyl ketone compound according to any one of claims 1 to 6 in the preparation of antibacterial, antitumor, antifungal, antihypertensive or anti-HIV drugs.

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