A method for electrosynthesis of furanquinone

Abstract

This invention discloses an electrosynthetic method for furanoquinones. The method involves synthesizing furanoquinones of formula 3 or 4 in a one-step electrochemical process using an enamine ketone (formula 1) and a naphthoquinone (formula 2) in an electrochemical reactor with an anode and cathode, under organic electrolyte conditions. This invention combines switchable synthesis of furanoquinones with organic electrocatalysis, resulting in a strategy for electrochemically synthesizing furanoquinones with excellent functional groups. Compared to existing technologies, this invention is highly efficient and economical, producing products without strong base residues, with short reaction times, readily available and simple raw materials, and high yields; it is more competitive in the field of biomedical materials.

Description

Technical Field

[0001] The invention belongs to the field of pharmaceutical chemistry and fine chemical synthesis, and specifically relates to an electric synthesis method of furanquinone. Background Art

[0002] Furanoquinone functions are widely present in a variety of natural products, including avikson C and napabacardin, which can be isolated from Thai mangroves and horsetail trees, respectively. The construction of furanone derivatives has attracted more and more attention from synthetic chemists and medicinal chemists due to their wide range of biological activities, including anti-hepatitis, anti-hypertension, anti-platelet aggregation, antibacterial, and anti-inflammatory activities. Among them, napabacardin has a significant inhibitory effect on various tumor cells and is an effective STAT-3 inhibitor. It has been designated as an orphan drug for gastric cancer and pancreatic cancer by the FDA. It has rich indicators and good market prospects.

[0003] Electrochemical synthesis is a natural sustainable development tool. It uses clean electrical energy to achieve redox reactions and avoids the use of oxidizing or reducing agents. Therefore, it provides many conveniences for human life. In traditional organic redox coupling reactions, oxidants or reducing agents are usually required. In addition, the pre-functionalization of raw materials and multi-step post-treatment processes inevitably produce equivalent chemical waste. From the perspective of atom economy and step economy, it does not conform to the concept of modern green chemical synthesis. In the past few decades, organic electrochemical synthesis has been favored by researchers and has developed rapidly. It uses electrons as traceless oxidants and reductants, which not only avoids the use of equivalent oxidants and reductants, but also can achieve substrate conversion efficiently and selectively in many cases. It is a clean and efficient synthesis strategy. Summary of the invention

[0004] Purpose of the invention: The technical problem to be solved by the present invention is to provide a method for the electrosynthesis of furanquinone in view of the shortcomings of the prior art, so as to solve the problems of low reaction efficiency and the need to add a strong base in the prior art.

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

[0006] A method for electrosynthesis of furanquinone, comprising: synthesizing a furanquinone compound of formula 3 or formula 4 by electrochemical one-step method in an electrochemical reaction device with a cathode and an anode under the condition of an organic electrolyte;

[0007] The reaction equation is as follows:

[0008]

[0009] Among them, R 1Any one selected from the group consisting of electron-donating hydrogen, 1-4 C alkyl, methoxy, electron-withdrawing halogen, cyano or phenyl; R 2 Any one selected from the group consisting of electron donating hydrogen, methyl, methoxy, electron withdrawing halogen or phenyl.

[0010] Specifically, in the above-mentioned electrosynthesis of furanquinone:

[0011] When enaminones of formula 1, hydroxynaphthoquinone compounds of formula 2, and organic electrolytes are dissolved in a solvent as a reaction solution and added to an electrochemical reaction device having a cathode and an anode, the electrochemical one-step synthesis product is a furanquinone compound shown in formula 3;

[0012] When enaminone of formula 1, hydroxynaphthoquinone compounds of formula 2, organic electrolyte and Lewis acid are dissolved in a solvent as a reaction solution and added into an electrochemical reaction device having a cathode and an anode, the electrochemical one-step synthesis product is a furanquinone compound shown in formula 4.

[0013] Specifically, the organic electrolyte is selected from any one of tetrabutylammonium tetrafluoroborate, tetrabutylammonium tetrafluoroacetate, tetrabutylammonium hexafluorophosphate, tetrabutylammonium tetrafluoroiodide, and tetrabutylammonium tetrafluoroperchlorate, or a combination of two or more thereof; preferably tetrabutylammonium hexafluorophosphate or tetrabutylammonium tetrafluoroborate, and more preferably tetrabutylammonium hexafluorophosphate.

[0014] Specifically, the Lewis acid is selected from any one or a combination of two or more of ytterbium trifluoromethanesulfonate, zinc trifluoromethanesulfonate, ruthenium trifluoromethanesulfonate, trifluoromethanesulfonic acid, and lanthanum trifluoromethanesulfonate; preferably any one or a combination of two or more of ytterbium trifluoromethanesulfonate, zinc trifluoromethanesulfonate, and ruthenium trifluoromethanesulfonate; more preferably zinc trifluoromethanesulfonate.

[0015] Specifically, the solvent is selected from any one or a combination of two or more of dichloroethane, N,N-dimethylformamide, dimethyl sulfoxide, trifluoroethanol, acetonitrile, hexafluoroisopropanol, trichloroethylene or N,N-dimethylaniline, and tetrahydrofuran; preferably trifluoroethanol, acetonitrile or hexafluoroisopropanol, and more preferably acetonitrile.

[0016] Specifically, the reaction molar ratio of the enaminone of formula 1 to the hydroxynaphthoquinone compound of formula 2 is 1 to 2:1, preferably 1.2-1.5:1, and more preferably 1.5:1; the reaction molar ratio of the enaminone of formula 1 to the Lewis acid is 1.5:0.5.

[0017] Specifically, the concentration of enaminone of formula 1 in the reaction solution is 0.03-0.12 mmol / mL, preferably 0.03-0.06 mmol / mL, and more preferably 0.03 mmol / mL; the concentration of hydroxynaphthoquinone compound of formula 2 in the reaction solution is 0.02-0.08 mmol / mL, preferably 0.02 mmol / mL; the concentration of organic electrolyte in the reaction solution is 0.04-0.16 mmol / mL, preferably 0.04 mmol / mL; the concentration of Lewis acid in the reaction solution is 0.004-0.01 mmol / mL, preferably 0.006-0.01 mmol / mL, and more preferably 0.01 mmol / mL.

[0018] Specifically, the current intensity passed into the electrochemical reaction device is 8-20 mA, preferably 8-15 mA, and more preferably 10 mA; the temperature of the electrochemical reaction is 20-80° C., preferably 20-50° C., and more preferably 25° C.; the electrochemical reaction time is 90-150 min, preferably 90-120 min, and more preferably 120 min.

[0019] Specifically, the above-mentioned furanquinone electrosynthesis also includes extracting the reaction solution obtained from the electrochemical reaction to obtain an organic phase, concentrating it, and performing column chromatography to obtain a pure furanquinone compound.

[0020] Specifically, the extraction is to extract the reaction solution with ethyl acetate and saturated sodium chloride aqueous solution;

[0021] Column chromatography used silica gel column chromatography;

[0022] The eluent for column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 1:0.1 to 0.25.

[0023] Beneficial effects:

[0024] The present invention combines the switchable synthesis of furanquinone with organic electrocatalysis technology, and the electrochemical synthesis strategy of furanquinone compounds has excellent functional groups. Compared with the prior art, the present invention is efficient and economical, has no strong base residue in the product, has a short reaction time, simple and easy-to-obtain raw materials, and a high yield; it is more competitive in the field of biomedical materials. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] The present invention will be further described in detail below in conjunction with the accompanying drawings and specific embodiments, and the above and / or other advantages of the present invention will become more clear.

[0026] Figure 1 The following is a reaction flow chart for synthesizing furanquinone compounds according to the present invention.

[0027] Figure 2 This is a physical diagram of the reaction device for synthesizing furanquinone compounds of the present invention.

[0028] Figure 3 This is the hydrogen nuclear magnetic resonance spectrum of the product 2a in Example 1.

[0029] Figure 4 This is the carbon NMR spectrum of product 2a in Example 1.

[0030] Figure 5 This is the hydrogen nuclear magnetic resonance spectrum of product 2b in Example 2.

[0031] Figure 6 This is the carbon NMR spectrum of product 2b in Example 2.

[0032] Figure 7 This is the hydrogen nuclear magnetic resonance spectrum of the product 2c in Example 3.

[0033] Figure 8 This is the carbon NMR spectrum of product 2c in Example 3.

[0034] Fig. 9 This is the hydrogen nuclear magnetic resonance spectrum of the product 2d in Example 4.

[0035] Fig.10 This is the carbon NMR spectrum of product 2d in Example 4.

[0036] Fig.11 This is the hydrogen nuclear magnetic resonance spectrum of the product 2e in Example 5.

[0037] Fig.12 This is the carbon NMR spectrum of product 2e in Example 5.

[0038] Fig.13 This is the hydrogen nuclear magnetic resonance spectrum of the product 2f in Example 6.

[0039] Fig.14 This is the carbon NMR spectrum of the product 2f in Example 6.

[0040] Fig.15 This is the hydrogen nuclear magnetic resonance spectrum of the product 2g in Example 7.

[0041] Fig.16 This is the carbon NMR spectrum of product 2g in Example 7.

[0042] Fig.17 This is the hydrogen nuclear magnetic resonance spectrum of the product 2h in Example 8.

[0043] Fig.18 This is the carbon NMR spectrum of the product 2h in Example 8.

[0044] Fig.19 This is the hydrogen nuclear magnetic resonance spectrum of the product 2i in Example 9.

[0045] Fig. 20 This is the carbon NMR spectrum of the product 2i in Example 9.

[0046] Fig.21 This is the hydrogen nuclear magnetic resonance spectrum of the product 2j in Example 10.

[0047] Fig. 22 This is the carbon NMR spectrum of product 2j in Example 10.

[0048] Fig.23 This is the NMR fluorine spectrum of product 2j in Example 10.

[0049] Fig.24 This is the hydrogen nuclear magnetic resonance spectrum of the product 2k in Example 11.

[0050] Fig.25 This is the carbon NMR spectrum of the product 2k in Example 11.

[0051] Fig.26 This is the hydrogen nuclear magnetic resonance spectrum of the product 2m in Example 12.

[0052] Fig. 27 This is the carbon NMR spectrum of product 2m in Example 12. DETAILED DESCRIPTION

[0053] The present invention can be better understood with reference to the following examples.

[0054] The present invention provides a method for electrosynthesis of furanquinone, wherein enaminone of formula 1 and hydroxynaphthoquinone compounds of formula 2 are subjected to an organic electrolyte in an electrochemical reaction device having a cathode and an anode to synthesize a furanquinone compound of formula 3 or formula 4 by a one-step electrochemical method. The reaction flow is as follows: Figure 1 As shown, the reaction device is as Figure 2 shown.

[0055] The present invention provides specific embodiments of the 12 furanquinone compounds shown in Table 1 below.

[0056] Table 1

[0057]

[0058] Example 1

[0059]

[0060] At 25°C, 3-(dimethylamino)-1-phenylprop-2-ene-1-one (52.5 mg, 0.3 mmol, 1.5 equivalents), 2-hydroxynaphthalene-1,4-dione (34.8 mg, 0.2 mmol, 1 equivalent), and tetrabutylammonium hexafluorophosphate (155.0 mg, 0.4 mmol, 2 equivalents) were dissolved in solvent ACN to obtain a homogeneous solution, which was added to a 10 mL three-necked round-bottom flask equipped with a carbon cloth (40 mm x 20 mm) anode and a platinum sheet (20 mm × 20 mm × 0.1 mm) cathode. The current was controlled to be 10 mA and the reaction time was 120 min. After the reaction was completed, the product was identified by TLC. The solvent was removed in vacuo. The product was separated with an eluent of 10:1 petroleum ether and ethyl acetate, and the obtained product was dried in vacuo for 4 h. The obtained product 2a had a conversion rate of 80%.

[0061] The H NMR spectrum of product 2a is shown in Figure 3 , see C NMR spectrum Figure 4 .

[0062] 1 H NMR(400MHz,Chloroform-d)δ8.14(dd,J=7.6,1Hz,1H),7.95-7.91(m,2H),7.87(dd,J=7.9,1 .3Hz,1H),7.67(td,J=7.5,1.3Hz,1H),7.63-7.53(m,2H),7.47(t,J=7.7Hz,2H),3.13(s,6H); 13 C NMR(101MHz,Chloroform-d)δ190.21,180.41,170.44,161.38,142.13,139.27,133.77,133.26 ,133.05,132.76,132.68,129.37,128.51,126.69,126.17,96.61,40.14; HRMS(ESI-TOF)Calcd for C 21 H 16 NO4[M+H] + :346.1096; found:346.1094.

[0063] Example 2

[0064]

[0065] At 25°C, 3-(dimethylamino)-1-(p-tolyl)prop-2-en-1-one (56.7 mg, 0.3 mmol, 1.5 equivalents), 2-hydroxynaphthalene-1,4-dione (34.8 mg, 0.2 mmol, 1 equivalent), and tetrabutylammonium hexafluorophosphate (155.0 mg, 0.4 mmol, 2 equivalents) were dissolved in solvent ACN to obtain a homogeneous solution, which was added to a 10 mL three-necked round-bottom flask equipped with a carbon cloth (40 mm x 20 mm) anode and a platinum sheet (20 mm × 20 mm × 0.1 mm) cathode. The current was controlled to be 10 mA and the reaction time was 120 min. After the reaction was completed, the product was identified by TLC. The solvent was removed in vacuo. The product was separated with an eluent of 10:1 petroleum ether and ethyl acetate, and vacuum dried for 4 h. The conversion rate of product 2b was 78%.

[0066] The H NMR spectrum of product 2b is shown in Figure 5 , see C NMR spectrum Figure 6 .

[0067] 1 H NMR(400MHz,Chloroform-d)δ8.13(d,J=7.6Hz,1H),7.86(dd,J=13.4,7.8Hz,3H),7.66( t,J=7.4Hz,1H),7.56(t,J=7.5Hz,1H),7.26(d,J=7.9Hz,2H),3.11(s,6H),2.43(s,3H); 13 C NMR(101MHz,Chloroform-d)δ189.88,180.47,170.29,161.20,144.21,142.03,136.69,133.76,13 3.13,132.75,132.62,129.57,129.30,126.67,126.14,96.74,40.03,21.75; HRMS(ESI-TOF)Calcd for C 22 H 18 NO4[M+H] + :360.1230; found:360.1238.

[0068] Example 3

[0069]

[0070] At 25°C, 3-(dimethylamino)-1-(4-methoxyphenyl)prop-2-en-1-one (61.5 mg, 0.3 mmol, 1.5 equivalents), 2-hydroxynaphthalene-1,4-dione (34.8 mg, 0.2 mmol, 1 equivalent), and tetrabutylammonium hexafluorophosphate (155.0 mg, 0.4 mmol, 2 equivalents) were dissolved in solvent ACN to obtain a homogeneous solution, which was added to a 10 mL three-necked round-bottom flask equipped with a carbon cloth (40 mm x 20 mm) anode and a platinum sheet (20 mm × 20 mm × 0.1 mm) cathode. The current was controlled to be 10 mA and the reaction time was 120 min. After the reaction was completed, the product was identified by TLC. The solvent was removed in vacuo. The product was separated with an eluent of 10:1 petroleum ether and ethyl acetate, and the obtained product was dried in vacuo for 4 h. The conversion rate of the product 2c was 79%.

[0071] The H NMR spectrum of product 2c is shown in Figure 7 , see C NMR spectrum Figure 8 .

[0072] 1 H NMR(400MHz,Chloroform-d)δ8.14(d,J=7.5Hz,1H),7.94-7.89(m,3H),7.65(t,J =7.5Hz,1H),7.60-7.54(m,1H),6.94(d,J=8.8Hz,2H),3.86(s,3H),3.09(s,6H); 13 CNMR(101MHz,Chloroform-d)δ188.79,180.54,170.19,163.78,161.03,142.01,133.77,133.10,132.8 0,132.74,132.59,132.17,131.81,126.63,126.14,113.80,96.70,55.51,39.96; HRMS(ESI-TOF)Calcd for C 22 H 18 NO5[M+H] + :376.1179; found:376.1201.

[0073] Example 4

[0074]

[0075] At 25°C, 1-(4-bromophenyl)-3-(dimethylamino)prop-2-en-1-one (75.9 mg, 0.3 mmol, 1.5 equivalents), 2-hydroxynaphthalene-1,4-dione (34.8 mg, 0.2 mmol, 1 equivalent), and tetrabutylammonium hexafluorophosphate (155.0 mg, 0.4 mmol, 2 equivalents) were dissolved in solvent ACN to obtain a homogeneous solution, which was added to a 10 mL three-necked round-bottom flask equipped with a carbon cloth (40 mm x 20 mm) anode and a platinum sheet (20 mm × 20 mm × 0.1 mm) cathode. The current was controlled to be 10 mA and the reaction time was 120 min. After the reaction was completed, the product was identified by TLC. The solvent was removed in vacuo. The product was separated with an eluent of 10:1 petroleum ether and ethyl acetate, and vacuum dried for 4 h. The conversion rate of product 2d was 77%.

[0076] The H NMR spectrum of product 2d is shown in Fig. 9 , see C NMR spectrum Fig.10 .

[0077] 1 H NMR (400MHz, Chloroform-d) δ8.13(d,J=7.5Hz,1H),7.87(d,J=7.5Hz,1H),7.78(d,J=8.2Hz,2H),7.68(t,J=7.4Hz,1H),7.59(d,J=8.1Hz,3H),3.12(s,6H); 13 C NMR(101MHz,Chloroform-d)δ188.96,180.45,170.54,161.55,142.20,138.17,133.89,132.81,13 2.74,132.68,132.57,131.81,130.77,128.38,126.72,126.22,96.08,40.20; HRMS(ESI-TOF)Calcd for C 21 H 15 NO4Br[M+H] + :424.0179; found:424.0210.

[0078] Example 5

[0079]

[0080] At 25°C, 4-(3-(dimethylamino)acryloyl)benzonitrile (60.0 mg, 0.3 mmol, 1 equivalent), 2-hydroxynaphthalene-1,4-dione (34.8 mg, 0.2 mmol, 1 equivalent), and tetrabutylammonium hexafluorophosphate (155.0 mg, 0.4 mmol, 2 equivalents) were dissolved in solvent ACN to obtain a homogeneous solution, which was added to a 10 mL three-necked round-bottom flask equipped with a carbon cloth (40 mm x 20 mm) anode and a platinum sheet (20 mm × 20 mm × 0.1 mm) cathode. The current was controlled to be 10 mA and the reaction time was 120 min. After the reaction was completed, the product was identified by TLC. The solvent was removed in vacuo. The product was separated with an eluent of 10:1 petroleum ether and ethyl acetate, and vacuum dried for 4 h. The conversion rate of the product 2e was 71%.

[0081] The H NMR spectrum of product 2e is shown in Fig.11 , see C NMR spectrum Fig.12 .

[0082] 1 H NMR(400MHz,Chloroform-d)δ8.13(d,J=7.1Hz,1H),7.98(d,J=8.0Hz,2H),7.83(d,J= 7.8Hz,1H),7.75(d,J=8.0Hz,2H),7.72-7.65(m,1H),7.63-7.53(m,1H),3.16(s,6H); 13 C NMR(101MHz,Chloroform-d)δ188.22,180.41,170.79,162.08,142.89,142.39,134.00,133.00,13 2.60,132.36,132.29,129.46,126.74,126.27,118.24,115.97,95.80,40.43; HRMS(ESI-TOF)Calcd for C 22 H 15 N2O4[M+H] + :371.1026; found:371.1007.

[0083] Example 6

[0084]

[0085] At 25°C, 1-([1,1'-biphenyl]-4-yl)-3-(dimethylamino)prop-2-en-1-one (75.3 mg, 0.3 mmol, 1.5 equivalents), 2-hydroxynaphthalene-1,4-dione (34.8 mg, 0.2 mmol, 1 equivalent), and tetrabutylammonium hexafluorophosphate (155.0 mg, 0.4 mmol, 2 equivalents) were dissolved in solvent ACN to obtain a homogeneous solution, which was added to a 10 mL three-necked round-bottom flask equipped with a carbon cloth (40 mm x 20 mm) anode and a platinum sheet (20 mm × 20 mm × 0.1 mm) cathode. The current was controlled to be 10 mA and the reaction time was 120 min. After the reaction was completed, the product was identified by TLC. The solvent was removed in vacuo. The product was separated with an eluent of 10:1 petroleum ether and ethyl acetate, and vacuum dried for 4 h. The conversion rate of the product 2f was 73%.

[0086] The H NMR spectrum of product 2f is shown in Fig.13 , see C NMR spectrum Fig.14 .

[0087] 1 H NMR(400MHz,Chloroform-d)δ8.15(dd,J=7.6,1.1Hz,1H),8.03-7.99(m,2H),7.88(dd,J=7.6,1.1Hz,1 H),7.71-7.63(m,5H),7.57(td,J=7.6,1.3Hz,1H),7.49-7.44(m,2H),7.42-7.35(m,1H),3.14(s,6H); 13 C NMR(101MHz,Chloroform-d)δ189.73,180.51,170.37,161.31,145.85,142.10,139.94,137.95,133.81,133.12 ,132.74,132.69,130.01,128.93,128.22,127.35,127.19,126.68,126.19,96.64,40.12; HRMS(ESI-TOF)Calcd forC 27 H 20 NO4[M+H] + :422.1387; found:422.1419.

[0088] Example 7

[0089]

[0090] At 25°C, 3-(dimethylamino)-1-phenylprop-2-ene-1-one (52.5 mg, 0.3 mmol, 1.5 equivalents), 2-hydroxy-7-methylnaphthalene-1,4-dione (37.6 mg, 0.2 mmol, 1 equivalent), and tetrabutylammonium hexafluorophosphate (155.0 mg, 0.4 mmol, 2 equivalents) were dissolved in solvent ACN to obtain a homogeneous solution, which was added to a 10 mL three-necked round-bottom flask equipped with a carbon cloth (40 mm x 20 mm) anode and a platinum sheet (20 mm × 20 mm × 0.1 mm) cathode. The current was controlled to be 10 mA and the reaction time was 120 min. After the reaction was completed, the product was identified by TLC. The solvent was removed in vacuo. The product was separated by an eluent of 10:1 petroleum ether and ethyl acetate, and vacuum dried for 4 h. The product was 2 g with a conversion rate of 75%.

[0091] The H NMR spectrum of product 2g is shown in Fig.15 , see C NMR spectrum Fig.16 .

[0092] 1 H NMR(400MHz,Chloroform-d)δ7.93-7.92(m,3H),7.74(d,J=7.8Hz,1H),7.60-7 .56(m,1H),7.47-7.44(m,2H),7.34(d,J=7.8Hz,1H),3.11(s,6H),2.45(s,3H); 13 C NMR(101MHz,Chloroform-d)δ190.29,180.28,170.70,161.32,144.91,142.13,139.30,133.19,133.1 9,133.16,132.62,130.47,129.37,128.48,126.92,126.72,96.66,40.10,21.77; HRMS(ESI-TOF)Calcd for C 22 H 18 NO4[M+H] + :360.1230; found:360.1235.

[0093] Example 8

[0094]

[0095] At 25°C, 3-(dimethylamino)-1-phenylprop-2-ene-1-one (52.5 mg, 0.3 mmol, 1.5 equivalents), 3-hydroxyphenanthrene-1,4-dione (44.8 mg, 0.2 mmol, 1 equivalent), and tetrabutylammonium hexafluorophosphate (155.0 mg, 0.4 mmol, 2 equivalents) were dissolved in solvent ACN to obtain a homogeneous solution, which was added to a 10 mL three-necked round-bottom flask equipped with a carbon cloth (40 mm x 20 mm) anode and a platinum sheet (20 mm × 20 mm × 0.1 mm) cathode. The current was controlled to be 10 mA and the reaction time was 120 min. After the reaction was completed, the product was identified by TLC. The solvent was removed in vacuo. The product was separated with an eluent of 10:1 of petroleum ether and ethyl acetate, and vacuum dried for 4 h. The product 2h conversion rate was 50%.

[0096] The H NMR spectrum of product 2h is shown in Fig.17 , see C NMR spectrum Fig.18 .

[0097] 1 H NMR(400MHz,Chloroform-d)δ9.77(d,J=8.9Hz,1H),8.03-7.98(m,2H),7.99-7.94(m,2H),7. 82(d,J=8.1Hz,1H),7.72-7.65(m,1H),7.63-7.55(m,2H),7.47(t,J=7.7Hz,2H),3.15(s,6H); 13 C NMR(101MHz,Chloroform-d)δ177.36,174.78,139.46,136.93,133.99,133.17,133.12,130.87 ,130.28,129.67,129.39,128.56,128.47,128.33,128.22,122.43,40.22; HRMS(ESI-TOF)Calcd for C 25 H 18 O4N[M+H] + :396.1230; found:396.1256.

[0098] Example 9

[0099]

[0100] At 25°C, 3-(dimethylamino)-1-phenylprop-2-ene-1-one (52.5 mg, 0.3 mmol, 1.5 equivalents), 2-hydroxynaphthalene-1,4-dione (34.8 mg, 0.2 mmol, 1 equivalent), zinc trifluoromethanesulfonate (36.3 mg, 0.1 mmol, 0.5 equivalents), and tetrabutylammonium hexafluorophosphate (155.0 mg, 0.4 mmol, 2 equivalents) were dissolved in solvent ACN to obtain a homogeneous solution, which was added to a 10 mL three-necked round-bottom flask equipped with a carbon cloth (40 mm x 20 mm) anode and a platinum sheet (20 mm × 20 mm × 0.1 mm) cathode. The current was controlled to be 10 mA and the reaction time was 120 min. After the reaction was completed, the product was identified by TLC. The solvent was removed in vacuo. The product was separated with an eluent of 10:1 petroleum ether and ethyl acetate, and the obtained product was dried in vacuo for 4 h. The conversion rate of the product 2i was 45%.

[0101] The H NMR spectrum of product 2i is shown in Fig.19 , see C NMR spectrum Fig. 20 .

[0102] 1 H NMR(400MHz,Chloroform-d)δ8.26-8.23(m,1H),8.14-8.11(m,1H),8.05(s,1H),7 .95-7.90(m,2H),7.81-7.72(m,2H),7.65(t,J=7.4Hz,1H),7.51(t,J=7.7Hz,1H); 13 C NMR(101MHz,Chloroform-d)δ187.55,179.03,173.80,153.10,149.55,137.04,134.37,134.07, 134.04,133.34,131.90,129.62,128.74,128.14,127.50,126.93,124.87; HRMS(ESI-TOF)Calcd for C 19 H 11 O4[M+H] + :303.0652; found:303.0677.

[0103] Example 10

[0104]

[0105] At 25°C, 3-(dimethylamino)-1-(4-fluorophenyl)prop-2-en-1-one (57.9 mg, 0.3 mmol, 1.5 equivalents), 2-hydroxynaphthalene-1,4-dione (34.8 mg, 0.2 mmol, 1 equivalent), zinc trifluoromethanesulfonate (36.3 mg, 0.1 mmol, 0.5 equivalents), and tetrabutylammonium hexafluorophosphate (155.0 mg, 0.4 mmol, 2 equivalents) were dissolved in solvent ACN to obtain a homogeneous solution, which was added to a 10 mL three-necked round-bottom flask equipped with a carbon cloth (40 mm x 20 mm) anode and a platinum sheet (20 mm × 20 mm × 0.1 mm) cathode, and the current was controlled to be 10 mA, and the reaction time was 120 min; after the reaction was completed, the product was identified by TLC. The solvent was removed in vacuo. The product was separated by an eluent of 10:1 petroleum ether and ethyl acetate, and vacuum dried for 4 h. The conversion rate of product 2j was 42%.

[0106] The H NMR spectrum of product 2j is shown in Fig.21 , see the carbon NMR spectra Fig. 22 , NMR fluorine spectrum see Fig.23 .

[0107] 1 H NMR (400MHz, Chloroform-d) δ8.25-8.22(m,1H),8.16-8.08(m,1H),8.06(s,1H),8.00-7.90(m,2H),7.84-7.71(m,2H),7.17(t,J=8.6Hz,2H); 13 C NMR(101MHz,Chloroform-d)δ186.09,179.10,173.71,167.59,165.03,153.06,149.40,134.42,134.17,133. 46(d,J=3.2Hz),133.23,132.30(d,J=9.8Hz),131.88,127.94,127.46,126.98,124.63,116.01(d,J=22.4Hz); 19 F NMR(376MHz,Chloroform-d)δ-103.12; HRMS(ESI-TOF)Calcd for C 19 H 10 O4F[M+H] + :321.2808; found:321.2886.

[0108] Embodiment 11

[0109]

[0110] At 25°C, methyl 4-(3-(dimethylamino)acryloyl)benzoate (69.9 mg, 0.3 mmol, 1.5 equivalents), 2-hydroxynaphthalene-1,4-dione (34.8 mg, 0.2 mmol, 1 equivalent), zinc trifluoromethanesulfonate (36.3 mg, 0.1 mmol, 0.5 equivalents), and tetrabutylammonium hexafluorophosphate (155.0 mg, 0.4 mmol, 2 equivalents) were dissolved in solvent ACN to obtain a homogeneous solution, which was added to a 10 mL three-necked round-bottom flask equipped with a carbon cloth (40 mm x 20 mm) anode and a platinum sheet (20 mm × 20 mm × 0.1 mm) cathode, and the current was controlled to be 10 mA, and the reaction time was 120 min; after the reaction was completed, the product was identified by TLC. The solvent was removed in vacuo. The product was separated with an eluent of 10:1 of petroleum ether and ethyl acetate, and the obtained product was dried in vacuo for 4 h. The conversion rate of the product 2k was 45%.

[0111] The H NMR spectrum of product 2k is shown in Fig.24 , see C NMR spectrum Fig.25 .

[0112] 1 H NMR(400MHz,Chloroform-d)δ8.26-8.23(m,1H),8.15(d,J=8.3Hz,2H),8.10(s,1 H),8.08(d,J=1.8Hz,1H),7.95(d,J=8.3Hz,2H),7.85-7.69(m,2H),3.96(s,2H); 13 CNMR(101MHz,Chloroform-d)δ187.20,179.01,173.70,166.08,153.15,150.00,140.31,134.55,134.44 ,134.19,133.21,131.86,129.89,129.36,127.85,127.49,126.99,124.62,52.57; HRMS(ESI-TOF)Calcd for C 21 H 13 O6[M+H] + :361.0707; found:361.0668.

[0113] Example 12

[0114]

[0115] At 25°C, 4-(3-(dimethylamino)acryloyl)benzonitrile (60.0 mg, 0.3 mmol, 1.5 equivalents), 2-hydroxynaphthalene-1,4-dione (34.8 mg, 0.2 mmol, 1 equivalent), zinc trifluoromethanesulfonate (36.3 mg, 0.01 mmol, 0.5 equivalents), and tetrabutylammonium hexafluorophosphate (155.0 mg, 0.4 mmol, 2 equivalents) were dissolved in solvent ACN to obtain a homogeneous solution, which was added to a 10 mL three-necked round-bottom flask equipped with a carbon cloth (40 mm x 20 mm) anode and a platinum sheet (20 mm × 20 mm × 0.1 mm) cathode, and the current was controlled to be 10 mA, and the reaction time was 120 min; after the reaction was completed, the product was identified by TLC. The solvent was removed in vacuo. The product was separated with an eluent of 10:1 of petroleum ether and ethyl acetate, and the obtained product was dried in vacuo for 4 h. The conversion rate of the product 2m was 40%.

[0116] The H NMR spectrum of product 2m is shown in Fig.26 , see C NMR spectrum Fig. 27 .

[0117] Comparative Example 1

[0118] A mixture of 2,3-dichloro-1,4-naphthoquinone (0.227 gram, 1 mmol), K CO (0.345 gram, 2.5 mmol) and 2,4-pentanedione (0.110 gram, 1.1 mmol) in MeCN (15 milliliters) was stirred at reflux temperature for 6 hours. The reaction mixture was poured into H O (150 milliliters) and filtered. The solid product collected by washing with H O (50 milliliters) was dried to obtain the product in a yield of 26%. Because the reaction temperature is too high, the method is more dangerous.

[0119] Comparative Example 2

[0120] 2-ethoxycarbonylcyclopentanone (about 1M in toluene) and 3-5 times molar excess of volatile butanone are mixed at room temperature. After the reaction is completed, the crude reaction product is evaporated. The residue is directly distilled in vacuum and chromatographed on a silica gel column with a hexane-ether mixture of increasing polarity, with a yield of 35%. Due to the low yield of the product generated by the reaction, the economic practicality of the method is very low.

[0121] The present invention provides a method and idea for the electrosynthesis of furanquinone. There are many methods and approaches to realize the technical solution. The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the protection scope of the present invention. All components not specified in this embodiment can be realized by existing technologies.

Claims

1. A method for electrosynthesis of furanquinone, characterized in that: The enaminone of formula 1 and the hydroxynaphthoquinone compound of formula 2 are placed in an electrochemical reaction device with a cathode and an anode under an organic electrolyte to synthesize the furanquinone compound of formula 3 or formula 4 by a one-step electrochemical method; The reaction equation is as follows: ； Among them, R 1 is selected from any one of electron-donating groups hydrogen, 1-4 C alkyl, methoxy, electron-withdrawing groups halogen, cyano or phenyl; R 2 Any one selected from the group consisting of electron-donating hydrogen, methyl, methoxy, electron-withdrawing halogen or phenyl; When enaminones of formula 1, hydroxynaphthoquinone compounds of formula 2, and organic electrolytes are dissolved in a solvent as a reaction solution and added to an electrochemical reaction device having a cathode and an anode, the electrochemical one-step synthesis product is a furanquinone compound shown in formula 3; When enaminones of formula 1, hydroxynaphthoquinone compounds of formula 2, organic electrolytes, and Lewis acids are dissolved in a solvent as a reaction solution and added to an electrochemical reaction device having a cathode and an anode, the electrochemical one-step synthesis product is a furanquinone compound shown in formula 4; The reaction molar ratio of the enaminone of formula 1 to the hydroxynaphthoquinone compound of formula 2 is 1-2:1; the reaction molar ratio of the enaminone of formula 1 to the Lewis acid is 1.5:0.5; The current intensity of the electrochemical reaction device is 8-20 mA, and the temperature of the electrochemical reaction is 20-80 o C, reaction time is 90~150 min.

2. The method for electrosynthesis of furanquinone according to claim 1, characterized in that: The organic electrolyte is selected from any one of tetrabutylammonium tetrafluoroborate, tetrabutylammonium tetrafluoroacetate, tetrabutylammonium hexafluorophosphate, tetrabutylammonium tetrafluoroiodide, and tetrabutylammonium tetrafluoroperchlorate, or a combination of two or more thereof.

3. The method for electrosynthesis of furanquinone according to claim 1, characterized in that: The Lewis acid is selected from any one of ytterbium trifluoromethanesulfonate, zinc trifluoromethanesulfonate, ruthenium trifluoromethanesulfonate, trifluoromethanesulfonic acid, and lanthanum trifluoromethanesulfonate, or a combination of two or more thereof.

4. The method for electrosynthesis of furanquinone according to claim 1, characterized in that: The solvent is selected from any one or a combination of two or more of dichloroethane, N,N-dimethylformamide, dimethyl sulfoxide, trifluoroethanol, acetonitrile, hexafluoroisopropanol, trichloroethylene or N,N-dimethylaniline, and tetrahydrofuran.

5. The method for electrosynthesis of furanquinone according to claim 1, characterized in that: The concentration of enaminone of formula 1 in the reaction solution is 0.03-0.12 mmol / mL; the concentration of hydroxynaphthoquinone compound of formula 2 in the reaction solution is 0.02-0.08 mmol / mL; the concentration of organic electrolyte in the reaction solution is 0.04-0.16 mmol / mL; and the concentration of Lewis acid in the reaction solution is 0.004-0.01 mmol / mL.

6. The method for electrosynthesis of furanquinone according to claim 1, characterized in that: The method also includes extracting the reaction liquid obtained by the electrochemical reaction to obtain an organic phase, concentrating it, and performing column chromatography to obtain a pure furanquinone compound.

7. The method for electrosynthesis of furanquinone according to claim 6, characterized in that: Extraction is to extract the reaction solution with ethyl acetate and saturated sodium chloride aqueous solution; Column chromatography used silica gel column chromatography; The eluent for column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 1:0.1-0.25.

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