CN113862710A - Electrochemical synthesis method of dihydrodipyrazolo [3,4-b:4',3' -e ] pyridine compound - Google Patents

Electrochemical synthesis method of dihydrodipyrazolo [3,4-b:4',3' -e ] pyridine compound Download PDF

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CN113862710A
CN113862710A CN202111094777.5A CN202111094777A CN113862710A CN 113862710 A CN113862710 A CN 113862710A CN 202111094777 A CN202111094777 A CN 202111094777A CN 113862710 A CN113862710 A CN 113862710A
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dihydrodipyrazolo
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钱朋
张文保
徐琳娜
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Abstract

The invention discloses an electrochemical synthesis method of a dihydrodipyrazole [3,4-b:4',3' -e ] pyridine compound, relating to the technical field of organic synthesis, and the electrochemical synthesis method of the dihydrodipyrazole [3,4-b:4',3' -e ] pyridine compound comprises the following steps: (1) electrocatalytic reaction; (2) and (5) separating and purifying. The dihydrodipyrazolo [3,4-b:4',3' -e ] pyridine compound is synthesized by a one-pot method through 2-methylquinoline compounds and 5-amino-3-methyl-1-phenylpyrazole compounds under electrochemical conditions, and the method does not need the use of metal and chemical oxidants, has clean reaction and is green and environment-friendly.

Description

Electrochemical synthesis method of dihydrodipyrazolo [3,4-b:4',3' -e ] pyridine compound
The technical field is as follows:
the invention relates to the technical field of organic synthesis, in particular to an electrochemical synthesis method of a dihydrodipyrazolo [3,4-b:4',3' -e ] pyridine compound.
Background art:
the polysubstituted pyridine compounds are important nitrogen-containing heterocycles and widely exist in bioactive molecules and photoelectric materials. In particular to 3, 5-dimethyl-1, 7-diphenyl-4- (quinoline-2-yl) -1, 7-dihydro-dipyrazolo [3,4-b:4',3' -e ] pyridine compounds, the molecules of which contain a plurality of aromatic groups, and the compounds are important potential organic functional molecules. Therefore, its synthesis has been the focus of research by organic chemists. However, due to the formation of multiple chemical bonds involved, there are currently few reports on 3, 5-dimethyl-1, 7-diphenyl-4- (quinolin-2-yl) -1, 7-dihydrodipyrazolo [3,4-b:4',3' -e ] pyridines.
Recently, the Zhu group of subjects utilized metal Cu (OTf)2Catalytic tandem synthesis of 3, 5-dimethyl-1, 7-diphenyl-4- (quinolin-2-yl) -1, 7-dihydrodipyrazolo [3,4-b:4',3' -e ] from 2-methylquinoline and 5-amino-3-methyl-1-phenylpyrazole]Pyridines (R-J.Xie, J-H.Liu, Q-Y, Zhang, Y-J.Yang, L-Q.Song, T-Q, Shao, K-X, LiuandY-P.Zhu, org.chem.Front,2021,8, 2274.). Although the method can well realize the synthesis, the metal residue often influences the effectiveness of synthesized drug molecules and functional molecules and needs multiple steps to be removed, the steps are complicated, and a large amount of waste liquid is discharged.
The invention content is as follows:
the technical problem to be solved by the invention is to provide an electrochemical synthesis method of a dihydrodipyrazolo [3,4-b:4',3' -e ] pyridine compound, which adopts a green organic electrochemical synthesis method to prepare the dihydrodipyrazolo [3,4-b:4',3' -e ] pyridine compound under a reaction environment without adding metal and chemical oxidants, so as to overcome the defects of the prior art.
The technical problem to be solved by the invention is realized by adopting the following technical scheme:
an electrochemical synthesis method of a dihydrodipyrazole [3,4-b:4',3' -e ] pyridine compound comprises the following steps:
(1) electrocatalytic reaction: respectively adding electrolyte, 2-methylquinoline compounds, 5-amino-3-methyl-1-phenylpyrazole compounds and a solvent into a reaction tank, installing a catalytic electrode, and electrifying and stirring for reaction;
(2) separation and purification: separating and purifying the solution after the electrocatalysis reaction is finished to obtain a dihydrodipyrazolo [3,4-b:4',3' -e ] pyridine compound;
the dihydrodipyrazolo [3,4-b:4',3' -e ] pyridine compound has the following structure:
Figure BDA0003268711230000021
wherein R is1Is hydrogen, C1～C5Alkyl radical, C1～C5One or more of alkoxy, halogen; r2Is phenyl or C1～C5An alkyl group; r3Is phenyl or C1～C5An alkyl group.
Optionally, the 2-methylquinoline compound has a structure shown as follows:
Figure BDA0003268711230000022
wherein R is1Is hydrogen, C1～C5Alkyl radical, C1～C5One or more of alkoxy and halogen.
Optionally, the 5-amino-3-methyl-1-phenylpyrazole compound has a structure shown as follows:
Figure BDA0003268711230000023
wherein R is2Is phenyl or C1～C5An alkyl group; r3Is phenyl or C1～C5An alkyl group.
Optionally, the mass ratio of the 2-methylquinoline compound to the 5-amino-3-methyl-1-phenylpyrazole compound is 1: 1-1: 4.
Optionally, the initial concentration of the 2-methylquinoline compound is 0.05-0.2 mol/L.
Optionally, the electrolyte is one of tetrabutylammonium tetrafluoroborate, lithium perchlorate, ammonium iodide, potassium iodide, sodium iodide, tetramethylammonium iodide and tetrabutylammonium iodide, and the amount of the substance is 30-120% of that of the 2-methylquinoline compound.
Optionally, the temperature of the stirring reaction is 0-140 ℃.
Optionally, the solvent is one of dimethyl sulfoxide, N-dimethylformamide, N-methylpyrrolidone, N-dimethylacetamide, acetonitrile, water, and 1, 2-dichloroethane.
Optionally, the catalytic electrode is a conventional electrode material.
Optionally, the separation and purification method is one of column chromatography, liquid chromatography, distillation and recrystallization separation.
More optionally, the separation and purification method is column chromatography.
Optionally, the eluent for column chromatography is petroleum ether/ethyl acetate. This is not to say that other eluent systems are not a requirement of the present application, as long as reagents meeting the purpose of elution can be used.
The invention has the beneficial effects that: the invention provides an electrosynthesis method of a dihydrodipyrazolo [3,4-b:4',3' -e ] pyridine compound, wherein the dihydrodipyrazolo [3,4-b:4',3' -e ] pyridine compound is synthesized by a one-pot method through a 2-methylquinoline compound and a 5-amino-3-methyl-1-phenylpyrazole compound under an electrochemical condition, and the method does not need the use of metal and a chemical oxidant, has clean reaction and is green and environment-friendly.
Description of the drawings:
FIG. 1 shows the product obtained in example 1 of the present invention1H NMR；
FIG. 2 shows the product obtained in example 1 of the present invention13C NMR；
FIG. 3 shows the product obtained in example 2 of the present invention1H NMR；
FIG. 4 shows the product obtained in example 2 of the present invention13C NMR；
FIG. 5 shows the product obtained in example 3 of the present invention1H NMR；
FIG. 6 shows the product obtained in example 3 of the present invention13C NMR；
FIG. 7 shows the product obtained in example 4 of the present invention1H NMR；
FIG. 8 shows the product obtained in example 4 of the present invention13C NMR；
FIG. 9 shows the results of example 5 of the present invention13C NMR；
FIG. 10 shows the results of example 5 of the present invention1H NMR；
FIG. 11 shows the results of example 6 of the present invention13C NMR；
FIG. 12 shows the results of example 6 of the present invention13C NMR；
FIG. 13 shows the results of example 7 of the present invention1H NMR；
FIG. 14 shows the results of example 7 of the present invention13C NMR；
FIG. 15 shows the results of example 8 of the present invention1H NMR；
FIG. 16 shows the results of example 8 of the present invention13C NMR。
The specific implementation mode is as follows:
in order to make the technical means, the original characteristics, the achieved purposes and the effects of the invention easy to understand, the invention is further explained by combining the specific embodiments and the drawings.
An electrosynthesis method of dihydrodipyrazole [3,4-b:4',3' -e ] pyridine compounds comprises the following steps:
(1) electrocatalytic reaction: respectively adding electrolyte, 2-methylquinoline compounds, 5-amino-3-methyl-1-phenylpyrazole compounds and a solvent into a reaction tank, installing a catalytic electrode, and electrifying and stirring for reaction;
(2) separation and purification: separating and purifying the solution after the electrocatalysis reaction is finished to obtain a dihydrodipyrazolo [3,4-b:4',3' -e ] pyridine compound;
the dihydrodipyrazolo [3,4-b:4',3' -e ] pyridine compound synthesized by the invention has the following structure:
Figure BDA0003268711230000041
wherein R is1Is hydrogen, C1～C5Alkyl radical, C1～C5One or more of alkoxy, halogen; r2Is phenyl or C1～C5An alkyl group; r3Is phenyl or C1～C5An alkyl group.
Specifically, in a 10mL non-separated electrolytic tank, an electrode, a 2-methylquinoline compound, a 5-amino-3-methyl-1-phenylpyrazole compound, an electrolyte and a solvent are respectively added into the non-separated electrolytic tank, and the mixture is electrified and stirred for reaction; the amount of the electrolyte substance is 30-120% of the amount of the 2-methylquinoline compound substance. The mass ratio of the 2-methylquinoline compound to the 5-amino-3-methyl-1-phenylpyrazole compound is 1: 1-1: 4. The initial concentration of the 2-methylquinoline compound is 0.05-0.2 mol/L, and the stirring reaction temperature is 0-140 ℃. The electrode is selected from conventional commercially available electrode materials, such as platinum electrodes, carbon electrodes, nickel electrodes, copper electrodes, and the like.
The solution after the reaction was dried by spinning under reduced pressure, and the residue was separated by silica gel column chromatography and passed through a column using petroleum ether/ethyl acetate system as eluent. This is not to say that other eluent systems are not a requirement of the present application, as long as reagents meeting the purpose of elution can be used.
The reaction formula is as follows:
Figure BDA0003268711230000051
the embodiment of the invention realizes the reaction of the isatin compounds and the benzoyl hydrazine compounds under the electrochemical condition for the first time, and the dihydro-dipyrazolo [3,4-b:4',3' -e ] pyridine compounds can be obtained highly selectively. The method is a green and efficient method for synthesizing the dihydrodipyrazolo [3,4-b:4',3' -e ] pyridine compound.
The 2-methylquinoline and 5-amino-3-methyl-1-phenylpyrazole compounds used in the examples were directly purchased as analytical reagents from Annaige, Jiuding, Aladdin and Adamas, without further treatment prior to use, and the solvents or eluents used were purchased from national pharmaceuticals.
Example 1
In a 10mL undivided electrolytic cell, 2-methylquinoline (0.3mmoL,42.9mg), 5-amino-3-methyl-1-phenylpyrazole (0.6mmoL,40.8mg), ammonium iodide (0.3mmoL,43.5mg), and N, N-dimethylformamide (3.0mL) were placed, and the reaction was carried out with electric stirring at 120 ℃. After completion of the reaction (TLC follow-up), the residue obtained by spin-drying was chromatographed on a column using ethyl acetate/petroleum ether system as eluent to give the product 3, 5-dimethyl-1, 7-diphenyl-4- (quinolin-2-yl) -1, 7-dihydrodipyrazolo [3,4-b:4',3' -e ] pyridine compound in 84% yield.
Subjecting the 3, 5-dimethyl-1, 7-diphenyl-4- (quinolin-2-yl) -1, 7-dihydrodipyrazolo [3,4-b:4',3' -e ] to nuclear magnetic resonance spectroscopy]The pyridine product is analyzed, and the result is shown in figures 1-2, wherein figure 1 shows that the 3, 5-dimethyl-1, 7-diphenyl-4- (quinoline-2-yl) -1, 7-dihydrodipyrazolo [3,4-b:4',3' -e ] provided in example 1 of the invention]Of pyridine products1H nuclear magnetic resonance (1H-NMR) spectrum; FIG. 2 shows 3, 5-dimethyl-1, 7-diphenyl-4- (quinolin-2-yl) -1, 7-dihydrodipyrazolo [3,4-b:4',3' -e ] provided in example 1 of the present invention]Of pyridine products13C nuclear magnetic resonance (13C-NMR) spectrum.
The obtained product is measured, and the characterization data is as follows1H NMR(CDCl3,400MHz,ppm):δ＝8.44–8.42(m,5H),8.25(d,J＝7.2Hz,1H),8.03(d,J＝6.8Hz,1H),7.91–7.87(m,1H),7.76–7.71(m,2H),7.58–7.54(m,4H),7.33–7.29(m,2H),2.07(s,6H)；13C NMR(CDCl3,100MHz,ppm):δ＝153.5,150.8,147.5,144.0,139.6,139.2,136.3,130.8,129.8,129.0,127.9,127.8,127.5,125.2,122.1,120.4,113.1,15.0。
The 3, 5-dimethyl-1, 7-diphenyl-4- (quinolin-2-yl) -1, 7-dihydrodipyrazolo [3,4-b:4',3' -e ] pyridine compound prepared in example 1 has the following structural formula:
Figure BDA0003268711230000061
example 2
In a 10mL undivided electrolytic cell, 2, 6-dimethylquinoline (0.3mmoL,47.1mg), 5-amino-3-methyl-1-phenylpyrazole (0.6mmoL,40.8mg), ammonium iodide (0.3mmoL,43.5mg), and N, N-dimethylformamide (3.0mL) were placed, and the reaction was carried out with energization at 120 ℃ with a platinum sheet electrode as both an anode and a cathode (I ═ 10 mA). After completion of the reaction (TLC follow-up), the residue obtained by spin-drying was chromatographed on a column using ethyl acetate/petroleum ether system as eluent to give the product 3, 5-dimethyl-4- (6-methylquinolin-2-yl) -1, 7-diphenyl-1, 7-dihydrodipyrazolo [3,4-b:4',3' -e ] pyridine compound in 74% yield.
Subjecting the 3, 5-dimethyl-4- (6-methylquinolin-2-yl) -1, 7-diphenyl-1, 7-dihydrodipyrazolo [3,4-b:4',3' -e ] to nuclear magnetic resonance spectroscopy]The pyridine product is analyzed, and the results are shown in figures 3-4, and figure 3 shows that 3, 5-dimethyl-4- (6-methylquinolin-2-yl) -1, 7-diphenyl-1, 7-dihydrodipyrazolo [3,4-b:4',3' -e ] provided in example 2 of the present invention]Of pyridine products1H nuclear magnetic resonance (1H-NMR) spectrum; FIG. 4 shows 3, 5-dimethyl-4- (6-methylquinolin-2-yl) -1, 7-diphenyl-1, 7-dihydrodipyrazolo [3,4-b:4',3' -e ] provided in example 2 of the present invention]Of pyridine products13C nuclear magnetic resonance (13C-NMR) spectrum.
The obtained product is measured, and the characterization data is as follows1H NMR(CDCl3,400MHz,ppm):δ＝8.44–8.42(m,4H),8.33(d,J＝7.6Hz,1H),8.13(d,J＝8.8Hz,1H),7.78(s,1H),7.73–7.70(m,1H),7.67(d,J＝8.4Hz,1H),7.58–7.54(m,4H),7.33–7.31(m,2H),2.65(s,3H),2.07(s,6H)；13C NMR(CDCl3,100MHz,ppm):δ＝152.5,150.8,146.1,144.1,139.6,139.4,137.9,136.0,133.1,129.4,129.0,127.5,126.7,125.2,122.0,120.4,113.2,21.7,14.9。
The 3, 5-dimethyl-4- (6-methylquinolin-2-yl) -1, 7-diphenyl-1, 7-dihydrodipyrazolo [3,4-b:4',3' -e ] pyridine compound prepared in example 2 has the following structural formula:
Figure BDA0003268711230000071
example 3
6-methoxy-2-methylquinoline (0.3mmoL,51.9mg), 5-amino-3-methyl-1-phenylpyrazole (0.6mmoL,40.8mg), ammonium iodide (0.3mmoL,43.5mg), and N, N-dimethylformamide (3.0mL) were placed in a 10mL undivided electrolytic cell, and the reaction was carried out with electric stirring (I ═ 10mA) at 120 ℃ using a platinum sheet electrode as both an anode and a cathode. After completion of the reaction (TLC follow-up), the residue obtained by spin-drying was chromatographed on a column using ethyl acetate/petroleum ether system as eluent to give the product 4- (6-methoxyquinolin-2-yl) -3, 5-dimethyl-1, 7-diphenyl-1, 7-dihydrodipyrazolo [3,4-b:4',3' -e ] pyridine compound in 40% yield.
Subjecting the 4- (6-methoxyquinolin-2-yl) -3, 5-dimethyl-1, 7-diphenyl-1, 7-dihydrodipyrazolo [3,4-b:4',3' -e to nuclear magnetic resonance spectroscopy]The pyridine product is analyzed, and the results are shown in FIGS. 5-6, and FIG. 5 shows that 4- (6-methoxyquinolin-2-yl) -3, 5-dimethyl-1, 7-diphenyl-1, 7-dihydrodipyrazolo [3,4-b:4',3' -e ] provided in example 3 of the present invention]Of pyridine products1H nuclear magnetic resonance (1H-NMR) spectrum; FIG. 6 shows 4- (6-methoxyquinolin-2-yl) -3, 5-dimethyl-1, 7-diphenyl-1, 7-dihydrodipyrazolo [3,4-b:4',3' -e ] provided in example 3 of the present invention]Of pyridine products13C nuclear magnetic resonance (13C-NMR) spectrum.
The obtained product is measured, and the characterization data is as follows1H NMR(CDCl3,400MHz,ppm):δ＝8.44–8.42(m,4H),8.31(d,J＝7.6Hz,1H),8.13(d,J＝8.8Hz,1H),7.66(d,J＝8.4Hz,1H),7.58–7.52(m,5H),7.33–7.29(m,2H),7.27–7.26(m,1H),4.03(s,3H),2.08(s,6H)；13C NMR(CDCl3,100MHz,ppm):δ＝158.7,150.8,150.7,144.1,143.6,139.6,139.4,134.9,131.2,129.0,128.7,125.2,123.7,122.3,120.4,113.2,105.1,55.7,14.9。
The 4- (6-methoxyquinolin-2-yl) -3, 5-dimethyl-1, 7-diphenyl-1, 7-dihydrodipyrazolo [3,4-b:4',3' -e ] pyridine compound prepared in example 3 has the following structural formula:
Figure BDA0003268711230000081
example 4
6-chloro-2-methylquinoline (0.3mmoL,53.1mg), 5-amino-3-methyl-1-phenylpyrazole (0.6mmoL,40.8mg), ammonium iodide (0.3mmoL,43.5mg), and N, N-dimethylformamide (3.0mL) were placed in a 10mL undivided electrolytic cell, and the reaction was carried out with electric stirring (I ═ 10mA) at 120 ℃ using a platinum sheet electrode as both an anode and a cathode. After completion of the reaction (TLC follow-up), the residue obtained by spin-drying was chromatographed on a column using ethyl acetate/petroleum ether system as eluent to give the product 4- (6-chloroquinolin-2-yl) -3, 5-dimethyl-1, 7-diphenyl-1, 7-dihydrodipyrazolo [3,4-b:4',3' -e ] pyridine compound in 83% yield.
Subjecting the 4- (6-chloroquinolin-2-yl) -3, 5-dimethyl-1, 7-diphenyl-1, 7-dihydrodipyrazolo [3,4-b:4',3' -e ] to nuclear magnetic resonance spectroscopy]The pyridine products are analyzed, and the results are shown in FIGS. 7-8, and FIG. 7 shows that 4- (6-chloroquinolin-2-yl) -3, 5-dimethyl-1, 7-diphenyl-1, 7-dihydrodipyrazolo [3,4-b:4',3' -e ] provided in example 4 of the present invention]Of pyridine products1H nuclear magnetic resonance (1H-NMR) spectrum; FIG. 8 shows 4- (6-chloroquinolin-2-yl) -3, 5-dimethyl-1, 7-diphenyl-1, 7-dihydrodipyrazolo [3,4-b:4',3' -e ] provided in example 4 of the present invention]Of pyridine products13C nuclear magnetic resonance (13C-NMR) spectrum.
The obtained product is measured, and the characterization data is as follows1HNMR(CDCl3,400MHz,ppm):δ＝8.43–8.41(m,4H),8.34(d,J＝8.0Hz,1H),8.18(d,J＝8.8Hz,1H),8.02–8.01(m,1H),7.82(dd,J＝9.2Hz,J＝2.4Hz,1H),7.74(d,J＝8.4Hz,1H),7.58–7.54(m,4H),7.34–7.29(m,2H),2.06(s,6H)；13C NMR(CDCl3,100MHz,ppm):δ＝153.8,150.8,145.8,143.8,139.6,138.6,135.4,133.7,131.8,131.4,129.0,128.0,126.6,125.3,123.0,120.4,113.0,14.9。
The 4- (6-chloroquinolin-2-yl) -3, 5-dimethyl-1, 7-diphenyl-1, 7-dihydrodipyrazolo [3,4-b:4',3' -e ] pyridine compound prepared in example 4 has the following structural formula:
Figure BDA0003268711230000091
example 5
6-bromo-2-methylquinoline (0.3mmoL,66.3mg), 5-amino-3-methyl-1-phenylpyrazole (0.6mmoL,40.8mg), ammonium iodide (0.3mmoL,43.5mg), and N, N-dimethylformamide (3.0mL) were placed in a 10mL undivided electrolytic cell, and the reaction was carried out with electric stirring (I ═ 10mA) at 120 ℃ using a platinum sheet electrode as both an anode and a cathode. After completion of the reaction (TLC follow-up), the residue obtained by spin-drying was chromatographed on a column using ethyl acetate/petroleum ether system as eluent to give the product 4- (6-bromoquinolin-2-yl) -3, 5-dimethyl-1, 7-diphenyl-1, 7-dihydrodipyrazolo [3,4-b:4',3' -e ] pyridine compound in 83% yield.
Subjecting the 4- (6-bromoquinolin-2-yl) -3, 5-dimethyl-1, 7-diphenyl-1, 7-dihydrodipyrazolo [3,4-b:4',3' -e ] to nuclear magnetic resonance spectroscopy]The pyridine products are analyzed, and the results are shown in FIGS. 9-10, and FIG. 9 shows that 4- (6-bromoquinolin-2-yl) -3, 5-dimethyl-1, 7-diphenyl-1, 7-dihydrodipyrazolo [3,4-b:4',3' -e ] provided in example 5 of the present invention]Of pyridine products1H nuclear magnetic resonance (1H-NMR) spectrum; FIG. 10 shows 4- (6-bromoquinolin-2-yl) -3, 5-dimethyl-1, 7-diphenyl-1, 7-dihydrodipyrazolo [3,4-b:4',3' -e ] provided in example 5 of the present invention]Of pyridine products13C nuclear magnetic resonance (13C-NMR) spectrum.
The obtained product is measured, and the characterization data is as follows1H NMR(CDCl3,400MHz,ppm):δ＝8.43–8.40(m,4H),8.32(d,J＝8.0Hz,1H),8.19(d,J＝2.4Hz,1H),8.11(d,J＝9.2Hz,1H),7.95(d,J＝8.8Hz,J＝2.4Hz,1H),7.73(d,J＝8.4Hz,1H),7.58–7.53(m,4H),7.34–7.29(m,2H),2.05(s,6H)；13C NMR(CDCl3,100MHz,ppm):δ＝153.9,150.7,146.0,143.8,139.5,138.6,135.3,134.3,131.4,129.9,129.0,128.5,125.3,123.0,121.9,120.4,112.9,14.9。
The 4- (6-bromoquinolin-2-yl) -3, 5-dimethyl-1, 7-diphenyl-1, 7-dihydrodipyrazolo [3,4-b:4',3' -e ] pyridine compound prepared in example 5 has the following structural formula:
Figure BDA0003268711230000101
example 6
In a 10mL undivided electrolytic cell, 7-chloro-2-methylquinoline (0.3mmoL,53.1mg), 5-amino-3-methyl-1-phenylpyrazole (0.6mmoL,40.8mg), ammonium iodide (0.3mmoL,43.5mg), and N, N-dimethylformamide (3.0mL) were placed, and the reaction was carried out with energization at 120 ℃ while using a platinum sheet electrode as both an anode and a cathode (I ═ 10 mA). After completion of the reaction (TLC follow-up), the residue obtained by spin-drying was chromatographed on a column using ethyl acetate/petroleum ether system as eluent to give the product 4- (7-chloroquinolin-2-yl) -3, 5-dimethyl-1, 7-diphenyl-1, 7-dihydrodipyrazolo [3,4-b:4',3' -e ] pyridine compound in 63% yield.
Subjecting the 4- (7-chloroquinolin-2-yl) -3, 5-dimethyl-1, 7-diphenyl-1, 7-dihydrodipyrazolo [3,4-b:4',3' -e to nuclear magnetic resonance spectroscopy]The pyridine products are analyzed, and the results are shown in FIGS. 11-12, and FIG. 11 shows that 4- (7-chloroquinolin-2-yl) -3, 5-dimethyl-1, 7-diphenyl-1, 7-dihydrodipyrazolo [3,4-b:4',3' -e ] provided in example 6 of the present invention]Of pyridine products1H nuclear magnetic resonance (1H-NMR) spectrum; FIG. 12 is 4- (7-chloroquinolin-2-yl) -3, 5-dimethyl-1, 7-diphenyl-1, 7-dihydrodipyrazolo [3,4-b:4',3' -e ] provided in example 6 of the present invention]Of pyridine products13C nuclear magnetic resonance (13C-NMR) spectrum.
The obtained product is measured, and the characterization data is as follows1HNMR(CDCl3,400MHz,ppm):δ＝8.43–8.40(m,5H),8.24(d,J＝2.0Hz,1H),7.97(d,J＝8.8Hz,1H),7.72–7.68(m,2H),7.58–7.54(m,4H),7.34–7.30(m,2H),2.07(s,6H)；13C NMR(CDCl3,100MHz,ppm):δ＝154.7,150.8,147.8,143.8,139.6,138.6,136.8,136.2,129.1,129.0,129.0,128.8,125.8,125.3,122.3,120.5,113.0,14.9。
The 4- (7-chloroquinolin-2-yl) -3, 5-dimethyl-1, 7-diphenyl-1, 7-dihydrodipyrazolo [3,4-b:4',3' -e ] pyridine compound prepared in example 6 has the following structural formula:
Figure BDA0003268711230000111
example 7
In a 10mL undivided electrolytic cell, 2, 8-dimethylquinoline (0.3mmoL,47.1mg), 5-amino-3-methyl-1-phenylpyrazole (0.6mmoL,40.8mg), ammonium iodide (0.3mmoL,43.5mg), and N, N-dimethylformamide (3.0mL) were placed, and the reaction was carried out with energization at 120 ℃ with a platinum sheet electrode as both an anode and a cathode (I ═ 10 mA). After completion of the reaction (TLC follow-up), the residue obtained by spin-drying was chromatographed on a column using ethyl acetate/petroleum ether system as eluent to give the product 3, 5-dimethyl-4- (8-methylquinolin-2-yl) -1, 7-diphenyl-1, 7-dihydrodipyrazolo [3,4-b:4',3' -e ] pyridine compound in 69% yield.
Subjecting the 3, 5-dimethyl-4- (8-methylquinolin-2-yl) -1, 7-diphenyl-1, 7-dihydrodipyrazolo [3,4-b:4',3' -e ] to nuclear magnetic resonance spectroscopy]The pyridine products are analyzed, and the results are shown in FIGS. 13-14, and FIG. 13 shows that 3, 5-dimethyl-4- (8-methylquinolin-2-yl) -1, 7-diphenyl-1, 7-dihydrodipyrazolo [3,4-b:4',3' -e ] provided in example 7 of the present invention]Of pyridine products1H nuclear magnetic resonance (1H-NMR) spectrum; FIG. 14 shows 3, 5-dimethyl-4- (8-methylquinolin-2-yl) -1, 7-diphenyl-1, 7-dihydrodipyrazolo [3,4-b:4',3' -e ] provided in example 7 of the present invention]Of pyridine products13C nuclear magnetic resonance (13C-NMR) spectrum.
The obtained product is measured, and the characterization data is as follows1H NMR(CDCl3,400MHz,ppm):δ＝8.45(d,J＝7.6Hz,4H),8.35(d,J＝8.4Hz,1H),7.85(d,J＝6.4Hz,1H),7.72(d,J＝6.8Hz,1H),7.68(d,J＝8.4Hz,1H),7.62–7.55(m,5H),7.34–7.30(m,2H),2.85(s,3H),2.09(s,6H)；13C NMR(CDCl3,100MHz,ppm):δ＝152.1,150.8,146.6,144.2,140.0,139.6,137.9,136.3,130.6,128.9,127.5,127.4,125.8,125.1,122.1,120.3,113.1,18.1,15.1。
The 3, 5-dimethyl-4- (8-methylquinolin-2-yl) -1, 7-diphenyl-1, 7-dihydrodipyrazolo [3,4-b:4',3' -e ] pyridine compound prepared in example 7 has the following structural formula:
Figure BDA0003268711230000121
example 8
In a 10mL undivided electrolytic cell, 2-methylquinoline (0.3mmoL,42.9mg), 1, 3-dimethyl-1H-pyrazol-5-amino group (0.6mmoL,66.6mg), ammonium iodide (0.3mmoL,43.5mg), and N, N-dimethylformamide (3.0mL) were placed, and the reaction was carried out with energization at 120 ℃ with a platinum sheet electrode as both an anode and a cathode (I ═ 10 mA). After completion of the reaction (TLC follow-up), the residue obtained by spin-drying was chromatographed using ethyl acetate/petroleum ether system as eluent to give the product 1,3,5, 7-tetramethyl-4- (quinolin-2-yl) -1, 7-dihydrodipyrazolo [3,4-b:4',3' -e ] pyridine compound in 54% yield.
Subjecting the 1,3,5, 7-tetramethyl-4- (quinolin-2-yl) -1, 7-dihydrodipyrazolo [3,4-b:4',3' -e to nuclear magnetic resonance spectroscopy]The pyridine products are analyzed, and the results are shown in FIGS. 15-16, and FIG. 15 shows that 1,3,5, 7-tetramethyl-4- (quinolin-2-yl) -1, 7-dihydrodipyrazolo [3,4-b:4',3' -e ] provided in example 8 of the present invention]Of pyridine products1H nuclear magnetic resonance (1H-NMR) spectrum; FIG. 16 shows 1,3,5, 7-tetramethyl-4- (quinolin-2-yl) -1, 7-dihydrodipyrazolo [3,4-b:4',3' -e ] according to example 8 of the present invention]Of pyridine products13C nuclear magnetic resonance (13C-NMR) spectrum.
The obtained product is measured, and the characterization data is as follows1HNMR(CDCl3,400MHz,ppm):δ＝8.37(d,J＝7.6Hz,1H),8.21(d,J＝7.6Hz,1H),7.99(d,J＝6.8Hz,1H),7.87–7.83(m,1H),7.71–7.67(m,1H),7.62(d,J＝8.0Hz,1H),4.10(s,6H),1.99(s,6H)；13C NMR(CDCl3,100MHz,ppm):δ＝154.0,152.2,147.4,141.7,138.7,136.1,130.6,129.7,127.8,127.5,127.4,122.1,111.1,33.5,14.8。
The 1,3,5, 7-tetramethyl-4- (quinolin-2-yl) -1, 7-dihydrodipyrazolo [3,4-b:4',3' -e ] pyridine prepared in example 8 has the following structural formula:
Figure BDA0003268711230000122
the reaction time of the electrification and stirring in the embodiment of the invention can be any, and the 3, 5-dimethyl-1, 7-diphenyl-4- (quinoline-2-yl) -1, 7-dihydro-dipyrazolo [3,4-b:4',3' -e ] pyridine compound can be prepared as long as the electrification is carried out, the optimal electrification time is about 15 hours, and the yield of the obtained product is highest. 3, 5-dimethyl-1, 7-diphenyl-4- (quinolin-2-yl) -1, 7-dihydrodipyrazolo [3,4-b:4',3' -e ] pyridines were prepared at any other time except that the yield varied, increasing from the start of electrification to 15h, and decreased over 15h, possibly as a result of conversion of the product formed to other by-products due to too long an electrocatalytic period.
The foregoing shows and describes the general principles and broad features of the present invention and advantages thereof. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, which are described in the specification and illustrated only to illustrate the principle of the present invention, but that various changes and modifications may be made therein without departing from the spirit and scope of the present invention, which fall within the scope of the invention as claimed. The scope of the invention is defined by the appended claims and equivalents thereof.

Claims (10)

1. An electrochemical synthesis method of a dihydrodipyrazole [3,4-b:4',3' -e ] pyridine compound is characterized by comprising the following steps:
(1) electrocatalytic reaction: respectively adding electrolyte, 2-methylquinoline compounds, 5-amino-3-methyl-1-phenylpyrazole compounds and a solvent into a reaction tank, installing a catalytic electrode, and electrifying and stirring for reaction;
(2) separation and purification: separating and purifying the solution after the electrocatalysis reaction is finished to obtain a dihydrodipyrazolo [3,4-b:4',3' -e ] pyridine compound;
the dihydrodipyrazolo [3,4-b:4',3' -e ] pyridine compound has the following structure:
Figure FDA0003268711220000011
wherein R is1Is hydrogen, C1～C5Alkyl radical, C1～C5One or more of alkoxy, halogen; r2Is phenyl or C1～C5An alkyl group; r3Is phenyl or C1～C5An alkyl group.
2. The method of synthesis according to claim 1, characterized in that: the 2-methylquinoline compound has the following structure:
Figure FDA0003268711220000012
wherein R is1Is hydrogen, C1～C5Alkyl radical, C1～C5One or more of alkoxy and halogen.
3. The method of synthesis according to claim 1, characterized in that: the 5-amino-3-methyl-1-phenylpyrazole compound has the following structure:
Figure FDA0003268711220000013
wherein R is2Is phenyl or C1～C5An alkyl group; r3Is phenyl or C1～C5An alkyl group.
4. The method of synthesis according to claim 1, characterized in that: the mass ratio of the 2-methylquinoline compound to the 5-amino-3-methyl-1-phenylpyrazole compound is 1: 1-1: 4.
5. The method of synthesis according to claim 1, characterized in that: the initial concentration of the 2-methylquinoline compound is 0.05-0.2 mol/L.
6. The method of synthesis according to claim 1, characterized in that: the electrolyte is one of tetrabutylammonium tetrafluoroborate, lithium perchlorate, ammonium iodide, potassium iodide, sodium iodide, tetramethylammonium iodide and tetrabutylammonium iodide, and the amount of the electrolyte is 30-120% of that of the 2-methylquinoline compound.
7. The method of synthesis according to claim 1, characterized in that: the temperature of the stirring reaction is 0-140 ℃.
8. The method of synthesis according to claim 1, characterized in that: the solvent is one of dimethyl sulfoxide, N-dimethylformamide, N-methylpyrrolidone, N-dimethylacetamide, acetonitrile, water and 1, 2-dichloroethane.
9. The method of synthesis according to claim 1, characterized in that: the catalytic electrode is a conventional electrode material.
10. The method of synthesis according to claim 1, characterized in that: the separation and purification method is one of column chromatography, liquid chromatography, distillation and recrystallization separation.
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