CN106749139B - Polysubstituted condensed benzofuran derivative of one kind and preparation method thereof - Google Patents
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- 150000001907 coumarones Chemical class 0.000 title claims abstract description 44
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- 230000035484 reaction time Effects 0.000 claims abstract description 5
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 30
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 15
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 14
- 238000006243 chemical reaction Methods 0.000 claims description 13
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 claims description 10
- -1 Phosphino- Chemical class 0.000 claims description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- 239000002243 precursor Substances 0.000 claims description 9
- 239000003054 catalyst Substances 0.000 claims description 8
- AZQCFLDDJHERFZ-UHFFFAOYSA-N Br.C#Cc1ccccc1 Chemical compound Br.C#Cc1ccccc1 AZQCFLDDJHERFZ-UHFFFAOYSA-N 0.000 claims description 7
- 229940125782 compound 2 Drugs 0.000 claims description 7
- 239000007787 solid Substances 0.000 claims description 7
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 claims description 6
- 229940125904 compound 1 Drugs 0.000 claims description 6
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 6
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 5
- 150000001875 compounds Chemical class 0.000 claims description 5
- YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 claims description 5
- 239000012312 sodium hydride Substances 0.000 claims description 5
- 239000002585 base Substances 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- 239000003513 alkali Substances 0.000 claims description 3
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 239000005457 ice water Substances 0.000 claims description 3
- 239000000463 material Substances 0.000 claims description 3
- 238000000746 purification Methods 0.000 claims description 2
- YJTKZCDBKVTVBY-UHFFFAOYSA-N 1,3-Diphenylbenzene Chemical group C1=CC=CC=C1C1=CC=CC(C=2C=CC=CC=2)=C1 YJTKZCDBKVTVBY-UHFFFAOYSA-N 0.000 claims 1
- 150000001412 amines Chemical class 0.000 claims 1
- 125000003367 polycyclic group Chemical group 0.000 abstract description 3
- 239000000126 substance Substances 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- 239000000047 product Substances 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 6
- 125000000217 alkyl group Chemical group 0.000 description 6
- 230000006837 decompression Effects 0.000 description 6
- 238000000926 separation method Methods 0.000 description 5
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- 239000012265 solid product Substances 0.000 description 4
- 238000000034 method Methods 0.000 description 3
- YFKBXYGUSOXJGS-UHFFFAOYSA-N 1,3-Diphenyl-2-propanone Chemical class C=1C=CC=CC=1CC(=O)CC1=CC=CC=C1 YFKBXYGUSOXJGS-UHFFFAOYSA-N 0.000 description 2
- DVQWNQBEUKXONL-UHFFFAOYSA-N 1-iodo-2-methoxybenzene Chemical class COC1=CC=CC=C1I DVQWNQBEUKXONL-UHFFFAOYSA-N 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- 238000003477 Sonogashira cross-coupling reaction Methods 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 238000003810 ethyl acetate extraction Methods 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 229940124258 Adenosine A1 receptor antagonist Drugs 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 1
- 241001671204 Stemona Species 0.000 description 1
- 235000019013 Viburnum opulus Nutrition 0.000 description 1
- 244000071378 Viburnum opulus Species 0.000 description 1
- 239000002598 adenosine A1 receptor antagonist Substances 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000003064 anti-oxidating effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 150000004826 dibenzofurans Chemical class 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 150000002240 furans Chemical class 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 125000001979 organolithium group Chemical group 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- WJCXADMLESSGRI-UHFFFAOYSA-N phenyl selenohypochlorite Chemical compound Cl[Se]C1=CC=CC=C1 WJCXADMLESSGRI-UHFFFAOYSA-N 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 230000003334 potential effect Effects 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229930195734 saturated hydrocarbon Chemical class 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 229930195735 unsaturated hydrocarbon Chemical class 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
- C07D307/93—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 condensed with a ring other than six-membered
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The present invention provides a kind of polysubstituted condensed benzofuran derivatives and preparation method thereof, and compared with prior art, the present invention provides a series of new polysubstituted condensed benzofuran derivatives.Relative to common polysubstituted condensed benzofuran derivative, polysubstituted condensed benzofuran derivative prepared by the present invention has polycyclic presence, and the more complicated multiplicity of structure will also show more wide purposes prospect in Chemical Manufacture, clinical medicine.Also, preparation method provided by the invention is easy, efficient, and the reaction time is short, high-efficient.
Description
Technical field
The invention belongs to organic compound fields, more particularly to a kind of polysubstituted condensed benzofuran derivative and its system
Preparation Method.
Background technique
Benzofuran compounds because its extensive pharmacological activity and they in being widely present for nature cause people
Attention.For example, the benzofurans chemical combination that the 2- aryl extracted from the plants such as Radix Salviae Miltiorrhizae, the tuber of stemona, snowball replaces
Object has good physiological activity, such as antiviral and antitumor, antibacterial, free radical resisting, antioxidation, is usually used in selectivity
Adenosine A 1 receptor antagonists, immunosuppressor etc..
Find that functionalized list or dibenzofurans analog derivative are also used as blue light emitting material and are applied to again recently
In OLED, and Jung etc. also carries out the application of the organic dyestuff polymer containing benzofuran monomer in solar cells
Research；Romagnoli etc. has synthesized a series of 2- (3,4,5- trimethoxybenzoy)-benzofuran derivatives, finds this
Class compound has potential activity in terms of the growth for inhibiting cancer cell.
Yue etc. sets out in 2005 Nian Conglin iodo anisoles, first with end-group alkyne occur Sonogashira coupling, after in I2,
PhSeCl, or p-O2NC6H4Electrophilic cyclisation occurs in the presence of SCl, 2,3- disubstituted benzenes are generated with higher yield
And furan nucleus, as shown in Fig. 1.Cho etc. has carried out library to benzofuran compounds using parallel synthesis on this basis
Synthesis, has successfully obtained 121 kinds of polysubstituted benzofuran compounds.
Carril etc. makees solvent with water, generates alkyl (or aryl) benzyl ketone derivatives under the catalysis of CuI-TMEDA
Corresponding benzofuran compound, as shown in Figure 2.
Sanz etc. forms organolithium intermediate from the halogenated phenylate of benzyl -2-, with the t-BuLi processing of 3 equivalents, then
It is reacted again with carboxylate, then acidified or dehydration just obtains corresponding 2- aryl -3- and replaces benzofuran derivatives, such as Fig. 3
It is shown.
Sanz etc. from a haloamino carbamoyl ester, with NaH or n-BuLi processing followed by with corresponding electrophilic reagent
Reaction, obtains the halogenated carbaniloyl ester of o-2 (F, Cl) -3-, obtains 4- through hydrolysis, Sonogashira coupling and ring closure reaction
Halogenated benzofuran derivatives, as shown in figure 4,4- halogens are easily converted to other functional groups, and 4- position functional
The benzofuran compound that group replaces is difficult to obtain with other methods.
It is intended to complete reaction condition, the effect of highly basic and the presence of ligand that such reaction need to be harsh in summary.
Summary of the invention
In order to solve the above technical problems, the present invention provides a kind of preparation sides of polysubstituted condensed benzofuran derivative
Method, easy, efficient, the reaction time is short, high-efficient.
The present invention also provides a kind of polysubstituted condensed benzofuran derivatives, have polycyclic presence, and structure is more complicated,
Have broad application prospects.
The preparation method of the polysubstituted condensed benzofuran derivative of one kind provided by the invention, comprising the following steps:
(1) using sodium hydride as catalyst, malonate and propargyl bromide is added to ice-water bath in anhydrous acetonitrile, reacted,
Then purifies and separates obtain compound as white solid 1；
(2) compound 1 and phenylacetylene bromide or substituted phenylacetylene bromide are blended in Pd (PPh3)2Cl2/ CuI's is anhydrous
In anaerobic catalyst system, alkali is made with triethylamine, using anhydrous acetonitrile as solvent, is stirred to react, is produced after purifies and separates at room temperature
Object, i.e. precursor compound 2；
(3) under conditions of 95-100 DEG C, precursor compound 2 prepared by step (2) in toluene solvant with 2- (triphen
Base phosphoranyl) propionic aldehyde reaction, cooled to room temperature stopping reaction；Product purification is separated, white solid is obtained, i.e., it is polysubstituted
Condensed benzofuran derivative.
Further, the molar ratio of sodium hydride in step (1), malonate, propargyl bromide and anhydrous acetonitrile is 4-5:1:
2.2-3.2:20-23；The malonate is dimethyl malenate.
The reaction temperature of step (1) is at 0-5 DEG C；Reaction time was at 5 hours or more；
Purifies and separates described in step (1) specifically: product adds water washing, is extracted with ethyl acetate, and decompression is spin-dried for, and obtains
Brown solid product, i.e. compound 1.
Compound 1 described in step (2) and phenylacetylene bromide or substituted phenylacetylene bromide, Pd (PPh3)2Cl2/ CuI, three
The mass ratio of the material of ethamine and anhydrous acetonitrile is 1:2.2-3.2:0.03-0.04:4-5:30-45；Step (2) stirring is anti-
It answers, the time was at 10 hours or more.
Separation is washed described in step (2) specifically: product is washed with water, and is extracted with ethyl acetate, and decompression is spin-dried for, and uses body
Product is than the ethyl acetate for 1:60: petroleum ether column chromatography for separation obtains product as light yellow solid, i.e. precursor compound 2.
Pd (PPh described in step (2)3)2Cl2In the anhydrous and oxygen-free catalyst system of/CuI, molar ratio Pd (PPh3) 2Cl2:
CuI=3:1.
The molar ratio of precursor compound 2,2- (dihalotriphenylphosphoranes base) propionic aldehyde and toluene is 1.2-1.5:1 in step (3):
28-66；
It is reacted described in step (3), refers to 100-105 DEG C of reaction 8-9 hours；
Purifies and separates described in step (3) specifically: products therefrom is washed with water, ethyl acetate extraction, decompression is spin-dried for,
With the ethyl acetate of volume ratio 1:40: the column chromatography for separation of petroleum ether obtains white solid, i.e., polysubstituted condensed benzofurans
Derivative, i.e. compound 3, it is about 77.8% that column, which chromatographs yield,.
Polysubstituted condensed benzofuran derivative, structural formula prepared by the present invention are as follows:
Wherein E1And E2It is identical, it is CO2R, R are straight chained alkyl, branched alkyl, saturated hydrocarbons, unsaturated hydro carbons or aromatic hydrocarbon
Class group；R1For halogen, straight chained alkyl, branched alkyl, ester group, alkoxy and its corresponding derivative.
Further, the R is methyl, R1For hydrogen, structural formula are as follows::
Compared with prior art, preparation method provided by the invention is related to methyl using witting reagent from new angle
The reaction process such as the transfer of migration electronics that benzofurans have simply, efficiently been synthesized under conditions of no catalyst is derivative
Object, and the reaction time is short, it is high-efficient.Also, provide a series of new polysubstituted condensed benzofuran derivatives.Relative to
Common polysubstituted condensed benzofuran derivative, polysubstituted condensed benzofuran derivative prepared by the present invention has polycyclic
In the presence of the more complicated multiplicity of structure will also show more wide purposes prospect in Chemical Manufacture, clinical medicine.
Detailed description of the invention
Fig. 1 sets out in 2005 Nian Conglin iodo anisoles for Yue etc. and prepares the reaction side of 2,3- disubstituted benzofuran ring
Formula；
Fig. 2 is that Carril etc. is generated accordingly using alkyl (or aryl) benzyl ketone derivatives under the catalysis of CuI-TMEDA
Benzofuran compound equation；
Fig. 3 is the equation that Sanz etc. prepares that 2- aryl -3- replaces benzofuran derivatives from the halogenated phenylate of benzyl -2-
Formula；
Fig. 4 is that Sanz etc. obtains the equation of the halogenated benzofuran derivatives of 4- from a haloamino carbamoyl ester；
Fig. 5 is the structural formula of polysubstituted condensed benzofuran derivative；
Fig. 6 is the structural formula of polysubstituted condensed benzofuran derivative prepared by embodiment 1；
Fig. 7 is the nuclear magnetic resonance spectroscopy of polysubstituted condensed benzofuran derivative prepared by embodiment 1；
Fig. 8 is the carbon-13 nmr spectra of polysubstituted condensed benzofuran derivative prepared by embodiment 1；
Fig. 9 is the reaction process of polysubstituted condensed benzofuran derivative prepared by embodiment 1.
Specific embodiment
Embodiment 1
A kind of polysubstituted condensed benzofuran derivative, structural formula are as follows:
A kind of preparation method of polysubstituted condensed benzofuran derivative, comprising the following steps:
(1) using 830mmol sodium hydride as catalyst, 200mmol dimethyl malenate and 440mmol propargyl bromide are added
The ice-water bath into 210mL anhydrous acetonitrile is stirred to react 8 hours, and product adds water washing, is extracted with ethyl acetate, and decompression is spin-dried for, and obtains
To yellow-brown solid product, i.e. compound 1；
(2) 80mmol compound 1 and 200mmol phenylacetylene bromide are blended in Pd (PPh3)2Cl2/CuI(2.56mmol/
In anhydrous and oxygen-free catalyst system 0.85mmol), molar ratio Pd (PPh3)2Cl2: CuI=3:1 makees alkali with 336mmol triethylamine,
It using 150mL anhydrous acetonitrile as solvent, is stirred to react at room temperature 12 hours, product is washed with water, and is extracted with ethyl acetate, decompression rotation
Dry, the ethyl acetate for being 1:60 with volume ratio: petroleum ether column chromatography for separation obtains product as light yellow solid, i.e. precursor compound
2。
(3) under conditions of 100 DEG C, 1.2mmol precursor compound 2 prepared by step (2) 5mL toluene solvant with
1mmol 2- (dihalotriphenylphosphoranes base) propionic aldehyde reacts 18 hours, obtains compound 3, i.e., polysubstituted condensed benzofuran derivative
Crude product；The crude product with water of the polysubstituted condensed benzofuran derivative of preparation is washed, ethyl acetate extraction, decompression rotation
Dry, with volume ratio ethyl acetate: petroleum ether=1:40 column chromatography for separation obtains white solid product, i.e., polysubstituted condensed benzo
Furan derivative, it is about 77.8% that column, which chromatographs yield,.
Prepared polysubstituted condensed benzofuran derivative structure passes through；1H NMR；13C NMR is measured.
White solid product:
1H NMR(300MHz,CDCl3)δ7.64-7.25(m,10H),6.31(s,1H),3.92-3.89(d,2H),3.80
(s,6H),2.42(s,3H).
13C NMR(125MHz,CDCl3) δ 172.53,156.09,150.67,139.77,138.83,135.99,
131.65,130.41,128.69,128.59,128.26,127.81,124.16,121.19,112.73,103.24,94.59,
87.98,60.33,53.42,42.00,38.21,14.32.
Claims (8)
1. a kind of preparation method of polysubstituted condensed benzofuran derivative, which is characterized in that the preparation method include with
Lower step:
(1) using sodium hydride as catalyst, malonate and propargyl bromide is added to ice-water bath in anhydrous acetonitrile, reacted, then
Purifies and separates, obtain compound as white solid 1, and structural formula is
(2) compound 1 and phenylacetylene bromide are blended in Pd (PPh3)2Cl2In the anhydrous and oxygen-free catalyst system of/CuI, with three second
Amine makees alkali, using anhydrous acetonitrile as solvent, is stirred to react at room temperature, and product, i.e. precursor compound 2 are obtained after purifies and separates, knot
Structure formula are as follows:
(3) under conditions of 95-100 DEG C, (triphenyl is just with 2- in toluene solvant for precursor compound 2 prepared by step (2)
Phosphino-) propionic aldehyde reaction, cooled to room temperature stopping reaction；Product purification is separated, white solid is obtained, i.e., it is polysubstituted condensed
Benzofuran derivative, structural formula are as follows:
2. the preparation method of polysubstituted condensed benzofuran derivative according to claim 1, which is characterized in that step
(1) sodium hydride in, malonate, propargyl bromide and anhydrous acetonitrile molar ratio be 4-5:1:2.2-3.2:20-23.
3. the preparation method of polysubstituted condensed benzofuran derivative according to claim 1 or 2, which is characterized in that
Malonate described in step (1) is dimethyl malenate.
4. the preparation method of polysubstituted condensed benzofuran derivative according to claim 1 or 2, which is characterized in that
The reaction temperature of step (1) is at 0-5 DEG C；Reaction time was at 5 hours or more.
5. the preparation method of polysubstituted condensed benzofuran derivative according to claim 1 or 2, which is characterized in that
Compound 1 described in step (2) and phenylacetylene bromide, Pd (PPh3)2Cl2The mass ratio of the material of/CuI, triethylamine and anhydrous acetonitrile
For 1:2.2-3.2:0.03-0.04:4-5:30-45.
6. the preparation method of polysubstituted condensed benzofuran derivative according to claim 1 or 2, which is characterized in that
Step (2) is described to be stirred to react, and the time was at 10 hours or more.
7. the preparation method of polysubstituted condensed benzofuran derivative according to claim 1 or 2, which is characterized in that
The molar ratio of precursor compound 2,2- (dihalotriphenylphosphoranes base) propionic aldehyde and toluene is 1.2-1.5:1:28-66 in step (3).
8. the preparation method of polysubstituted condensed benzofuran derivative according to claim 1 or 2, which is characterized in that
It is reacted described in step (3), time 8-9 hour.
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| CN107954873B (en) * | 2017-12-07 | 2020-06-19 | 安徽师范大学 | Polysubstituted olefine acid ester derivative and preparation method thereof |
| CN107986969B (en) * | 2017-12-07 | 2020-06-19 | 安徽师范大学 | Dodecahydron as benzodiindenophenanthrene derivative and synthesis method thereof |
| CN109369508B (en) * | 2018-11-28 | 2021-08-27 | 安徽师范大学 | Polysubstituted indole derivative and preparation method thereof |
| CN109879791A (en) * | 2019-03-26 | 2019-06-14 | 安徽师范大学 | A kind of isoindoline derivative and preparation method thereof |
| CN114605341A (en) * | 2022-04-25 | 2022-06-10 | 安徽师范大学 | Benzisoxazole compound and preparation method thereof |
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| CN105777679A (en) * | 2016-04-07 | 2016-07-20 | 安徽师范大学 | Benzodihydropyran ring derivative and preparation method thereof |
| CN105949152A (en) * | 2016-07-08 | 2016-09-21 | 安徽师范大学 | Benzofuran derivative and preparation method thereof |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105777679A (en) * | 2016-04-07 | 2016-07-20 | 安徽师范大学 | Benzodihydropyran ring derivative and preparation method thereof |
| CN105949152A (en) * | 2016-07-08 | 2016-09-21 | 安徽师范大学 | Benzofuran derivative and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| Fused Multifunctionalized Chromenes from Tetraynes and α,β-Unsaturated Aldehydes;Xiangzhen Meng 等;《Chem. Eur. J.》;20170410;第23卷;6264-6271 * |
| 四炔的芳炔环加成反应简便合成芳胺;吴玉芹 等;《有机化学》;20150315;第35卷(第3期);724-730 * |
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