CN108586401A - A kind of preparation method of 2- substitutions-benzofuran compounds - Google Patents
A kind of preparation method of 2- substitutions-benzofuran compounds Download PDFInfo
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- CN108586401A CN108586401A CN201810528302.4A CN201810528302A CN108586401A CN 108586401 A CN108586401 A CN 108586401A CN 201810528302 A CN201810528302 A CN 201810528302A CN 108586401 A CN108586401 A CN 108586401A
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- Prior art keywords
- silica gel
- nahso
- sio
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- salicylide
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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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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J27/00—Catalysts comprising the elements or compounds of halogens, sulfur, selenium, tellurium, phosphorus or nitrogen; Catalysts comprising carbon compounds
- B01J27/02—Sulfur, selenium or tellurium; Compounds thereof
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- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Furan Compounds (AREA)
Abstract
The present invention relates to a kind of preparation methods of 2 substitution benzofuran compounds, specifically comprise the following steps：At room temperature, after salicylide being mixed with nitroethane, the sodium hydrogensulfite (NaHSO of silica gel load is added3/SiO2), be warming up to 70 80 DEG C reaction 68 hours after to get 2 methyl benzofurans.
Description
Technical field
The invention belongs to organic synthesis and catalytic fields, and in particular to a kind of system of 2- substitutions-benzofuran compounds
Preparation Method.
Background technology
Benzofuran compounds and its derivative are widespread in nature, and because such as anti-with multiple biological activities
Viral, antitumor, antibacterial, anti-oxidant etc., and be concerned.Benzofuran is the important skeleton of natural products and pharmaceutical molecules,
The synthesis common starting material of benzofuran compounds has 2- chavicols, O-bromo methyl phenol, neighbour two in the prior art
Halogeno-benzene, 2- bromobenzyls bromine, 2- halogenated phenols etc., but need to use the metallic catalyst of price costly in synthetic method more.This
Invention offer is a kind of using the bisulfites of silica gel load as catalyst, is that raw material directly synthesizes benzofuran by salicylide
Ring.
Invention content
The present invention provides a kind of synthetic method of benzofuran, it is characterised in that includes the following steps：
At room temperature, after salicylide being mixed with nitromethane, the sodium hydrogensulfite (NaHSO of silica gel load is added3/SiO2),
Be warming up to 60-80 DEG C reaction 4-6 hours after to get benzofuran.
The molar ratio of salicylide and nitromethane is 1:1.5-2.5；NaHSO3/SiO2Mole dosage be salicylide mole
0.10-0.15 times of dosage；
Sodium hydrogensulfite (the NaHSO of the silica gel load3/SiO2) preparation method include the following steps：Take 300-400
Mesh silica gel after grinding 2-3 hours, is placed in 180-200 DEG C of baking oven after heating 6-8 hours, nitrogen with after sodium hydrogensulfite mixing
Under gas shielded, it is down to room temperature naturally to get the sodium hydrogensulfite (NaHSO of silica gel load3/SiO2)；Wherein every gram of silica gel uses
4mmol sodium hydrogensulfites.
" NaHSO of the present invention3/SiO2Mole dosage " be with NaHSO3Mole calculate.
Another embodiment of the present invention provides a kind of preparation method of 2- substitutions-benzofuran compounds, feature
It is to include the following steps：
At room temperature, after salicylide being mixed with nitroethane, the sodium hydrogensulfite (NaHSO of silica gel load is added3/SiO2),
Be warming up to 70-80 DEG C reaction 6-8 hours after to get 2- methyl benzofurans.
The molar ratio of salicylide and nitroethane is 1:2.0-2.5；NaHSO3/SiO2Mole dosage be salicylide mole
0.12-0.15 times of dosage；
Sodium hydrogensulfite (the NaHSO of the silica gel load3/SiO2) preparation method include the following steps：Take 300-400
Mesh silica gel after grinding 2-3 hours, is placed in 180-200 DEG C of baking oven after heating 6-8 hours, nitrogen with after sodium hydrogensulfite mixing
Under gas shielded, it is down to room temperature naturally to get the sodium hydrogensulfite (NaHSO of silica gel load3/SiO2)；Wherein every gram of silica gel uses
4mmol sodium hydrogensulfites.
" NaHSO of the present invention3/SiO2Mole dosage " be with NaHSO3Mole calculate.
Another embodiment of the present invention provides a kind of sodium hydrogensulfite (NaHSO of silica gel load3/SiO2) catalyst,
It is characterized in that the sodium hydrogensulfite (NaHSO of the silica gel load3/SiO2) preparation method of catalyst includes the following steps：It takes
After grinding 2-3 hours, it is small to be placed in heating 6-8 in 180-200 DEG C of baking oven with after sodium hydrogensulfite mixing for 300-400 mesh silica gel
Shi Hou under nitrogen protection, is down to room temperature to get the sodium hydrogensulfite (NaHSO of silica gel load naturally3/SiO2) catalyst；Wherein
Every gram of silica gel uses 4mmol sodium hydrogensulfites.
Another embodiment of the present invention provides the sodium hydrogensulfite (NaHSO of above-mentioned silica gel load3/SiO2) catalyst
Preparation method includes the following steps：It takes 300-400 mesh silica gel with after sodium hydrogensulfite mixing, after grinding 2-3 hours, is placed in 180-
After being heated 6-8 hours in 200 DEG C of baking oven, under nitrogen protection, it is down to room temperature naturally to get the sodium hydrogensulfite of silica gel load
(NaHSO3/SiO2) catalyst；Wherein every gram of silica gel uses 4mmol sodium hydrogensulfites.
Another embodiment of the present invention provides the sodium hydrogensulfite (NaHSO of above-mentioned silica gel load3/SiO2) catalyst exists
Prepare the application in benzofuran or 2- substitution benzofurans.
" NaHSO of the present invention3/SiO2Mole dosage " be with NaHSO3Mole calculate.
Compared with the prior art, the advantages of the present invention are as follows：The present invention utilizes the sodium hydrogensulfite of silica gel load
(NaHSO3/SiO2) catalyst salicylide, substituted salicylic aldehydes and nitromethane or nitroethane one-step method prepare benzofuran
And its derivative, provide new research method for the structure of benzofuran skeleton.
Specific implementation mode
For the ease of a further understanding of the present invention, examples provided below has done more detailed description to it.But
It is that these embodiments are only not supposed to be a limitation to the present invention or implementation principle for being better understood from invention, reality of the invention
The mode of applying is not limited to the following contents.
Embodiment 1
It takes 300-400 mesh silica gel (10g) with after sodium hydrogensulfite (40mmol) mixing, after grinding 2 hours, is placed in 180 DEG C
Baking oven in heat 8 hours after, under nitrogen protection, be down to room temperature naturally to get the sodium hydrogensulfite (NaHSO of silica gel load3/
SiO2), hereinafter referred to as product A.
Embodiment 2
It takes 300-400 mesh silica gel (10g) with after sodium hydrogensulfite (40mmol) mixing, after grinding 3 hours, is placed in 200 DEG C
Baking oven in heat 6 hours after, under nitrogen protection, be down to room temperature naturally to get the sodium hydrogensulfite (NaHSO of silica gel load3/
SiO2), hereinafter referred to as product B.
Embodiment 3
At room temperature, after salicylide (10mmol) being mixed with nitromethane (15mmol), product A (1.5mmol) is added, rises
After temperature is reacted 4 hours to 75-80 DEG C, vacuum distillation collects 172-175 DEG C of fraction up to benzofuran (0.88g, yield
74.5%,1H NMR datas are consistent with known report).
Embodiment 4
At room temperature, after salicylide (10mmol) being mixed with nitromethane (25mmol), product B (1.0mmol) is added, rises
After temperature is reacted 6 hours to 60-65 DEG C, vacuum distillation collects 172-175 DEG C of fraction up to benzofuran (0.79g, yield
66.9%,1H NMR datas are consistent with known report).
Embodiment 5
At room temperature, after salicylide (10mmol) being mixed with nitromethane (15mmol), sodium hydrogensulfite is added
(1.5mmol), 300-400 mesh silica gel (375mg), be warming up to 75-80 DEG C reaction 4 hours after, TLC detection do not find benzo furan
It mutters.
Embodiment 6
At room temperature, after salicylide (10mmol) being mixed with nitroethane (20mmol), product A (1.5mmol) is added, rises
After temperature is reacted 6 hours to 75-80 DEG C, vacuum distillation obtains 2- methyl benzofurans (0.81g, yield 61.3%)；1H NMR
(600MHz,CDCl3) δ 7.46 (d, J=7.0Hz, 1H), 7.41 (d, J=8.0Hz, 1H), 7.24-7.16 (m, 2H), 6.38
(d, J=0.8Hz, 1H), 2.47 (d, J=0.8Hz, 3H)；13C NMR(150MHz,CDCl3)δ155.39,154.71,
129.18,123.01,122.37,120.04,110.59,102.55,14.06。
Embodiment 7
At room temperature, after salicylide (10mmol) being mixed with nitroethane (25mmol), product B (1.2mmol) is added, rises
After temperature is reacted 8 hours to 70-75 DEG C, vacuum distillation obtains 2- methyl benzofurans (0.84g, yield 63.6%, NMR data and reality
It is consistent to apply example 6).
Embodiment 8
At room temperature, after salicylide (10mmol) being mixed with nitroethane (20mmol), sodium hydrogensulfite is added
(1.5mmol), 300-400 mesh silica gel (375mg), be warming up to 75-80 DEG C reaction 6 hours after, TLC detection do not find 2- methylbenzenes
And furans.
Embodiment 9
At room temperature, after 3- cresotinic acids aldehyde (10mmol) being mixed with nitroethane (20mmol), product A is added
(1.5mmol), be warming up to 75-80 DEG C reaction 6 hours after, through silica gel column chromatography obtain 2,7- dimethyl benzofurans (0.85g, receive
Rate 58.1%)；1H NMR(600MHz,CDCl3) δ 7.32 (d, J=7.6Hz, 1H), 7.10 (t, J=7.5Hz, 1H), 7.01 (d,
J=7.3Hz, 1H), 6.36 (d, J=1.0Hz, 1H), 2.52 (s, 3H), 2.47 (d, J=1.0Hz, 3H)；13C NMR
(150MHz,CDCl3)δ155.05,153.74,128.64,124.01,122.39,120.78,117.50,102.77,15.05,
14.10。
Embodiment 10
At room temperature, after 3- cresotinic acids aldehyde (10mmol) being mixed with nitroethane (25mmol), product B is added
(1.2mmol), be warming up to 70-75 DEG C reaction 8 hours after, through silica gel column chromatography obtain 2,7- dimethyl benzofurans (0.80g, receive
Rate 54.7%, NMR data are consistent with embodiment 9).
Claims (6)
1. a kind of preparation method of 2- substitutions-benzofuran compounds, it is characterised in that include the following steps：
At room temperature, after salicylide being mixed with nitroethane, the sodium hydrogensulfite (NaHSO of silica gel load is added3/SiO2), heating
To get 2- methyl benzofurans after being reacted 6-8 hours to 70-80 DEG C.
2. preparation method described in claim 1, it is characterised in that the molar ratio of salicylide and nitroethane is 1:2.0-2.5.
3. claim 1-2 any one of them preparation methods, it is characterised in that NaHSO3/SiO2Mole dosage be salicylide
0.12-0.15 times of mole dosage.
4. claim 1-3 any one of them preparation methods, it is characterised in that the sodium hydrogensulfite of the silica gel load
(NaHSO3/SiO2) preparation method include the following steps：It takes 300-400 mesh silica gel with after sodium hydrogensulfite mixing, grinds 2-3
It after hour, is placed in 180-200 DEG C of baking oven after heating 6-8 hours, under nitrogen protection, it is negative to get silica gel to be down to room temperature naturally
Sodium hydrogensulfite (the NaHSO of load3/SiO2)。
5. the preparation method described in claim 4, it is characterised in that every gram of silica gel uses 4mmol sodium hydrogensulfites.
6. claim 1-5 any one of them preparation methods, it is characterised in that substitute salicylide with 3- cresotinic acid aldehyde.
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| CN201810528302.4A CN108586401A (en) | 2018-05-27 | 2018-05-27 | A kind of preparation method of 2- substitutions-benzofuran compounds |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104478836A (en) * | 2014-12-09 | 2015-04-01 | 上海交通大学 | Benzofuran compound as well as preparation method and application thereof |
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- 2018-05-27 CN CN201810528302.4A patent/CN108586401A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104478836A (en) * | 2014-12-09 | 2015-04-01 | 上海交通大学 | Benzofuran compound as well as preparation method and application thereof |
Non-Patent Citations (3)
| Title |
|---|
| BANG-LE ZHANG ET AL.: "A New Efficient Method for the Total Synthesis of Linear Furocoumarins", 《SYNLETT》 * |
| CHIA-YU HUANG ET AL.: "Syntheses of 2-Benzylbenzofuran Derivatives and 2-Aryl-nitro nitrochroman", 《EUR. J. ORG. CHEM.》 * |
| FANZHI YANG ET AL.: "Aldehyde-Assisted Ruthenium(II)-Catalyzed C-H Oxygenations", 《ANGEW. CHEM. INT. ED.》 * |
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Application publication date: 20180928 |