CN105801538B - A kind of method for preparing 2,3- dihydro-benzofuran derivatives - Google Patents

A kind of method for preparing 2,3- dihydro-benzofuran derivatives Download PDF

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CN105801538B
CN105801538B CN201610204289.8A CN201610204289A CN105801538B CN 105801538 B CN105801538 B CN 105801538B CN 201610204289 A CN201610204289 A CN 201610204289A CN 105801538 B CN105801538 B CN 105801538B
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dihydrobenzofuranes
ethyl acrylate
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dihydro
preparing
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CN105801538A (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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    • 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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Abstract

The present invention discloses a kind of method for preparing 2,3 dihydro-benzofuran derivatives, and this method is using phenylbenzyl ethers compound as raw material, in Pd (dppe) Cl2, under tetrabutylammonium chloride catalytic action, NaHCO3For alkali, dimethylformamide is solvent, and under nitrogen protection system, reaction temperature is 90 degrees Celsius, and when reaction 8 is small, synthesising target compound, the synthetic method is simple, yield is higher, mild condition, and one pot process has a good application prospect.

Description

A kind of method for preparing 2,3- dihydro-benzofuran derivatives
Technical field
The present invention relates to a kind of chemical reactions efficiently, easy, in relatively mild reaction system, pass through one pot process The method of 2,3- dihydro-benzofuran derivatives.
Background technology
2,3- Dihydrobenzofuranes are widely used in the conjunction of heterocycle compound as a kind of important organic intermediate Into, at the same still synthesize some important drugs intermediates 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), the disappointing second ammonia of protease inhibitors amino acid 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, first, benzene The disubstituted synthetic method in ortho position on ring；Second is that benzofuran hydrogenates synthetic method；Third, monosubstituted synthetic method on phenyl ring, but this three classes is closed 2, the 3- Dihydrobenzofuranes functional group obtained into method is all relatively simple, is unfavorable for synthesizing the complexity of active structure fragment Compound, and the domestic ability and process route that there is no such compound of large-scale production.
The coupling reaction of palladium chtalyst is the research hotspot of organic chemistry in recent years, for building new carbon-carbon bond and carbon-miscellaneous Key is all highly effective, and has the characteristics that efficient, green, therefore as the important component in modern organic synthesis field (Organic Reactions 1982,345；Tetrahedron Letters 1999,1673； Angew.Chem.Int.Ed.1995,2379；Chem.Rev.2000,3009).Heck reactions are a kind of important halogenated aryl hydrocarbons Olefination is the reaction of the new carbon-carbon bond of structure, and Mizoroki and Heck were found that such respectively at 1971 and 1972 React (Bulletin of the Chemical Society of Japan 1971,581；J.Org.Chem.1972, 2320), it was developing progressively in past more than 40 years as a kind of widely used methodology of organic synthesis (Adv.Syn.＆ Cata.2002,393), organic chemist has synthesized many active structures using the Heck reactions of intramolecular in recent years Heterocyclic compound and high-molecular compound (Synthesis 2003,1383；Polymer Bulletin 2001,29), especially It is to suffer from being widely applied (Chem.Rev.2007,133 in terms of some medicine intermediates are synthesized；Tetrahedron 2007,6949), reactant the urging in zeroth order palladium or palladium complex that be mainly halogenated aryl hydrocarbon with the alkene with α-electron withdrawing group The lower reaction generation virtue of change effect is for alkene.
Based on above synthesis feature, we have invented using benzyl phenyl ether as raw material, acted on down by palladium chtalyst, benzylic ether Key disconnects, and forms the compound with conjugated diene hydrocarbon structure, and the conjugated diene then formed occurs with another molecule fragment Heck and addition reaction, 2,3- dihydro-benzofuran derivative of the synthesis with highly useful acrylic-functional.The synthesis Method is simple, and the reaction being related to has disconnected ehter bond to be rearranged into conjugated diene, and Heck reactions and addition reaction then occurs, but can pass through One pot process target molecule.
The content of the invention
The present invention is using phenylbenzyl ethers compound as raw material, and dimethylformamide is solvent, in nitrogen protection system Under, synthesising target compound.The synthetic method is simple, and three-step reaction is completed in one pot, and yield is higher, is 2,3- dihydrobenzos The synthesis of furan derivatives provides a kind of efficient synthetic method.
According to the present invention, the reaction of 2, the 3- dihydro-benzofuran derivatives, main synthesis step are：With benzene Base benzyl ethers compounds are raw material, in Pd (dppe) Cl2, tetrabutylammonium chloride be catalyst, NaHCO3For alkali, dimethyl methyl Amide is solvent, and under nitrogen protection system, reaction temperature is 90 degrees Celsius, when reaction 8 is small, synthesising target compound, wherein, The synthetic reaction formula of target compound is：
Specific product structure is as follows：
Above-mentioned reacting middle catalyst Pd (dppe) Cl2It is 1 with raw material molar ratio：20, NaHCO3It feeds intake mole with raw material Than for 1：0.5, tetrabutylammonium chloride is 1 with raw material molar ratio：1, dimethylformamide is solvent, in nitrogen protection system Under, reaction temperature is 90 degrees Celsius, when reaction 8 is small.
By above-mentioned synthetic method, be prepared for (E) -1- phenyl -2- (2,3- Dihydrobenzofuranes) ETHYL CYANOACRYLATE, (E) - 1- (2- tolyls) -2- (2,3- Dihydrobenzofuranes) ETHYL CYANOACRYLATE, (E) -1- (3- tolyls) -2- (2,3- dihydrobenzos Furans) ETHYL CYANOACRYLATE, (E) -1- (4- tolyls) -2- (2,3- Dihydrobenzofuranes) ETHYL CYANOACRYLATE, (E) -1- (2- fluorobenzene Base) -2- (2,3- Dihydrobenzofuranes) ETHYL CYANOACRYLATE, (E) -1- (4- fluorophenyls) -2- (2,3- Dihydrobenzofuranes) propylene Sour second fat, (E) -1- (2- chlorphenyls) -2- (2,3- Dihydrobenzofuranes) ETHYL CYANOACRYLATE, (E) -1- (3- chlorphenyls) -2- (2, 3- Dihydrobenzofuranes) ETHYL CYANOACRYLATE, (E) -1- (4- chlorphenyls) -2- (2,3- Dihydrobenzofuranes) ETHYL CYANOACRYLATE, (E) -1- (4- bromophenyls) -2- (2,3- Dihydrobenzofuranes) ETHYL CYANOACRYLATE, (E) -1- (2- naphthalenes) -2- (2,3- dihydrobenzenes And furans) ETHYL CYANOACRYLATE, (E) -1- phenyl -2- (2,3- Dihydrobenzofuranes) 12 compounds of methacrylate.
It is above-mentioned to cool down at room temperature after reaction, add a small amount of water dissolution, then extracted 3 times with dichloromethane, merge extraction The organic solvent of taking-up, is dried with anhydrous magnesium sulfate, then concentrates organic solvent, is further purified by column chromatography, obtains mesh Mark product.
Specific embodiment
Below with reference to embodiment, the present invention will be further described, and the embodiment of the present invention is merely to illustrate the present invention's Technical solution, and the non-limiting present invention.
Embodiment 1
In the reaction tube of 20mL dryings, by Pd (dppe) Cl2(0.025mmol), NaHCO3(1mmol), tetrabutyl chlorination Raw material phenyl benzyl ethers compounds are dissolved in the dimethylformamide of 2mL dryings by ammonium (0.5mmol), and disposable injection is anti- Ying Guanzhong, when 90 DEG C of reactions 8 are small, magnetic agitation, TLC detections, raw material disappearance adds appropriate water dissolution, anti-with dichloromethane extraction It answers liquid, merges organic phase, concentrate organic solvent, then be further purified with column chromatography to 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 of 20mL dryings, by Pd (dppe) Cl2(0.025mmol), NaHCO3(1mmol), tetrabutyl chlorination Raw material phenyl benzyl ethers compounds are dissolved in the dimethylformamide of 2mL dryings by ammonium (0.5mmol), and disposable injection is anti- Ying Guanzhong, when 90 DEG C of reactions 8 are small, magnetic agitation, TLC detections, raw material disappearance adds appropriate water dissolution, anti-with dichloromethane extraction It answers liquid, merges organic phase, concentrate organic solvent, then be further purified with column chromatography to obtain product, yield 63%.
(E) -1- (2- tolyls) -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 of 20mL dryings, by Pd (dppe) Cl2(0.025mmol), NaHCO3(1mmol), tetrabutyl chlorination Raw material phenyl benzyl ethers compounds are dissolved in the dimethylformamide of 2mL dryings by ammonium (0.5mmol), and disposable injection is anti- Ying Guanzhong, when 90 DEG C of reactions 8 are small, magnetic agitation, TLC detections, raw material disappearance adds appropriate water dissolution, anti-with dichloromethane extraction It answers liquid, merges organic phase, concentrate organic solvent, then be further purified with column chromatography to obtain product, yield 66%.
(E) -1- (3- tolyls) -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 of 20mL dryings, by Pd (dppe) Cl2(0.025mmol), NaHCO3(1mmol), tetrabutyl chlorination Raw material phenyl benzyl ethers compounds are dissolved in the dimethylformamide of 2mL dryings by ammonium (0.5mmol), and disposable injection is anti- Ying Guanzhong, when 90 DEG C of reactions 8 are small, magnetic agitation, TLC detections, raw material disappearance adds appropriate water dissolution, anti-with dichloromethane extraction It answers liquid, merges organic phase, concentrate organic solvent, then be further purified with column chromatography to obtain product, yield 71%.
(E) -1- (4- tolyls) -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 of 20mL dryings, by Pd (dppe) Cl2(0.025mmol), NaHCO3(1mmol), tetrabutyl chlorination Raw material phenyl benzyl ethers compounds are dissolved in the dimethylformamide of 2mL dryings by ammonium (0.5mmol), and disposable injection is anti- Ying Guanzhong, when 90 DEG C of reactions 8 are small, magnetic agitation, TLC detections, raw material disappearance adds appropriate water dissolution, anti-with dichloromethane extraction It answers liquid, merges organic phase, concentrate organic solvent, then be further purified with column chromatography to obtain product, yield 61%.
(E) -1- (2- fluorophenyls) -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 of 20mL dryings, by Pd (dppe) Cl2(0.025mmol), NaHCO3(1mmol), tetrabutyl chlorination Raw material phenyl benzyl ethers compounds are dissolved in the dimethylformamide of 2mL dryings by ammonium (0.5mmol), and disposable injection is anti- Ying Guanzhong, when 90 DEG C of reactions 8 are small, magnetic agitation, TLC detections, raw material disappearance adds appropriate water dissolution, anti-with dichloromethane extraction It answers liquid, merges organic phase, concentrate organic solvent, then be further purified with column chromatography to obtain product, yield 44%.
(E) -1- (4- fluorophenyls) -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 of 20mL dryings, by Pd (dppe) Cl2(0.025mmol), NaHCO3(1mmol), tetrabutyl chlorination Raw material phenyl benzyl ethers compounds are dissolved in the dimethylformamide of 2mL dryings by ammonium (0.5mmol), and disposable injection is anti- Ying Guanzhong, when 90 DEG C of reactions 8 are small, magnetic agitation, TLC detections, raw material disappearance adds appropriate water dissolution, anti-with dichloromethane extraction It answers liquid, merges organic phase, concentrate organic solvent, then be further purified with column chromatography to obtain product, yield 77%.
(E) -1- (2- chlorphenyls) -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 of 20mL dryings, by Pd (dppe) Cl2(0.025mmol), NaHCO3(1mmol), tetrabutyl chlorination Raw material phenyl benzyl ethers compounds are dissolved in the dimethylformamide of 2mL dryings by ammonium (0.5mmol), and disposable injection is anti- Ying Guanzhong, when 90 DEG C of reactions 8 are small, magnetic agitation, TLC detections, raw material disappearance adds appropriate water dissolution, anti-with dichloromethane extraction It answers liquid, merges organic phase, concentrate organic solvent, then be further purified with column chromatography to obtain product, yield 71%.
(E) -1- (3- chlorphenyls) -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 of 20mL dryings, by Pd (dppe) Cl2(0.025mmol), NaHCO3(1mmol), tetrabutyl chlorine Change ammonium (0.5mmol), raw material phenyl benzyl ethers compounds are dissolved in the dimethylformamide of 2mL dryings, it is disposable to inject In reaction tube, when 90 DEG C of reactions 8 are small, magnetic agitation, TLC is detected, and raw material disappears, and adds appropriate water dissolution, is extracted with dichloromethane Reaction solution merges organic phase, concentrates organic solvent, then is further purified with column chromatography to obtain product, yield 48%.
(E) -1- (4- chlorphenyls) -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 of 20mL dryings, by Pd (dppe) Cl2(0.025mmol), NaHCO3(1mmol), tetrabutyl chlorination Raw material phenyl benzyl ethers compounds are dissolved in the dimethylformamide of 2mL dryings by ammonium (0.5mmol), and disposable injection is anti- Ying Guanzhong, when 90 DEG C of reactions 8 are small, magnetic agitation, TLC detections, raw material disappearance adds appropriate water dissolution, anti-with dichloromethane extraction It answers liquid, merges organic phase, concentrate organic solvent, then be further purified with column chromatography to obtain product, yield 35%.
(E) -1- (4- bromophenyls) -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 of 20mL dryings, by Pd (dppe) Cl2(0.025mmol), NaHCO3(1mmol), tetrabutyl chlorination Raw material phenyl benzyl ethers compounds are dissolved in the dimethylformamide of 2mL dryings by ammonium (0.5mmol), and disposable injection is anti- Ying Guanzhong, when 90 DEG C of reactions 8 are small, magnetic agitation, TLC detections, raw material disappearance adds appropriate water dissolution, anti-with dichloromethane extraction It answers liquid, merges organic phase, concentrate organic solvent, then be further purified with column chromatography to obtain product, yield 59%.
(E) -1- (2- naphthalenes) -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 of 20mL dryings, by Pd (dppe) Cl2(0.025mmol), NaHCO3(1mmol), tetrabutyl chlorine Change ammonium (0.5mmol), raw material phenyl benzyl ethers compounds are dissolved in the dimethylformamide of 2mL dryings, it is disposable to inject In reaction tube, when 90 DEG C of reactions 8 are small, magnetic agitation, TLC is detected, and raw material disappears, and adds appropriate water dissolution, is extracted with dichloromethane Reaction solution merges organic phase, concentrates organic solvent, then is further purified with column chromatography to 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 specific embodiment are intended to prove technical solution provided by the present invention Practical application should not be construed as limiting the scope of the present invention.Those skilled in the art are in spirit and principles of the present invention It is interior, when can various modifications may be made, equivalent substitution or improve.Protection scope of the present invention is subject to the appended claims.

Claims (6)

  1. A kind of 1. method for preparing 2,3- dihydro-benzofuran derivatives, which is characterized in that the method is protected down with nitrogen, Sequentially add Pd (dppe) Cl2, NaHCO3, tetrabutylammonium chloride, by raw material phenyl benzyl ethers compounds be dissolved in 2mL drying Disposable to inject in reactor in dimethylformamide, 90 DEG C of reactions obtain target compound, the synthesis of target compound is anti- Ying Shiwei：
    Specific product structure is as follows：
  2. 2. a kind of method for preparing 2,3- dihydro-benzofuran derivatives as described in claim 1, which is characterized in that described to urge Agent Pd (dppe) Cl2It is 1 with raw material molar ratio：20.
  3. 3. a kind of method for preparing 2,3- dihydro-benzofuran derivatives as described in claim 1, which is characterized in that described NaHCO3It is 1 with raw material molar ratio：0.5.
  4. 4. a kind of method for preparing 2,3- dihydro-benzofuran derivatives as described in claim 1, which is characterized in that described Tetrabutylammonium chloride is 1 with raw material molar ratio：1.
  5. 5. a kind of method for preparing 2,3- dihydro-benzofuran derivatives as described in claim 1, which is characterized in that during reaction Between for 8 it is small when.
  6. 6. a kind of method for preparing 2,3- dihydro-benzofuran derivatives as described in claim 1, which is characterized in that described Synthesising target compound for (E) -1- phenyl -2- (2,3- Dihydrobenzofuranes) ethyl acrylate, (E) -1- (2- tolyls) - 2- (2,3- Dihydrobenzofuranes) ethyl acrylate, (E) -1- (3- tolyls) -2- (2,3- Dihydrobenzofuranes) acrylic acid second Ester, (E) -1- (4- tolyls) -2- (2,3- Dihydrobenzofuranes) ethyl acrylate, (E) -1- (2- fluorophenyls) -2- (2,3- Dihydrobenzofuranes) ethyl acrylate, (E) -1- (4- fluorophenyls) -2- (2,3- Dihydrobenzofuranes) ethyl acrylate, (E) -1- (2- chlorphenyls) -2- (2,3- Dihydrobenzofuranes) ethyl acrylate, (E) -1- (3- chlorphenyls) -2- (2,3- dihydros Benzofuran) ethyl acrylate, (E) -1- (4- chlorphenyls) -2- (2,3- Dihydrobenzofuranes) ethyl acrylate, (E) -1- (4- bromophenyls) -2- (2,3- Dihydrobenzofuranes) ethyl acrylate, (E) -1- (2- naphthalenes) -2- (2,3- dihydrobenzo furans Mutter) ethyl acrylate, (E) -1- phenyl -2- (2,3- Dihydrobenzofuranes) methyl acrylate.
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Efficient synthetic approach to heterocycles possessing the 3,3-disubstituted-2,3-dihydrobenzofuran skeleton via diverse palladium-catalyzed tandem reactions;Magali Szlosek-Pinaud et al.;《Tetrahedron》;20071231;第63卷;3340-3349 *
Palladium-catalyzed cascade allylation/carbopalladation/cross coupling: a novel three-component reaction for the synthesis of 3,3-disubstituted-2,3-dihydrobenzofurans;Magali Szlosek-Pinaud;《TETRAHEDRON LETTERS》;20031231;第44卷;8657-8659 *

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