CN117903095A - 8 (E) -4- (3-aryl acryloyl) -7-hydroxycoumarin and preparation method thereof - Google Patents
8 (E) -4- (3-aryl acryloyl) -7-hydroxycoumarin and preparation method thereof Download PDFInfo
- Publication number
- CN117903095A CN117903095A CN202410036953.7A CN202410036953A CN117903095A CN 117903095 A CN117903095 A CN 117903095A CN 202410036953 A CN202410036953 A CN 202410036953A CN 117903095 A CN117903095 A CN 117903095A
- Authority
- CN
- China
- Prior art keywords
- reaction
- intermediate compound
- hydroxycoumarin
- solvent
- ethanol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000002360 preparation method Methods 0.000 title abstract description 8
- GHMLBKRAJCXXBS-UHFFFAOYSA-N resorcinol Chemical compound OC1=CC=CC(O)=C1 GHMLBKRAJCXXBS-UHFFFAOYSA-N 0.000 claims abstract description 16
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 claims abstract description 9
- 238000000034 method Methods 0.000 claims abstract description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 41
- 150000001875 compounds Chemical class 0.000 claims description 38
- -1 acetyl aromatic compound Chemical class 0.000 claims description 35
- 238000006243 chemical reaction Methods 0.000 claims description 35
- 239000007787 solid Substances 0.000 claims description 28
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 18
- 239000002904 solvent Substances 0.000 claims description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 12
- 239000012043 crude product Substances 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
- 238000010438 heat treatment Methods 0.000 claims description 9
- 239000005457 ice water Substances 0.000 claims description 9
- 238000003756 stirring Methods 0.000 claims description 9
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 8
- 239000003054 catalyst Substances 0.000 claims description 8
- 238000001035 drying Methods 0.000 claims description 8
- 238000001914 filtration Methods 0.000 claims description 8
- 238000010992 reflux Methods 0.000 claims description 8
- 238000005406 washing Methods 0.000 claims description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 claims description 6
- 239000000243 solution Substances 0.000 claims description 6
- 238000001816 cooling Methods 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 239000002244 precipitate Substances 0.000 claims description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 4
- 239000011259 mixed solution Substances 0.000 claims description 4
- 238000004440 column chromatography Methods 0.000 claims description 3
- 239000000706 filtrate Substances 0.000 claims description 3
- 239000011541 reaction mixture Substances 0.000 claims description 3
- 239000007810 chemical reaction solvent Substances 0.000 claims description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 2
- 229940043279 diisopropylamine Drugs 0.000 claims description 2
- 238000001704 evaporation Methods 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- 239000000376 reactant Substances 0.000 claims description 2
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 claims 1
- HSHNITRMYYLLCV-UHFFFAOYSA-N 4-methylumbelliferone Chemical class C1=C(O)C=CC2=C1OC(=O)C=C2C HSHNITRMYYLLCV-UHFFFAOYSA-N 0.000 abstract description 5
- 238000003786 synthesis reaction Methods 0.000 abstract description 5
- SXVYHPBYCWPTOE-UHFFFAOYSA-N (4-formyl-2-oxochromen-7-yl) acetate Chemical compound O=CC1=CC(=O)OC2=CC(OC(=O)C)=CC=C21 SXVYHPBYCWPTOE-UHFFFAOYSA-N 0.000 abstract description 3
- HXVZGASCDAGAPS-UHFFFAOYSA-N 4-methylumbelliferyl acetate Chemical compound CC1=CC(=O)OC2=CC(OC(=O)C)=CC=C21 HXVZGASCDAGAPS-UHFFFAOYSA-N 0.000 abstract description 3
- QBRWVMWVGKFOQS-UHFFFAOYSA-N 7-hydroxy-2-oxochromene-4-carbaldehyde Chemical compound O=CC1=CC(=O)OC2=CC(O)=CC=C21 QBRWVMWVGKFOQS-UHFFFAOYSA-N 0.000 abstract description 3
- 238000005882 aldol condensation reaction Methods 0.000 abstract description 3
- 238000009833 condensation Methods 0.000 abstract description 3
- 230000005494 condensation Effects 0.000 abstract description 3
- 238000005886 esterification reaction Methods 0.000 abstract description 3
- 238000006460 hydrolysis reaction Methods 0.000 abstract description 3
- 238000007254 oxidation reaction Methods 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 3
- 230000002194 synthesizing effect Effects 0.000 abstract description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 20
- 238000005481 NMR spectroscopy Methods 0.000 description 18
- 238000001228 spectrum Methods 0.000 description 15
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 9
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 8
- 238000004896 high resolution mass spectrometry Methods 0.000 description 8
- 229910052739 hydrogen Inorganic materials 0.000 description 8
- 239000001257 hydrogen Substances 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- 229910052799 carbon Inorganic materials 0.000 description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
- 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
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 230000001766 physiological effect Effects 0.000 description 3
- 238000000967 suction filtration Methods 0.000 description 3
- SULYEHHGGXARJS-UHFFFAOYSA-N 2',4'-dihydroxyacetophenone Chemical compound CC(=O)C1=CC=C(O)C=C1O SULYEHHGGXARJS-UHFFFAOYSA-N 0.000 description 2
- UCQUAMAQHHEXGD-UHFFFAOYSA-N 3',4'-dihydroxyacetophenone Chemical compound CC(=O)C1=CC=C(O)C(O)=C1 UCQUAMAQHHEXGD-UHFFFAOYSA-N 0.000 description 2
- 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
- NTPLXRHDUXRPNE-UHFFFAOYSA-N 4-methoxyacetophenone Chemical compound COC1=CC=C(C(C)=O)C=C1 NTPLXRHDUXRPNE-UHFFFAOYSA-N 0.000 description 2
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 2
- DQFBYFPFKXHELB-UHFFFAOYSA-N Chalcone Natural products C=1C=CC=CC=1C(=O)C=CC1=CC=CC=C1 DQFBYFPFKXHELB-UHFFFAOYSA-N 0.000 description 2
- 230000003064 anti-oxidating effect Effects 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- DFYRUELUNQRZTB-UHFFFAOYSA-N apocynin Chemical compound COC1=CC(C(C)=O)=CC=C1O DFYRUELUNQRZTB-UHFFFAOYSA-N 0.000 description 2
- 235000005513 chalcones Nutrition 0.000 description 2
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- IVSZLXZYQVIEFR-UHFFFAOYSA-N m-xylene Chemical group CC1=CC=CC(C)=C1 IVSZLXZYQVIEFR-UHFFFAOYSA-N 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- DQFBYFPFKXHELB-VAWYXSNFSA-N trans-chalcone Chemical compound C=1C=CC=CC=1C(=O)\C=C\C1=CC=CC=C1 DQFBYFPFKXHELB-VAWYXSNFSA-N 0.000 description 2
- ARKIFHPFTHVKDT-UHFFFAOYSA-N 1-(3-nitrophenyl)ethanone Chemical compound CC(=O)C1=CC=CC([N+]([O-])=O)=C1 ARKIFHPFTHVKDT-UHFFFAOYSA-N 0.000 description 1
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- ZWVHTXAYIKBMEE-UHFFFAOYSA-N 2-hydroxyacetophenone Chemical compound OCC(=O)C1=CC=CC=C1 ZWVHTXAYIKBMEE-UHFFFAOYSA-N 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 150000008375 benzopyrones Chemical class 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 150000001788 chalcone derivatives Chemical class 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229960000956 coumarin Drugs 0.000 description 1
- 235000001671 coumarin Nutrition 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- KLAKIAVEMQMVBT-UHFFFAOYSA-N p-hydroxy-phenacyl alcohol Natural products OCC(=O)C1=CC=C(O)C=C1 KLAKIAVEMQMVBT-UHFFFAOYSA-N 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
Landscapes
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
The invention belongs to the technical field of organic synthesis, and particularly relates to 8 (E) -4- (3-aryl acryloyl) -7-hydroxycoumarins and a preparation method thereof, wherein resorcinol and ethyl acetoacetate are used as raw materials, and the preparation method comprises the steps of firstly preparing the 4-methyl-7-hydroxycoumarins through Knoevenaga l condensation; secondly, synthesizing 4-methyl-7-acetoxycoumarin by adopting esterification reaction; thirdly, obtaining 4-formyl-7-acetoxycoumarin through oxidation reaction; fourthly, preparing 4-formyl-7-hydroxycoumarin by adopting hydrolysis reaction; finally, 8 (E) -4- (3-aryl acryloyl) -7-hydroxycoumarin are synthesized through aldol condensation reaction, and the method has potential application value.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to 8 (E) -4- (3-aryl acryloyl) -7-hydroxycoumarin and a preparation method thereof.
Background
The integration of various natural framework structures and functional groups into one molecule has become a hotspot in the field of current organic synthesis research. Coumarin and chalcone compounds have natural structure skeletons of benzopyrone and alpha, beta-unsaturated ketone respectively, are widely used in various natural products, and have various physiological and pharmacological activities such as antioxidation, antitumor, antibacterial and the like. The hydroxyl and ferrocene groups are functional groups, and the physiological and pharmacological activities such as antioxidation, anti-tumor, antibiosis and the like can be obviously improved by introducing the hydroxyl and ferrocene groups into the compound. Therefore, coumarin, chalcone, hydroxyl and ferrocenyl groups are integrated into one molecule, and a novel compound with higher physiological and pharmacological activity can be developed, so that the synthesis of the hydroxyl and ferrocenyl coumarin-chalcone compound is necessary to be carried out. However, no report has been made to compounds and syntheses of coumarin, chalcone, hydroxyl and ferrocene groups integrated into one molecule at home and abroad.
Disclosure of Invention
The invention aims to provide 8 (E) -4- (3-aryl acryloyl) -7-hydroxycoumarin and a preparation method thereof, wherein resorcinol and ethyl acetoacetate are used as raw materials, and the 8 (E) -4- (3-aryl acryloyl) -7-hydroxycoumarin is synthesized through five steps of condensation, esterification, oxidation, hydrolysis and aldol condensation of Knoevenagal.
In order to achieve the above purpose, the application is realized by the following technical scheme:
8 (E) -4- (3-aryl acryloyl) -7-hydroxy coumarin, the structural formulas are respectively as follows:
The preparation method of the (E) -4- (3-aryl acryloyl) -7-hydroxy coumarin comprises the following steps:
step 1), adding concentrated H 2SO4 into a reaction bottle, cooling to-5 ℃ in an ice bath, slowly dripping an acetoacetic ester solution of resorcinol into the cooled concentrated H 2SO4 under the stirring condition, keeping the reaction temperature to-5 ℃, continuously stirring for 1-4 hours at the temperature of <10 ℃ after the dripping is finished, then stirring for 10-30 hours after the dripping is finished, pouring into an ice-water mixture to precipitate, filtering and collecting the precipitate, washing with ice water, drying, and recrystallizing with 95% ethanol to obtain a white flocculent intermediate compound (1);
Step 2), sequentially adding the intermediate compound (1) and acetic anhydride into a reaction bottle, heating and refluxing for reaction for 1-4 hours, pouring the reaction mixture into ice water to separate out white solid after the reaction is finished, filtering and collecting the solid, washing with water, drying, and recrystallizing the crude product with 95% ethanol to obtain a white flaky solid intermediate compound (2);
Step 3), sequentially adding an intermediate compound (2), toluene, seO 2 and nitrogen into a reaction bottle, heating and refluxing for reaction for 12-24 hours under the protection of nitrogen, filtering while the reaction is hot after the reaction is finished, concentrating filtrate, and recrystallizing a crude product with 95% ethanol to obtain a pale yellow needle-shaped solid intermediate compound (3);
Step 4), sequentially adding an intermediate compound (3), a solvent and NH 4 OAc into a reaction bottle, reacting for 4-10 hours at room temperature, extracting a reaction solution with ethyl acetate after the reaction is finished, washing with water, drying with anhydrous sodium sulfate, evaporating the solvent under reduced pressure, and separating a crude product by column chromatography to obtain a pale yellow solid intermediate compound (4);
Step 5), sequentially adding an intermediate compound (4), an acetyl aromatic compound, a solvent and a catalyst into a reaction bottle, heating and refluxing for reaction for 4-8 h, cooling to room temperature after the reaction is finished, filtering to obtain a solid, washing with ethanol, drying, and recrystallizing a crude product with 95% ethanol to obtain the target compound (5).
Preferably, in step 1), concentrated H 2SO4 is both solvent and catalyst; resorcinol, ethyl acetoacetate and concentrated H 2SO4 in a molar ratio of 1: (1-1.2): (3-8).
Preferably, in step 2), acetic anhydride is both a solvent and a reactant; the molar ratio of the intermediate compound (1) to the acetic anhydride is 1: (3-10).
Preferably, in step 3), the molar ratio of intermediate compound (2) to SeO 2 is 1: (1-3), the solvent toluene needs to be dried in advance.
Preferably, in step 4), the molar ratio of intermediate compound (3) to NH 4 OAc is 1: (2-5); the solvent is a mixed solution of DMF and water or a mixed solution of DMSO and water.
Preferably, in step 5), the reaction solvent is one of methanol, ethanol or isopropanol; the catalyst is one of piperidine, diethylamine, triethylamine, pyridine or diisopropylamine; the molar ratio of the intermediate compound (4), the acetyl aromatic compound and the catalyst is 1: (1-1.2): (0.05-0.1).
The beneficial effects of the invention are as follows:
According to the technical scheme, resorcinol and ethyl acetoacetate are used as raw materials, and 4-methyl-7-hydroxycoumarin is prepared through Knoevenagal condensation; secondly, synthesizing 4-methyl-7-acetoxycoumarin by adopting esterification reaction; thirdly, obtaining 4-formyl-7-acetoxycoumarin through oxidation reaction; fourthly, preparing 4-formyl-7-hydroxycoumarin by adopting hydrolysis reaction; finally, 8 (E) -4- (3-aryl acryloyl) -7-hydroxycoumarin are synthesized through aldol condensation reaction, and the method has potential application value.
Drawings
FIG. 1 is a nuclear magnetic resonance hydrogen spectrum of (E) -4- (3-phenylpropenoyl) -7-hydroxycoumarin;
FIG. 2 is a nuclear magnetic resonance carbon spectrum of (E) -4- (3-phenylpropenoyl) -7-hydroxycoumarin;
FIG. 3 is a nuclear magnetic resonance hydrogen spectrum of (E) -4- (3-ferrocenyl-acryl) -7-hydroxycoumarin;
FIG. 4 is a nuclear magnetic resonance carbon spectrum of (E) -4- (3-ferrocenyl-acryl) -7-hydroxycoumarin;
FIG. 5 is a nuclear magnetic resonance hydrogen spectrum of (E) -4- (3- (4-methoxyphenyl) acryloyl) -7-hydroxycoumarin;
FIG. 6 is a nuclear magnetic resonance carbon spectrum of (E) -4- (3- (4-methoxyphenyl) acryloyl) -7-hydroxycoumarin;
FIG. 7 is a nuclear magnetic resonance hydrogen spectrum of (E) -4- (3- (3-nitrophenyl) acryloyl) -7-hydroxycoumarin;
FIG. 8 is a nuclear magnetic resonance carbon spectrum of (E) -4- (3- (3-nitrophenyl) acryloyl) -7-hydroxycoumarin;
FIG. 9 is a nuclear magnetic resonance hydrogen spectrum of (E) -4- (3- (2-hydroxyphenyl) acryloyl) -7-hydroxycoumarin;
FIG. 10 is a nuclear magnetic resonance carbon spectrum of (E) -4- (3- (2-hydroxyphenyl) acryloyl) -7-hydroxycoumarin;
FIG. 11 is a nuclear magnetic resonance hydrogen spectrum of (E) -4- (3- (3-methoxy-4-hydroxyphenyl) acryloyl) -7-hydroxycoumarin;
FIG. 12 is a nuclear magnetic resonance chromatogram of (E) -4- (3- (3-methoxy-4-hydroxyphenyl) acryloyl) -7-hydroxycoumarin;
FIG. 13 is a nuclear magnetic resonance hydrogen spectrum of (E) -4- (3, 4-dihydroxyphenyl) acryloyl) -7-hydroxycoumarin;
FIG. 14 is a nuclear magnetic resonance carbon spectrum of (E) -4- (3, 4-dihydroxyphenyl) acryloyl) -7-hydroxycoumarin;
FIG. 15 is a nuclear magnetic resonance hydrogen spectrum of (E) -4- (3- (2, 4-dihydroxyphenyl) acryloyl) -7-hydroxycoumarin;
FIG. 16 is a nuclear magnetic resonance carbon spectrum of (E) -4- (3- (2, 4-dihydroxyphenyl) acryloyl) -7-hydroxycoumarin.
Detailed Description
The following examples are given by way of illustration only and are not to be construed as limiting the scope of the invention.
Main experimental reagents and instruments:
Resorcinol, ethyl acetoacetate, H 2SO4, acetic anhydride, toluene, seO 2、NH4 OAc, anhydrous sodium sulfate, acetophenone, acetyl ferrocene, 4-methoxyacetophenone, 3-nitroacetophenone, 2-hydroxyacetophenone, 3-methoxy-4-hydroxyacetophenone, 3, 4-dihydroxyacetophenone, 2, 4-dihydroxyacetophenone, piperidine, ethanol, ethyl acetate, electronic balance, rotary evaporator, electromagnetic heating mantle, bruker AVANCE III MHz nuclear magnetic resonance spectrometer (Bruker Co., U.S.).
The structural formulas of the 8 (E) -4- (3-aryl acryloyl) -7-hydroxycoumarin are respectively as follows:
The preparation method of the (E) -4- (3-aryl acryloyl) -7-hydroxycoumarin comprises the following steps:
In a 250mL round bottom flask, 150mL of H 2SO4 (98%) was added and after cooling to-5-5℃in an ice bath, a solution of 33.0g (300 mmol) of m-xylene in 42.9g of ethyl acetoacetate (330 mmol) was slowly dropped into cooled concentrated H 2SO4 with stirring and the reaction temperature was maintained <10 ℃. After the end of the dropwise addition, stirring is continued for 4 hours at <10 ℃, then stirring is continued for 48 hours after the temperature is raised to room temperature, the mixture is poured into an ice-water mixture to separate out a precipitate, the precipitate is collected by suction filtration, washed by ice water and dried, and recrystallized by 95% ethanol, 45.9g of white flocculent intermediate compound (1) (4-methyl-7-hydroxycoumarin) is obtained, and the yield is 87%, m.p.182-184 ℃.
In a 250mL round bottom flask, 35.2g (200 mmol) of intermediate compound (1) and acetic anhydride (100 mL) were added, and after refluxing under heating for 4h, the reaction mixture was poured into ice water to precipitate a white solid. The solid was collected by suction filtration, washed with water and dried, and the crude product was recrystallized from 95% ethanol to give 42.3g of intermediate compound (2) (4-methyl-7-acetoxycoumarin) as a white flaky solid in 97% yield, m.p.133-134 ℃.
In a 500mL round-bottomed flask, 32.7g (150 mmol) of intermediate compound (2), anhydrous toluene (350 mL) and 3835.0 g (300 mmol) of SeO 2 were added, and under nitrogen protection, after refluxing under heating for 16 hours, the reaction was filtered while it is still hot, the filtrate was concentrated, and the crude product was recrystallized from 95% ethanol to give 29.3g of intermediate compound (3) (4-formyl-7-acetoxycoumarin) as pale yellow needle-like solid in a yield of 84%, m.p.145-146 ℃.
In a 250mL round bottom flask, 23.2g (100 mmol) of intermediate compound (3), DMF (30 mL), water (150 mL) and 15.4g (200 mmol) of NH 4 OAc were added, the reaction was carried out at room temperature for 8 hours, after the completion of the reaction, the reaction solution was extracted with ethyl acetate, washed with water, dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the crude product was separated by column chromatography to give 18.2g of pale yellow solid intermediate compound (4) (4-formyl-7-hydroxycoumarin) in 96% yield, m.p.129-130 ℃.
1.9G (10 mmol) of intermediate compound (4), 12mmol of acetyl aromatic compound (12 mmol) and 15mL of 95% ethanol and 0.5mL of piperidine are added into a 50mL round bottom flask, the mixture is refluxed and stirred for 6 hours, cooled to room temperature, and suction filtration is carried out to obtain a solid, the solid is washed with a small amount of ethanol, then with petroleum ether, the solid is dried, and the crude product is recrystallized with 95% ethanol to obtain the target product (5) ((E) -4- (3-aryl acryloyl) -7-hydroxy coumarin) with a yield of more than 70%.
The structures of the target compounds 5a to 5H were detected by Bruker AVANCE III MHz nuclear magnetic resonance spectrometer (Bruker Co., U.S.A.), and 1H NMR and 13C NMR are shown in the accompanying drawings.
(E) -structural characterization data of 4- (3-aryl-acryl) -7-hydroxycoumarin:
(E) -4- (3-phenylpropenoyl) -7-hydroxycoumarin (5 a): yellow solid, yield 84％,m.p.158-159℃.1H NMR(300MHz,CDCl3)δ:13.805(s,1H),8.239-8.291(m,1H),7.950-8.002(m,1H),7.674-7.745(m,3H),7.436(s,3H),6.958(d,J＝9.0Hz,1H),6.195(s,1H)13CNMR(75MHz,CDC|3)：193.377,167.295,159.260,154.828,153.142,145.908,134.783,131.088,131.013,130.152,129.071,128.169,126.132,125.256,115.223,112.034 111.070,109.646.HR-MS(ESI)m/z:Calcd for C18H13O4{[M+H]+}293.080 9,found 293.081 3.
(E) -4- (3-ferrocenylacryloyl) -7-hydroxycoumarin (5 b): red solid, yield 75％,m.p.140-142℃.1H NMR(400MHz,CDCl3)δ:13.805(s,1H),8.265(d,J＝20.8Hz,1H),7.436(s,3H),6.195(s,1H),4.671(s,2H),4.554(s,2H),4.388(s,5H);13C NMR(100MHz,CDCl3)：159.277,157.354,152.605,150.998,130.133,129.185,127.567,126.398,124.857,124.100,117.173,115.819,114.492,88.495,72.389,69.963,68.529.HR-MS(ESI)m/z:Calcd for C22H17FeO4{[M+H]+}401.047 1,found 401.047 8.
(E) -4- (3- (4-methoxyphenyl) acryloyl) -7-hydroxycoumarin (5 c): yellow solid, yield 87％,m.p.174-175℃.1H NMR(300MHz,CDCl3)δ:14.007(s,1H),8.147-8.198(m,1H),7.946-7.998(m,1H),7.655-7.716(m,3H),6.931-6.977(m,3H),6.187(s,1H),3.866(s,3H).13C NMR(75MHz,CDCl3)：193.054,167.284,162.091,159.340,154.730,153.068,146.034,130.939,130.690,127.552,123.633,115.145,114.499,111.921,110.903,109.700,55.348.HR-MS(ESI)m/z:Calcd for C19H15O5{[M+H]+}323.091 4,found 323.092 5.
(E) -4- (3- (3-nitrophenyl) acryloyl) -7-hydroxycoumarin (5 d): yellow solid, yield 69％,m.p.211-213℃.1H NMR(300MHz,DMSO-d6)δ:10.982(s,1H),8.578(s,1H),8.259(d,J＝7.8Hz,2H),7.686-7.755(m,2H),7.550-7.604(m,1H),7.344-7.398(m,1H),6.967(d,J＝8.7Hz,1H),6.196(s,1H).13C NMR(75MHz,DMSO-d6)δ:192.337,159.524,158.243,153.507,151.583,148.279,143.074,136.108,134.205,130.328,127.386,124.872,123.651,114.952,112.763,112.060,110.592.HR-MS(ESI)m/z:Calcd for C18H12NO6{[M+H]+}338.066 0,found 338.066 9.
(E) -4- (3- (2-hydroxyphenyl) acryloyl) -7-hydroxycoumarin (5 e): yellow solid, yield 86％,m.p.187-189℃.1H NMR(300MHz,DMSO-d6)δ:10.955(s,1H),10.208(s,1H),7.715(d,J＝8.7Hz,1H),7.659(dd,J＝7.8Hz,J＝1.2Hz,1H),7.556-7.610(m,1H),7.265(td,J＝7.5Hz,J＝1.5Hz,1H),7.118-7.173(m,1H),6.962(d,J＝8.7Hz,1H),6.893(d,J＝8.1Hz,1H),6.845(t,J＝7.5Hz,1H),6.187(d,J＝1.2Hz,1H).13C NMR(75MHz,DMSO-d6)δ:192.638,159.595,158.210,156.952,153.656,151.494,141.419,132.399,128.774,127.287,127.176,120.751,119.580,116.265,115.353,112.762,111.982,110.559.HR-MS(ESI)m/z:Calcd for C18H13O5{[M+H]+}309.075 8,found 309.077 2.
(E) -4- (3- (3-methoxy-4-hydroxyphenyl) acryloyl) -7-hydroxycoumarin (5 f): orange-red solid, yield 82％,m.p.195-197℃.1H NMR(300MHz,DMSO-d6)δ:10.915(s,1H),9.741(s,1H),7.706(d,J＝8.7Hz,1H),7.320(d,J＝1.8Hz,1H),7.198-7.252(m,1H),7.130(dd,J＝8.4Hz,J＝2.1Hz,1H),6.996-7.050(m,1H),6.947(d,J＝8.7Hz,1H),6.784(d,J＝8.1Hz,1H),6.184(d,J＝1.2Hz,1H),3.800(s,3H).13C NMR(75MHz,DMSO-d6)δ:192.234,159.668,158.166,153.614,151.473,149.875,147.974,146.858,126.979,125.634,125.192,123.684,115.633,115.499,112.769,112.002,111.778,110.533,55.683.HR-MS(ESI)m/z:Calcd for C19H15O6{[M+H]+}339.086 4,found 339.086 8.
(E) -4- (3, 4-dihydroxyphenyl) acryloyl) -7-hydroxycoumarin (5 g): red solid, yield 74％,m.p.227-229℃.1H NMR(300MHz,DMSO-d6)δ:10.928(s,1H),9.719(s,1H),9.173(s,1H),7.696(d,J＝8.7Hz,1H),7.135-7.189(m,1H),7.062(s,1H),6.924-6.994(m,2H),6.736-6.852(m,2H),6.172(s,1H).13C NMR(75MHz,DMSO-d6)δ:191.913,159.637,158.207,153.595,151.486,149.037,146.781,145.685,127.078,125.548,124.627,122.356,115.812,115.376,114.946,112.750,112.006,110.519.HR-MS(ESI)m/z:Calcd for C18H13O6{[M+H]+}325.070 7,found 325.071 9.
(E) -4- (3- (2, 4-dihydroxyphenyl) acryloyl) -7-hydroxycoumarin (5 h): red solid, yield 74％,m.p.240-242℃.1H NMR(300MHz,DMSO-d6)δ:10.908(s,1H),10.114(s,1H),10.003(s,1H),7.690(d,J＝8.7Hz,1H),7.493(d,J＝5.4Hz,1H),7.452(d,J＝1.8Hz,1H),6.962(d,J＝3.3Hz,1H),6.920(d,J＝3.9Hz,1H),6.329(d,J＝2.4Hz,1H),6.287(dd,J＝8.7Hz,J＝2.4Hz,1H),6.174(s,1H).13C NMR(75MHz,DMSO-d6)δ:192.268,161.775,159.708,158.885,158.238,153.715,151.492,142.252,130.455,126.940,123.850,115.714,112.780,112.689,111.972,110.526,108.266,102.479.HR-MS(ESI)m/z:Calcd for C18H13O6{[M+H]+}325.070 7,found 325.072 2.
The above description is only of the preferred embodiments of the present invention, and is not intended to limit the present invention. Various modifications and alterations of this invention will occur to those skilled in the art. Any modification, equivalent replacement, improvement, etc. made within the related principles of the present invention and the implementation methods thereof should be included in the protection scope of the present invention.
Claims (7)
1.8 (E) -4- (3-aryl-acryl) -7-hydroxycoumarin, characterized in that the structural formulae are respectively:
2. The method for preparing 8 (E) -4- (3-aryl-acryloyl) -7-hydroxycoumarin according to claim 1, wherein the following steps are adopted:
Step 1), adding concentrated H 2SO4 into a reaction bottle, cooling to-5 ℃ in an ice bath, slowly dripping an acetoacetic ester solution of resorcinol into the cooled concentrated H 2SO4 under the stirring condition, keeping the reaction temperature at-5 ℃, continuously stirring for 1-4 hours at the temperature of <10 ℃ after the dripping is finished, then stirring for 10-30 hours after the dripping is finished, pouring into an ice-water mixture to separate out precipitate, filtering and collecting the precipitate, washing with ice water, drying, and recrystallizing with 95% ethanol to obtain a white flocculent intermediate compound (1);
Step 2), sequentially adding the intermediate compound (1) and acetic anhydride into a reaction bottle, heating and refluxing for reaction for 1-4 hours, pouring the reaction mixture into ice water to separate out white solid after the reaction is finished, filtering and collecting the solid, washing with water, drying, and recrystallizing the crude product with 95% ethanol to obtain a white flaky solid intermediate compound (2);
Step 3), sequentially adding an intermediate compound (2), toluene, seO 2 and nitrogen into a reaction bottle, heating and refluxing for reaction for 12-24 hours under the protection of nitrogen, filtering while the reaction is hot after the reaction is finished, concentrating filtrate, and recrystallizing a crude product with 95% ethanol to obtain a pale yellow needle-shaped solid intermediate compound (3);
Step 4), sequentially adding an intermediate compound (3), a solvent and NH 4 OAc into a reaction bottle, reacting for 4-10 hours at room temperature, extracting a reaction solution with ethyl acetate after the reaction is finished, washing with water, drying with anhydrous sodium sulfate, evaporating the solvent under reduced pressure, and separating a crude product by column chromatography to obtain a pale yellow solid intermediate compound (4);
Step 5), sequentially adding an intermediate compound (4), an acetyl aromatic compound, a solvent and a catalyst into a reaction bottle, heating and refluxing for reaction for 4-8 h, cooling to room temperature after the reaction is finished, filtering to obtain a solid, washing with ethanol, drying, and recrystallizing a crude product with 95% ethanol to obtain the target compound (5).
3. The method according to claim 2, wherein in step 1), concentrated H 2SO4 is both solvent and catalyst; resorcinol, ethyl acetoacetate and concentrated H 2SO4 in a molar ratio of 1: (1-1.2): (3-8).
4. The method according to claim 2, wherein in step 2), acetic anhydride is both solvent and reactant; the molar ratio of the intermediate compound (1) to the acetic anhydride is 1: (3-10).
5. The process according to claim 2, wherein in step 3), the molar ratio of intermediate compound (2) to SeO 2 is 1: (1-3), the solvent toluene needs to be dried in advance.
6. The method according to claim 2, wherein in step 4), the molar ratio of intermediate compound (3) to NH4OAc is 1: (2-5); the solvent is a mixed solution of DMF and water or a mixed solution of DMSO and water.
7. The method according to claim 2, wherein in step 5), the reaction solvent is one of methanol, ethanol or isopropanol; the catalyst is one of piperidine, diethylamine, triethylamine, pyridine or diisopropylamine; the molar ratio of the intermediate compound (4), the acetyl aromatic compound and the catalyst is 1: (1-1.2): (0.05-0.1).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410036953.7A CN117903095A (en) | 2024-01-10 | 2024-01-10 | 8 (E) -4- (3-aryl acryloyl) -7-hydroxycoumarin and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410036953.7A CN117903095A (en) | 2024-01-10 | 2024-01-10 | 8 (E) -4- (3-aryl acryloyl) -7-hydroxycoumarin and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN117903095A true CN117903095A (en) | 2024-04-19 |
Family
ID=90697011
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202410036953.7A Pending CN117903095A (en) | 2024-01-10 | 2024-01-10 | 8 (E) -4- (3-aryl acryloyl) -7-hydroxycoumarin and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN117903095A (en) |
-
2024
- 2024-01-10 CN CN202410036953.7A patent/CN117903095A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7906660B2 (en) | Production of isoflavone derivatives | |
| CN105541773B (en) | A kind of preparation method of 3,4- dihydros -4- aryl-coumarin class compounds | |
| CN117903095A (en) | 8 (E) -4- (3-aryl acryloyl) -7-hydroxycoumarin and preparation method thereof | |
| EP1523478B1 (en) | Manufacture of isoflavones | |
| CN112851652B (en) | Catalytic oxidation synthesis method of 2- (substituted xanthyl) benzofuran compound | |
| CN112812066B (en) | Synthesis method of dihydropyrimidinone compound | |
| CN113336703A (en) | Synthesis of 1,3,4, 5-tetrasubstituted 1H-pyrazole derivatives | |
| CN110092751B (en) | Synthesis method of 2-alkyl quinoline | |
| CN113698358A (en) | Method for synthesizing quinazolinone compound under induction of visible light | |
| CN110117258B (en) | Preparation method of 2,4, 6-triaryl substituted pyrimidine compound | |
| CN113024499A (en) | Green synthesis method of coumarin-3-carboxylic acid compounds | |
| CN110684003A (en) | Simple and efficient total synthesis method of icaritin and derivatives thereof | |
| CN113512074B (en) | (E) -4-methyl-7-hydroxy-8- (3- (ferrocenyl) acryloyl) coumarin, and preparation method and application thereof | |
| Athanasellis et al. | Novel short-step synthesis of functionalized γ-phenyl-β-hydroxybutenoates and their cyclization to 4-hydroxycoumarins via the N-hydroxybenzotriazole methodology | |
| CN111100085A (en) | Preparation method of 3-aryl-2H-benzo [ β ] [1,4] benzoxazine-2-one compound | |
| CN112939916B (en) | Method for synthesizing coumarin-3-carboxylic acid compounds by one-pot two-step method | |
| CN111718301B (en) | Synthetic method of quinazolinone derivative | |
| CN109369597B (en) | Synthetic method of isocoumarin compound | |
| CN108467382A (en) | A kind of preparation method of 4H- chromene derivatives | |
| CN115073485B (en) | 3-aryl-7, 8-pyranocoumarin derivative, and preparation method and application thereof | |
| CN112778261B (en) | Method for synthesizing isocoumarin derivatives under catalysis of silver and application of isocoumarin derivatives | |
| CN113979943A (en) | 3-fluoro-5H-indeno [1,2-b ] pyridine compound and synthetic method thereof | |
| CN113999242B (en) | 3-fluoro-benzofuro [3,2-b ] pyridine compound and synthesis method thereof | |
| CN115466171B (en) | Preparation method of 2, 3-dihydro-1H-cyclopenteno [ a ] naphthalene derivative | |
| CN108558807A (en) | The method of one pot process cumarin base chalcone compounds |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |