Method for electrochemical synthesis of 3,4-dihydroquinolinone compounds

Abstract

The present invention discloses a method for electrochemically synthesizing 3,4-dihydroquinolinone compounds, comprising: N Aryl haloacrylamide, phenanthrene and electrolyte are dissolved in a solvent, an aluminum sheet is used as an anode, a platinum sheet is used as a cathode, and the reaction is carried out by stirring at a constant current of 5-10 mA and 30-60 ° C; after the reaction is completed, the mixture is extracted with ethyl acetate; the organic layer is dried over anhydrous sodium sulfate, filtered, the solvent is dried under reduced pressure, and the residue is purified by column chromatography to obtain the target product. The present invention uses electric current to replace the stoichiometric redox reagent, thereby minimizing the pollution and waste of the reagent, and does not need to use expensive transition metal catalysis, and has the advantages of mild reaction conditions, short reaction time and high yield.

Description

Technical Field

[0001] The invention relates to the field of organic compound synthesis, and relates to a method for synthesizing quinolinone compounds, in particular to a method for electrochemically synthesizing 3,4-dihydroquinolinone compounds. Background Art

[0002] The skeleton of 3,4-dihydroquinolinone compounds is widely present in drugs, dyes, polymers, and natural products, and plays an irreplaceable and important role in life and production.

[0003] The structural formula of 3,4-dihydroquinolinone compounds is:

[0004]

[0005] Where R 1 is an aromatic group, an aliphatic group or an alkyl group; R 2 is an aromatic group or an alkyl group, R 3 It is an aromatic group, an aliphatic group or an alkyl group.

[0006] The skeleton of 3,4-dihydroquinolinone is an important component of many natural products and active pharmaceutical compounds (Bioorg.Med.Chem.Lett.,2015,25,3415-3419). 3,4-dihydroquinolinone compounds can be used to synthesize a series of allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) (Bioorg.Med.Chem.Lett.,2016,26,4748-4752); a potent protease inhibitor can also be synthesized through this skeleton (J.Med.Chem.,2016,59,6136-6148) with good oral bioavailability; 3,4-dihydroquinolinone compounds have good effects on the bioavailability of human retinoblastoma cell line Y 79. The leukemia cell lines CCRF-CEM and SR and the melanoma cell line LOX-IMVI are cytotoxic (J.Nat.Prod., 2015, 78, 2917-2923). It can also be used to synthesize antihypertensive drugs (Bioorg.Med.Chem.Lett., 1998, 6, 1657-1662) and the antipsychotic drug aripiprazole (Bioorg.Med.Chem.Lett., 2010, 20, 2983-2986).

[0007] For example, Z. Kuang et al. reported a Cu / Pd-catalyzed hydroboration reaction and an intramolecular sp2-sp3 cross-coupling reaction. The halogenated aromatic unsaturated amide was first in situ generated into an alkyl borate ester by copper and boron reagents, and then reacted with an active palladium species to synthesize 3,4-dihydroquinolinone compounds (Chem. Commun., 2018, 54, 34-37). The current synthesis method of this type of 3,4-dihydroquinolinone compounds is limited by transition metal-catalyzed intermolecular coupling reactions, and requires complex substrates and harsh reaction conditions such as long time and high temperature. Summary of the invention

[0008] The purpose of the present invention is to provide a method for electrochemically synthesizing 3,4-dihydroquinolinone compounds to solve the shortcomings of the prior art, such as the need for expensive transition metal catalysis, high temperature, and a long reaction time. The present invention uses electric current to replace stoichiometric redox reagents, thereby minimizing the pollution and waste of reagents, and does not require the use of expensive transition metal catalysts. It has the advantages of mild reaction conditions, short reaction time, and high yield.

[0009] The technical solution for achieving the purpose of the present invention is:

[0010] A method for electrochemically synthesizing 3,4-dihydroquinolinone compounds, comprising:

[0011] N-aryl halogenated acrylamide, phenanthrene and electrolyte are dissolved in a solvent, an aluminum sheet is used as an anode, a platinum sheet is used as a cathode, and a reaction is carried out by stirring at a constant current of 5 to 10 mA and 30 to 60° C. After the reaction is completed, the mixture is extracted with ethyl acetate; the organic layer is dried with anhydrous sodium sulfate, filtered, the solvent is dried under reduced pressure, and the residue is purified by column chromatography to obtain the target product.

[0012] The general formula of the synthesis method is:

[0013]

[0014] R 1 , R 2 is an aromatic group, an aliphatic group or an alkyl group; R 3 is an aromatic group, an aliphatic group or an alkyl group; X is Br or Cl; anode: aluminum (Al); cathode: platinum (Pt); electrolyte: tetraethylammonium tetrafluoroborate, tetrabutylammonium tetrafluoroborate or tetrabutylammonium hexafluorophosphate; solvent: acetonitrile, dimethyl sulfoxide or N,N-dimethylformamide.

[0015] Furthermore, the molar ratio of the N-aryl halogenated acrylamide, phenanthrene and electrolyte is 1:0.2-1.5:1.0-2.0.

[0016] Preferably, the molar ratio of the N-aryl halogenated acrylamide, phenanthrene and electrolyte is 1:1:1.5.

[0017] Furthermore, the molar volume ratio of the N-aryl halogenated acrylamide, phenanthrene, electrolyte and solvent is 0.3 mmol: 0.06-0.45 mmol: 0.3-0.6 mmol: 5 mL.

[0018] Furthermore, the electrolyte is tetraethylammonium tetrafluoroborate, tetrabutylammonium tetrafluoroborate or tetrabutylammonium hexafluorophosphate.

[0019] Furthermore, the solvent is acetonitrile, dimethyl sulfoxide or N,N-dimethylformamide.

[0020] Furthermore, while stirring the reaction, the reaction is monitored by thin layer chromatography (TLC) for 3 to 5 hours until the reaction is complete. TLC can quickly monitor the reaction rate, and the reaction rate of each substrate is different. Too long a reaction time may lead to the production of by-products or excessive electrode loss.

[0021] Furthermore, the column chromatography is silica gel column chromatography, and the volume ratio of the eluent petroleum ether to ethyl acetate is 20:1 to 10:1.

[0022] The aluminum sheet is 1 cm long and 1 cm wide; the platinum sheet is 1 cm long and 1 cm wide.

[0023] Existing synthesis methods of 3,4-dihydroquinolinone compounds are limited by transition metal-catalyzed intermolecular coupling reactions and require complex substrates and harsh reaction conditions such as long time and high temperature. Free radical chemistry can occur at a higher rate under mild conditions and has good functional group tolerance and reaction controllability. The present invention reduces the aryl halogenated unsaturated amide to free radicals and then performs a free radical tandem reaction to synthesize such compounds.

[0024] As an effective tool for realizing free radical conversion, electro-organic synthesis realizes the redox reaction of organic compounds through the gain and loss of electrons to synthesize various substances, which can not only improve the atomic efficiency, but also replace the stoichiometric redox reagent with electric current, thereby minimizing the pollution and waste of reagents. Since the electrochemical reduction of aryl halides requires a higher reduction potential, the present invention adopts a redox medium, phenanthrene, and utilizes an indirect electrochemical reaction to avoid the use of transition metal reagents, thereby realizing the electrochemical reduction of aryl halides under mild conditions. The redox medium can be continuously regenerated on the electrode during the reaction, which can reduce the reduction potential and realize an effective catalytic cycle.

[0025] The present invention utilizes electric current to replace stoichiometric redox reagents, thereby minimizing the pollution and waste of reagents, and does not require the use of expensive transition metal catalysts, and has the advantages of mild reaction conditions, short reaction time and high yield. DETAILED DESCRIPTION

[0026] The method for electrochemically synthesizing 3,4-dihydroquinolinone compounds of the present invention is further described below in conjunction with examples, but the present invention is not limited thereto.

[0027] Embodiment 1:

[0028] Synthesis and Characterization of 1-Benzyl-3-methyl-3,4-dihydroquinolin-2(1H)-one:

[0029] 0.3 mmol of N-benzyl-N-(2-bromophenyl)methacrylamide, 53.4 mg of phenanthrene and 148.1 mg of tetrabutylammonium tetrafluoroborate were placed in a 10 mL three-necked round-bottom flask, 5 mL of N,N-dimethylformamide was added to dissolve, a 1 cm x 1 cm aluminum sheet was used as an anode, a 1 cm x 1 cm platinum sheet was used as a cathode, and the reaction was stirred at a constant current of 5 mA and 50° C. for 3 h, and monitored by thin layer chromatography; after the reaction was completed, the mixture was extracted with 15 mL of ethyl acetate, the organic layer was dried over anhydrous sodium sulfate, filtered, the solvent was dried under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the target product with a yield of 82%, namely 1-benzyl-3-methyl-3,4-dihydroquinolin-2(1H)-one, with the structural formula being:

[0030]

[0031] The NMR and mass spectrometry data of the compound:

[0032] 1 H NMR(400MHz,Chloroform-d)δ7.33–7.28(m,2H),7.26–7.18(m,4H),7.14–7.08(m,1H),7.03–6.98(m,1H),6.91–6.87(m,1H ),5.27–5.14(m,2H),3.18–3.08(m,1H),2.88(dd,J=15.6,5.4Hz,1H),2.61(dd,J=15.6,7.2Hz,1H),1.33(d,J=7.0Hz,3H); 13C NMR(151MHz,Chloroform-d)δ170.13,139.09,137.16,131.29,128.84,127.51,127.19,12 6.59,126.56,123.30,115.81,46.14,39.32,30.70,19.62; HRMS(ESI,m / z)calculatedfor C 17 H 18 NO + [M+H] + :252.1383; found:252.1384.

[0033] Embodiment 2:

[0034] Synthesis and Characterization of 1-Benzyl-3,8-dimethyl-3,4-dihydroquinolin-2(1H)-one:

[0035] 0.3 mmol of N-benzyl-N-(2-bromo-6-methylphenyl)methacrylamide, 53.4 mg of phenanthrene and 148.1 mg of tetrabutylammonium tetrafluoroborate were placed in a 10 mL three-necked round-bottom flask, 5 mL of N,N-dimethylformamide was added to dissolve, a 1 cm x 1 cm aluminum sheet was used as an anode, a 1 cm x 1 cm platinum sheet was used as a cathode, and the reaction was stirred at 5 mA constant current and 50° C. for 5 h, and monitored by thin layer chromatography; after the reaction was completed, the mixture was extracted with 15 mL of ethyl acetate, the organic layer was dried over anhydrous sodium sulfate, filtered, the solvent was dried under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the target product with a yield of 65%, namely 1-benzyl-3,8-dimethyl-3,4-dihydroquinolin-2(1H)-one, with the structural formula being:

[0036]

[0037] The NMR and mass spectrometry data of the compound:

[0038] 1 H NMR(600MHz,Chloroform-d)δ7.22–7.20(m,2H),7.19–7.17(m,1H),7.14–7.12(m,2H),7.07–7.05(m,1H),7.03–7.00(m,2H),5.23(d,J=15 .3Hz,1H),4.93(d,J=15.3Hz,1H),2.92–2.87(m,1H),2.62(dd,J=14.7,4.4Hz,1H),2.39–2.35(m,1H),2.34(s,3H),1.11(d,J=7.0Hz,3H); 13C NMR(151MHz,Chloroform-d)δ173.23,140.06,137.91,136.50,131.04,128.33,128.16,127. 79,127.17,124.50,123.43,49.66,40.68,31.12,21.37,18.21.HRMS(m / z)[ESI]:calculated for C 18 H 19 NO + [M+H] + :266.1539; found:266.1541.

[0039] Embodiment 3:

[0040] Synthesis and Characterization of 1-Benzyl-3,7-dimethyl-3,4-dihydroquinolin-2(1H)-one:

[0041] 0.3 mmol of N-benzyl-N-(2-bromo-5-methylphenyl)methacrylamide, 53.4 mg of phenanthrene and 148.1 mg of tetrabutylammonium tetrafluoroborate were placed in a 10 mL three-necked round-bottom flask, 5 mL of dimethyl sulfoxide was added to dissolve, a 1 cm x 1 cm aluminum sheet was used as an anode, a 1 cm x 1 cm platinum sheet was used as a cathode, and the mixture was stirred at a constant current of 5 mA and 50° C. for 3 h, and monitored by thin layer chromatography; after the reaction was completed, the mixture was extracted with 15 mL of ethyl acetate, the organic layer was dried over anhydrous sodium sulfate, filtered, the solvent was dried under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the target product with a yield of 75%, namely 1-benzyl-3,7-dimethyl-3,4-dihydroquinolin-2(1H)-one, with the structural formula being:

[0042]

[0043] The NMR and mass spectrometry data of the compound:

[0044] 1 H NMR(600MHz,Chloroform-d)δ7.33–7.29(m,2H),7.25–7.22(m,3H),7.10–7.08(m,1H),6.83(d,J=8.2Hz,1H),6.73(s,1H),5.24 –5.14(m,2H),3.12–3.06(m,1H),2.85(dd,J=15.6,5.4Hz,1H),2.58(dd,J=15.6,7.3Hz,1H),2.23(s,3H),1.31(d,J=7.0Hz,3H); 13CNMR(151MHz,Chloroform-d)δ170.22,139.04,137.28,128.80,128.37,127.12,126.59, 126.38,123.90,116.50,46.11,39.53,30.31,21.52,19.70.HRMS(m / z)[ESI]:calculated for C 18 H 19 NO + [M+H] + :266.1539; found:266.1544.

[0045] Embodiment 4:

[0046] Synthesis and Characterization of 1-Benzyl-3,6-dimethyl-3,4-dihydroquinolin-2(1H)-one:

[0047] 0.3 mmol of N-benzyl-N-(2-bromo-4-methylphenyl)methacrylamide, 53.4 mg of phenanthrene and 148.1 mg of tetrabutylammonium tetrafluoroborate were placed in a 10 mL three-necked round-bottom flask, 5 mL of N,N-dimethylformamide was added to dissolve, a 1 cm x 1 cm aluminum sheet was used as an anode, a 1 cm x 1 cm platinum sheet was used as a cathode, and the reaction was stirred at 5 mA constant current and 50° C. for 3 h, and monitored by thin layer chromatography; after the reaction was completed, the mixture was extracted with 15 mL of ethyl acetate, the organic layer was dried over anhydrous sodium sulfate, filtered, the solvent was dried under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the target product with a yield of 75%, namely 1-benzyl-3,6-dimethyl-3,4-dihydroquinolin-2(1H)-one, with the structural formula being:

[0048]

[0049] The NMR and mass spectrometry data of the compound:

[0050] 1 H NMR(600MHz,Chloroform-d)δ7.32–7.29(m,2H),7.24–7.21(m,3H),7.02(s,1H),6.93–6.90(m,1H),6.80–6.78(m,1H),5.19(q,J =16.2Hz,2H),3.12–3.06(m,1H),2.86(dd,J=15.6,5.4Hz,1H),2.60(dd,J=15.6,7.1Hz,1H),2.29(s,3H),1.32(d,J=7.0Hz,3H); 13CNMR(151MHz,Chloroform-d)δ169.93,137.22,136.57,132.76,131.13,128.76,127.84,127. 28,127.10,126.58,115.67,46.01,39.37,30.67,20.74,19.65.HRMS(m / z)[ESI]:calculated for C 18 H 19 NO + [M+H] + :266.1539; found:266.1543.

[0051] Embodiment 5:

[0052] Synthesis and Characterization of 1-Benzyl-3,5-dimethyl-3,4-dihydroquinolin-2(1H)-one:

[0053] 0.3 mmol of N-benzyl-N-(2-bromo-3-methylphenyl)methacrylamide, 53.4 mg of phenanthrene and 148.1 mg of electrolyte tetrabutylammonium tetrafluoroborate were placed in a 10 mL three-necked round-bottom flask, 5 mL of solvent N,N-dimethylformamide was added to dissolve, a 1 cm x 1 cm aluminum sheet was used as an anode, a 1 cm x 1 cm platinum sheet was used as a cathode, and the reaction was stirred at 5 mA constant current and 50° C. for 4 h, and monitored by thin layer chromatography; after the reaction was completed, the mixture was extracted with 15 mL of ethyl acetate, the organic layer was dried over anhydrous sodium sulfate, filtered, the solvent was dried under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the target product with a yield of 70%, namely 1-benzyl-3,5-dimethyl-3,4-dihydroquinolin-2(1H)-one, with the structural formula being:

[0054]

[0055] The NMR and mass spectrometry data of the compound:

[0056] 1 H NMR(400MHz,Chloroform-d)δ7.33–7.28(m,2H),7.25–7.20(m,3H),7.03–6.98(m,1H),6.88–6.85(m,1H),6.79–6.76(m,1H),5.44(d,J=16.2Hz ,1H),4.97(d,J=16.2Hz,1H),3.33–3.25(m,1H),2.89(dd,J=15.7,6.0Hz,1H),2.70(dd,J=15.7,1.9Hz,1H),2.34(s,3H),1.21(d,J=7.1Hz,3H);13 C NMR(101MHz,Chloroform-d)δ169.62,138.84,137.32,135.17,129.42,128.79,127.13,127. 02,126.64,125.43,114.16,46.34,38.58,27.43,18.96,18.18.HRMS(m / z)[ESI]:calculated for C 18 H 19 NO + [M+H] + :266.1539; found:266.1539.

[0057] Embodiment 6:

[0058] Synthesis and Characterization of 1-Benzyl-6-methoxy-3-methyl-3,4-dihydroquinolin-2(1H)-one:

[0059] 0.3 mmol of N-benzyl-N-(2-bromo-4-methoxyphenyl)methacrylamide, 53.4 mg of phenanthrene and 174.3 mg of electrolyte tetrabutylammonium hexafluorophosphate were placed in a 10 mL three-necked round-bottom flask, 5 mL of solvent acetonitrile was added to dissolve, a 1 cm x 1 cm aluminum sheet was used as an anode, a 1 cm x 1 cm platinum sheet was used as a cathode, and the reaction was stirred at 5 mA constant current and 50 ° C for 3 h, and monitored by thin layer chromatography. After the reaction was completed, the mixture was extracted with 15 mL of ethyl acetate, the organic layer was dried over anhydrous sodium sulfate, filtered, the solvent was dried under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the target product with a yield of 75%, namely 1-benzyl-6-methoxy-3-methyl-3,4-dihydroquinolin-2(1H)-one, with the structural formula:

[0060]

[0061] The NMR and mass spectrometry data of the compound:

[0062] 1 H NMR(400MHz,Chloroform-d)δ7.31–7.27(m,2H),7.24–7.20(m,3H),6.82–6.75(m,2H),6.64–6.60(m,1H),5.22–5.11(m ,2H),3.75(s,3H),3.13–3.04(m,1H),2.85(dd,J=15.6,5.3Hz,1H),2.57(dd,J=15.6,7.4Hz,1H),1.31(d,J=7.0Hz,3H); 13C NMR(101MHz,Chloroform-d)δ155.55,137.16,132.83,132.52,130.69,128.72,127.07,126. 53,116.60,112.83,111.46,55.49,46.11,39.22,30.80,19.39.HRMS(m / z)[ESI]:calculated forC 18 H 19 NO 2 Na + [M+Na] + :304.1308; found:304.1304.

[0063] Embodiment 7:

[0064] Synthesis and Characterization of 1-Benzyl-6-bromo-3-methyl-3,4-dihydroquinolin-2(1H)-one:

[0065] 0.3 mmol of N-benzyl-N-(2,4-dibromophenyl)methacrylamide, 53.4 mg of phenanthrene and 174.3 mg of electrolyte tetrabutylammonium hexafluorophosphate were placed in a 10 mL three-necked round-bottom flask, 5 mL of solvent acetonitrile was added to dissolve, a 1 cm x 1 cm aluminum sheet was used as an anode, a 1 cm x 1 cm platinum sheet was used as a cathode, and the reaction was stirred at 5 mA constant current and 50 ° C for 5 h, and monitored by thin layer chromatography. After the reaction was completed, the mixture was extracted with 15 mL of ethyl acetate, the organic layer was dried over anhydrous sodium sulfate, filtered, the solvent was dried under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the target product with a yield of 71%, namely 1-benzyl-6-bromo-3-methyl-3,4-dihydroquinolin-2(1H)-one, with the structural formula:

[0066]

[0067] The NMR and mass spectrometry data of the compound:

[0068] 1 H NMR(600MHz,Chloroform-d)δ7.32–7.28(m,2H),7.23–7.20(m,3H),7.13–7.09(m,1H),7.02–6.99(m,1H),6.90–6.88(m,1H ),5.25–5.15(m,2H),3.16–3.10(m,1H),2.88(dd,J=15.6,5.4Hz,1H),2.61(dd,J=15.6,7.2Hz,1H),1.32(d,J=7.0Hz,3H); 13C NMR(151MHz,Chloroform-d)δ170.14,139.11,137.17,131.31,128.85,127.52,127.21,126 .60,126.57,123.31,115.83,46.16,39.34,30.71,19.63.HRMS(m / z)[ESI]:calculatedfor C 17 H 17 BrNO + [M+H] + :330.0488; found:330.0481.

[0069] Embodiment 8:

[0070] Synthesis and Characterization of 1-Benzyl-6-chloro-3-methyl-3,4-dihydroquinolin-2(1H)-one:

[0071] 0.3 mmol of N-benzyl-N-(2-bromo-4-chlorophenyl)methacrylamide, 53.4 mg of phenanthrene and 174.3 mg of electrolyte tetrabutylammonium hexafluorophosphate were placed in a 10 mL three-necked round-bottom flask, 5 mL of solvent dimethyl sulfoxide was added to dissolve, a 1 cm x 1 cm aluminum sheet was used as an anode, a 1 cm x 1 cm platinum sheet was used as a cathode, and the reaction was stirred at 5 mA constant current and 50 ° C for 5 h, and monitored by thin layer chromatography. After the reaction was completed, the mixture was extracted with 15 mL of ethyl acetate, the organic layer was dried over anhydrous sodium sulfate, filtered, the solvent was dried under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the target product with a yield of 70%, namely 1-benzyl-6-chloro-3-methyl-3,4-dihydroquinolin-2(1H)-one, with the structural formula:

[0072]

[0073] The NMR and mass spectrometry data of the compound:

[0074] 1 H NMR(400MHz,Chloroform-d)δ7.33–7.28(m,2H),7.23–7.16(m,4H),7.08–7.03(m,1H),6.83–6.77(m,1H),5.22–5 .16(m,2H),3.14–3.06(m,1H),2.86(dd,J=15.7,5.4Hz,1H),2.59(dd,J=15.7,7.5Hz,1H),1.32(d,J=7.0Hz,3H); 13C NMR(101MHz,Chloroform-d)δ169.72,137.67,136.67,133.09,129.40,128.92,127.38,1 27.33,126.62,126.56,117.05,46.10,38.99,30.59,19.36.HRMS(m / z)[ESI]:calculated for C 17 H 17 ClNO[M+H] + :286.0993; found:286.0992.

[0075] Embodiment 9:

[0076] Synthesis and Characterization of 1-Benzyl-6-fluoro-3-methyl-3,4-dihydroquinolin-2(1H)-one:

[0077] 0.3 mmol of N-benzyl-N-(2-bromo-4-fluorophenyl)methacrylamide, 53.4 mg of phenanthrene and 174.3 mg of electrolyte tetrabutylammonium hexafluorophosphate were placed in a 10 mL three-necked round-bottom flask, 5 mL of solvent acetonitrile was added to dissolve, a 1 cm x 1 cm aluminum sheet was used as an anode, a 1 cm x 1 cm platinum sheet was used as a cathode, and the reaction was stirred at 5 mA constant current and 50 ° C for 5 h, and monitored by thin layer chromatography. After the reaction was completed, the mixture was extracted with 15 mL of ethyl acetate, the organic layer was dried over anhydrous sodium sulfate, filtered, the solvent was dried under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the target product with a yield of 55%, namely 1-benzyl-6-fluoro-3-methyl-3,4-dihydroquinolin-2(1H)-one, with the structural formula:

[0078]

[0079] The NMR and mass spectrometry data of the compound:

[0080] 1 H NMR(400MHz,Chloroform-d)δ7.33–7.28(m,2H),7.26–7.19(m,3H),6.94–6.90(m,1H),6.84–6.75(m,2H),5.1 8(s,2H),3.15–3.06(m,1H),2.86(dd,J=15.7,5.3Hz,1H),2.58(dd,J=15.7,7.9Hz,1H),1.32(d,J=7.0Hz,3H); 13C NMR(101MHz,Chloroform-d)δ169.70,158.86(d,J=243.8Hz),136.85,135.25(d,J=2.6Hz),133.47(d,J=7.2Hz),128 .90,127.32,126.56,116.98(d,J=8.2Hz),113.70(d,J=22.5Hz),113.54(d,J=23.2Hz),46.30,39.03,30.59,19.22; 19 F NMR(376MHz,Chloroform-d)δ-120.13.HRMS(m / z)[ESI]:calculated for C 17 H 16 F + [M+Na] + :292.1108; found:292.1103.

[0081] Embodiment 10:

[0082] Preparation and characterization of 3-benzyl-1-methyl-3,4-dihydroquinolin-2(1H)-one:

[0083]

[0084] 0.3 mmol of 2-benzyl-N-(2-bromophenyl)-N-methylacrylamide, 53.4 mg of phenanthrene and 97.6 mg of electrolyte tetraethylammonium tetrafluoroborate were placed in a 10 mL three-necked round-bottom flask, 5 mL of solvent dimethyl sulfoxide was added to dissolve, a 1 cm x 1 cm aluminum sheet was used as an anode, a 1 cm x 1 cm platinum sheet was used as a cathode, and the reaction was stirred at 5 mA constant current and 50 ° C for 5 h, and monitored by thin layer chromatography. After the reaction was completed, the mixture was extracted with 15 mL of ethyl acetate, the organic layer was dried over anhydrous sodium sulfate, filtered, the solvent was dried under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the target product with a yield of 63%, namely 3-benzyl-1-methyl-3,4-dihydroquinolin-2(1H)-one, with the structural formula:

[0085]

[0086] The NMR and mass spectrometry data of the compound:

[0087] 1H NMR(600MHz,Chloroform-d)δ7.33–7.30(m,1H),7.28–7.26(m,1H),7.25–7.25(m,1H),7.22–7.19(m,1H),7.06–7.04(m,2H),7.02–6.98( m,3H),3.33(s,3H),3.13–3.09(m,1H),2.90(dd,J=13.4,6.4Hz,1H),2.74–2.70(m,1H),2.68–2.64(m,1H),2.60(dd,J=16.0,3.8Hz,1H); 13 C NMR(151MHz,Chloroform-d)δ169.43,139.88,138.76,129.43,129.06,128.45,127.80,1 27.78,126.52,122.90,114.95,40.61,38.29,35.97,29.43.HRMS(m / z)[ESI]:calculated for C 17 H 18 NO + [M+H] + :252.1383; found:252.1380.

[0088] Embodiment 11:

[0089] Synthesis and Characterization of 1-Methyl-3-phenyl-3,4-dihydroquinolin-2(1H)-one:

[0090] 0.3 mmol of N-(2-bromophenyl)-N-methyl-2-phenylacrylamide, 53.4 mg of phenanthrene and 97.6 mg of electrolyte tetraethylammonium tetrafluoroborate were placed in a 10 mL three-necked round-bottom flask, 5 mL of solvent acetonitrile was added to dissolve, a 1 cm x 1 cm aluminum sheet was used as an anode, a 1 cm x 1 cm platinum sheet was used as a cathode, and the reaction was stirred at 5 mA constant current and 30 ° C for 5 h, and monitored by thin layer chromatography. After the reaction was completed, the mixture was extracted with 15 mL of ethyl acetate, the organic layer was dried over anhydrous sodium sulfate, filtered, the solvent was dried under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the target product with a yield of 67%, namely 1-methyl-3-phenyl-3,4-dihydroquinoline-2(1H)-one, with the structural formula:

[0091]

[0092] The NMR and mass spectrometry data of the compound:

[0093] light yellow oily(0.048g,67%),1 H NMR(400MHz,Chloroform-d)δ7.35–7.31(m,2H),7.30–7.26(m,2H),7.18–7.15(m,2H),7.06(d,J=8.1 Hz,1H),7.07–7.05(m,1H),7.02–6.97(m,1H),4.23(t,J=7.3Hz,1H),3.40(s,3H),3.00–2.93(m,2H); 13 C NMR(101MHz,Chloroform-d)δ169.50,141.16,140.49,129.28,128.99,128.19,128.0 0,127.94,127.31,123.16,115.02,41.61,38.97,29.68.HRMS(m / z)[ESI]:calculated for C 16 H 16 NO + [M+H] + :238.1154; found:238.1155.

[0094] Embodiment 12:

[0095] Synthesis and characterization of 1,3-dimethyl-3,4-dihydroquinolin-2(1H)-one:

[0096] 0.3 mmol of N-(2-bromophenyl)-N-methylmethylacrylamide, 53.4 mg of phenanthrene and 97.6 mg of electrolyte tetraethylammonium tetrafluoroborate were placed in a 10 mL three-necked round-bottom flask, 5 mL of solvent dimethyl sulfoxide was added to dissolve, 1 cm x 1 cm aluminum sheet was used as anode, 1 cm x 1 cm platinum sheet was used as cathode, stirring reaction was carried out at 5 mA constant current and 50 ° C for 3 h, and monitored by thin layer chromatography. After the reaction was completed, the mixture was extracted with 15 mL of ethyl acetate, the organic layer was dried over anhydrous sodium sulfate, filtered, the solvent was dried under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the target product with a yield of 75%, namely 1,3-dimethyl-3,4-dihydroquinolin-2(1H)-one, with the structural formula:

[0097]

[0098] The NMR and mass spectrometry data of the compound:

[0099] 1H NMR(600MHz,Chloroform-d)δ7.25–7.24(m,1H),7.21–7.19(m,1H),7.07–7.04(m,1H),7.01–6.98(m,1H),3.3 7(s,3H),3.09–3.03(m,1H),2.73(dd,J=15.8,5.4Hz,1H),2.46(dd,J=15.8,7.6Hz,1H),1.28(d,J=7.0Hz,3H); 13 C NMR(151MHz,Chloroform-d)δ170.07,139.94,131.20,127.54,126.36,123.18,114.93,39.28,30.43,29.57,19.41.HRMS(m / z)[ESI]:calculated for C 11 H 14 NO + [M+H] + :176.1070; found:176.1069.

[0100] Embodiment 13:

[0101] Synthesis and characterization of 1-ethyl-3-methyl-3,4-dihydroquinolin-2(1H)-one:

[0102] 0.3 mmol of N-(2-bromophenyl)-N-ethylmethylacrylamide, 53.4 mg of phenanthrene and 97.6 mg of electrolyte tetraethylammonium tetrafluoroborate were placed in a 10 mL three-necked round-bottom flask, 5 mL of solvent dimethyl sulfoxide was added to dissolve, a 1 cm x 1 cm aluminum sheet was used as an anode, a 1 cm x 1 cm platinum sheet was used as a cathode, and the reaction was stirred at 5 mA constant current and 50 ° C for 3 h, and monitored by thin layer chromatography. After the reaction was completed, the mixture was extracted with 15 mL of ethyl acetate, the organic layer was dried over anhydrous sodium sulfate, filtered, the solvent was dried under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the target product with a yield of 67%, namely 1-ethyl-3-methyl-3,4-dihydroquinolin-2(1H)-one, with the structural formula:

[0103]

[0104] The NMR and mass spectrometry data of the compound:

[0105] 1H NMR(400MHz,Chloroform-d)δ7.62–7.58(m,1H),7.32–7.26(m,1H),7.18–7.11(m,2H),4.94 (d,J=16.0Hz,2H),4.17–4.07(m,1H),3.44–3.33(m,1H),1.79(s,3H),1.11(t,J=7.2Hz,3H); 13 C NMR(101MHz,Chloroform-d)δ171.40,133.86,131.22,129.15,128.16,123.64,118.38,43.46,39.26,30.57,20.39,12.51.HRMS(m / z)[ESI]:calculated for C 12 H 15 NONa + [M+Na] + :212.1046; found:212.1049.

[0106] Embodiment 14:

[0107] Synthesis and Characterization of 1-(4-(tert-butyl)benzyl)-3-methyl-3,4-dihydroquinolin-2(1H)-one:

[0108] 0.3 mmol of N-(2-bromophenyl)-N-(4-(tert-butyl)benzyl)methacrylamide, 53.4 mg of phenanthrene and 97.6 mg of electrolyte tetraethylammonium tetrafluoroborate were placed in a 10 mL three-necked round-bottom flask, 5 mL of solvent dimethyl sulfoxide was added to dissolve, a 1 cm x 1 cm aluminum sheet was used as an anode, a 1 cm x 1 cm platinum sheet was used as a cathode, and the reaction was stirred at 10 mA constant current and 60 ° C for 5 h, and monitored by thin layer chromatography. After the reaction was completed, the mixture was extracted with 15 mL of ethyl acetate, the organic layer was dried over anhydrous sodium sulfate, filtered, the solvent was dried under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the target product with a yield of 60%, namely 1-(4-(tert-butyl)benzyl)-3-methyl-3,4-dihydroquinolin-2(1H)-one, with the structural formula:

[0109]

[0110] The NMR and mass spectrometry data of the compound:

[0111] 1H NMR(400MHz,Chloroform-d)δ7.45–7.41(m,2H),7.33–7.28(m,2H),7.26–7.22(m,2H),7.14–7.11(m,1H),7.07–7.04(m,1H),5.3 5–5.21(m,2H),3.29–3.19(m,1H),2.98(dd,J=15.6,5.4Hz,1H),2.71(dd,J=15.6,7.2Hz,1H),1.44(d,J=7.0Hz,3H),1.40(s,9H); 13 C NMR(101MHz,Chloroform-d)δ170.11,150.02,139.23,134.03,131.28,127.52,126.52,126.26, 125.74,123.24,115.88,45.90,39.34,34.55,31.45,30.71,19.62.HRMS(m / z)[ESI]:calculated for C 21 H 26 NO + [M+H] + :308.1936; found:308.1937.

[0112] The invention discloses a method for synthesizing novel 3,4-dihydroquinolinone compounds without metal and oxidant. Under mild electrochemical conditions, phenanthrene is used as a reducing medium to carry out single-electron reduction of aromatic halogenated unsaturated amides to obtain a series of novel 3,4-dihydroquinolinone compounds. The method has rapid reaction and medium to excellent yield of 55% to 82%, and can be applied to the synthesis and transformation of various substrates with different functional groups, such as methyl, methoxy, trifluoromethyl and the like.

[0113] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of protection of the present invention is defined by the appended claims and their equivalents.

Claims

1. A method for electrochemically synthesizing 3,4-dihydroquinolinone compounds, characterized in that: include: Will N -Aryl halogenated acrylamide, phenanthrene and electrolyte are dissolved in a solvent, an aluminum sheet is used as an anode, a platinum sheet is used as a cathode, and the reaction is carried out by stirring at a constant current of 5-10 mA and 30-60°C; after the reaction is completed, the mixture is extracted with ethyl acetate; the organic layer is dried over anhydrous sodium sulfate, filtered, the solvent is dried under reduced pressure, and the residue is purified by column chromatography to obtain the target product; Said N -The structural formula of aryl haloacrylamide is: ， R 1 , R 2 is an aromatic group or an aliphatic group; R 3 is an aromatic group or an aliphatic group; X is Br or Cl; The electrolyte is tetraethylammonium tetrafluoroborate, tetrabutylammonium tetrafluoroborate or tetrabutylammonium hexafluorophosphate; The solvent is acetonitrile, dimethyl sulfoxide or N, N-dimethylformamide.

2. The method for electrochemically synthesizing 3,4-dihydroquinolinone compounds according to claim 1, characterized in that: Said N -The molar ratio of aryl halogenated acrylamide, phenanthrene and electrolyte is 1:0.2-1.5:1.0-2.

0.

3. The method for electrochemically synthesizing 3,4-dihydroquinolinone compounds according to claim 1, characterized in that: Said N -The molar ratio of aryl haloacrylamide, phenanthrene and electrolyte is 1:1:1.

5.

4. The method for electrochemically synthesizing 3,4-dihydroquinolinone compounds according to claim 1, characterized in that: Said N -The molar volume ratio of aryl haloacrylamide, phenanthrene, electrolyte and solvent is 0.3mmol:0.06-0.45mmol:0.3-0.6mmol:5mL.

5. The method for electrochemically synthesizing 3,4-dihydroquinolinone compounds according to claim 1, characterized in that: While the reaction was stirred, the reaction was monitored by thin layer chromatography for 3 to 5 hours until the reaction was completed.

6. The method for electrochemically synthesizing 3,4-dihydroquinolinone compounds according to claim 1, characterized in that: The column chromatography is silica gel column chromatography, and the volume ratio of the eluent petroleum ether to ethyl acetate is 20:1-10:1.

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