CN106749139A - One kind is polysubstituted to condense benzofuran derivative and preparation method thereof - Google Patents
One kind is polysubstituted to condense benzofuran derivative and preparation method thereof Download PDFInfo
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- CN106749139A CN106749139A CN201611069814.6A CN201611069814A CN106749139A CN 106749139 A CN106749139 A CN 106749139A CN 201611069814 A CN201611069814 A CN 201611069814A CN 106749139 A CN106749139 A CN 106749139A
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- polysubstituted
- benzofuran derivative
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- JWDDEJIGKJOFAW-UHFFFAOYSA-N Cc1cc2c(-c3ccccc3)c(C#Cc3ccccc3)c(CC(C3)(C(OC)=O)C(OC)=O)c3c2[o]1 Chemical compound Cc1cc2c(-c3ccccc3)c(C#Cc3ccccc3)c(CC(C3)(C(OC)=O)C(OC)=O)c3c2[o]1 JWDDEJIGKJOFAW-UHFFFAOYSA-N 0.000 description 1
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- 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
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Abstract
Benzofuran derivative and preparation method thereof is condensed the invention provides one kind is polysubstituted, compared with prior art, new polysubstituted benzofuran derivative is condensed the invention provides a series of.Benzofuran derivative is condensed relative to commonly polysubstituted, the polysubstituted benzofuran derivative that condenses prepared by the present invention has polycyclic presence, and its structure is more complicated various, and more wide purposes prospect will be also shown in Chemical Manufacture, clinical medicine.Also, the present invention provide preparation method is simple, efficiently, the reaction time is short, efficiency high.
Description
Technical field
It is specifically related to a kind of polysubstituted to condense benzofuran derivative and its system the invention belongs to organic compound field
Preparation Method.
Background technology
Benzofuran compounds because its extensive pharmacological activity and they cause people in being widely present for nature
Attention.Such as, the benzofurans chemical combination of the 2- aryl substitution for being extracted from the plants such as the red sage root, the tuber of stemona, snowball
Thing has good physiologically active, and such as antiviral, antitumor, antibacterial, Green Tea Extract, antioxidation are usually used in selectivity
Adenosine A 1 receptor antagonists, immunodepressant etc..
Find that the list or dibenzofurans analog derivative of functionalization are also used as blue light emitting material and are applied to again recently
In OLED, and the application also to the organic dyestuff polymer containing benzofuran monomer in solar cells such as Jung is carried out
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 of cancer cell is suppressed.
From adjacent iodo anisole, first there is Sonogashira couplings with end-group alkyne in 2005 in Yue etc., after in I2,
PhSeCl, or p-O2NC6H4There is electrophilic cyclisation in the presence of SCl, 2,3- disubstituted benzenes are generated with yield higher
And furan nucleus, as shown in Figure 1.Cho etc. has carried out storehouse using parallel synthesis to benzofuran compounds on this basis
Synthesis, has successfully obtained 121 kinds of polysubstituted benzofuran compounds.
Carril etc. makees solvent with water, alkyl (or aryl) benzyl ketone derivatives is generated under the catalysis of CuI-TMEDA
Corresponding benzofuran compound, as shown in Figure 2.
Sanz etc. forms organolithium intermediate, then from benzyl -2- halo phenylates with the t-BuLi treatment of 3 equivalents
Reacted with carboxylate again, then acidified or dehydration just obtains corresponding 2- aryl -3- substitutions benzofuran derivatives, such as Fig. 3
It is shown.
Sanz etc. from a haloamino carbamoyl ester, with NaH or n-BuLi process followed by with corresponding electrophilic reagent
Reaction, obtains o-2 (F, Cl) -3- halo carbaniloyl esters, and 4- is obtained through hydrolysis, Sonogashira couplings and ring closure reaction
Halo benzofuran derivatives, as shown in figure 4, the halogen of 4- is easily converted to other functional groups, and 4- position functionals
The benzofuran compound others method of substituent group is difficult to obtain.
It is intended to complete the harsh reaction condition of such reaction need, the effect of highly basic and the presence of part in sum.
The content of the invention
In order to solve the above technical problems, the invention provides a kind of polysubstituted preparation side for condensing benzofuran derivative
Method, easy, efficient, the reaction time is short, efficiency high.
Present invention also offers one kind it is polysubstituted condense benzofuran derivative, with polycyclic presence, structure is more complicated,
Have broad application prospects.
A kind of polysubstituted preparation method for condensing benzofuran derivative that the present invention is provided, comprises the following steps：
(1) with sodium hydride as catalyst, malonate and propargyl bromide are added to ice-water bath in anhydrous acetonitrile, reaction,
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 and catalyzing, alkali is made with triethylamine, with anhydrous acetonitrile as solvent, stirring reaction, is produced after purifies and separates at room temperature
Thing, 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- (triphens
Base phosphoranyl) propionic aldehyde reaction, naturally cool to room temperature and stop reaction；Product purification is separated, white solid is obtained, i.e., it is polysubstituted
Condense benzofuran derivative.
Further, the mol ratio of sodium hydride, malonate, propargyl bromide and anhydrous acetonitrile is 4-5 in step (1)：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 is more than 5 hours；
Purifies and separates are specially described in step (1)：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 amount 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-
Should, the time is more than 10 hours.
Separation is washed described in step (2) to be specially：Product is washed with water, is extracted with ethyl acetate, and decompression is spin-dried for, and uses body
Product is than being 1:60 ethyl acetate：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 and catalyzing of/CuI, mol ratio Pd (PPh3) 2Cl2:
CuI=3:1.
The mol ratio of precursor compound 2,2- (dihalotriphenylphosphoranes base) propionic aldehyde and toluene is 1.2-1.5 in step (3)：1：
28-66；
Reacted described in step (3), refer to 100-105 DEG C and react 8-9 hours；
Purifies and separates are specially described in step (3)：Products therefrom is washed with water, ethyl acetate extraction, decompression is spin-dried for,
With volume ratio 1:40 ethyl acetate：The column chromatography for separation of petroleum ether, obtains white solid, i.e., polysubstituted to condense benzofurans
Derivative, i.e. compound 3, column chromatography yield are about 77.8%.
Polysubstituted prepared by the present invention condenses benzofuran derivative, and structural formula is:
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；R1It is halogen, straight chained alkyl, branched alkyl, ester group, alkoxy and its corresponding derivative.
Further, the R is methyl, R1It is hydrogen, its structural formula is：：
Compared with prior art, the preparation method that the present invention is provided is related to methyl from new angle using witting reagents
The course of reaction such as the transfer of migration electronics simply, efficiently synthesized benzofurans derivative under conditions of without catalyst
Thing, and the reaction time is short, efficiency high.Also, new polysubstituted condense benzofuran derivative there is provided a series of.Relative to
Commonly polysubstituted to condense benzofuran derivative, the polysubstituted benzofuran derivative that condenses prepared by the present invention has polycyclic
In the presence of its structure is more complicated various, and more wide purposes prospect will be also shown in Chemical Manufacture, clinical medicine.
Brief description of the drawings
Fig. 1 is the reaction side that Yue etc. prepared 2,3- disubstituted benzofuran rings in 2005 from adjacent iodo anisole
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 that Sanz etc. prepares the equation that 2- aryl -3- replaces benzofuran derivatives from benzyl -2- halo phenylates
Formula；
Fig. 4 is the equation that Sanz etc. obtains 4- halo benzofuran derivatives from a haloamino carbamoyl ester；
Fig. 5 is the polysubstituted structural formula for condensing benzofuran derivative；
Fig. 6 is the polysubstituted structural formula for condensing benzofuran derivative prepared by embodiment 1；
Fig. 7 is the polysubstituted proton nmr spectra for condensing benzofuran derivative prepared by embodiment 1；
Fig. 8 is the polysubstituted carbon-13 nmr spectra for condensing benzofuran derivative prepared by embodiment 1；
Fig. 9 is the polysubstituted course of reaction for condensing benzofuran derivative prepared by embodiment 1.
Specific embodiment
Embodiment 1
One kind is polysubstituted to condense benzofuran derivative, and its structural formula is：
A kind of polysubstituted preparation method for condensing benzofuran derivative, comprises the following steps：
(1) with 830mmol sodium hydrides as catalyst, 200mmol dimethyl malenates and 440mmol propargyl bromides are added
The ice-water bath in 210mL anhydrous acetonitriles, stirring reaction 8 hours, 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 compounds 1 and 200mmol phenylacetylene bromides are blended in Pd (PPh3)2Cl2/CuI(2.56mmol/
In anhydrous and oxygen-free catalyst system and catalyzing 0.85mmol), mol ratio Pd (PPh3)2Cl2:CuI=3:1, alkali is made with 336mmol triethylamines,
With 150mL anhydrous acetonitriles as solvent, stirring reaction 12 hours at room temperature, product is washed with water, is extracted with ethyl acetate, decompression rotation
It is dry, it is 1 with volume ratio:60 ethyl acetate：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 compounds 2 prepared by step (2) 5mL toluene solvants with
1mmol 2- (dihalotriphenylphosphoranes base) propionic aldehyde reacts 18 hours, obtain compound 3, i.e., the polysubstituted benzofuran derivative that condenses
Crude product；The polysubstituted crude product with water washing for condensing benzofuran derivative that will be prepared, ethyl acetate extraction, decompression rotation
It is dry, use volume ratio ethyl acetate：Petroleum ether=1:40 column chromatography for separation, obtain white solid product, i.e., polysubstituted to condense benzo
Furan derivative, column chromatography yield is about 77.8%.
The prepared polysubstituted benzofuran derivative structure that condenses passes through；1H NMR；13C NMR are determined.
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 (10)
1. a kind of polysubstituted preparation method for condensing benzofuran derivative, it is characterised in that the preparation method include with
Lower step：
(1) with sodium hydride as catalyst, malonate and propargyl bromide are added to ice-water bath in anhydrous acetonitrile, reaction, 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)2Cl2The anhydrous and oxygen-free of/CuI
In catalyst system and catalyzing, alkali is made with triethylamine, with anhydrous acetonitrile as solvent, stirring reaction, obtains product, i.e., at room temperature after purifies and separates
Precursor compound 2；
(3) under conditions of 95-100 DEG C, (triphenyl is just with 2- in toluene solvant for the precursor compound 2 prepared by step (2)
Phosphino-) propionic aldehyde reaction, naturally cool to room temperature and stop reaction；Product purification is separated, white solid is obtained, i.e., it is polysubstituted to condense
Benzofuran derivative.
2. the polysubstituted preparation method for condensing benzofuran derivative according to claim 1, it is characterised in that step
(1) mol ratio of sodium hydride, malonate, propargyl bromide and anhydrous acetonitrile is 4-5 in：1：2.2-3.2：20-23.
3. the polysubstituted preparation method for condensing benzofuran derivative according to claim 1 and 2, it is characterised in that
Malonate described in step (1) is dimethyl malenate.
4. the polysubstituted preparation method for condensing benzofuran derivative according to claim 1 and 2, it is characterised in that
The reaction temperature of step (1) is at 0-5 DEG C；Reaction time is more than 5 hours.
5. the polysubstituted preparation method for condensing benzofuran derivative according to claim 1 and 2, it is characterised in that
Compound 1 described in step (2) and phenylacetylene bromide or substituted phenylacetylene bromide, Pd (PPh3)2Cl2/ CuI, triethylamine and nothing
The amount ratio of the material of water-acetonitrile is 1:2.2-3.2：0.03-0.04：4-5：30-45.
6. the polysubstituted preparation method for condensing benzofuran derivative according to claim 1 and 2, it is characterised in that
Step (2) described stirring reaction, the time is more than 10 hours.
7. the polysubstituted preparation method for condensing benzofuran derivative according to claim 1 and 2, it is characterised in that
The mol ratio of precursor compound 2,2- (dihalotriphenylphosphoranes base) propionic aldehyde and toluene is 1.2-1.5 in step (3)：1：28-66.
8. the polysubstituted preparation method for condensing benzofuran derivative according to claim 1 and 2, it is characterised in that
Reacted described in step (3), time 8-9 hours.
9. polysubstituted prepared by a kind of any one of claim 1-8 condenses benzofuran derivative, it is characterised in that described
The polysubstituted benzofuran derivative structural formula that condenses is:
Wherein E1And E2It is identical, it is CO2R, R are straight chained alkyl, branched alkyl, saturated hydrocarbons, unsaturated hydro carbons or arene base
Group；R1It is halogen, straight chained alkyl, branched alkyl, ester group, alkoxy and its corresponding derivative.
10. it is according to claim 9 polysubstituted to condense benzofuran derivative, it is characterised in that described polysubstituted thick
Closing benzofuran derivative structural formula is:
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107501234A (en) * | 2017-09-23 | 2017-12-22 | 安徽师范大学 | A kind of oil-source rock correlation and preparation method thereof |
| CN107954873A (en) * | 2017-12-07 | 2018-04-24 | 安徽师范大学 | A kind of polysubstituted olefin(e) acid ester derivant and preparation method thereof |
| CN107986969A (en) * | 2017-12-07 | 2018-05-04 | 安徽师范大学 | A kind of ten dihydros are as two indeno phenanthrene derivative of benzo and its synthetic method |
| CN109369508A (en) * | 2018-11-28 | 2019-02-22 | 安徽师范大学 | A kind of polysubstituted indole derivatives 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 |
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 |
-
2016
- 2016-11-29 CN CN201611069814.6A patent/CN106749139B/en active Active
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 |
|---|
| XIANGZHEN MENG 等: "Fused Multifunctionalized Chromenes from Tetraynes and α,β-Unsaturated Aldehydes", 《CHEM. EUR. J.》 * |
| 吴玉芹 等: "四炔的芳炔环加成反应简便合成芳胺", 《有机化学》 * |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107501234A (en) * | 2017-09-23 | 2017-12-22 | 安徽师范大学 | A kind of oil-source rock correlation and preparation method thereof |
| CN107501234B (en) * | 2017-09-23 | 2019-07-19 | 安徽师范大学 | A kind of oil-source rock correlation and preparation method thereof |
| CN107954873A (en) * | 2017-12-07 | 2018-04-24 | 安徽师范大学 | A kind of polysubstituted olefin(e) acid ester derivant and preparation method thereof |
| CN107986969A (en) * | 2017-12-07 | 2018-05-04 | 安徽师范大学 | A kind of ten dihydros are as two indeno phenanthrene derivative of benzo and its synthetic method |
| CN107986969B (en) * | 2017-12-07 | 2020-06-19 | 安徽师范大学 | Dodecahydron as benzodiindenophenanthrene derivative and synthesis method thereof |
| CN107954873B (en) * | 2017-12-07 | 2020-06-19 | 安徽师范大学 | Polysubstituted olefine acid ester derivative and preparation method thereof |
| CN109369508A (en) * | 2018-11-28 | 2019-02-22 | 安徽师范大学 | A kind of polysubstituted indole derivatives and preparation 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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