CN108727323A - A kind of method that N-heterocyclic carbine catalyzes and synthesizes trifluoromethyl substitution homoisoflavone class compound - Google Patents
A kind of method that N-heterocyclic carbine catalyzes and synthesizes trifluoromethyl substitution homoisoflavone class compound Download PDFInfo
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- CN108727323A CN108727323A CN201810727602.5A CN201810727602A CN108727323A CN 108727323 A CN108727323 A CN 108727323A CN 201810727602 A CN201810727602 A CN 201810727602A CN 108727323 A CN108727323 A CN 108727323A
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- class compound
- heterocyclic carbine
- trifluoromethyl
- trifluoromethyl substitution
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- C—CHEMISTRY; METALLURGY
- 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
Abstract
The invention belongs to synthetic organic chemical arts, and in particular to a kind of method that N-heterocyclic carbine catalyzes and synthesizes trifluoromethyl substitution homoisoflavone class compound.The alkene aldehyde compound that the present invention is replaced using trifluoromethyl is raw material, under the action of organic solvent and alkali, under room temperature environment, using N-heterocyclic carbine as catalyst, react a few hours obtained intermediate flavone compound, it is reacted then under the action of iodine, the concentrated sulfuric acid and organic solvent, under 50-100 degrees Celsius and trifluoromethyl substitution homoisoflavone class compound is made, products therefrom is isolated and purified by recrystallization or thin-layer chromatography or column chromatography.Preparation method green high-efficient of the present invention, compared with the conventional method, this method can fit that substrate spectrum is wide, and substrate is conveniently easy to get, and reaction condition is mild, easy to operate, and reaction efficiency is high, selectivity is good.
Description
Technical field
The invention belongs to synthetic organic chemical arts, and in particular to a kind of N-heterocyclic carbine catalyzes and synthesizes trifluoromethyl substitution
The method of homoisoflavone class compound.
Background technology
Homoisoflavone class compound has as a kind of important organic compound in biological medicine and study on the synthesis
Highly important effect (Mulholland, D. A.; Schwikkard, S. L.; Crouch, N. R.Nat. Prod. Rep.2013, 30, 1165.).Currently, the representative synthetic schemes of the synthesis of homoisoflavone class compound has biological enzyme
Chromone and halogenated hydrocarbons coupling reaction；Louis acid catalysis chromone derives the dehydration coupling reaction ((a) of alcohol and terminal alkyne
Singh, P.; Kumar, A.; Kaur, S.; Kaur, J.; Singh, H. Chem. Commun.2016, 52,
2936. (b) W. Chen, Z. Hao, L. Zhe, L. Li, W. Dong and C. Yongjun, Chin. J. Chem., 2011, 29, 2732–2738.).But these methods have certain limitation, as raw material needs pre- functional group
Change, reaction condition is relative complex harsh（Expensive catalyst etc.）, low yield（Atom economy is not high）, limited substrate spectrum
And in terms of Green Chemistry, so limiting its application in big quantitative response or industrial production.Thus develop a kind of raw material
Cheap and easy to get, step is simple and convenient to operate, mild condition, wide application range of substrates and efficient synthesis trifluoromethyl takes
Method for homoisoflavone class compound is key points and difficulties.The present inventor development using alkene aldehyde compound as raw material, with nitrogen
Heterocycle carbine (N-Heterocyclic Carbene, NHC) is used as catalyst, after being reacted using suitable alkali, in elemental iodine and
It is a kind of simple and practical synthetic method that trifluoromethyl substitution homoisoflavone class compound method is synthesized under the action of the concentrated sulfuric acid.
Invention content
Trifluoromethyl is catalyzed and synthesized the invention aims to providing a kind of N-heterocyclic carbine and replaces homoisoflavone class compound
Method.
To achieve the goals above, the present invention uses following technical method：
The alkene aldehyde compound that the present invention is replaced using trifluoromethyl is raw material, under the action of organic solvent and alkali, room temperature environment
Under, using N-heterocyclic carbine as catalyst, 3-10 hours obtained intermediate flavone compounds are reacted, then in iodine, dense
It is reacted under the action of sulfuric acid and organic solvent, under 50-100 degrees Celsius and trifluoromethyl substitution homoisoflavone class compound, institute is made
Product is obtained to be isolated and purified by recrystallization or thin-layer chromatography or column chromatography.
It can be represented by the formula：
The general molecular formula of the alkene aldehyde compound is：；Synthesized homoisoflavone class compound
General molecular formula is：.In formula：R1For one in alkyl, halogen atom, hydrogen atom, alkoxy, ester group, nitro
Kind；R2For alkyl, alkenyl, one kind in aryl.
The N-heterocyclic carbine (NHC) is one kind in imidazoles, triazole, thiazoles salt；
The alkali is the common inorganic bases such as potassium carbonate, sodium carbonate, potassium phosphate, potassium acetate, sodium alkoxide, sodium hydroxide, potassium hydroxide
And one kind in the common organic base such as triethylamine, 11 carbon -7- alkene of 1,8- diazabicylos；
The alkene aldehyde compound of trifluoromethyl substitution and the molar ratio of N-heterocyclic carbine is 1: 0.1 ~1 : 0.2；
The alkene aldehyde compound of trifluoromethyl substitution and the molar ratio of alkali is 1: 0.1~1 : 1.5；
The organic solvent is acetonitrile, toluene, tetrahydrofuran, ether, methyl tertiary butyl ether, dichloromethane, 1,4- dioxane, two
One kind in first sulfoxide, dimethylformamide.
Iodine is as oxidant.
The present invention prepares products therefrom and is detached by recrystallization or the methods of thin-layer chromatography or column chromatography.Such as with tying again
Brilliant method, it is the mixed solvent of polar solvent and nonpolar solvent to recommend solvent, recommend solvent can be dichloromethane-just oneself
Alkane, isopropanol-petroleum ether, ethyl acetate-light petrol, ethyl acetate-hexane or isopropanol-ethyl acetate-light petrol etc. are mixed
Bonding solvent.With thin-layer chromatography and column chromatography method, solvent used is the mixed solvent of polar solvent and nonpolar solvent, is pushed away
It can be isopropanol-petroleum ether, ethyl acetate-light petrol, ethyl acetate-hexane or isopropanol-ethyl acetate-pet to recommend solvent
The mixed solvents such as ether, volume ratio can be respectively：Polar solvent：Nonpolar solvent=1: 3~1 : 10.Such as：Acetic acid
Ethyl ester：Petroleum ether=1: 3~1 :10, isopropanol：Petroleum ether=1: 3~1 : 10.
Beneficial effects of the present invention：
The present invention provides a kind of method that N-heterocyclic carbine catalyzes and synthesizes trifluoromethyl substitution homoisoflavone class compound.With it is existing
Method is compared, and this method is applicable to a variety of different types of alkene aldehyde compounds, and reaction condition is mild, and raw material is cheap and easy to get,
Easy to operate, the yield of reaction is high, has Atom economy, also embodies the theory of Green Chemistry well.
Description of the drawings
Fig. 1 is the nuclear magnetic resonance spectroscopy of substrate 1a；
Fig. 2 is the nuclear magnetic resonance spectroscopy of substrate 1b；
Fig. 3 is the nuclear magnetic resonance spectroscopy of 1 product of embodiment；
Fig. 4 is the carbon-13 nmr spectra of 1 product of embodiment；
Fig. 5 is the nuclear magnetic resonance spectroscopy of 2 product of embodiment；
Fig. 6 is the carbon-13 nmr spectra of 2 product of embodiment.
Specific implementation mode
It will be helpful to understand the present invention by following embodiments, but be not intended to limit present disclosure.
Substrate 1a synthesis
Under nitrogen protection, salicylide (10.0 mmol), K2CO3 (15 mmol) are sequentially added into a drying there-necked flask
With DMF (30 mL), it is added in stirring（The bromo- 1,1,1- trifluoros but-2-ene -2- bases of 4-）Benzene（10.0 mmol）（Jeong,
I. H., Park, Y. S., Chung, M. W., & Kim, B. T. Synth. Commun.,2001, 31, 2261-
2270.）, it is stirred overnight at room temperature until salicylide completely consumes（It is monitored by TLC）.Then reaction mixture is quenched with water
Ether is used in combination（50mL×3）Extraction.Combined organic layer is washed with brine, is dried with anhydrous sodium sulfate.Then it is removed under reduced pressure
Then solvent passes through silica gel column chromatography（10:1 hexane/ethyl acetate）Residue is purified, it is that white is solid to obtain corresponding product
Body, (E) -2- ((4,4,4- tri- fluoro- 3- phenyl butyls -2- alkene -1- oxygroups) benzaldehydes.Structural formula is as follows：
The fusing point of the product Compound is as follows：m. p. 69-70 °C, 2.0 g, 66% yield;The nuclear magnetic resonance of compound
Hydrogen modal data is as follows：1H NMR (400 MHz, Chloroform-d) δ 10.45 (s, 1H), 7.83 (d, J = 7.8
Hz, 1H), 7.59 – 7.39 (m, 4H), 7.37 – 7.20 (m, 2H), 7.03 (t, J = 7.5 Hz, 1H),
6.84 – 6.57 (m, 2H), 4.63 (d, J = 4.2 Hz, 2H)。
Substrate 1b synthesis
Under nitrogen protection, to one drying there-necked flask in sequentially add 5- chloro-salicylic aldehydes (1.0 mmol), K2CO3 (608 mg,
1.5 mmol) and DMF (2.5 mL), it is added in stirring（The bromo- 1,1,1- trifluoros but-2-ene -2- bases of 4-）Benzene（1.0
mmol）, it is stirred overnight at room temperature until salicylide completely consumes（It is monitored by TLC）.Then reaction mixture is quenched with water simultaneously
Use ether（8mL×3）Extraction.Combined organic layer is washed with brine, is dried with anhydrous sodium sulfate.Then it is removed under reduced pressure molten
Then agent passes through silica gel column chromatography（10:1 hexane/ethyl acetate）Residue is purified, it is white solid to obtain corresponding product,
(E) the chloro- 2- of -5- ((tri- fluoro- 3- phenyl butyls -2- alkene -1- oxygroups of 4,4,4-) benzaldehydes.Structural formula is as follows：
The fusing point of the product Compound is as follows：m. p. 90 °C, 246 mg, 64% yield;The hydrogen nuclear magnetic resonance of compound
Modal data is as follows：1H NMR (400 MHz, Chloroform-d) δ 10.36 (s, 1H), 7.76 (d, J = 2.6
Hz, 1H), 7.50 – 7.36 (m, 4H), 7.33 – 7.26 (m, 2H), 6.69 (t, J = 8.6 Hz, 2H),
4.76 – 4.45 (m, 2H)。
Embodiment 1
Under nitrogen protection, substrate 1a (4 mmol), NHC (0.4 mmol) are sequentially added into a dry reaction pipe,
Na2CO3 (0.8 mmol) 80 mL DMSO are then added into system, reacts 10 h at room temperature and terminates, and stop stirring.It is added
I2 (0.8 mmol) is dissolved in 40 mL DMSO, and dense H is being added2SO4(4 mmol) reacts 5 hours at 50 DEG C.Washing
DMSO is removed, ether extraction, ethyl acetate and petroleum ether are with volume ratio 1:10 recrystallizations, it is white solid, production to obtain corresponding product
Rate 87.6%.Product it is entitled：3- (tri- fluoro- 1- phenethyls of 2,2,2-) -4H- benzopyran-4-ones.Structural formula is as follows：
The fusing point of the product Compound is as follows：Mp 123.8 °C；The hydrogen nuclear magnetic resonance modal data of compound is as follows：1H NMR
(400 MHz, Chloroform-d) δ 8.18 (d, J = 9.5 Hz, 2H), 7.70 – 7.58 (m, 1H), 7.44
(q, J = 3.4 Hz, 3H), 7.34 (tt, J = 16.9, 7.3 Hz, 4H), 5.33 (q, J = 10.3 Hz,
1H);The carbon-13 nmr spectra data of compound are as follows：13C NMR (101 MHz, Chloroform-d) δ 175.54 ,
156.03 , 154.02 (q, J = 2.6 Hz), 134.01 , 133.64 (d, J = 1.5 Hz), 128.97 ,
128.77 , 128.28 , 126.09 , 126.04 (q, J = 279.8 Hz),125.44 , 123.46 , 120.25
, 118.05 , 44.31 (q, J = 29.0 Hz)。
Embodiment 2
Under nitrogen protection, substrate 1b (0.3 mmol), NHC (0.05 mmol) are sequentially added into a dry reaction pipe,
Et3N (0.06 mmol), is then added 3 mL DMF into system, reacts 3 h at room temperature and terminates, and stops stirring.I is added2
(0.06 mmol) is dissolved in 1.5 mL DMSO, and dense H is being added2SO4(0.3 mmol) reacts 2 hours at 70 DEG C.Water
Solvent, ethyl acetate extraction, column chromatography, eluent are removed in washout：Ethyl acetate and petroleum ether are with volume ratio 1:1 mixing, collection group
Point, it is white solid, yield 91% to obtain corresponding product.Product it is entitled：The chloro- 3- of 6- (tri- fluoro- 1- phenethyls of 2,2,2-) -4H-
Benzopyran-4-one.Structural formula is as follows：
The fusing point of the product Compound is as follows：Mp 120-121 °C；The hydrogen nuclear magnetic resonance modal data of compound is as follows：1H NMR
(400 MHz, Chloroform-d) δ 8.16 (d, J = 16.6 Hz, 2H), 7.61 (d, J = 9.0 Hz,
1H), 7.48 – 7.39 (m, 3H), 7.35 (q, J = 7.4 Hz, 3H), 5.29 (q, J = 10.5 Hz,
1H);The carbon-13 nmr spectra data of compound are as follows：13C NMR (100 MHz, Chloroform-d) δ 174.49 ,
154.41 , 154.17 (q, J = 2.6 Hz), 134.31 , 133.40 , 131.53 , 128.96 , 128.87 ,
128.43 , 125.95 (d, J = 279.9 Hz), 125.56 , 124.42, 120.47, 119.86 , 44.38
(q, J = 29.1 Hz);。
The foregoing is merely presently preferred embodiments of the present invention, all equivalent changes done according to scope of the present invention patent with
Modification should all belong to the covering scope of the present invention.
Claims (7)
1. a kind of method that N-heterocyclic carbine catalyzes and synthesizes trifluoromethyl substitution homoisoflavone class compound, it is characterised in that：With
The alkene aldehyde compound of trifluoromethyl substitution is raw material, under the action of organic solvent and alkali, under room temperature environment, with azacyclo- card
Guest reacts 3-10 hours obtained intermediate flavone compounds, then in iodine, the concentrated sulfuric acid and organic solvent as catalyst
Under the action of, 50-100 degrees Celsius of reaction is made trifluoromethyl and replaces homoisoflavone class compound, and products therefrom is by recrystallization
Or thin-layer chromatography or column chromatography are isolated and purified.
2. a kind of N-heterocyclic carbine according to claim 1 catalyzes and synthesizes trifluoromethyl substitution homoisoflavone class compound
Method, it is characterised in that：The olefine aldehydr class structural formula of compound of the described trifluoromethyl substitution is：, R1For
One kind in alkyl, halogen atom, hydrogen atom, alkoxy, ester group, nitro, R2For alkyl, alkenyl, one kind in aryl；It is described
Trifluoromethyl substitution homoisoflavone class compound structural formula be：, R1For alkyl, halogen atom, hydrogen atom,
One kind in alkoxy, ester group, nitro, R2For alkyl, alkenyl, one kind in aryl.
3. a kind of N-heterocyclic carbine according to claim 1 catalyzes and synthesizes trifluoromethyl substitution homoisoflavone class compound
Method, it is characterised in that：The alkali be potassium carbonate, sodium carbonate, potassium hydroxide, sodium hydroxide, potassium phosphate, potassium acetate, sodium alkoxide,
One kind in triethylamine, 11 carbon -7- alkene of 1,8- diazabicylos.
4. a kind of side of N-heterocyclic carbine synthesis trifluoromethyl substitution homoisoflavone class compound according to claim 1
Method, it is characterised in that：The N-heterocyclic carbine catalyst is thiazoles, imidazoles or triazole salt.
5. a kind of N-heterocyclic carbine according to claim 1 catalyzes and synthesizes trifluoromethyl substitution homoisoflavone class compound
Method, it is characterised in that：The organic solvent is acetonitrile, toluene, tetrahydrofuran, ether, methyl tertiary butyl ether, dichloromethane, 1,
One kind in 4- dioxane, dimethyl sulfoxide, dimethylformamide.
6. a kind of N-heterocyclic carbine according to claim 1 catalyzes and synthesizes trifluoromethyl substitution homoisoflavone class compound
Method, it is characterised in that：The alkene aldehyde compound of trifluoromethyl substitution and the molar ratio of N-heterocyclic carbine is 1: 0.1
~1 : 0.2。
7. a kind of N-heterocyclic carbine according to claim 1 catalyzes and synthesizes trifluoromethyl substitution homoisoflavone class compound
Method, it is characterised in that：The alkene aldehyde compound of trifluoromethyl substitution and the molar ratio of alkali is 1: 0.1~1 :
1.5。
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111205255A (en) * | 2019-11-18 | 2020-05-29 | 温州大学 | CMe-containing liquid crystal display2CF3Synthesis method of radical flavonoid compound |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111205255A (en) * | 2019-11-18 | 2020-05-29 | 温州大学 | CMe-containing liquid crystal display2CF3Synthesis method of radical flavonoid compound |
| CN111205255B (en) * | 2019-11-18 | 2023-07-25 | 温州大学 | CMe-containing material 2 CF 3 Synthesis method of flavonoid compound of group |
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