CN109384753B - A kind of synthetic method of 2-phenyl-3-methylbenzofuran compounds - Google Patents
A kind of synthetic method of 2-phenyl-3-methylbenzofuran compounds Download PDFInfo
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- GMITZEGBZMWAOQ-UHFFFAOYSA-N 3-methyl-2-phenyl-1-benzofuran Chemical class O1C2=CC=CC=C2C(C)=C1C1=CC=CC=C1 GMITZEGBZMWAOQ-UHFFFAOYSA-N 0.000 title claims abstract description 21
- 238000010189 synthetic method Methods 0.000 title claims description 8
- 238000006243 chemical reaction Methods 0.000 claims abstract description 37
- 238000000034 method Methods 0.000 claims abstract description 21
- -1 2-phenyl-3-methylbenzofuran compound Chemical class 0.000 claims abstract description 16
- 239000000758 substrate Substances 0.000 claims abstract description 16
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 claims abstract description 13
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 claims abstract description 7
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 claims abstract description 6
- 238000003756 stirring Methods 0.000 claims abstract description 6
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Natural products CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 52
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 27
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 24
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 24
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 16
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 14
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- 239000003208 petroleum Substances 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 6
- 239000000741 silica gel Substances 0.000 claims description 6
- 229910002027 silica gel Inorganic materials 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 5
- 239000011541 reaction mixture Substances 0.000 claims description 5
- 238000004809 thin layer chromatography Methods 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 238000004440 column chromatography Methods 0.000 claims description 4
- 239000012429 reaction media Substances 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- 238000000746 purification Methods 0.000 claims description 3
- 238000000926 separation method Methods 0.000 claims description 3
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 239000000376 reactant Substances 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- 238000010438 heat treatment Methods 0.000 abstract description 5
- 239000006227 byproduct Substances 0.000 abstract description 2
- 238000006467 substitution reaction Methods 0.000 abstract description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 20
- 239000003054 catalyst Substances 0.000 description 11
- 239000000047 product Substances 0.000 description 10
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- 230000003595 spectral effect Effects 0.000 description 5
- 230000004071 biological effect Effects 0.000 description 4
- 238000006555 catalytic reaction Methods 0.000 description 4
- 229930014626 natural product Natural products 0.000 description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000003818 flash chromatography Methods 0.000 description 3
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- FWJGTOABGBFQNT-UHFFFAOYSA-N trifluoromethylsulfonyl 2,2,2-trifluoroacetate Chemical compound FC(F)(F)C(=O)OS(=O)(=O)C(F)(F)F FWJGTOABGBFQNT-UHFFFAOYSA-N 0.000 description 2
- UEVPPUDQJRWOLT-UHFFFAOYSA-N (2-acetylphenyl) benzoate Chemical compound CC(=O)C1=CC=CC=C1OC(=O)C1=CC=CC=C1 UEVPPUDQJRWOLT-UHFFFAOYSA-N 0.000 description 1
- ZXSQEZNORDWBGZ-UHFFFAOYSA-N 1,3-dihydropyrrolo[2,3-b]pyridin-2-one Chemical compound C1=CN=C2NC(=O)CC2=C1 ZXSQEZNORDWBGZ-UHFFFAOYSA-N 0.000 description 1
- ZRXHLJNBNWVNIM-UHFFFAOYSA-N 3-methyl-1-benzofuran Chemical compound C1=CC=C2C(C)=COC2=C1 ZRXHLJNBNWVNIM-UHFFFAOYSA-N 0.000 description 1
- 238000010499 C–H functionalization reaction Methods 0.000 description 1
- 238000006751 Mitsunobu reaction Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000003178 anti-diabetic effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- YCOXTKKNXUZSKD-UHFFFAOYSA-N as-o-xylenol Natural products CC1=CC=C(O)C=C1C YCOXTKKNXUZSKD-UHFFFAOYSA-N 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 150000001733 carboxylic acid esters Chemical class 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- PSCMQHVBLHHWTO-UHFFFAOYSA-K indium(iii) chloride Chemical compound Cl[In](Cl)Cl PSCMQHVBLHHWTO-UHFFFAOYSA-K 0.000 description 1
- SNHMUERNLJLMHN-UHFFFAOYSA-N iodobenzene Chemical compound IC1=CC=CC=C1 SNHMUERNLJLMHN-UHFFFAOYSA-N 0.000 description 1
- 150000002611 lead compounds Chemical class 0.000 description 1
- 238000006138 lithiation reaction Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- AUHZEENZYGFFBQ-UHFFFAOYSA-N mesitylene Substances CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 1
- 125000001827 mesitylenyl group Chemical group [H]C1=C(C(*)=C(C([H])=C1C([H])([H])[H])C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- SQDFHQJTAWCFIB-UHFFFAOYSA-N n-methylidenehydroxylamine Chemical class ON=C SQDFHQJTAWCFIB-UHFFFAOYSA-N 0.000 description 1
- QCPORYSHAZPBCG-UHFFFAOYSA-N n-phenoxyacetamide Chemical compound CC(=O)NOC1=CC=CC=C1 QCPORYSHAZPBCG-UHFFFAOYSA-N 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000006462 rearrangement reaction Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229910001958 silver carbonate Inorganic materials 0.000 description 1
- LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- YONPGGFAJWQGJC-UHFFFAOYSA-K titanium(iii) chloride Chemical compound Cl[Ti](Cl)Cl YONPGGFAJWQGJC-UHFFFAOYSA-K 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
- C07D307/80—Radicals substituted by oxygen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
本发明属于药物化学技术领域，提供了一种2‑苯基‑3‑甲基苯并呋喃化合物的合成方法。反应通式如下所示，该方法的反应底物为不同取代的3‑苯并呋喃甲基苯基醚，在无催化剂和无溶剂条件下通过搅拌加热促进反应进行。此反应可重排生成一系列2‑苯基‑3‑甲基苯并呋喃类化合物，具有操作简单、应用范围广、副产物少、收率高和反应绿色的特点。 The invention belongs to the technical field of medicinal chemistry and provides a method for synthesizing a 2-phenyl-3-methylbenzofuran compound. The general reaction formula is shown below, and the reaction substrate of this method is 3-benzofuran methyl phenyl ether with different substitutions, and the reaction is promoted by stirring and heating under catalyst-free and solvent-free conditions. This reaction can be rearranged to generate a series of 2-phenyl-3-methylbenzofuran compounds, and has the characteristics of simple operation, wide application range, few by-products, high yield and green reaction.
Description
Technical Field
The invention belongs to the technical field of medicinal chemistry, and relates to a synthetic method of a 2-phenyl-3-methylbenzofuran compound. In particular to a method for generating 2-phenyl-3-methyl benzofuran compounds by rearranging 3-benzofuran methyl phenyl ethers with specific substitution under the condition of no catalyst and no solvent.
Background
The 2-phenyl-3-methylbenzofuran is a natural product which is separated from plants and has various structures and various activities, attracts the attention of many scientists because of wide biological activity, and is a lead compound which can be used for drug development. Various natural products with 2-phenyl-3-methylbenzofuran as a framework have various biological activities and pharmacological effects, such as antibacterial activity (J.Nat.Prod.2006,69, 121-19-124.), antioxidant activity (biosci.Biotechnol.biochem.2001,65, 1402-1405), antitumor activity (chem.Commun.2009,14,1879-1881.), antidiabetic activity (bioorg.Med.chem.Lett.2010,20, 5398-5401-1303-J.Nat.prod.2014, 77, 1297-1303-A). Therefore, the 2-phenyl-3-methylbenzofuran compound has important research significance in the aspects of biological activity and full-synthetic application of medicines or natural products. The methods reported to date for the synthesis of 2-phenyl-3-methylbenzofurans are mainly achieved by catalytic coupling of expensive metal catalysts.
In 2004, the Gillmore topic group discovered a Pd-mediated process2(dba)3The substituted 2-phenyl-3-methylbenzofuran compound can be synthesized by constructing an intramolecular C-O bond through catalysis, and the yield is about 80%. However, this method requires the use of an expensive catalyst (org. Lett.2004,6, 4755-.
In 2004, Naito topic group found that trifluoroacetyl triflate and 4-dimethylaminopyridine catalyzed oxime ether compounds can be acylated and rearranged at 0 ℃ for 1.5-5 hours to obtain substituted 2-phenyl-3-methylbenzofuran compounds, and the yield is 15-99%. However, this process also has the disadvantage of requiring the use of expensive trifluoroacetyl triflate as catalyst (org. Lett.2004,6, 1761-1763.).
In 2006, the Sanz project group reported a method for synthesizing 2-phenyl-3-methylbenzofuran compounds. Cyclizing the product with carboxylic ester through lithium halogen exchange and benzyl methylene lithiation reaction, and dehydrating under the catalysis of indium chloride to obtain the substituted 2-phenyl-3-methylbenzofuran compound with the yield of 35-73% (J.Org.chem.2006,71, 4024-.
In 2011, 2-phenyl-3-methylbenzofuran compounds are obtained by the Jumbam project group through the cyclization reaction of 2-acetyl phenyl benzoate in tetrahydrofuran under the catalysis of titanium trichloride or titanium tetrachloride for 48 hours, and the yield is between 65 and 76 percent (Bull. chem. Soc. Ethiop.2011,25, 157-160.).
In 2015, Chung project group obtained 40% yield of 2-phenyl-3-methylbenzofuran compounds by coupling reaction of 3-methylbenzofuran and iodobenzene under catalysis of palladium acetate and silver carbonate (chem.Commun.,2015,51, 14543-14546.).
In 2015, the Li group obtained 2-phenyl-3-methylbenzofuran compounds (J.Org.chem.2015,80,10686-10693) by rhodium-catalyzed C-H activation of N-phenoxyacetamide.
In summary, natural products of 2-phenyl-3-methylbenzofuran have various structures, have various biological activities, and have very important functions in many aspects, and known reaction conditions for synthesizing 2-phenyl-3-methylbenzofuran analogues require expensive catalysts, and the solvents pollute the environment. According to the atom economy principle of the reaction, the most ideal, economical and green reaction should avoid the use of expensive catalysts and environmentally-polluting solvents and reduce the production of environmentally-unfriendly by-products. However, no such process is known in the art which does not require a catalyst or solvent.
Disclosure of Invention
The technical problem solved by the invention is to overcome the defects of expensive catalyst and serious environmental pollution in the prior art, and provide a novel method for synthesizing the 2-phenyl-3-methylbenzofuran compound by taking the 3-benzofuran methyl phenyl ether compound as a substrate, not requiring a catalyst and a solvent, and adding silica gel as an additive, so that the reaction temperature can be reduced, the reaction yield can be improved, and the 2-phenyl-3-methylbenzofuran compound can be synthesized through a rearrangement reaction.
The invention is realized by the following technical scheme:
the method comprises the following steps of carrying out mitsunobu reaction on a 3-benzofuran methanol compound and a phenol compound under the condition of no catalyst and no solvent heating to prepare 3-benzofuran methyl phenyl ether, and carrying out rearrangement on the 3-benzofuran methyl phenyl ether to obtain the 2-phenyl-3-methylbenzofuran compound. The chemical reaction formula is shown as follows:
wherein R is1，R2Is hydrogen, benzyloxy, C1-C4An alkoxy group.
The preparation method of the invention comprises the following steps:
1. charging of
Adding a 3-benzofuran methyl phenyl ether substrate into a round-bottom flask, adding a reaction medium with the molar volume dosage of 1-10 times that of the substrate, adding silica gel with the dosage of 1-3 times of the weight ratio, and evaporating the medium by a rotary evaporator. The reaction medium is as follows: dichloromethane, ethyl acetate, chloroform, acetone, tetrahydrofuran, preferably: dichloromethane in an amount of: 1 to 10 times, preferably 5 times the molar volume of the substrate. 2. Reaction of
Stirring the mixture for reaction at the temperature of 120-160 ℃, wherein the reaction time is 3-5h, and detecting the reaction process by thin layer chromatography. The developing agent for thin-layer chromatography is petroleum ether, ethyl acetate, n-hexane, methanol, chloroform, dichloromethane, acetone, tetrahydrofuran, water or a mixture of two or three of the above, wherein petroleum ether/ethyl acetate (v/v: 50/1-2/1) or n-hexane/ethyl acetate (v/v: 50/1-2/1) or petroleum ether/n-hexane/ethyl acetate (v/v/v: 25/25/1-1/1/1) is preferred
3. Post-treatment of the reaction solution
And (3) directly carrying out column chromatography separation and purification on the cooled reactant and a reaction mixture by using silica gel to obtain a target product, wherein the developing agent system is as follows: petroleum ether, ethyl acetate, n-hexane, methanol, chloroform, dichloromethane, acetone, tetrahydrofuran, water or a mixture of two or three of them, wherein a petroleum ether/ethyl acetate (v/v: 50/1-2/1) or n-hexane/ethyl acetate (v/v: 50/1-2/1) system or a petroleum ether/n-hexane/ethyl acetate (v/v/v: 25/25/1-1/1/1) system is preferable.
The invention has the advantages that 2-phenyl-3-methyl benzofuran compounds can be generated from 3-benzofuran methyl phenyl ether without heating a catalyst and a solvent, the reaction application range is wider, the substrate is cheap and easy to obtain, and the reaction operation is simple and convenient. Compared with the synthesis method of the 2-phenyl-3-methylbenzofuran compound in the prior art, the method conforms to the concept of green chemistry and also ensures higher reaction yield.
Detailed Description
The advantages and the preparation of the present invention will be better understood in connection with the following examples, which are intended to illustrate, but not to limit the scope of the invention.
Example 1
Dissolving a substrate 1(1mmol) in mesitylene (2mL), heating the reaction mixture to 180 ℃, stirring and reacting for 4 hours, and separating by using a flash column chromatography method after the reaction is finished to obtain a target product a with the yield of 35%. The reaction equation is as follows:
spectral data for product a were:1H NMR(600MHz,CDCl3)δ7.46(d,J＝7.4Hz,2H),7.42(d,J＝7.1Hz,2H),7.39(t,J＝8.4Hz,5H),7.33(m,2H),7.25(m,5H),7.08(d,J＝2.2Hz,1H),6.97(dd,J＝8.5,2.2Hz,1H),6.32(d,J＝2.2Hz,1H),6.29(d,J＝2.2Hz,1H),5.93(s,1H),5.12(s,2H),5.04(s,2H),5.02(s,2H),2.09(s,3H)；13C NMR(150MHz,CDCl3)δ161.7,158.6,157.3,156.7,155.6,143.9,137.1,136.8,136.7,128.8,128.7,128.6,128.3,128.1,127.8,127.7,127.6,127.1,124.1,119.7,115.8,112.2,100.4,97.3,94.7,94.2,70.8,70.6,70.30,9.26；HRMS(ESI):m/z:Calcd.for C36H30O5[M+H]+543.2166,Found 543.2173。
example 2
Substrate 1(1mmol) was dissolved in toluene (2mL) and ZnCl was added2(0.2mmol,27mg) of Triton, andheating the reaction mixture to 140 ℃, stirring and reacting for 4 hours, and separating by using a flash column chromatography method after the reaction is finished to obtain a target product a with the yield of 40%. The reaction equation is as follows:
spectral data for product a were:1H NMR(600MHz,CDCl3)δ7.46(d,J＝7.4Hz,2H),7.42(d,J＝7.1Hz,2H),7.39(t,J＝8.4Hz,5H),7.33(m,2H),7.25(m,5H),7.08(d,J＝2.2Hz,1H),6.97(dd,J＝8.5,2.2Hz,1H),6.32(d,J＝2.2Hz,1H),6.29(d,J＝2.2Hz,1H),5.93(s,1H),5.12(s,2H),5.04(s,2H),5.02(s,2H),2.09(s,3H)；13C NMR(150MHz,CDCl3)δ161.7,158.6,157.3,156.7,155.6,143.9,137.1,136.8,136.7,128.8,128.7,128.6,128.3,128.1,127.8,127.7,127.6,127.1,124.1,119.7,115.8,112.2,100.4,97.3,94.7,94.2,70.8,70.6,70.30,9.26；HRMS(ESI):m/z:Calcd.for C36H30O5[M+H]+543.2166,Found 543.2173。
example 3
Dissolving the substrate 1(1mmol) in dichloromethane (2mL), adding silica gel (1g), distilling under reduced pressure to evaporate dichloromethane to dryness, heating the reaction mixture to 140 ℃, stirring for reaction for 4 hours, and separating by using a flash column chromatography method after the reaction is finished to obtain the target product a with the yield of 75%. The reaction equation is as follows:
spectral data for product a were:1H NMR(600MHz,CDCl3)δ7.46(d,J＝7.4Hz,2H),7.42(d,J＝7.1Hz,2H),7.39(t,J＝8.4Hz,5H),7.33(m,2H),7.25(m,5H),7.08(d,J＝2.2Hz,1H),6.97(dd,J＝8.5,2.2Hz,1H),6.32(d,J＝2.2Hz,1H),6.29(d,J＝2.2Hz,1H),5.93(s,1H),5.12(s,2H),5.04(s,2H),5.02(s,2H),2.09(s,3H)；13C NMR(150MHz,CDCl3)δ161.7,158.6,157.3,156.7,155.6,143.9,137.1,136.8,136.7,128.8,128.7,128.6,128.3,128.1,127.8,127.7,127.6,127.1,124.1,119.7,115.8,112.2,100.4,97.3,94.7,94.2,70.8,70.6,70.30,9.26；HRMS(ESI):m/z:Calcd.for C36H30O5[M+H]+543.2166,Found 543.2173。
example 4
The reaction substrate 1 was changed to the reaction substrate 2, and the same procedure as in example 3 was repeated to give the objective compound b in a reaction yield of 63%. The reaction equation is as follows:
spectral data for product b were:1H NMR(600MHz,CDCl3)δ7.47(t,J＝8.3Hz,4H),7.42(m,5H),7.35(m,3H),7.09(d,J＝2.1Hz,1H),7.01(dd,J＝8.5,2.1Hz,1H),6.96(s,1H),6.69(d,J＝2.5Hz,1H),6.66(dd,J＝8.5,2.5Hz,1H),5.14(s,2H),5.10(s,2H),2.34(s,3H)；13C NMR(150MHz,CDCl3)δ155.5,136.9,136.8,129.9,128.8,128.2,128.1,127.7,126.6,119.6,112.6,112.0,110.0,108.0,103.0,97.2,70.8,70.2,9.3；HRMS(ESI):m/z:Calcd.for C29H24O4[M+H]+437.1747,Found 437.1750。
example 5
The reaction substrate 1 was changed to the reaction substrate 3, and the same procedure as in example 3 was repeated to give the objective compound c in a reaction yield of 79%. The reaction equation is as follows:
spectral data for product c were:1H NMR(600MHz,CDCl3)δ7.61(s,1H),7.53(d,J＝8.5Hz,1H),7.47(d,J＝7.4Hz,2H),7.41(t,J＝7.4Hz,2H),7.35(d,J＝7.4Hz,1H),7.22(t,J＝8.2Hz,1H),7.11(d,J＝2.2Hz,1H),7.00(dd,J＝8.0,2.2Hz,1H),6.63(dd,J＝8.0,2.1Hz,1H),6.58(t,J＝2.1Hz,1H),6.56(dd,J＝8.2,2.2Hz,1H),5.15(d,J＝0.6Hz,2H),5.12(s,2H),3.80(s,3H)；13C NMR(150MHz,CDCl3)δ161.0,16.0,157.5,156.6,142.5,136.9,130.1,128.8,128.2,127.6,120.5,120.4,116.8,112.8,106.9,109.8,101.5,97.5,70.7,61.4,55.4；HRMS(ESI):m/z:Calcd.for C23H20O4[M+H]+361.1434,Found 361.1439。
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