CN113563391A - Method for synthesizing ferrocenyl coumarin quinoline compound by using composite catalyst - Google Patents
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- -1 coumarin quinoline compound Chemical class 0.000 title claims abstract description 35
- 238000000034 method Methods 0.000 title claims abstract description 27
- 239000003054 catalyst Substances 0.000 title claims abstract description 25
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 19
- 239000002131 composite material Substances 0.000 title claims abstract description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims abstract description 45
- GLNDAGDHSLMOKX-UHFFFAOYSA-N coumarin 120 Chemical compound C1=C(N)C=CC2=C1OC(=O)C=C2C GLNDAGDHSLMOKX-UHFFFAOYSA-N 0.000 claims abstract description 20
- 150000003934 aromatic aldehydes Chemical class 0.000 claims abstract description 18
- 238000010438 heat treatment Methods 0.000 claims abstract description 7
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000002994 raw material Substances 0.000 claims abstract description 6
- 238000010898 silica gel chromatography Methods 0.000 claims abstract description 5
- 239000002904 solvent Substances 0.000 claims abstract description 5
- 238000001816 cooling Methods 0.000 claims abstract description 4
- 238000002156 mixing Methods 0.000 claims abstract description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 24
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 24
- 230000035484 reaction time Effects 0.000 claims description 6
- 239000003480 eluent Substances 0.000 claims description 4
- 238000004440 column chromatography Methods 0.000 claims description 3
- 239000011259 mixed solution Substances 0.000 claims description 3
- 238000006555 catalytic reaction Methods 0.000 abstract description 5
- WIKZKBCBKLFMSZ-UHFFFAOYSA-N chromen-2-one;quinoline Chemical class N1=CC=CC2=CC=CC=C21.C1=CC=C2OC(=O)C=CC2=C1 WIKZKBCBKLFMSZ-UHFFFAOYSA-N 0.000 abstract description 5
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 abstract description 4
- 238000010490 three component reaction Methods 0.000 abstract description 4
- 238000010992 reflux Methods 0.000 abstract description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 28
- 238000005481 NMR spectroscopy Methods 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 11
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- 238000004896 high resolution mass spectrometry Methods 0.000 description 9
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
- 229910052799 carbon Inorganic materials 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 8
- 238000001819 mass spectrum Methods 0.000 description 8
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 238000001228 spectrum Methods 0.000 description 8
- 238000013313 FeNO test Methods 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 4
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 230000001766 physiological effect Effects 0.000 description 4
- SMQUZDBALVYZAC-UHFFFAOYSA-N salicylaldehyde Chemical compound OC1=CC=CC=C1C=O SMQUZDBALVYZAC-UHFFFAOYSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 3
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical group [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 3
- GVOISEJVFFIGQE-YCZSINBZSA-N n-[(1r,2s,5r)-5-[methyl(propan-2-yl)amino]-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](N(C)C(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 GVOISEJVFFIGQE-YCZSINBZSA-N 0.000 description 3
- GOLORTLGFDVFDW-UHFFFAOYSA-N 3-(1h-benzimidazol-2-yl)-7-(diethylamino)chromen-2-one Chemical compound C1=CC=C2NC(C3=CC4=CC=C(C=C4OC3=O)N(CC)CC)=NC2=C1 GOLORTLGFDVFDW-UHFFFAOYSA-N 0.000 description 2
- BGNGWHSBYQYVRX-UHFFFAOYSA-N 4-(dimethylamino)benzaldehyde Chemical compound CN(C)C1=CC=C(C=O)C=C1 BGNGWHSBYQYVRX-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- HYBBIBNJHNGZAN-UHFFFAOYSA-N furfural Chemical compound O=CC1=CC=CO1 HYBBIBNJHNGZAN-UHFFFAOYSA-N 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- HZXJVDYQRYYYOR-UHFFFAOYSA-K scandium(iii) trifluoromethanesulfonate Chemical compound [Sc+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F HZXJVDYQRYYYOR-UHFFFAOYSA-K 0.000 description 2
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 2
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 2
- 235000012141 vanillin Nutrition 0.000 description 2
- FPYUJUBAXZAQNL-UHFFFAOYSA-N 2-chlorobenzaldehyde Chemical compound ClC1=CC=CC=C1C=O FPYUJUBAXZAQNL-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- PHSMPGGNMIPKTH-UHFFFAOYSA-K cerium(3+);trifluoromethanesulfonate Chemical compound [Ce+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F PHSMPGGNMIPKTH-UHFFFAOYSA-K 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 229960000956 coumarin Drugs 0.000 description 1
- 235000001671 coumarin Nutrition 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F17/00—Metallocenes
- C07F17/02—Metallocenes of metals of Groups 8, 9 or 10 of the Periodic Table
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0215—Sulfur-containing compounds
- B01J31/0225—Sulfur-containing compounds comprising sulfonic acid groups or the corresponding salts
- B01J31/0227—Sulfur-containing compounds comprising sulfonic acid groups or the corresponding salts being perfluorinated, i.e. comprising at least one perfluorinated moiety as substructure in case of polyfunctional compounds
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J35/00—Catalysts, in general, characterised by their form or physical properties
- B01J35/19—Catalysts containing parts with different compositions
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
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Abstract
The invention discloses a method for synthesizing ferrocenyl coumarin quinoline compound by using a composite catalyst, which comprises the following steps: taking ferroceneacetylene, aromatic aldehyde and 4-methyl-7-aminocoumarin as raw materials, and Ce (OTf)3And Sc (OTf)3Mixing ferroceneacetylene, aromatic aldehyde, 4-methyl-7-aminocoumarin, Ce (OTf)3、Sc(OTf)3And toluene, heating in an oil bath for a period of time, cooling to room temperature, concentrating the solvent, and purifying the residue by silica gel column chromatography to obtain the ferrocenyl coumarin quinoline compound. The method takes 4-methyl-7-aminocoumarin, aromatic aldehyde and ferrocenyl acetylene as raw materials and adopts Ce (OTf)3And Sc (OTf)3As a composite catalyst, the Povarov three-component reaction is realized under the condition of heating reflux, a plurality of ferrocenyl coumarin quinoline compounds are efficiently synthesized by catalysis, and the yield is highCan reach 40.0-66.8%, and the efficiency and yield are obviously improved compared with single catalyst catalysis method.
Description
Technical Field
The invention relates to the field of organic synthesis, and in particular relates to a method for synthesizing a ferrocenyl coumarin quinoline compound by using a composite catalyst.
Background
Currently, modification of natural framework structures, especially integration of various natural framework structures or functional groups, has become a hot spot in the field of organic synthesis research today. The coumarin and quinoline compounds respectively have natural structural frameworks of oxygen heterocycle and nitrogen heterocycle, related compounds are widely present in various natural products, and have various physiological and pharmacological activities of oxidation resistance, tumor resistance, antibiosis and the like.
The ferrocene group is a metal organic functional group, and the derivative thereof also has various physiological and pharmacological activities, so that the coumarin, quinoline and ferrocene groups are integrated into one molecule, and a novel compound with higher physiological and pharmacological activity performance can be developed.
However, the synthesis and biological performance studies of integrating coumarin, quinoline and ferrocene groups into one molecule are reported at home and abroad so far. In recent years, there has been a study on the Povarov three-component reaction, which is reported in Ce (OTf)3Is a single catalyst for catalyzing 4-methyl-7-aminocoumarin and arylThe ferrocenyl coumarin quinoline compound is synthesized by vanillin and ferrocenyl acetylene, and is found to have certain free radical capturing performance, but the synthesis yield is not high and is only 24% -62%.
Therefore, how to provide a method for efficiently synthesizing ferrocenyl coumarin quinoline compounds is a technical problem to be solved urgently in the field.
Disclosure of Invention
The invention aims to provide a novel technical scheme of a method for efficiently synthesizing ferrocenyl coumarin quinoline compounds by using a composite catalyst.
According to a first aspect of the present invention, there is provided a method for synthesizing a ferrocenyl coumarinoquinoline compound using a composite catalyst.
The method for synthesizing the ferrocenyl coumarin quinoline compound by using the composite catalyst comprises the following steps:
taking ferroceneacetylene, aromatic aldehyde and 4-methyl-7-aminocoumarin as raw materials, and Ce (OTf)3And Sc (OTf)3Mixing ferroceneacetylene, aromatic aldehyde, 4-methyl-7-aminocoumarin, Ce (OTf)3、Sc(OTf)3And toluene, heating in an oil bath for a period of time, cooling to room temperature, concentrating the solvent, and purifying the residue by silica gel column chromatography to obtain the ferrocenyl coumarin quinoline compound.
Optionally, ferroceneacetylene, aromatic aldehyde, 4-methyl-7-aminocoumarin, Ce (OTf)3、Sc(OTf)3The molar ratio of toluene to toluene is 100 (90-150): 80-150): 3-8): 4000-5000.
Optionally, ferroceneacetylene, aromatic aldehyde, 4-methyl-7-aminocoumarin, Ce (OTf)3、Sc(OTf)3And toluene at a molar ratio of 100:120:120:5:5: 4700.
Optionally, the oil bath temperature is 50-120 ℃.
Alternatively, the oil bath temperature is 110 ℃.
Optionally, the reaction time is 1-4 h.
Optionally, the reaction time is 2 h.
Optionally, the eluent for column chromatography is a mixed solution of dichloromethane and ethyl acetate.
Optionally, the volume ratio of dichloromethane to ethyl acetate is 20: 1.
The method takes 4-methyl-7-aminocoumarin, aromatic aldehyde and ferrocenyl acetylene as raw materials and adopts Ce (OTf)3And Sc (OTf)3As a composite catalyst, Povarov three-component reaction is realized under the condition of heating reflux, a plurality of ferrocenyl coumarin quinoline compounds are synthesized by high-efficiency catalysis, the yield can reach 40.0-66.8%, and the efficiency and the yield are obviously improved compared with a single catalyst catalysis method.
Other features of the present invention and advantages thereof will become apparent from the following detailed description of exemplary embodiments thereof, which proceeds with reference to the accompanying drawings.
Drawings
The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and together with the description, serve to explain the principles of the invention.
FIG. 1 is a NMR spectrum of 4-methyl-6-ferrocenyl-8-phenylcoumarinoquinoline (1 a);
FIG. 2 is a NMR carbon spectrum of 4-methyl-6-ferrocenyl-8-phenylcoumarinoquinoline (1 a);
FIG. 3 is a mass spectrum of 4-methyl-6-ferrocenyl-8-phenylcoumarinoquinoline (1 a);
FIG. 4 is a NMR spectrum of 4-methyl-6-ferrocenyl-8-furanylcoumarinoquinoline (1 b);
FIG. 5 is a NMR carbon spectrum of 4-methyl-6-ferrocenyl-8-furanylcoumarinoquinoline (1 b);
FIG. 6 is a mass spectrum of 4-methyl-6-ferrocenyl-8-furanylcoumarinoquinoline (1 b);
FIG. 7 is a NMR spectrum of 4-methyl-6, 8-diferrocenyl coumarinoquinoline (1 c);
FIG. 8 is a NMR carbon spectrum of 4-methyl-6, 8-diferrocenyl coumarinoquinoline (1 c);
FIG. 9 is a mass spectrum of 4-methyl-6, 8-diferrocenyl coumarinoquinoline (1 c);
FIG. 10 is a NMR spectrum of 4-methyl-6-ferrocenyl-8- (4-dimethylaminophenyl) coumarinoquinoline (1 d);
FIG. 11 is a NMR carbon spectrum of 4-methyl-6-ferrocenyl-8- (4-dimethylaminophenyl) coumarinoquinoline (1 d);
FIG. 12 is a mass spectrum of 4-methyl-6-ferrocenyl-8- (4-dimethylaminophenyl) coumarinoquinoline (1 d);
FIG. 13 is a NMR spectrum of 4-methyl-6-ferrocenyl-8- (2-methoxyphenyl) coumarinoquinoline (1 e);
FIG. 14 is a NMR carbon spectrum of 4-methyl-6-ferrocenyl-8- (2-methoxyphenyl) coumarinoquinoline (1 e);
FIG. 15 is a mass spectrum of 4-methyl-6-ferrocenyl-8- (2-methoxyphenyl) coumarinoquinoline (1 e);
FIG. 16 is a NMR spectrum of 4-methyl-6-ferrocenyl-8- (2-chlorophenyl) coumarinoquinoline (1 f);
FIG. 17 is a NMR carbon spectrum of 4-methyl-6-ferrocenyl-8- (2-chlorophenyl) coumarinoquinoline (1 f);
FIG. 18 is a mass spectrum of 4-methyl-6-ferrocenyl-8- (2-chlorophenyl) coumarinoquinoline (1 f);
FIG. 19 is a NMR spectrum of 4-methyl-6-ferrocenyl-8- (2-hydroxyphenyl) coumarinoquinoline (1 g);
FIG. 20 is a NMR carbon spectrum of 4-methyl-6-ferrocenyl-8- (2-hydroxyphenyl) coumarinoquinoline (1 g);
FIG. 21 is a mass spectrum of 4-methyl-6-ferrocenyl-8- (2-hydroxyphenyl) coumarinoquinoline (1 g);
FIG. 22 is a NMR spectrum of 4-methyl-6-ferrocenyl-8- (3-methoxy-4-hydroxyphenyl) coumarinoquinoline (1 h);
FIG. 23 is a NMR carbon spectrum of 4-methyl-6-ferrocenyl-8- (3-methoxy-4-hydroxyphenyl) coumarinoquinoline (1 h);
FIG. 24 is a mass spectrum of 4-methyl-6-ferrocenyl-8- (3-methoxy-4-hydroxyphenyl) coumarinoquinoline (1 h).
Detailed Description
Various exemplary embodiments of the present invention will now be described in detail with reference to the accompanying drawings. It should be noted that: the relative arrangement of the components and steps, the numerical expressions and numerical values set forth in these embodiments do not limit the scope of the present invention unless specifically stated otherwise.
The following description of at least one exemplary embodiment is merely illustrative in nature and is in no way intended to limit the invention, its application, or uses.
Techniques, methods, and apparatus known to those of ordinary skill in the relevant art may not be discussed in detail but are intended to be part of the specification where appropriate.
In all examples shown and discussed herein, any particular value should be construed as merely illustrative, and not limiting. Thus, other examples of the exemplary embodiments may have different values.
The invention provides a method for synthesizing ferrocenyl coumarin quinoline compound by using a composite catalyst, which comprises the following steps:
taking ferroceneacetylene, aromatic aldehyde and 4-methyl-7-aminocoumarin as raw materials, and Ce (OTf)3And Sc (OTf)3Mixing ferroceneacetylene, aromatic aldehyde, 4-methyl-7-aminocoumarin, Ce (OTf)3、Sc(OTf)3And toluene, heating in an oil bath for a period of time, cooling to room temperature, concentrating the solvent, and purifying the residue by silica gel column chromatography to obtain the ferrocenyl coumarin quinoline compound.
During the reaction, the reaction was monitored by TLC in real time.
The reaction process is as follows:
at least 8 ferrocenyl coumarin quinoline compounds can be obtained by reaction, wherein R is C6H5-、2-C4H3O-、C5H5FeC5H4-、4-N(CH3)2C6H4-、2-CH3OC6H4-、2-ClC6H4-、2-HOC6H4-、3-CH3O-4-HOC6H3-. The ferrocenyl coumarin quinoline compound has higher physiological and pharmacological activities of oxidation resistance, tumor resistance, antibiosis and the like, and has certain capacity of capturing free radicals.
Ferroceneacetylenes, aromatic aldehydes, 4-methyl-7-aminocoumarin, Ce (OTf)3、Sc(OTf)3The molar ratio of toluene to toluene can be 100 (90-150): 80-150): 3-8): 4000-5000.
Ferroceneacetylenes, aromatic aldehydes, 4-methyl-7-aminocoumarin, Ce (OTf)3、Sc(OTf)3The molar ratio to toluene may be 100:120:120:5:5: 4700.
The oil bath temperature can be 50-120 ℃.
The oil bath temperature may be 110 ℃.
The reaction time can be 1-4 h.
The reaction time may be 2 h.
The eluent for column chromatography can be a mixed solution of dichloromethane and ethyl acetate.
Further, the volume ratio of dichloromethane to ethyl acetate may be 20: 1.
The experimental procedures used in the examples below are conventional unless otherwise specified, the materials and reagents used therein are commercially available, and the equipment used in the experiments are well known to those skilled in the art without otherwise specified.
The main experimental reagents and instruments are as follows: 4-methyl-7-aminobenzopyrone, toluene, cerium trifluoromethanesulfonate, scandium trifluoromethanesulfonate, benzaldehyde, furfural, ferrocenecarboxaldehyde, 4-dimethylaminobenzaldehyde, salicylaldehyde, 2-chlorobenzaldehyde, 2-benzaldehyde, 2-hydroxybenzaldehyde, vanillin, dichloromethane, ethyl acetate, an electronic balance, a rotary evaporator, an oil bath, a Bruker Avance III 400MHz nuclear magnetic resonance spectrometer (Bruker, USA), and an ultra performance liquid chromatography-electrospray ion source-mass spectrometer (Agilent technologies, Inc.).
Examples
Adding 0.42g (2.0mmol) of ferroceneethyne, 2.4mmol of aromatic aldehyde, 0.42g (2.4mmol) of 4-methyl-7-aminocoumarin, Ce (OTf)3 0.06g(0.1mmol)、Sc(OTf)30.05g (0.1mmol) and 10mL of toluene were charged into a 25mL round-bottom flask and reacted at reflux (110 ℃ C.) with stirring for 2h (TLC detection). Cooled to room temperature, the solvent was concentrated, and the residue was purified by silica gel column chromatography [ eluent: v (dichloromethane)/V (ethyl acetate) ═ 20/1]Purifying to obtain 1a-1h, wherein the yield is more than 40%.
The reaction process is as follows:
the obtained target compound 1a-1h structure is detected by a Bruker Avance III 400MHz nuclear magnetic resonance spectrometer (Bruker company in America) and an ultra-high performance liquid chromatography-electrospray ion source-mass spectrometer (Agilent technologies, Inc.),1H NMR、13c NMR and HR-MS are shown in the figure.
Structural characterization data for ferrocenyl coumarinoquinoline compounds (1a-1 h):
4-methyl-6-ferrocenyl-8-phenylcoumarinoquinoline (1 a): a solid in color, the yield is 64.8 percent, and the m.p.218-220 ℃;1H NMR(400MHz,CDCl3)δ:8.68(s,1H),8.27(s,2H),8.10(s,1H),7.82(s,1H),7.60(d,J＝6.0Hz,2H),7.54(t,J＝6.8Hz,1H),6.27(s,1H),4.71(s,2H),4.53(s,2H),4.22(s,5H),2.51(s,3H)；13C NMR(100MHz,CDCl3)δ:159.2,157.3,152.6,150.9,130.1,129.1,127.5,126.3,124.8,124.1,117.1,115.8,114.4,88.4,72.3,69.9,68.5,19.5；HR-MS(ESI)m/z:Calcd for C29H21FeNO2{[M+H]+}472.100 0,found 472.103 8。
4-methyl-6-ferrocenyl-8-furanylcoumarinoquinoline (1 b): yellow solid, yield 59.7%, m.p.253-255 ℃;1H NMR(400MHz,CDCl3)δ:8.63(s,1H),7.99(d,J＝8.8Hz,1H),7.79(d,J＝9.2Hz,1H),7.71(s,1H),7.34(s,1H),6.66-6.67(m,1H),6.25(s,1H),4.69(s,2H),4.51(s,2H),4.23(s,5H),2.49(s,3H)；13C NMR(100MHz,CDCl3)δ:159.2,153.2,152.5,150.9,149.1,147.5,144.7,126.1,124.1,123.3,117.0,115.6,114.3,112.5,111.1,88.4,72.2,69.9,68.3,19.5；HR-MS(ESI)m/z:Calcd for C27H19FeNO3{[M+H]+}462.079 3,found 462.083 9。
4-methyl-6, 8-diferrocenyl coumarinoquinoline (1 c): red solid, yield 62.2%, m.p.242-244 ℃;1H NMR(400MHz,CDCl3)δ:8.30(s,1H),7.94(s,1H),7.76(s,1H),6.24(s,1H),5.17(s,2H),4.70(s,2H),4.58(s,2H),4.53(s,2H),4.29(s,5H),4.15(s,5H),2.49(s,3H)；13C NMR(100MHz,CDCl3)δ:160.5,159.5,152.7,151.1,145.5,145.4,125.9,125.1,123.7,116.4,115.2,113.8,88.8,72.3,71.0,69.9,69.8,68.2,68.1,19.5；HR-MS(ESI)m/z:Calcd for C33H25Fe2NO2{[M+H]+}580.066 2,found 580.072 7。
4-methyl-6-ferrocenyl-8- (4-dimethylaminophenyl) coumarinoquinoline (1 d): yellow solid, yield 47.7%, m.p.285-287 ℃;1H NMR(400MHz,CDCl3)δ:8.53(s,1H),8.27(s,3H),7.81(s,1H),6.91(s,2H),6.27(s,1H),4.79(s,2H),4.58(s,2H),4.30(s,5H),3.12(s,6H),2.51(s,3H)；13C NMR(100MHz,CDCl3)δ:159.5,152.6,151.8,151.0,128.6,127.7,125.9,124.0,123.8,120.9,116.4,115.2,113.8,112.3,89.0,72.2,69.8,68.2,40.3,19.5；HR-MS(ESI)m/z:Calcd for C31H26FeN2O2{[M+H]+}515.142 2,found 515.148 5。
4-methyl-6-ferrocenyl-8- (2-methoxyphenyl) coumarinoquinoline (1 e): yellow solid, yield 66.8%, m.p.214-216 ℃;1H NMR(400MHz,CDCl3)δ:8.69(s,1H),8.12(s,1H),7.91(d,J＝7.2Hz,1H),7.81(d,J＝6.0Hz,1H),7.49(t,J＝7.6Hz,1H),7.18(t,J＝7.6Hz,1H),7.12(d,J＝8.4Hz,1H),6.28(s,1H),4.67(s,2H),4.50(s,2H),4.24(s,5H),3.97(s,3H),2.51(s,3H)；13C NMR(100MHz,CDCl3)δ:159.4,157.4,157.3,152.6,151.0,150.6,145.9,131.9,130.9,128.9,128.7,126.5,123.5,121.4,117.0,115.7,114.3,111.5,88.1,72.3,69.8,68.3,55.5,19.5；HR-MS(ESI)m/z:Calcd for C30H23FeNO3{[M+H]+}502.110 6,found 502.117 3。
4-methyl-6-ferrocenyl-8- (2-chlorophenyl) coumarinoquinoline (1 f): yellow solid, yield 66.3%, m.p.243-245 ℃;1H NMR(400MHz,CDCl3)δ:8.54(s,1H),8.05(d,J＝8.8Hz,1H),7.84(d,J＝8.8Hz,1H),7.79(dd,J＝2.4Hz,J＝6.8Hz,1H),7.58(dd,J＝2.0Hz,J＝7.2Hz,1H),7.42-7.49(m,2H),6.29(s,1H),4.69(s,2H),4.51(s,2H),4.19(s,5H),2.52(s,3H)；13C NMR(100MHz,CDCl3)δ:159.2,157.8,152.6,151.1,150.4,146.9,138.9,132.3,131.8,130.5,130.4,128.3,127.4,126.6,124.0,117.3,116.1,114.7,87.9,72.4,69.9,68.6,19.6；HR-MS(ESI)m/z:Calcd for C29H20ClFeNO2{[M+H]+}506.061 0,found 506.065 9。
4-methyl-6-ferrocenyl-8- (2-hydroxyphenyl) coumarinoquinoline (1 g): yellow solid, yield 48.3%, m.p.248-250 ℃;1H NMR(400MHz,CDCl3)δ:8.81(s,1H),8.08(s,1H),7.96(d,J＝6.8Hz,1H),7.80(s,1H),7.37(t,J＝7.2Hz,1H),7.13(d,J＝8.0Hz,1H),7.05(t,J＝7.2Hz,1H),6.29(s,1H),4.74(s,2H),4.57(s,2H),4.12(s,5H),2.49(s,3H)；13C NMR(100MHz,CDCl3)δ:158.9,152.4,150.8,148.8,148.8,147.4,125.1,123.9,123.8,123.8,123.8,116.2,114.8,88.4,72.6,70.1,68.8,19.7；HR-MS(ESI)m/z:Calcd for C29H21FeNO3{[M+H]+}488.094 9,found 488.098 7。
4-methyl-6-ferrocenyl-8- (3-methoxy-4-hydroxyphenyl) coumarinoquinoline (1 h): yellow solid, yield 47.4%, m.p.281-283 ℃;1H NMR(400MHz,DMSO-d6)δ:9.63(s,1H),8.68(s,1H),7.97(dd,J＝8.8Hz,J＝16.8Hz,2H),7.93(d,J＝2.0Hz,1H),7.86(dd,J＝2.0Hz,J＝8.4Hz,1H),7.02(d,J＝8.0Hz,1H),6.38(d,J＝1.2Hz,1H),4.87(s,2H),4.46(s,2H),4.19(s,5H),3.97(s,3H),3.32(s,3H)；13C NMR(100MHz,DMSO-d6)δ:158.9,156.3,153.9,150.9,150.5,149.6,148.5,147.0,129.4,126.1,125.3,124.1,121.0,116.4,116.0,115.7,114.0,111.2,88.1,72.5,70.3,68.4,56.1,19.3；HR-MS(ESI)m/z:Calcd for C30H23FeNO4{[M+H]+}518.105 5,found 518.109 2。
the effect of reaction conditions on the yield of compound 1a was investigated using the synthesis example of compound 1a, and the results are shown in table 1.
TABLE 1 Effect of reaction conditions on 1a yield
As can be seen from Table 1, with Ce (OTf)3And Sc (OTf)3The compound catalyst is a composite catalyst, the reaction is carried out for 2 hours under the heating condition of 110 ℃, the method is a preferred method for synthesizing the target compound, and the yield of the compound 1a is 64.8 percent and is higher than that of a literature method. The reason is Ce (OTf)3And Sc (OTf)3Both have the function of catalyzing Povarov-3CR, the two have synergistic effect after being compounded, and the unique interaction can enhance the catalysis of each other and generate more than Ce (OTf)3And Sc (OTf)3The catalytic efficiency when the catalyst is used alone enables the reaction to be carried out in the positive direction, reduces the generation of byproducts and greatly improves the reaction efficiency of Povarov-3 CR.
The discovery of the present disclosure employs Ce (OTf)3And Sc (OTf)3The compound catalyst is used for catalyzing 4-methyl-7-aminocoumarin, aromatic aldehyde and ferrocenyl acetylene to generate Povarov three-component reaction, the yield of the synthesized ferrocenyl coumarin quinoline compound is obviously single catalyst reaction, the work efficiency is improved, the time is saved, the environment is protected, and the cost is reduced.
Although some specific embodiments of the present invention have been described in detail by way of examples, it should be understood by those skilled in the art that the above examples are for illustrative purposes only and are not intended to limit the scope of the present invention. It will be appreciated by those skilled in the art that modifications may be made to the above embodiments without departing from the scope and spirit of the invention. The scope of the invention is defined by the appended claims.
Claims (9)
1. A method for synthesizing ferrocenyl coumarin quinoline compound by using a composite catalyst is characterized by comprising the following steps:
taking ferroceneacetylene, aromatic aldehyde and 4-methyl-7-aminocoumarin as raw materials, and Ce (OTf)3And Sc (OTf)3Mixing ferroceneacetylene, aromatic aldehyde, 4-methyl-7-aminocoumarin, Ce (OTf)3、Sc(OTf)3And toluene, heating in an oil bath for a period of time, cooling to room temperature, concentrating the solvent, and purifying the residue by silica gel column chromatography to obtain the ferrocenyl coumarin quinoline compound.
2. The method for synthesizing ferrocenyl coumarin quinoline compound according to claim 1, wherein the ferrocene acetylene, the aromatic aldehyde, the 4-methyl-7-aminocoumarin, the Ce (OTf)3、Sc(OTf)3The molar ratio of toluene to toluene is 100 (90-150): 80-150): 3-8): 4000-5000.
3. The method for synthesizing ferrocenyl coumarin quinoline compound according to claim 2, wherein the ferrocene acetylene, the aromatic aldehyde, the 4-methyl-7-aminocoumarin, the Ce (OTf)3、Sc(OTf)3And toluene at a molar ratio of 100:120:120:5:5: 4700.
4. The method for synthesizing the ferrocenyl coumarin quinoline compound by using the composite catalyst as claimed in claim 1, wherein the oil bath temperature is 50-120 ℃.
5. The method for synthesizing the ferrocenyl coumarin quinoline compound with the composite catalyst as claimed in claim 4, wherein the oil bath temperature is 110 ℃.
6. The method for synthesizing a ferrocenyl coumarin quinoline compound using a composite catalyst as claimed in claim 1, wherein the reaction time is 1-4 hours.
7. The method for synthesizing a ferrocenyl coumarin quinoline compound using a composite catalyst according to claim 6, wherein the reaction time is 2 hours.
8. The method for synthesizing a ferrocenyl coumarin quinoline compound using a composite catalyst as claimed in claim 1, wherein the eluent for column chromatography is a mixed solution of dichloromethane and ethyl acetate.
9. The method for synthesizing a ferrocenyl coumarin quinoline compound using a composite catalyst according to claim 8, wherein a volume ratio of dichloromethane to ethyl acetate is 20: 1.
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