CN105801538A - Method for preparing 2, 3-dihydrobenzofuran derivative - Google Patents

Method for preparing 2, 3-dihydrobenzofuran derivative Download PDF

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CN105801538A
CN105801538A CN201610204289.8A CN201610204289A CN105801538A CN 105801538 A CN105801538 A CN 105801538A CN 201610204289 A CN201610204289 A CN 201610204289A CN 105801538 A CN105801538 A CN 105801538A
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dihydrobenzofuranes
ethyl cyanoacrylate
dihydro
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phenyl
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CN105801538B (en
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杨健国
莫寒劼
吴海建
王治明
陈定奔
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Taizhou University
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Taizhou University
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    • 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

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  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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Abstract

The invention discloses a method for preparing a 2, 3-dihydrobenzofuran derivative. The method comprises the steps as follows: benzyl phenyl ether compounds are taken as raw materials, NaHCO3 is taken as alkali, and dimethyl formamide is taken as a solvent to react under the catalytic action of Pd(dppe) Cl2 and tetra-n-butylammonium chloride for 8 hours at a reaction temperature of 90 DEG C under a nitrogen protection system, and a target compound is synthesized. The synthetic method is simple, the yield is higher, conditions are mild, one-pot synthesis is adopted, and accordingly, the method has a good application prospect.

Description

A kind of method preparing 2,3-dihydro-benzofuran derivative
Technical field
The present invention relates to a kind of efficient, easy chemical reaction, in relatively mild reaction system, by one pot process 2, the method for 3-dihydro-benzofuran derivative.
Background technology
2,3-Dihydrobenzofuranes, as a kind of important organic intermediate, are widely used in the synthesis of heterocycle compound, still synthesize simultaneously some important drugs intermediate raw material (Chin.J.Chem.Eng.2009,17,42；Phyto Chem.1996,1261；Phyto Chem.2002,635；J.Med.Chem.2009,3184).Such as anti-tumor agent benzofuran ureide derivative compound (Helv.Chim.Acta 2010,272；J.Chem.Res.2010,514；Arch.Pharm.Res.2008,965), protease inhibitor aminoacid disappointing second ammonia is for (J.Nat.Prod.2009,1465 such as sulphonyl；Bioorg.Med.Chem.Lett.2009,6922), 2,3-Dihydrobenzofuranes synthetic methods mainly have three routes, and one is the disubstituted synthetic method in ortho position on phenyl ring；Two is that benzofuran hydrogenates synthetic method；Three is monosubstituted synthetic method on phenyl ring, but this three classes synthetic method obtain 2,3-Dihydrobenzofuranes functional group is the most single, is unfavorable for synthesizing the complex compound of active structure fragment, and the domestic ability that there is no this compounds of large-scale production and process route.
The coupling reaction of palladium chtalyst is the most vitochemical study hotspot, the most highly effective for building new carbon-carbon bond and carbon-heterodesmic, and there is the features such as efficient, green, therefore become important component part (the Organic Reactions 1982,345 in modern organic synthesis field；Tetrahedron Letters 1999,1673；Angew.Chem.Int.Ed.1995,2379；Chem.Rev.2000,3009).Heck reaction is the halogenated aryl hydrocarbon olefination that a class is important, it it is the reaction building new carbon-carbon bond, Mizoroki and Heck is found that respectively at 1971 and 1972 such reacts (Bulletin of the Chemical Society of Japan 1971 581；J.Org.Chem.1972,2320), more than 40 year of past is developing progressively into a kind of widely used methodology of organic synthesis (Adv.Syn.&Cata.2002,393), organic chemist utilizes intramolecular Heck that heterocyclic compound and the macromolecular compound (Synthesis 2003,1383 of a lot of active structure have been synthesized in recent years；Polymer Bulletin 2001,29), particularly suffer from terms of some medicine intermediate being widely applied synthesizing (Chem.Rev.2007,133；Tetrahedron 2007,6949), reactant is mainly the alkene of halogenated aryl hydrocarbon and band α-electron withdraw group and reacts generation virtue under the catalytic action of zeroth order palladium or palladium complex for alkene.
Based on synthesizing feature above, we have invented with benzyl phenyl ether as raw material, by under palladium chtalyst effect, benzyl ehter bond disconnects, form the compound with conjugated diene hydrocarbon structure, then the conjugated diene formed and another molecule fragment occur Heck and additive reaction, synthesis to have the 2 of highly useful acrylic-functional, 3-dihydro-benzofuran derivative.This synthetic method is simple, and the reaction related to has disconnected ehter bond to be rearranged into conjugated diene, then Heck reaction and additive reaction occurs, but can pass through one pot process target molecule.
Summary of the invention
The present invention is with phenylbenzyl ether compound as raw material, and dimethylformamide is solvent, under nitrogen protection system, and synthesising target compound.This synthetic method is simple, completes three-step reaction in one pot, and productivity is higher, is 2, and the synthesis of 3-dihydro-benzofuran derivative provides a kind of efficient synthetic method.
According to the present invention, described 2, the reaction of 3-dihydro-benzofuran derivative, its main synthesis step is: with phenylbenzyl ether compound as raw material, at Pd (dppe) Cl2, tetrabutylammonium chloride be catalyst, NaHCO3For alkali, dimethylformamide is solvent, and under nitrogen protection system, reaction temperature is 90 degrees Celsius, reacts 8 hours, synthesising target compound, and wherein, the synthetic reaction formula of target compound is:
Concrete product structure is as follows:
Above-mentioned reacting middle catalyst Pd (dppe) Cl2It is 1:20, NaHCO with raw material molar ratio3Being 1:0.5 with raw material molar ratio, tetrabutylammonium chloride and raw material molar ratio are 1:1, and dimethylformamide is solvent, and under nitrogen protection system, reaction temperature is 90 degrees Celsius, reacts 8 hours.
nullBy above-mentioned synthetic method，It is prepared for (E)-1-phenyl-2-(2,3-Dihydrobenzofuranes) ETHYL CYANOACRYLATE、(E)-1-(2-tolyl)-2-(2,3-Dihydrobenzofuranes) ETHYL CYANOACRYLATE、(E)-1-(3-tolyl)-2-(2,3-Dihydrobenzofuranes) ETHYL CYANOACRYLATE、(E)-1-(4-tolyl)-2-(2,3-Dihydrobenzofuranes) ETHYL CYANOACRYLATE、(E)-1-(2-fluorophenyl)-2-(2,3-Dihydrobenzofuranes) ETHYL CYANOACRYLATE、(E)-1-(4-fluorophenyl)-2-(2,3-Dihydrobenzofuranes) ETHYL CYANOACRYLATE、(E)-1-(2-chlorphenyl)-2-(2,3-Dihydrobenzofuranes) ETHYL CYANOACRYLATE、(E)-1-(3-chlorphenyl)-2-(2,3-Dihydrobenzofuranes) ETHYL CYANOACRYLATE、(E)-1-(4-chlorphenyl)-2-(2,3-Dihydrobenzofuranes) ETHYL CYANOACRYLATE、(E)-1-(4-bromophenyl)-2-(2,3-Dihydrobenzofuranes) ETHYL CYANOACRYLATE、(E)-1-(2-naphthyl)-2-(2,3-Dihydrobenzofuranes) ETHYL CYANOACRYLATE、(E)-1-phenyl-2-(2,3-Dihydrobenzofuranes) 12 compounds of methacrylate.
After above-mentioned reaction terminates, cool down at room temperature, add a small amount of water dissolution, then extract 3 times with dichloromethane, merge the organic solvent extracted, be dried with anhydrous magnesium sulfate, then concentrate organic solvent, be further purified by column chromatography, obtain target product.
Detailed description of the invention
Below with reference to embodiment, the present invention will be further described, and embodiments of the invention are merely to illustrate technical scheme, and the non-limiting present invention.
Embodiment 1
In the reaction tube that 20mL is dried, by Pd (dppe) Cl2(0.025mmol), NaHCO3(1mmol), tetrabutylammonium chloride (0.5mmol), raw material phenyl benzyl ethers compounds is dissolved in the dimethylformamide that 2mL is dried, in disposable injection reaction tube, 90 DEG C are reacted 8 hours, magnetic agitation, TLC detects, raw material disappears, and adds suitable quantity of water and dissolves, with dichloromethane extractive reaction liquid, merge organic facies, concentrate organic solvent, then be further purified by column chromatography and obtain product, yield 84%.
(E)-1-phenyl-2-(2,3-Dihydrobenzofuranes) ETHYL CYANOACRYLATE
White solid.M.p.:75-76℃.1H NMR(400MHz,CDCl3) δ (ppm): 7.89 (s, 1H), 7.42-7.35 (m, 5H), 7.16-7.07 (m, 2H), 6.83 (t, J=7.6Hz, 1H), 6.73 (d, J=8.0Hz, 1H), 4.17-4.09 (m, 2H), 3.60-3.88 (m, 2H), 0.97 (t, J=7.6Hz, 1H)；13C NMR(100MHz, CDCl3)δ(ppm):166.45,159.81,142.53,134.45,131.92,129.22,128.98,128.55,127.81,127.33,124.42,120.22,109.02,77.58,60.81,35.91,13.56.IR(neat):3019,1215,758,669cm-1.MS (70eV, EI) m/z=294.HRMS (EI): m/z calcd for C19H18O3(M+):294.1256.Found,294.1254。
Embodiment 2
In the reaction tube that 20mL is dried, by Pd (dppe) Cl2(0.025mmol), NaHCO3(1mmol), tetrabutylammonium chloride (0.5mmol), raw material phenyl benzyl ethers compounds is dissolved in the dimethylformamide that 2mL is dried, in disposable injection reaction tube, 90 DEG C are reacted 8 hours, magnetic agitation, TLC detects, raw material disappears, and adds suitable quantity of water and dissolves, with dichloromethane extractive reaction liquid, merge organic facies, concentrate organic solvent, then be further purified by column chromatography and obtain product, yield 63%.
(E)-1-(2-tolyl)-2-(2,3-Dihydrobenzofuranes) ETHYL CYANOACRYLATE
White solid.M.p.:86-87℃.1H NMR(400MHz,CDCl3) δ (ppm): 7.96 (s, 1H), 7.29-7.06 (m, 6H), 6.83-6.79 (m, 1H), 6.71 (d, J=8.0Hz, 1H), 5.67-5.62 (m, 1H), 4.19-4.08 (m, 2H), 3.53-3.47 (m, 1H), 3.40-3.34 (m, 1H), 2.35 (s, 3H), 0.96 (t, J=7.2Hz, 3H)；13C NMR(100MHz,CDCl3)δ(ppm):166.27,159.82,142.34,137.03,133.78,132.17,130.22,129.01,128.87,127.78,127.38,125.75,124.40,120.16,108.95,77.82,60.82,35.91,20.06,13.54.IR(neat):3019,2399,2365,1719,1701,1470,1439,1215,1018,930,760,669cm-1.MS (70eV, EI) m/z=308.HRMS (EI): m/z calcd for C20H20O3(M+):308.1412.Found,308.1413。
Embodiment 3
In the reaction tube that 20mL is dried, by Pd (dppe) Cl2(0.025mmol), NaHCO3(1mmol), tetrabutylammonium chloride (0.5mmol), raw material phenyl benzyl ethers compounds is dissolved in the dimethylformamide that 2mL is dried, in disposable injection reaction tube, 90 DEG C are reacted 8 hours, magnetic agitation, TLC detects, raw material disappears, and adds suitable quantity of water and dissolves, with dichloromethane extractive reaction liquid, merge organic facies, concentrate organic solvent, then be further purified by column chromatography and obtain product, yield 66%.
(E)-1-(3-tolyl)-2-(2,3-Dihydrobenzofuranes) ETHYL CYANOACRYLATE
White solid.M.p.:85-86℃.1H NMR(400MHz,CDCl3) δ (ppm): 7.87 (s, 1H), 7.31-7.26 (m, 1H), 7.19-7.08 (m, 5H), 6.85-6.81 (m, 1H), 6.74 (d, J=8.0Hz, 1H), 5.85-5.81 (m, 1H), 4.17-4.09 (m, 2H), 3.54-3.39 (m, 2H), 2.36 (s, 3H), 0.98 (t, J=7.2Hz, 3H)；13C NMR(100MHz,CDCl3)δ(ppm):166.50,159.80,142.78,138.24,134.35,131.60,129.89,129.78,128.42,127.81,127.35,126.29,124.42,120.18,109.01,77.59,60.78,35.91,21.40,13.55.IR(neat):3019,1215,758,669cm-1.MS (70eV, EI) m/z=308.HRMS (EI): m/z calcd for C20H20O3(M+):308.1412.Found,308.1408。
Embodiment 4
In the reaction tube that 20mL is dried, by Pd (dppe) Cl2(0.025mmol), NaHCO3(1mmol), tetrabutylammonium chloride (0.5mmol), raw material phenyl benzyl ethers compounds is dissolved in the dimethylformamide that 2mL is dried, in disposable injection reaction tube, 90 DEG C are reacted 8 hours, magnetic agitation, TLC detects, raw material disappears, and adds suitable quantity of water and dissolves, with dichloromethane extractive reaction liquid, merge organic facies, concentrate organic solvent, then be further purified by column chromatography and obtain product, yield 71%.
(E)-1-(4-tolyl)-2-(2,3-Dihydrobenzofuranes) ETHYL CYANOACRYLATE
White solid.M.p.:77-78℃.1H NMR(400MHz,CDCl3) δ (ppm): 7.86 (s, 1H), 7.27-7.07 (m, 6H), 6.82 (t, J=7.2Hz, 1H), 6.73 (d, J=8.0Hz, 1H), 5.86-5.81 (m, 1H), 4.16-4.08 (m, 2H), 3.54-3.37 (m, 2H), 2.37 (s, 3H), 0.97 (t, J=7.2Hz, 3H)；13C NMR (100MHz,CDCl3)δ(ppm):166.58,159.85,142.67,139.27,131.54,131.12,129.33,129.28,127.79,127.42,124.42,120.17,109.01,77.65,60.72,35.86,21.34,13.57.IR(neat):3019,1705,1481,1215,758,669cm-1.MS (70eV, EI) m/z=308.HRMS (EI): m/z calcd for C20H20O3(M+):308.1412.Found,308.1415。
Embodiment 5
In the reaction tube that 20mL is dried, by Pd (dppe) Cl2(0.025mmol), NaHCO3(1mmol), tetrabutylammonium chloride (0.5mmol), raw material phenyl benzyl ethers compounds is dissolved in the dimethylformamide that 2mL is dried, in disposable injection reaction tube, 90 DEG C are reacted 8 hours, magnetic agitation, TLC detects, raw material disappears, and adds suitable quantity of water and dissolves, with dichloromethane extractive reaction liquid, merge organic facies, concentrate organic solvent, then be further purified by column chromatography and obtain product, yield 61%.
(E)-1-(2-fluorophenyl)-2-(2,3-Dihydrobenzofuranes) ETHYL CYANOACRYLATE
White solid.M.p.:67-68℃.1H NMR(400MHz,CDCl3) δ (ppm): 7.86 (s, 1H), 7.39-7.31 (m, 2H), 7.19-7.07 (m, 4H), 6.85-6.81 (m, 1H), 6.71 (d, J=8.0Hz, 1H), 5.68 (t, J=7.2Hz, 1H), 4.19-4.11 (m, 2H), 3.55-3.41 (m, 2H), (1.00 t, J=7.2Hz, 3H)；13C NMR(100MHz,CDCl3)δ(ppm):165.81,161.47,159.65,158.99,135.57,135.55,133.73,131.01,130.92,130.69,130.66,127.77,127.32,124.43,124.11,124.07,122.44,122.29,120.27,115.90,115.69,108.98,78.03,60.95,35.55,13.56.IR(neat):3019,1717,1481,1215,758,669cm-1.MS (70eV, EI) m/z=312.HRMS (EI): m/z calcd for C19H17FO3(M+):312.1162.Found,312.1162。
Embodiment 6
In the reaction tube that 20mL is dried, by Pd (dppe) Cl2(0.025mmol), NaHCO3(1mmol), tetrabutylammonium chloride (0.5mmol), raw material phenyl benzyl ethers compounds is dissolved in the dimethylformamide that 2mL is dried, in disposable injection reaction tube, 90 DEG C are reacted 8 hours, magnetic agitation, TLC detects, raw material disappears, and adds suitable quantity of water and dissolves, with dichloromethane extractive reaction liquid, merge organic facies, concentrate organic solvent, then be further purified by column chromatography and obtain product, yield 44%.
(E)-1-(4-fluorophenyl)-2-(2,3-Dihydrobenzofuranes) ETHYL CYANOACRYLATE
White solid.M.p.:76-77℃.1H NMR(400MHz,CDCl3) δ (ppm): 7.84 (s, 1H), 7.37-7.33 (m, 2H), 7.16-7.07 (m, 4H), 6.84 (t, J=7.2Hz, 1H), 6.73 (d, J=8.0Hz, 1H), 5.79-5.74 (m, 1H), 4.17-4.09 (m, 2H), 3.53-3.38 (m, 2H), 0.98 (t, J=7.2Hz, 3H)；13C NMR(100MHz,CDCl3)δ(ppm):166.35,164.28,161.80,159.69,141.45,131.83,131.29,131.20,130.48,130.44,127.89,127.23,124.48,120.34,115.62,109.06,77.45,60.91,35.84,13.58.IR(neat):3019,2357,1506,1215,758,669cm-1.MS (70eV, EI) m/z=312.HRMS (EI): m/z calcd for C19H17FO3(M+):312.1162.Found,312.1161。
Embodiment 7
In the reaction tube that 20mL is dried, by Pd (dppe) Cl2(0.025mmol), NaHCO3(1mmol), tetrabutylammonium chloride (0.5mmol), raw material phenyl benzyl ethers compounds is dissolved in the dimethylformamide that 2mL is dried, in disposable injection reaction tube, 90 DEG C are reacted 8 hours, magnetic agitation, TLC detects, raw material disappears, and adds suitable quantity of water and dissolves, with dichloromethane extractive reaction liquid, merge organic facies, concentrate organic solvent, then be further purified by column chromatography and obtain product, yield 77%.
(E)-1-(2-chlorphenyl)-2-(2,3-Dihydrobenzofuranes) ETHYL CYANOACRYLATE
White solid.M.p.:76-77℃.1H NMR(400MHz,CDCl3) δ (ppm): 7.94 (s, 1H), 7.43 (d, J=8.0Hz, 1H), 7.32-7.24 (m, 3H), 7.14-7.05 (m, 2H), 6.82 (t, J=7.2Hz, 1H), 6.69 (d, J=7.6Hz, 1H), 5.64-5.59 (m, 1H), 4.20-4.12 (m, 2H), 3.52-3.35 (m, 2H), 1.02 (t J=7.2Hz, 3H)；13C NMR(100MHz,CDCl3)δ(ppm):165.80,159.66,139.82,134.07,133.33,133.29,130.44,130.11,129.66,127.80,127.20,126.60,124.42,120.28,109.02,77.86,60.96,35.80,13.61.IR(neat):3019,1215,756,669cm-1.MS (70eV, EI) m/z=328.HRMS (EI): m/z calcd for C19H17ClO3(M+):328.0866.Found,328.0866.
Embodiment 8
In the reaction tube that 20mL is dried, by Pd (dppe) Cl2(0.025mmol), NaHCO3(1mmol), tetrabutylammonium chloride (0.5mmol), raw material phenyl benzyl ethers compounds is dissolved in the dimethylformamide that 2mL is dried, in disposable injection reaction tube, 90 DEG C are reacted 8 hours, magnetic agitation, TLC detects, raw material disappears, and adds suitable quantity of water and dissolves, with dichloromethane extractive reaction liquid, merge organic facies, concentrate organic solvent, then be further purified by column chromatography and obtain product, yield 71%.
(E)-1-(3-chlorphenyl)-2-(2,3-Dihydrobenzofuranes) ETHYL CYANOACRYLATE
White solid.M.p.:91-92℃.1H NMR(400MHz,CDCl3) δ (ppm): 7.79 (s, 1H), 7.33-7.30 (m, 3H), 7.24-7.21 (m, 1H), 7.16-7.07 (m, 2H), 6.72 (t, J=7.2Hz, 1H), 6.72 (d, J=8.0Hz, 1H), 5.75-5.71 (m, 1H), 4.18-4.10 (m, 2H), 3.53-3.39 (m, 2H), 0.99 (t, J=7.2Hz, 3H)；13C NMR(100MHz,CDCl3)δ(ppm):166.08,159.67,140.64,136.24,134.55,133.27,129.79,129.06,128.96,127.91,127.23,127.07,124.45,120.36,109.08,77.42,60.99,35.97,13.57.IR(neat):3019,1215,758,669cm-1.MS (70eV, EI) m/z=328.HRMS (EI): m/z calcd for C19H17ClO3(M+):328.0866.Found,328.0870。
Embodiment 9
In the reaction tube that 20mL is dried, by Pd (dppe) Cl2(0.025mmol), NaHCO3(1mmol), tetrabutylammonium chloride (0.5mmol), raw material phenyl benzyl ethers compounds is dissolved in the dimethylformamide that 2mL is dried, in disposable injection reaction tube, 90 DEG C are reacted 8 hours, magnetic agitation, TLC detects, raw material disappears, and adds suitable quantity of water and dissolves, with dichloromethane extractive reaction liquid, merge organic facies, concentrate organic solvent, then be further purified by column chromatography and obtain product, yield 48%.
(E)-1-(4-chlorphenyl)-2-(2,3-Dihydrobenzofuranes) ETHYL CYANOACRYLATE
White solid.M.p.:88-89℃.1H NMR(400MHz,CDCl3) δ (ppm): 7.82 (s, 1H), 7.38-7.08 (m, 6H), 6.85-6.71 (m, 2H), 5.74 (t, J=7.2Hz, 1H), 4.15-4.11 (m, 2H), 3.52-3.37 (m, 2H), 0.99 (t, J=6.8Hz, 3H)；13C NMR(100MHz,CDCl3)δ(ppm):166.22,159.66,141.11,135.12,132.86,132.53,130.54,128.82,127.89,127.13,124.44,120.35,109.06,77.44,60.94,35.87,13.56.IR(neat):3019,1717,1481,1261,1215,1094,1015,758,669cm-1.MS (70eV, EI) m/z=328.HRMS (EI): m/z calcd for C19H17ClO3(M+):328.0866.Found,328.0869。
Embodiment 10
In the reaction tube that 20mL is dried, by Pd (dppe) Cl2(0.025mmol), NaHCO3(1mmol), tetrabutylammonium chloride (0.5mmol), raw material phenyl benzyl ethers compounds is dissolved in the dimethylformamide that 2mL is dried, in disposable injection reaction tube, 90 DEG C are reacted 8 hours, magnetic agitation, TLC detects, raw material disappears, and adds suitable quantity of water and dissolves, with dichloromethane extractive reaction liquid, merge organic facies, concentrate organic solvent, then be further purified by column chromatography and obtain product, yield 35%.
(E)-1-(4-bromophenyl)-2-(2,3-Dihydrobenzofuranes) ETHYL CYANOACRYLATE
White solid.M.p.:90-91℃.1H NMR(400MHz,CDCl3) δ (ppm): 7.80 (s, 1H), 7.54-7.52 (m, 2H), 7.23 (d, J=8.4Hz, 2H), 7.16-7.08 (m, 2H), 6.86-6.82 (m, 1H), 6.73 (d, J=8.0Hz, 1H), 5.76-5.71 (m, 1H), 4.17-4.09 (m, 2H), 3.52-3.37 (m, 2H) 0.98 (t, J=7.2Hz, 3H)；13C NMR(100MHz,CDCl3)δ(ppm):166.22,159.64,141.22,133.27,132.50,131.80,130.79,127.91,127.14,124.47,123.39,120.37,109.06,77.40,60.99,35.86,13.57.IR(neat):3443,3019,1715,1636,1481,1462,1261,1215,1074,1011,758,669cm-1.MS (70eV, EI) m/z=372.HRMS (EI): m/z calcd for C19H17BrO3(M+):372.0361.Found,372.0359。
Embodiment 11
In the reaction tube that 20mL is dried, by Pd (dppe) Cl2(0.025mmol), NaHCO3(1mmol), tetrabutylammonium chloride (0.5mmol), raw material phenyl benzyl ethers compounds is dissolved in the dimethylformamide that 2mL is dried, in disposable injection reaction tube, 90 DEG C are reacted 8 hours, magnetic agitation, TLC detects, raw material disappears, and adds suitable quantity of water and dissolves, with dichloromethane extractive reaction liquid, merge organic facies, concentrate organic solvent, then be further purified by column chromatography and obtain product, yield 59%.
(E)-1-(2-naphthyl)-2-(2,3-Dihydrobenzofuranes) ETHYL CYANOACRYLATE
White solid.M.p.:124-125℃.1H NMR(400MHz,CDCl3) δ (ppm): 8.05 (s, 1H), 7.88-7.84 (m, 4H), 7.55-7.46 (m, 3H), 7.17 (d, J=8.0Hz, 1H), 7.10 (t, J=7.6Hz, 1H), 6.86-6.82 (m, 1H), 6.75 (d, J=8.0Hz, 1H), 5.95-5.91 (m, 1H), 4.21-4.13 (m, 2H), 3.60-3.44 (m, 2H), (1.01 t, J=7.2Hz, 3H)；13C NMR(100MHz,CDCl3)δ(ppm):166.49,159.77,142.67,133.21,132.93,131.94,131.85,129.07,128.36,128.25,127.84,127.71,127.02,126.66,126.50,124.45,120.25,109.06,77.68,60.88,35.92,13.59.IR(neat):3019,1215,756,669cm-1.MS (70eV, EI) m/z=344.HRMS (EI): m/z calcd for C23H20O3(M+):344.1412.Found,344.1409。
Embodiment 12
In the reaction tube that 20mL is dried, by Pd (dppe) Cl2(0.025mmol), NaHCO3(1mmol), tetrabutylammonium chloride (0.5mmol), raw material phenyl benzyl ethers compounds is dissolved in the dimethylformamide that 2mL is dried, in disposable injection reaction tube, 90 DEG C are reacted 8 hours, magnetic agitation, TLC detects, raw material disappears, and adds suitable quantity of water and dissolves, with dichloromethane extractive reaction liquid, merge organic facies, concentrate organic solvent, then be further purified by column chromatography and obtain product, yield 76%.
(E)-1-phenyl-2-(2,3-Dihydrobenzofuranes) methacrylate
White solid.M.p.:91-92℃.1H NMR(400MHz,CDCl3) δ (ppm): 7.92 (s, 1H), 7.43-7.35 (m, 5H), 7.17-7.09 (m, 2H), 6.87-6.83 (m, 1H), 6.75 (d, J=8.0Hz, 1H), 5.82-5.77 (m, 1H), 3.71 (s, 3H), 3.59-3.53 (m, 1H), 3.41-3.35 (m, 1H)；13C NMR(100MHz,CDCl3)δ(ppm):166.64,159.57,143.05,134.31,131.24,129.20,129.07,128.55,127.85,127.21,124.50,120.32,109.06,77.76,51.89,35.71.IR(neat):3019,1717,1215,758,669cm-1.MS (70eV, EI) m/z=280.HRMS (EI): m/z calcd for C18H16O3(M+):280.1099.Found,280.1098。
It should be noted that foregoing invention content and detailed description of the invention are intended to prove the actual application of technical scheme provided by the present invention, should not be construed as limiting the scope of the present invention.Those skilled in the art in spirit and principles of the present invention, when can various modifications may be made, equivalent or improve.Protection scope of the present invention is as the criterion with appended claims.

Claims (6)

1. prepare 2 for one kind, the method for 3-dihydro-benzofuran derivative, it is characterised in that described method with Under nitrogen protection, it is sequentially added into Pd (dppe) Cl2, NaHCO3, tetrabutylammonium chloride, by raw material phenylbenzyl Ether compound (0.5mmol) is dissolved in the dimethylformamide that 2mL is dried, disposable injecting reactor In, 90 DEG C of reactions, obtain target compound, the synthetic reaction formula of target compound is:
Concrete product structure is as follows:
2. one as claimed in claim 1 prepares 2, the method for 3-dihydro-benzofuran derivative, its feature It is, described catalyst Pd (dppe) Cl2It is 1:20 with raw material molar ratio.
3. one as claimed in claim 1 prepares 2, the method for 3-dihydro-benzofuran derivative, its feature It is, described NaHCO3It is 1:0.5 with raw material molar ratio.
4. one as claimed in claim 1 prepares 2, the method for 3-dihydro-benzofuran derivative, its feature Being, described tetrabutylammonium chloride and raw material molar ratio are 1:1.
5. one as claimed in claim 1 prepares 2, the method for 3-dihydro-benzofuran derivative, its feature Being, the response time is 8 hours.
6. one as claimed in claim 1 prepares 2, the method for 3-dihydro-benzofuran derivative, its feature Being, described synthesising target compound is (E)-1-phenyl-2-(2,3-Dihydrobenzofuranes) acrylic acid second Fat, (E)-1-(2-tolyl)-2-(2,3-Dihydrobenzofuranes) ETHYL CYANOACRYLATE, (E)-1-(3-first Phenyl)-2-(2,3-Dihydrobenzofuranes) ETHYL CYANOACRYLATE, (E)-1-(4-tolyl)-2-(2,3-dihydro Benzofuran) ETHYL CYANOACRYLATE, (E)-1-(2-fluorophenyl)-2-(2,3-Dihydrobenzofuranes) acrylic acid second Fat, (E)-1-(4-fluorophenyl)-2-(2,3-Dihydrobenzofuranes) ETHYL CYANOACRYLATE, (E)-1-(2-chlorine Phenyl)-2-(2,3-Dihydrobenzofuranes) ETHYL CYANOACRYLATE, (E)-1-(3-chlorphenyl)-2-(2,3-dihydro Benzofuran) ETHYL CYANOACRYLATE, (E)-1-(4-chlorphenyl)-2-(2,3-Dihydrobenzofuranes) acrylic acid second Fat, (E)-1-(4-bromophenyl)-2-(2,3-Dihydrobenzofuranes) ETHYL CYANOACRYLATE, (E)-1-(2-naphthalene Base)-2-(2,3-Dihydrobenzofuranes) ETHYL CYANOACRYLATE, (E)-1-phenyl-2-(2,3-Dihydrobenzofuranes) Methacrylate.
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Publication number Priority date Publication date Assignee Title
CN107540649A (en) * 2017-09-30 2018-01-05 台州学院 A kind of method for preparing 3 substituted isochroman compounds

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Title
MAGALI SZLOSEK-PINAUD ET AL.: "Efficient synthetic approach to heterocycles possessing the 3,3-disubstituted-2,3-dihydrobenzofuran skeleton via diverse palladium-catalyzed tandem reactions", 《TETRAHEDRON》 *
MAGALI SZLOSEK-PINAUD: "Palladium-catalyzed cascade allylation/carbopalladation/cross coupling: a novel three-component reaction for the synthesis of 3,3-disubstituted-2,3-dihydrobenzofurans", 《TETRAHEDRON LETTERS》 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107540649A (en) * 2017-09-30 2018-01-05 台州学院 A kind of method for preparing 3 substituted isochroman compounds

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