CN106946831A - A kind of 2 aryl 3 (fluoroalkyl) flavone compounds and preparation method thereof - Google Patents
A kind of 2 aryl 3 (fluoroalkyl) flavone compounds and preparation method thereof Download PDFInfo
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- CN106946831A CN106946831A CN201710277710.2A CN201710277710A CN106946831A CN 106946831 A CN106946831 A CN 106946831A CN 201710277710 A CN201710277710 A CN 201710277710A CN 106946831 A CN106946831 A CN 106946831A
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
- C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
- C07D311/28—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only
- C07D311/30—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only not hydrogenated in the hetero ring, e.g. flavones
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Abstract
The present invention discloses a kind of 2 aryl 3 (fluoroalkyl) flavone compound and preparation method thereof, is related to technical field of organic chemistry.Methods described comprises the following steps：(1) 2 (4 aminomethyl phenyl) chromones are added in reaction tube at room temperature, triethylene diamine and three (2 phenylpyridines) close iridium, air in test tube is replaced as after high-purity nitrogen to add solvent DMF (N, N dimethylformamides and ethyl bromide difluoride, are then stirred at room temperature under 35W fluorescent lamps；(2) reaction solution is extracted with ethyl acetate, and uses water and saturated common salt water washing successively, is concentrated after drying, and is separated with preparative thin-layer chromatography method, obtains the flavone compound.Flavone compound preparation method of the present invention is simply efficient, and selectivity is good, and side reaction is few, and product purity is high, is easy to separating-purifying；Reaction temperature be 25 DEG C, mild condition, substrate it is applied widely.
Description
Technical field
The present invention relates to technical field of organic chemistry, and in particular to a kind of 2- aryl -3- (fluoroalkyl) flavonoid
Thing and preparation method thereof.
Background technology
Flavone compound is widely present in plant, shows a variety of biochemistries and pharmacological activity, such as anti-inflammatory, anti-
Cancer, antibacterial, antiviral, anti-oxidant, antiatherosclerosis.These activity, which come from flavones, can adjust the uniqueness of human body enzyme system
Ability.Lavonoid backbone is one of important structure in natural products, there is very big medical value, has weight in confrontation human diseases
The purposes wanted.There are some researches show the wind of the high amount of eating and reduction cancer, coronary heart disease, chronic inflammation and osteoporosis of flavones
Danger is relevant.Because flavone compound has great medical value, the structure and property around flavones, which have been carried out, in recent years is permitted
Many researchs.
Its physics, chemical property can be changed by introducing fluorine atom in the molecule, and increase its bioactivity.Due to fluorine atom
It is the atom of strong electronegativity and hypopolarization, good stability and fat-soluble good high with easy hydrogen bond, the C-F keys bond energy of being formed
Property.Functional fluoropolymer organic molecule is increasingly paid attention in the application of the energy, material, medicine and other fields by people.Many has been listed
Drug molecule in contain together with difluoride group, also there are many work on being introduced in organic molecule together with difluoride group to be reported
Road, it is in medicinal chemistry art by larger concern.
Photochemical reaction is a kind of efficient, green, easily synthesis strategy, and using light-sensitive catalyst as mediation, illumination makes light
Quick dose is changed into excitation state, then by single electron transfer, carries out catalytic cycle, finally realize luminous energy to chemical conversion of energy.It is based on
This, the present invention is using ethyl bromide difluoride simple and easy to get as fluorine source, and three (2- phenylpyridines) close iridium (fac-Ir (ppy)
3) it is light-sensitive catalyst, is reacted under fluorescent light, by free radical addition, single electron transfer, aromatisation, realize flavones
Fluorination, so as to provide the new technology that a kind of simple and convenient method obtains 2- aryl -3- (fluoroalkyl) flavone compound.
The content of the invention
The problem to be solved in the present invention is to provide a kind of reaction simply efficiently, and selectivity is good, and side reaction is few, product purity
Height, is easy to separating-purifying；Mild condition, substrate it is applied widely；Flavones is fluorinated, can increase its potential bioactivity and
2- aryl -3- (fluoroalkyl) flavone compound of druggability and preparation method thereof.Therefore, now proposing following technical scheme：
The present invention provides a kind of 2- aryl -3- (fluoroalkyl) flavone compound, the molecule of the flavone compound
Structural formula is：
In formula, R1And R2For supplied for electronic or electrophilic substituent or heterocycle；Electron-donating group is selected from alkyl, alkoxy, hydroxyl
Base, the tert-butyl group；Electron withdraw group is selected from fluorine, chlorine, bromine, trifluoromethyl, nitro, ester group, itrile group；Heterocycle be selected from thiophene, furans,
Naphthalene.
The present invention also provides a kind of a kind of 2- aryl -3- (fluoroalkyl) flavone compound as described in above-mentioned scheme
Preparation method, its synthetic route is：
Further improvement of these options, specifically includes following steps：
(1) 2- aryl flavones is added in reaction tube at room temperature, triethylene diamine and three (2- phenylpyridines) close iridium, examination
Air in pipe is replaced as after high-purity nitrogen adding solvent DMF and ethyl bromide difluoride, Ran Hou
Reaction solution 48h is stirred at room temperature under 35W fluorescent lamps；
(2) reaction solution for reacting completion is extracted with ethyl acetate, and uses water and saturated common salt water washing successively, after drying
Concentration, then using the reaction solution after the separation concentration of preparative thin-layer chromatography method, obtains 2- aryl -3- (fluoroalkyl) flavonoids
Compound.
Further improvement of these options, 2- aryl flavones is 1.0 equivalents, and ethyl bromide difluoride consumption is 1.5-
2.5 equivalents, triethylene diamine consumption is 1.2-1.8 equivalents, and it is 1.5% equivalent that three (2- phenylpyridines), which close iridium consumption,.
Further improvement of these options, the system reaction temperature is 25 DEG C.
Compared with prior art, the beneficial effects of the present invention are：
(1) preparation method of 2- aryl -3- (fluoroalkyl) flavone compound of the present invention, in fluorescent lamp
Under illumination, three (2- phenylpyridines) close iridium and are activated and transit to excitation state, occur single electron transfer with ethyl bromide difluoride,
Carbon bromine key homolysis is set to generate ethyl difluoro free radical and bromine free radical, wherein ethyl difluoro free radical is to the double of flavones
Key attack, then occur single electron transfer with iridium, finally under conditions of triethylene diamine is alkali, slough proton and obtain product 2- virtues
Base -3- (fluoroalkyl) flavone compound, realizes the fluorination of flavones, it is former that the present invention introduces fluorine in flavone compound molecule
Son changes its physics, chemical property, and increases its bioactivity, because fluorine atom is strong electronegativity and the original of hypopolarization
Son, good stability and fat-soluble good high with easy hydrogen bond, the C-F keys bond energy of being formed, has extraordinary application in new medicament screen
Prospect.
(2) flavone compound preparation method of the present invention is simply efficient, need to only configure reactant and catalyst
It is good, the flavone compound can be generated under illumination condition, and side reaction is few, and without unnecessary accessory substance, product is pure
Degree is high, is easy to separating-purifying；Reaction temperature be 25 DEG C, mild condition, substrate it is applied widely.
Embodiment
To be easy to understand technological means, creation characteristic, reached purpose and effect of the invention realized, with reference to
Embodiment, is expanded on further the present invention.
Embodiment 1
The present embodiment provides a kind of preparation method of 2- aryl -3- (fluoroalkyl) flavone compound, specifically include as
Lower step：
(1) 2- (4- aminomethyl phenyls) chromone of 1 equivalent, the triethylene diamine of 1.2 equivalents are added in reaction tube at room temperature
Iridium is closed with three (2- phenylpyridines) of 1.5% equivalent, the air in test tube is replaced as after high-purity nitrogen to add solvent N, N-
Dimethylformamide 3ml and 1.5 equivalents ethyl bromide difluoride, then under 35W fluorescent lamps, are stirred under 25 DEG C of reaction temperatures
Reaction solution 48h；
(2) reaction solution for reacting completion is extracted with ethyl acetate, and uses water and saturated common salt water washing successively, after drying
Concentration, then using the reaction solution after the separation concentration of preparative thin-layer chromatography method, following structural formula is obtained with 87% yield
Flavonoids chemicals.
Embodiment 2
The present embodiment provides a kind of preparation method of 2- aryl -3- (fluoroalkyl) flavone compound, specifically include as
Lower step：
(1) add 2- (4- bromophenyls) chromone of 1 equivalent in reaction tube at room temperature, the triethylene diamine of 1.5 equivalents and
Three (2- phenylpyridines) of 1.5% equivalent close iridium, and the air in test tube is replaced as after high-purity nitrogen to add solvent N, N- bis-
NMF 3ml and 2 equivalents ethyl bromide difluoride, then under 35W fluorescent lamps, stirring reaction under 25 DEG C of reaction temperatures
Liquid 48h；
(2) reaction solution for reacting completion is extracted with ethyl acetate, and uses water and saturated common salt water washing successively, after drying
Concentration, then using the reaction solution after the separation concentration of preparative thin-layer chromatography method, following structural formula is obtained with 70% yield
Flavonoids chemicals.
Embodiment 3
The present embodiment provides a kind of preparation method of 2- aryl -3- (fluoroalkyl) flavone compound, specifically include as
Lower step：
(1) 2- (4- tert-butyl-phenyls) chromone of 1 equivalent, the triethylene two of 1.8 equivalents are added in reaction tube at room temperature
Three (2- phenylpyridines) of amine and 1.5% equivalent close iridium, and the air in test tube is replaced as after high-purity nitrogen to add solvent N,
Dinethylformamide 3ml and 2.5 equivalents ethyl bromide difluoride, then under 35W fluorescent lamps, are stirred under 25 DEG C of reaction temperatures
Mix reaction solution 48h；
(2) reaction solution for reacting completion is extracted with ethyl acetate, and uses water and saturated common salt water washing successively, after drying
Concentration, then using the reaction solution after the separation concentration of preparative thin-layer chromatography method, following structural formula is obtained with 75% yield
Flavonoids chemicals.
The preparation method of 2- aryl -3- (fluoroalkyl) flavone compound described in embodiment 1-3, in fluorescent lamp
Under illumination, three (2- phenylpyridines) close iridium and are activated and transit to excitation state, occur single electron transfer with ethyl bromide difluoride,
Carbon bromine key homolysis is set to generate ethyl difluoro free radical and bromine free radical, wherein ethyl difluoro free radical is to the double of flavones
Key attack, then occur single electron transfer with iridium, finally under conditions of triethylene diamine is alkali, slough proton and obtain product 2- virtues
Base -3- (fluoroalkyl) flavone compound, realizes the fluorination of flavones, it is former that the present invention introduces fluorine in flavone compound molecule
Son changes its physics, chemical property, and increases its bioactivity, because fluorine atom is strong electronegativity and the original of hypopolarization
Son, good stability and fat-soluble good high with easy hydrogen bond, the C-F keys bond energy of being formed, has extraordinary application in new medicament screen
Prospect.And flavone compound preparation method of the present invention is simply efficient, reactant and catalyst need to only be configured,
The flavone compound can be generated under illumination condition, and side reaction is few, and without unnecessary accessory substance, product yield is equal
More than 75%, product purity is high, is easy to separating-purifying；Reaction temperature be 25 DEG C, mild condition, substrate it is applied widely.
Those of ordinary skill in the art it should be appreciated that the embodiment of the above be intended merely to explanation the present invention,
And be not used as limitation of the invention, as long as in the spirit of the present invention, the change to embodiment described above
Change, modification will all fall in scope of the presently claimed invention.
Claims (5)
1. a kind of 2- aryl -3- (fluoroalkyl) flavone compound, it is characterised in that the molecule knot of the flavone compound
Structure formula is：
In formula, R1And R2For supplied for electronic or electrophilic substituent or heterocycle；Electron-donating group be selected from alkyl, alkoxy, hydroxyl,
The tert-butyl group；Electron withdraw group is selected from fluorine, chlorine, bromine, trifluoromethyl, nitro, ester group, itrile group；Heterocycle is selected from thiophene, furans, naphthalene.
2. a kind of a kind of preparation method of 2- aryl -3- (fluoroalkyl) flavone compound as claimed in claim 1, it is special
Levy and be, its synthetic route is：
。
3. a kind of preparation method of 2- aryl -3- (fluoroalkyl) flavone compound according to claim 2, its feature
It is to specifically include following steps：
(1) 2- aryl flavones is added in reaction tube at room temperature, triethylene diamine and three (2- phenylpyridines) close iridium, in test tube
Air be replaced as after high-purity nitrogen adding solvent DMF and ethyl bromide difluoride, it is then glimmering in 35W
Reaction solution 48h is stirred at room temperature under light lamp；
(2) reaction solution for reacting completion is extracted with ethyl acetate, and uses water and saturated common salt water washing successively, it is dense after drying
Contracting, then using the reaction solution after the separation concentration of preparative thin-layer chromatography method, obtains 2- aryl -3- (fluoroalkyl) flavonoids
Compound.
4. a kind of preparation method of 2- aryl -3- (fluoroalkyl) flavone compound according to claim 3, its feature
It is：2- aryl flavones is 1.0 equivalents, and ethyl bromide difluoride consumption is 1.5-2.5 equivalents, and triethylene diamine consumption is 1.2-
1.8 equivalents, it is 1.5% equivalent that three (2- phenylpyridines), which close iridium consumption,.
5. a kind of preparation method of 2- aryl -3- (fluoroalkyl) flavone compound according to claim 3, its feature
It is：The system reaction temperature is 25 DEG C.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201710277710.2A CN106946831B (en) | 2017-04-25 | 2017-04-25 | A kind of 2- aryl -3- (fluoroalkyl) flavone compound and preparation method thereof |
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| CN201710277710.2A CN106946831B (en) | 2017-04-25 | 2017-04-25 | A kind of 2- aryl -3- (fluoroalkyl) flavone compound and preparation method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110105293A (en) * | 2019-06-14 | 2019-08-09 | 浙江工业大学 | A kind of synthetic method of C-3 difluoromethyl substituted quinoxaline ketones derivant |
| CN111875570A (en) * | 2020-07-31 | 2020-11-03 | 郑州师范学院 | Synthetic method of fluorine-containing carboxylic acid flavone-amino acid derivative |
-
2017
- 2017-04-25 CN CN201710277710.2A patent/CN106946831B/en not_active Expired - Fee Related
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110105293A (en) * | 2019-06-14 | 2019-08-09 | 浙江工业大学 | A kind of synthetic method of C-3 difluoromethyl substituted quinoxaline ketones derivant |
| CN110105293B (en) * | 2019-06-14 | 2020-10-09 | 浙江工业大学 | Synthesis method of C-3-difluoromethyl substituted quinoxalinone derivative |
| CN111875570A (en) * | 2020-07-31 | 2020-11-03 | 郑州师范学院 | Synthetic method of fluorine-containing carboxylic acid flavone-amino acid derivative |
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Granted publication date: 20190719 Termination date: 20200425 |