CN113930791A - Electrosynthesis method of pyrido-bipyrimidine tetraketone compound - Google Patents
Electrosynthesis method of pyrido-bipyrimidine tetraketone compound Download PDFInfo
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 37
- 238000000034 method Methods 0.000 title claims abstract description 25
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims abstract description 46
- 238000006243 chemical reaction Methods 0.000 claims abstract description 34
- SMUQFGGVLNAIOZ-UHFFFAOYSA-N methylquinoline Natural products C1=CC=CC2=NC(C)=CC=C21 SMUQFGGVLNAIOZ-UHFFFAOYSA-N 0.000 claims abstract description 24
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims abstract description 23
- -1 2-methylquinoline compound Chemical class 0.000 claims abstract description 20
- 238000003756 stirring Methods 0.000 claims abstract description 13
- 239000003792 electrolyte Substances 0.000 claims abstract description 9
- 239000002904 solvent Substances 0.000 claims abstract description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 17
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 238000000926 separation method Methods 0.000 claims description 8
- XZXYQEHISUMZAT-UHFFFAOYSA-N 2-[(2-hydroxy-5-methylphenyl)methyl]-4-methylphenol Chemical compound CC1=CC=C(O)C(CC=2C(=CC=C(C)C=2)O)=C1 XZXYQEHISUMZAT-UHFFFAOYSA-N 0.000 claims description 7
- 229940107816 ammonium iodide Drugs 0.000 claims description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 claims description 6
- 238000000746 purification Methods 0.000 claims description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 230000003197 catalytic effect Effects 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- 238000004440 column chromatography Methods 0.000 claims description 4
- 239000007772 electrode material Substances 0.000 claims description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 2
- 238000004821 distillation Methods 0.000 claims description 2
- 238000004811 liquid chromatography Methods 0.000 claims description 2
- MHCFAGZWMAWTNR-UHFFFAOYSA-M lithium perchlorate Chemical compound [Li+].[O-]Cl(=O)(=O)=O MHCFAGZWMAWTNR-UHFFFAOYSA-M 0.000 claims description 2
- 229910001486 lithium perchlorate Inorganic materials 0.000 claims description 2
- 238000001953 recrystallisation Methods 0.000 claims description 2
- 235000009518 sodium iodide Nutrition 0.000 claims description 2
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 claims description 2
- RXMRGBVLCSYIBO-UHFFFAOYSA-M tetramethylazanium;iodide Chemical compound [I-].C[N+](C)(C)C RXMRGBVLCSYIBO-UHFFFAOYSA-M 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 2
- 239000000126 substance Substances 0.000 abstract description 8
- 229910052751 metal Inorganic materials 0.000 abstract description 4
- 239000002184 metal Substances 0.000 abstract description 4
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 239000007800 oxidant agent Substances 0.000 abstract description 3
- 238000012822 chemical development Methods 0.000 abstract description 2
- 230000001590 oxidative effect Effects 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 abstract 1
- 239000000047 product Substances 0.000 description 35
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 15
- 238000005160 1H NMR spectroscopy Methods 0.000 description 15
- 238000005481 NMR spectroscopy Methods 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 12
- 239000003480 eluent Substances 0.000 description 10
- 238000004519 manufacturing process Methods 0.000 description 10
- 238000001228 spectrum Methods 0.000 description 10
- 239000003208 petroleum Substances 0.000 description 7
- 229910052697 platinum Inorganic materials 0.000 description 6
- 238000012512 characterization method Methods 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 3
- 238000012916 structural analysis Methods 0.000 description 3
- 238000001308 synthesis method Methods 0.000 description 3
- JJPSZKIOGBRMHK-UHFFFAOYSA-N 2,6-dimethylquinoline Chemical compound N1=C(C)C=CC2=CC(C)=CC=C21 JJPSZKIOGBRMHK-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- SQRYQSKJZVQJAY-UHFFFAOYSA-N 6-bromo-2-methylquinoline Chemical compound C1=C(Br)C=CC2=NC(C)=CC=C21 SQRYQSKJZVQJAY-UHFFFAOYSA-N 0.000 description 1
- OCCIBGIEIBQGAJ-UHFFFAOYSA-N 6-chloro-2-methylquinoline Chemical compound C1=C(Cl)C=CC2=NC(C)=CC=C21 OCCIBGIEIBQGAJ-UHFFFAOYSA-N 0.000 description 1
- NAGJQQFMJKMXJQ-UHFFFAOYSA-N 6-methoxy-2-methylquinoline Chemical compound N1=C(C)C=CC2=CC(OC)=CC=C21 NAGJQQFMJKMXJQ-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 150000001879 copper Chemical class 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
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- C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
- C25B3/00—Electrolytic production of organic compounds
- C25B3/01—Products
- C25B3/05—Heterocyclic compounds
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/14—Ortho-condensed systems
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- C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
- C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
- C25B3/00—Electrolytic production of organic compounds
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- C25B3/07—Oxygen containing compounds
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- C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
- C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
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Abstract
The invention discloses an electrosynthesis method of a pyrido-bipyrimidine tetraketone compound, which relates to the technical field of organic synthesis and comprises the following steps: (1) respectively adding an electrolyte, a 2-methylquinoline compound, a 1, 3-dimethyl-6-semicarbazide compound, a solvent and an electrode into a non-separated electrolytic tank, and electrifying, stirring and reacting; (2) and separating and purifying the solution after the reaction is finished to obtain the pyridine [2,3-d:6,5-d' ] bipyrimidine-2, 4,6,8(1H,3H,7H,9H) -tetraone compound, wherein the preparation process does not need the use of metal and chemical oxidant, has high reaction atom economy and meets the requirement of green chemical development.
Description
The technical field is as follows:
the invention relates to the technical field of organic synthesis, in particular to an electrosynthesis method of a pyridine [2,3-d:6,5-d' ] bipyrimidine-2, 4,6,8(1H,3H,7H,9H) -tetraone compound.
Background art:
the polysubstituted pyridine compounds are important nitrogen-containing heterocycles and widely exist in bioactive molecules and photoelectric materials. In particular to a pyridine [2,3-d:6,5-d' ] bipyrimidine-2, 4,6,8(1H,3H,7H,9H) -tetraone compound, the molecular structure of which consists of one pyridine and two pyrimidine rings, and the compound is an important potential functional active molecule. Therefore, the research on the synthesis method thereof has been the focus of research of organic chemists. However, since the reaction involves the formation of two carbon-carbon bonds and one carbon-nitrogen bond, few studies are currently conducted on the synthesis of pyridine [2,3-d:6,5-d' ] bipyrimidine-2, 4,6,8(1H,3H,7H,9H) -tetrone compounds.
In 2021, Zhu subject group serially synthesized pyridine [2,3-d:6,5-d' ] bipyrimidine-2, 4,6,8(1H,3H,7H,9H) -tetrone compounds (R-J.Xie, J-H.Liu, Q-Y, Zhang, Y-J.Yang, L-Q.Song, T-Q, Shao, K-X, Liu and Y-P.Zhu, org.chem.front,2021,8,2274.) from 2-methylquinoline and 1, 3-dimethyl-6-semicarbazide pyrimidine using metallic copper salt as catalyst. 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 a synthesis method of a pyridine [2,3-d:6,5-d '] bipyrimidine-2, 4,6,8(1H,3H,7H,9H) -tetraone compound, which adopts a green organic electrochemical synthesis method to prepare the pyridine [2,3-d:6,5-d' ] bipyrimidine-2, 4,6,8(1H,3H,7H,9H) -tetraone compound under the reaction environment without adding metal and chemical oxidants, so as to overcome the defects in the prior art.
The technical problem to be solved by the invention is realized by adopting the following technical scheme:
an electrosynthesis method of pyridine [2,3-d:6,5-d' ] bipyrimidine-2, 4,6,8(1H,3H,7H,9H) -tetraone compounds comprises the following steps:
(1) electrocatalytic reaction: respectively adding electrolyte, 2-methylquinoline compound, 1, 3-dimethyl-6-semicarbazide compound and solvent into a reaction tank, installing a catalytic electrode, and electrifying and stirring for reaction;
(2) separation and purification: and separating and purifying the solution after the electrocatalysis reaction is finished to obtain the pyridine [2,3-d:6,5-d' ] bipyrimidine-2, 4,6,8(1H,3H,7H,9H) -tetraone compound.
The pyridine [2,3-d:6,5-d' ] bipyrimidine-2, 4,6,8(1H,3H,7H,9H) -tetraone compound has the following structure:
wherein R is1Is hydrogen, C1～C5Alkyl radical, C1～C5One or more of alkoxy, halogen; r2Is C1～C5An alkyl group; r3Is C1～C5An alkyl group.
Optionally, the 2-methylquinoline compound has a structure shown as follows:
wherein R is1Is hydrogen, C1～C5Alkyl radical, C1～C5One or more of alkoxy and halogen.
Optionally, the 1, 3-dimethyl-6-semicarbazide compound has a structure shown as follows:
wherein R is2Is C1～C5An alkyl group; r3Is C1～C5An alkyl group.
Optionally, the mass ratio of the 2-methylquinoline compound to the 1, 3-dimethyl-6-semicarbazide 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 pyridine [2,3-d:6,5-d '] bipyrimidine-2, 4,6,8(1H,3H,7H,9H) -tetraone compound, wherein the pyridine [2,3-d:6,5-d' ] bipyrimidine-2, 4,6,8(1H,3H,7H,9H) -tetraone compound is synthesized by a one-pot method under electrochemical conditions through a 2-methylquinoline compound and a 1, 3-dimethyl-6-aminouracil compound, and the method does not need to use metals and chemical oxidants, has high reaction atom economy and meets the requirement of green chemical development.
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；
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 pyridine [2,3-d:6,5-d' ] bipyrimidine-2, 4,6,8(1H,3H,7H,9H) -tetraone compounds comprises the following steps:
(1) electrocatalytic reaction: respectively adding electrolyte, 2-methylquinoline compound, 1, 3-dimethyl-6-semicarbazide compound and 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 pyridine [2,3-d:6,5-d' ] bipyrimidine-2, 4,6,8(1H,3H,7H,9H) -tetraone compounds;
the synthesized pyridine [2,3-d:6,5-d' ] bipyrimidine-2, 4,6,8(1H,3H,7H,9H) -tetraone compound has the following structure:
wherein R is1Is hydrogen, C1～C5Alkyl radical, C1～C5One or more of alkoxy, halogen; r2Is C1～C5An alkyl group; r3Is C1～C5An alkyl group.
Specifically, in a 10mL non-separated electrolytic tank, electrodes, 2-methylquinoline compounds, 1, 3-dimethyl-6-semicarbazide compounds, electrolytes and solvents are respectively added into the non-separated electrolytic tank, and the non-separated electrolytic tank 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 1, 3-dimethyl-6-semicarbazide 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:
the embodiment of the invention realizes the reaction of the 2-methylquinoline compound and the 1, 3-dimethyl-6-semicarbazide compound under the electrochemical condition for the first time, and the pyridine [2,3-d:6,5-d' ] bipyrimidine-2, 4,6,8(1H,3H,7H,9H) -tetraone compound is obtained with high selectivity. The method is a green and efficient method for synthesizing the pyridine [2,3-d:6,5-d' ] bipyrimidine-2, 4,6,8(1H,3H,7H,9H) -tetrone compound.
The 2-methylquinoline and 1, 3-dimethyl-6-semicarbazide compounds used in the examples were all analytical reagents purchased directly from Annaige chemical, Jiuding chemical, Aladdin and Adamax, without further treatment before use, and the solvents or eluents used were purchased from national medicine.
Example 1
In a 10mL undivided electrolytic cell, 2-methylquinoline (0.3mmoL,42.9mg), 1, 3-dimethyl-6-semicarbazide-pyrimidine (0.6mmoL,93.1mg), 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 ℃ 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 1,3,7, 9-tetramethyl-5- (quinolin-2-yl) -pyridine [2,3-d:6,5-d' ] bipyrimidinyl-2, 4,6,8(1H,3H,7H,9H) -tetraone compound in 81% yield.
Subjecting the obtained product 1,3,7, 9-tetramethyl-5- (quinolin-2-yl) -pyridine [2,3-d:6,5-d 'to nuclear magnetic resonance spectroscopy']The structure analysis of the dipyrimidine-2, 4,6,8(1H,3H,7H,9H) -tetraone product is shown in the figure 1-2. FIG. 1 is 1,3,7, 9-tetramethyl-5- (quinolin-2-yl) -pyridine [2,3-d:6,5-d 'provided in example 1 of the present invention']Process for preparing dipyrimidine-2, 4,6,8(1H,3H,7H,9H) -tetraone products1H nuclear magnetic resonance (1H-NMR) spectrum; FIG. 2 is 1,3,7, 9-tetramethyl-5- (quinolin-2-yl) -pyridine [2,3-d:6,5-d 'provided in example 1 of the present invention']Process for preparing dipyrimidine-2, 4,6,8(1H,3H,7H,9H) -tetraone products13C nuclear magnetic resonance (13C-NMR) spectrum.
The characterization data are1H NMR(CDCl3,400MHz,ppm):δ＝8.29(d,J＝8.0Hz,1H),8.02(d,J＝8.4Hz,1H),7.93(d,J＝6.8Hz,1H),7.73–7.69(m,1H),7.60–7.56(m,1H),7.43(d,J＝8.8Hz,1H),3.81(s,6H),3.27(s,6H)；13C NMR(CDCl3,100MHz,ppm):δ＝159.0,157.0,156.7,153.5,150.7,147.5,135.1,129.5,129.0,128.1,127.1,126.4,120.1,105.1,30.4,28.4。
The 1,3,7, 9-tetramethyl-5- (quinolin-2-yl) -pyridine [2,3-d:6,5-d' ] bipyrimidinyl-2, 4,6,8(1H,3H,7H,9H) -tetraone compound prepared in example 1 has the following structural formula:
example 2
In a 10mL undivided electrolytic cell, 2, 6-dimethylquinoline (0.3mmoL,47.1mg), 1, 3-dimethyl-6-semicarbazide-pyrimidine (0.6mmoL,93.1mg), ammonium iodide (0.3mmoL,43.5mg), and N, N-dimethylformamide (3.0mL) were placed, and the reaction was carried out by energizing and stirring 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 1,3,7, 9-tetramethyl-5- (6-methylquinolin-2-yl) -pyridine [2,3-d:6,5-d' ] bipyrimidine-2, 4,6,8(1H,3H,7H,9H) -tetraone compound in 83% yield.
Subjecting the obtained product 1,3,7, 9-tetramethyl-5- (6-methylquinolin-2-yl) -pyridine [2,3-d:6,5-d 'to nuclear magnetic resonance spectroscopy']The structure analysis of the dipyrimidine-2, 4,6,8(1H,3H,7H,9H) -tetraone product is shown in the figure 3-4. FIG. 3 is 1,3,7, 9-tetramethyl-5- (6-methylquinolin-2-yl) -pyridine [2,3-d:6,5-d']Process for preparing dipyrimidine-2, 4,6,8(1H,3H,7H,9H) -tetraone products1H nuclear magnetic resonance (1H-NMR) spectrum; FIG. 4 shows 1,3,7, 9-tetramethyl-5- (6-methylquinolin-2-yl) -pyridine [2,3-d:6,5-d']Process for preparing dipyrimidine-2, 4,6,8(1H,3H,7H,9H) -tetraone products13C nuclear magnetic resonance (13C-NMR) spectrum.
The characterization data are1H NMR(CDCl3,400MHz,ppm):δ＝8.20(d,J＝7.6Hz,1H),7.91(d,J＝8.4Hz,1H),7.69–7.68(m,1H),7.54(d,J＝8.4Hz,J＝2.0Hz,1H)，7.39(d,J＝8.4Hz,1H),3.80(s,6H),3.26(s,6H),2.56(s,3H)；13C NMR(CDCl3,100MHz,ppm):δ＝159.1,157.2,155.8,153.6,150.9,146.2,136.4,134.6,131.8,128.7,127.3,127.1,120.2,105.2,30.4,28.5,21.6。
The 1,3,7, 9-tetramethyl-5- (6-methylquinolin-2-yl) -pyridine [2,3-d:6,5-d' ] bipyrimidinyl-2, 4,6,8(1H,3H,7H,9H) -tetraone compound prepared in example 2 has the following structural formula:
example 3
6-methoxy-2-methylquinoline (0.3mmoL,51.9mg), 1, 3-dimethyl-6-semicarbazide-pyrimidine (0.6mmoL,93.1mg), 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 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 1,3,7, 9-tetramethyl-5- (6-methoxyquinolin-2-yl) -pyridine [2,3-d:6,5-d' ] bipyrimidine-2, 4,6,8(1H,3H,7H,9H) -tetraone compound in 76% yield.
Subjecting the obtained product 1,3,7, 9-tetramethyl-5- (6-methoxyquinolin-2-yl) -pyridine [2,3-d:6,5-d 'to nuclear magnetic resonance spectroscopy']The structural analysis of the dipyrimidine-2, 4,6,8(1H,3H,7H,9H) -tetraone product shows that the results are shown in figures 5-6, and figure 5 shows that the 1,3,7, 9-tetramethyl-5- (6-methoxyquinolin-2-yl) -pyridine [2,3-d:6,5-d 'provided in example 3 of the invention']Process for preparing dipyrimidine-2, 4,6,8(1H,3H,7H,9H) -tetraone products1H nuclear magnetic resonance (1H-NMR) spectrum; FIG. 6 shows 1,3,7, 9-tetramethyl-5- (6-methoxyquinolin-2-yl) -pyridine [2,3-d:6,5-d']Process for preparing dipyrimidine-2, 4,6,8(1H,3H,7H,9H) -tetraone products13C nuclear magnetic resonance (13C-NMR) spectrum.
The characterization data are1H NMR(CDCl3,400MHz,ppm):δ＝8.18(d,J＝8.0Hz,1H),7.91(d,J＝9.2Hz,1H),7.39–7.34(m,2H),7.20–7.19(m,1H),3.95(s,3H),3.79(s,6H),3.26(s,6H)；13C NMR(CDCl3,100MHz,ppm):δ＝159.1,157.8,157.3,154.1,153.6,150.9,143.6,134.1,130.4,128.2,122.1,120.4,106.0,105.2,55.6,30.4,28.5。
The 1,3,7, 9-tetramethyl-5- (6-methoxyquinolin-2-yl) -pyridin [2,3-d:6,5-d' ] bipyrimidinyl-2, 4,6,8(1H,3H,7H,9H) -tetraone compound prepared in example 3 has the following structural formula:
example 4
6-chloro-2-methylquinoline (0.3mmoL,53.1mg), 1, 3-dimethyl-6-semicarbazide-pyrimidine (0.6mmoL,93.1mg), 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 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 1,3,7, 9-tetramethyl-5- (6-chloroquinolin-2-yl) -pyridine [2,3-d:6,5-d' ] bipyrimidine-2, 4,6,8(1H,3H,7H,9H) -tetraone compound in 43% yield.
Subjecting the obtained product 1,3,7, 9-tetramethyl-5- (6-chloroquinolin-2-yl) -pyridine [2,3-d:6,5-d 'to nuclear magnetic resonance spectroscopy']The structural analysis of the dipyrimidine-2, 4,6,8(1H,3H,7H,9H) -tetraone product is shown in the figure 7-8. FIG. 7 shows 1,3,7, 9-tetramethyl-5- (6-chloroquinolin-2-yl) -pyridine [2,3-d:6,5-d']Process for preparing dipyrimidine-2, 4,6,8(1H,3H,7H,9H) -tetraone products1H nuclear magnetic resonance (1H-NMR) spectrum; FIG. 8 shows 1,3,7, 9-tetramethyl-5- (6-chloroquinolin-2-yl) -pyridine [2,3-d:6,5-d']Process for preparing dipyrimidine-2, 4,6,8(1H,3H,7H,9H) -tetraone products13C nuclear magnetic resonance (13C-NMR) spectrum.
The characterization data are1HNMR(CDCl3,400MHz,ppm):δ＝8.20(d,J＝8.8Hz,1H),7.95–7.91(m,2H),7.66–7.63(m,1H),7.44(d,J＝8.4Hz,1H),3.80(s,6H),3.26(s,6H)；13C NMR(CDCl3,100MHz,ppm):δ＝159.2,157.2,156.6,153.7,150.8,145.9,134.3,132.3,130.7,130.5,127.9,126.9,121.2,105.1,30.5,28.6。
The 1,3,7, 9-tetramethyl-5- (6-chloroquinolin-2-yl) -pyridine [2,3-d:6,5-d' ] bipyrimidinyl-2, 4,6,8(1H,3H,7H,9H) -tetraone compound prepared in example 4 has the following structural formula:
example 5
6-bromo-2-methylquinoline (0.3mmoL,66.3mg), 1, 3-dimethyl-6-semicarbazide-pyrimidine (0.6mmoL,93.1mg), 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 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 1,3,7, 9-tetramethyl-5- (6-bromoquinolin-2-yl) -pyridine [2,3-d:6,5-d' ] bipyrimidine-2, 4,6,8(1H,3H,7H,9H) -tetraone compound in 60% yield.
Subjecting the obtained product 1,3,7, 9-tetramethyl-5- (6-bromoquinolin-2-yl) -pyridine [2,3-d:6,5-d 'to nuclear magnetic resonance spectroscopy']The structural analysis of the dipyrimidine-2, 4,6,8(1H,3H,7H,9H) -tetraone product is shown in the figure 9-10. FIG. 9 is 1,3,7, 9-tetramethyl-5- (6-bromoquinolin-2-yl) -pyridine [2,3-d:6,5-d']Process for preparing dipyrimidine-2, 4,6,8(1H,3H,7H,9H) -tetraone products1H nuclear magnetic resonance (1H-NMR) spectrum; FIG. 10 is 1,3,7, 9-tetramethyl-5- (6-bromoquinolin-2-yl) -pyridine [2,3-d:6,5-d']Process for preparing dipyrimidine-2, 4,6,8(1H,3H,7H,9H) -tetraone products13C nuclear magnetic resonance (13C-NMR) spectrum.
The characterization data are1H NMR(CDCl3,400MHz,ppm):δ＝8.19(d,J＝8.0Hz,1H),8.09–8.08(m,1H),7.88(d,J＝8.8Hz,1H),7.79–7.76(m,1H),7.44(d,J＝8.4Hz,1H),3.80(s,6H),3.26(s,6H)；13C NMR(CDCl3,100MHz,ppm):δ＝159.2,157.4,156.5,153.7,150.8,146.1,134.2,133.1,130.8,130.2,128.4,121.2,120.4,105.1,30.5,28.6。
The 1,3,7, 9-tetramethyl-5- (6-bromoquinolin-2-yl) -pyridine [2,3-d:6,5-d' ] bipyrimidinyl-2, 4,6,8(1H,3H,7H,9H) -tetraone compound prepared in example 5 has the following structural formula:
the reaction time of the electrified stirring in the embodiment of the invention can be any, the pyridine [2,3-d:6,5-d' ] bipyrimidine-2, 4,6,8(1H,3H,7H,9H) -tetraone compound can be prepared as long as the power is electrified, the optimal power-on time is about 18H, and the yield of the obtained product is highest. The pyridine [2,3-d:6,5-d' ] bipyrimidine-2, 4,6,8(1H,3H,7H,9H) -tetrone compound can be prepared at any other time, only the yield is changed, the yield is gradually increased from the start of electrifying to 18H, and when the yield is decreased for more than 18H, the generated product is possibly converted into other byproducts due to overlong electrifying catalysis time.
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 electrosynthesis method of a pyridine [2,3-d:6,5-d' ] bipyrimidine-2, 4,6,8(1H,3H,7H,9H) -tetraone compound is characterized by comprising the following steps:
(1) electrocatalytic reaction: respectively adding electrolyte, 2-methylquinoline compound, 1, 3-dimethyl-6-semicarbazide compound and 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 pyridine [2,3-d:6,5-d' ] bipyrimidine-2, 4,6,8(1H,3H,7H,9H) -tetraone compounds;
the pyridine [2,3-d:6,5-d' ] bipyrimidine-2, 4,6,8(1H,3H,7H,9H) -tetraone compound has the following structure:
wherein R is1Is hydrogen, C1～C5Alkyl radical, C1～C5One or more of alkoxy, halogen; r2Is C1～C5An alkyl group; r3Is C1～C5Alkyl radical。
2. The electrosynthesis method as defined in claim 1, wherein: the 2-methylquinoline compound has the following structure:
wherein R is1Is hydrogen, C1～C5Alkyl radical, C1～C5One or more of alkoxy and halogen.
3. The electrosynthesis method as defined in claim 1, wherein: the 1, 3-dimethyl-6-semicarbazine compound has the following structure:
wherein R is2Is C1～C5An alkyl group; r3Is C1～C5An alkyl group.
4. The electrosynthesis method as defined in claim 1, wherein: the mass ratio of the 2-methylquinoline compound to the 1, 3-dimethyl-6-semicarbazide compound is 1: 1-1: 4.
5. The electrosynthesis method as defined in claim 1, wherein: the initial concentration of the 2-methylquinoline compound is 0.05-0.2 mol/L.
6. The electrosynthesis method as defined in claim 1, wherein: 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 electrosynthesis method as defined in claim 1, wherein: the temperature of the stirring reaction is 0-140 ℃.
8. The electrosynthesis method as defined in claim 1, wherein: the solvent is one of dimethyl sulfoxide, N-dimethylformamide, N-methylpyrrolidone, N-dimethylacetamide, acetonitrile, water and 1, 2-dichloroethane.
9. The electrosynthesis method as defined in claim 1, wherein: the catalytic electrode is a conventional electrode material.
10. The electrosynthesis method as defined in claim 1, wherein: the separation and purification method is one of column chromatography, liquid chromatography, distillation and recrystallization separation.
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