CN110194713A - A kind of ɑ, beta unsaturated ketone compound and its preparation method and application - Google Patents
A kind of ɑ, beta unsaturated ketone compound and its preparation method and application Download PDFInfo
- Publication number
- CN110194713A CN110194713A CN201910138125.3A CN201910138125A CN110194713A CN 110194713 A CN110194713 A CN 110194713A CN 201910138125 A CN201910138125 A CN 201910138125A CN 110194713 A CN110194713 A CN 110194713A
- Authority
- CN
- China
- Prior art keywords
- preparation
- compound
- formula
- reaction
- unsaturated ketone
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/22—Radicals substituted by doubly bound hetero atoms, or by two hetero atoms other than halogen singly bound to the same carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention belongs to technical field of organic synthesis more particularly to a kind of ɑ, beta unsaturated ketone compounds and its preparation method and application.The present invention provides a kind of ɑ, the preparation method of beta unsaturated ketone compound, the following steps are included: formula (I) compound and formula (II) compound are dissolved in atent solvent, under the action of metallic catalyst and oxidant, it is reacted, obtains formula (III) compound；Wherein, R1Selected from saturated or unsaturated alkyl, substituted hydrocarbon radical or heterocycle, R2Selected from saturated or unsaturated alkyl, substituted hydrocarbon radical, heterocycle, substituted heterocyclic radical or saturations or undersaturated straight chain alkyl or cyclic hydrocarbon radical containing functional group；The oxidant includes tetramethyl piperidine nitrogen oxides.In the present invention, substrate source is convenient, and simple and easy to get, substrate kind is more, and selectivity is good, and safe operation is simple, the ɑ of multiple types can be obtained, beta unsaturated ketone compound is ɑ, and the preparation of beta unsaturated ketone compound provides a kind of new method.
Description
Technical field
The invention belongs to technical field of organic synthesis more particularly to a kind of ɑ, beta unsaturated ketone compounds and preparation method thereof
And application.
Background technique
ɑ, beta unsaturated ketone are a kind of groups with pharmaceutical activity, and ɑ, it is anti-swollen that beta unsaturated ketone compound can be applied to treatment
Tumor medicine, plant are adjusted in the preparations of a variety of chemicals with pharmaceutical activity such as growth stimulator, in the industries such as medical treatment, agricultural
It is widely applied.The characteristics of due to its structure, ɑ, beta unsaturated ketone compound are a kind of chemical combination with huge subsequent transformation potentiality
Object, it is main in the prior art to be prepared by aldol reaction.Although ɑ, the preparation method of beta unsaturated ketone compound is more simple
It is single, but ɑ, the preparation method of beta unsaturated ketone compound is less, also needs to expand new preparation method.
Summary of the invention
In view of this, the present invention provides a kind of ɑ, beta unsaturated ketone compound and its preparation method and application, the preparation side
The substrate source of method is convenient, and substrate kind is more, and the ɑ of multiple types, beta unsaturated ketone compound can be obtained.
The specific technical solution of the present invention is as follows:
A kind of ɑ, the preparation method of beta unsaturated ketone compound, comprising the following steps:
Formula (I) compound and formula (II) compound are dissolved in atent solvent, in the effect of metallic catalyst and oxidant
Under, it is reacted, obtains formula (III) compound；
Wherein,R2-B(OH)2Formula (II),
R1Selected from saturated or unsaturated alkyl, substituted hydrocarbon radical or heterocycle, R2Selected from saturated or unsaturated alkyl, take
For alkyl, heterocycle, substituted heterocyclic radical or saturations or undersaturated straight chain alkyl or cyclic hydrocarbon radical containing functional group；
The oxidant includes tetramethyl piperidine nitrogen oxides.
Preferably, the functional group is selected from halogen, ester group, carbonyl, amino, nitro, cyano, sulfuryl or acyl group.
Preferably, the metallic catalyst is selected from copper acetate, copper trifluoromethanesulfcomposite, cuprous halide or copper halide.
Preferably, the oxidant further includes tert-butyl hydroperoxide and/or tert-butyl peroxide.
Preferably, the reaction is also added into additive；
The additive is selected from silver acetate, silver carbonate, silver nitrate, sodium acetate, lithium carbonate, potassium carbonate, cesium carbonate or acetic acid
Potassium.
Preferably, the temperature of the reaction is 60 DEG C~120 DEG C；
The time of the reaction is 6h~for 24 hours.
Preferably, the molar ratio of formula (I) compound and the formula (II) compound is (1~3): (3~1).
Preferably, the atent solvent be selected from toluene, tetrahydrofuran, Isosorbide-5-Nitrae-dioxane, N, N '-dimethyl formamide,
N, N '-dimethyl acetamide, N-Methyl pyrrolidone, dimethyl sulfoxide, acetonitrile or 1,2- dichloroethanes.
The present invention also provides ɑ made from preparation method described in above-mentioned technical proposal, beta unsaturated ketone compounds.
The present invention also provides ɑ made from preparation method described in above-mentioned technical proposal, and beta unsaturated ketone compound is in drug
And/or the application in materials synthesis.
In conclusion the present invention provides a kind of ɑ, the preparation method of beta unsaturated ketone compound, comprising the following steps: will
Formula (I) compound and formula (II) compound are dissolved in atent solvent, under the action of metallic catalyst and oxidant, are carried out anti-
It answers, obtains formula (III) compound；Wherein, R1Selected from saturated or unsaturated alkyl, substituted hydrocarbon radical or heterocycle, R2Selected from saturation
Or undersaturated alkyl, substituted hydrocarbon radical, heterocycle, substituted heterocyclic radical or saturations or undersaturated straight chain alkyl containing functional group or
Cyclic hydrocarbon radical；The oxidant includes tetramethyl piperidine nitrogen oxides.In the present invention, R1Selected from saturated or unsaturated alkyl, take
For alkyl or heterocycle, R2Selected from saturated or unsaturated alkyl, substituted hydrocarbon radical, heterocycle, substituted heterocyclic radical or contain functional group
Saturations or undersaturated straight chain alkyl or cyclic hydrocarbon radical, substrate source it is convenient, simple and easy to get, substrate kind is more, and selectivity is good, behaviour
Make safe and simple, can be obtained the ɑ of multiple types, beta unsaturated ketone compound is ɑ, and the preparation of beta unsaturated ketone compound provides one
The new method of kind.
Detailed description of the invention
In order to more clearly explain the embodiment of the invention or the technical proposal in the existing technology, to embodiment or will show below
There is attached drawing needed in technical description to be briefly described.
Fig. 1 is the nuclear-magnetism for (E) -3- (4- bromophenyl) -1- phenyl propyl- 2- alkene -1- ketone (3a) that the embodiment of the present invention 1 provides
Resonance1H spectrogram；
Fig. 2 is the nuclear-magnetism for (E) -3- (4- bromophenyl) -1- phenyl propyl- 2- alkene -1- ketone (3a) that the embodiment of the present invention 1 provides
Resonance13C spectrogram；
Fig. 3 is (E) -1- (4- methoxyphenyl) -3- phenyl propyl- 2- alkene -1- ketone (3b) that the embodiment of the present invention 2 provides
Nuclear magnetic resonance1H spectrogram；
Fig. 4 is (E) -1- (4- methoxyphenyl) -3- phenyl propyl- 2- alkene -1- ketone (3b) that the embodiment of the present invention 2 provides
Nuclear magnetic resonance13C spectrogram；
Fig. 5 is the nuclear-magnetism of (E) -3- (anthracene -9- base) -1- phenyl propyl- 2- alkene -1- ketone (3c) that the embodiment of the present invention 3 provides
Resonance1H spectrogram；
Fig. 6 is the nuclear-magnetism of (E) -3- (anthracene -9- base) -1- phenyl propyl- 2- alkene -1- ketone (3c) that the embodiment of the present invention 3 provides
Resonance13C spectrogram；
Fig. 7 is (E) -3- (3A, 3A-1- pyrene -1- base) -1- (thiophene -2- base) propyl- 2- alkene-that the embodiment of the present invention 4 provides
The nuclear magnetic resonance of 1- ketone (3d)1H spectrogram；
Fig. 8 is (E) -3- (3A, 3A-1- pyrene -1- base) -1- (thiophene -2- base) propyl- 2- alkene-that the embodiment of the present invention 4 provides
The nuclear magnetic resonance of 1- ketone (3d)13C spectrogram；
Fig. 9 is (E) -3- (furans -2- base) -1- (thiophene -2- base) propyl- 2- alkene -1- ketone that the embodiment of the present invention 5 provides
The nuclear magnetic resonance of (3e)1H spectrogram；
Figure 10 is (E) -3- (furans -2- base) -1- (thiophene -2- base) propyl- 2- alkene -1- ketone that the embodiment of the present invention 5 provides
The nuclear magnetic resonance of (3e)13C spectrogram；
Figure 11 is the nuclear-magnetism for the amyl- 2,4- diene -1- ketone (3f) of (2E, 4E) -1,5- diphenyl that the embodiment of the present invention 6 provides
Resonance1H spectrogram；
Figure 12 is the nuclear-magnetism for the amyl- 2,4- diene -1- ketone (3f) of (2E, 4E) -1,5- diphenyl that the embodiment of the present invention 6 provides
Resonance13C spectrogram；
Figure 13 is (1E, 3E, 7E, 8E) -1,1'- diphenyl -1,3,3,8- tetraene -5- ketone that the embodiment of the present invention 7 provides
The nuclear magnetic resonance of (3g)1H spectrogram；
Figure 14 is (1E, 3E, 7E, 8E) -1,1'- diphenyl -1,3,3,8- tetraene -5- ketone that the embodiment of the present invention 7 provides
The nuclear magnetic resonance of (3g)13C spectrogram.
Specific embodiment
The present invention provides a kind of ɑ, beta unsaturated ketone compound and its preparation method and application, the substrates of the preparation method
Convenient sources, substrate kind is more, and the ɑ of multiple types, beta unsaturated ketone compound can be obtained.
The technical scheme in the embodiments of the invention will be clearly and completely described below, it is clear that described implementation
Example is only a part of the embodiment of the present invention, instead of all the embodiments.Based on the embodiments of the present invention, this field is common
Technical staff's every other embodiment obtained without making creative work belongs to the model that the present invention protects
It encloses.
A kind of ɑ, the preparation method of beta unsaturated ketone compound, comprising the following steps:
Formula (I) compound and formula (II) compound are dissolved in atent solvent, in the effect of metallic catalyst and oxidant
Under, it is reacted, obtains formula (III) compound；
Wherein,R2-B(OH)2Formula (II),
R1 is selected from saturated or unsaturated alkyl, substituted hydrocarbon radical or heterocycle, and R2 is selected from saturated or unsaturated alkyl, takes
For alkyl, heterocycle, substituted heterocyclic radical or saturations or undersaturated straight chain alkyl or cyclic hydrocarbon radical containing functional group；
Oxidant includes tetramethyl piperidine nitrogen oxides.
In the embodiment of the present invention, R1Selected from saturated or unsaturated alkyl, substituted hydrocarbon radical or heterocycle, R2Selected from saturation or
Undersaturated alkyl, substituted hydrocarbon radical, heterocycle, substituted heterocyclic radical or saturations or undersaturated straight chain alkyl or ring containing functional group
Alkyl, substrate source is convenient, and simple and easy to get, substrate kind is more, and selectivity is good, and safe operation is simple, and the ɑ of multiple types, β can be obtained
Beta-unsaturated ketone compound, is ɑ, and the preparation of beta unsaturated ketone compound provides a kind of new method.Also, it closes in the prior art
Yield at the beta-unsaturated ketone compound of bilateral heterocycle, condensed ring and long-chain is very low, and preparation method of the present invention can be by yield
It greatly improves.
Inertia is presented in most of reaction in c h bond, makes C-H function dough be very difficult using traditional means.This
In inventive embodiments, ɑ, beta unsaturated ketone compound, using single catalyst are combined to by the direct functional group of c h bond
It realizes multiple dehydrogenation reaction, is broken c h bond in organic matter by catalytic dehydrogenation, achievees the purpose that dehydrogenation, be able to maintain that simultaneously
The C-C key being more easily broken off does not make its fracture, and dehydrogenation reaction can also increase degree of unsaturation, so that ɑ, β with function dough
Beta-unsaturated ketone compound has efficient reactivity, can be widely applied to the significant process in organic synthesis.The present invention is real
The catalyst for applying example is cheap metallic catalyst, and oxidant includes tetramethyl piperidine nitrogen oxides, by metallic catalyst and
The oxidation reaction of oxidant can form the combination of a variety of keys in single reaction, meet green and sustainable chemistry
Requirement, and it is selective it is good, process is simple, convenient, flexible, make formula (I) compound and formula (II) compound in metallic catalyst
ɑ, beta unsaturated ketone compound is prepared with multiple dehydrogenation coupling reaction is carried out under the action of oxidant, which has very much
Application value.Preparation method of the embodiment of the present invention is efficiently synthesized multifunctional dough ɑ by simple substrate, beta unsaturated ketone compound,
It is able to solve the prior art and ɑ is combined to by the direct functional group of c h bond, be difficult to control existing for beta unsaturated ketone compound de-
Hydrogen coupling is difficult to the technical problem that Efficient Conversion, reaction cost are high, reaction stability is not high and reaction is complicated.
In the embodiment of the present invention, R1The alkyl being selected from is phenyl, substituted-phenyl or cyclic hydrocarbon radical, preferably phenyl or substituted benzene
Base, more preferably phenyl, 4- methoxyphenyl or benzene butyl；R1The heterocycle being selected from is preferably thienyl；R2The alkyl being selected from is
Straight-chain alkyl, cyclic hydrocarbon radical, phenyl or fused ring aryl, R2The substituted hydrocarbon radical being selected from is substituted-phenyl or the alkyl of heterocyclic substituted containing O, R2
The substituted-phenyl being selected from is preferably 4- bromophenyl or phenethyl, R2The heterocycle being selected from is preferably furans -2- base, R2What is be selected from is thick
Cyclophane base is preferably anthracene -9- base.
In the embodiment of the present invention, functional group is selected from halogen, ester group, carbonyl, amino, nitro, cyano, sulfuryl or acyl group.
In the embodiment of the present invention, formula (I) compound is preferably propiophenone, substituted propiophenone or cyclohexanone, and formula (II) is changed
Closing object is preferably the phenyl boric acid that phenyl boric acid or phenyl ring have substituent group.
In the embodiment of the present invention, cuprous salt or cupric salt are transition-metal catalyst, using cuprous salt or divalent
Mantoquita carries out multiple dehydrogenation coupling reaction as metallic catalyst, using formula (I) compound and formula (II) compound as substrate, can be with
Obtain polysubstituted ɑ, β unsaturated compound efficiently synthesizes the ɑ of multifunctional dough by simple substrate, β unsaturation in an orderly manner
Close object.The preparation method substrate spectrum is extensive, and functional group compatibility is preferable, has good universality.
In the embodiment of the present invention, metallic catalyst is selected from copper acetate, copper trifluoromethanesulfcomposite, cuprous halide or copper halide.This
The metallic catalyst that inventive embodiments use is cheap, can save preparation ɑ, the cost of beta unsaturated ketone compound.
In the embodiment of the present invention, oxidant further includes tert-butyl hydroperoxide and/or tert-butyl peroxide.Oxidant is
Easily conversion, free of contamination peroxide, meet sustainable Green Chemistry.
In the embodiment of the present invention, reaction is also added into additive；
Additive is selected from silver acetate, silver carbonate, silver nitrate, sodium acetate, lithium carbonate, potassium carbonate, cesium carbonate or potassium acetate.
In the embodiment of the present invention, the temperature of reaction is 60 DEG C~120 DEG C, preferably 80 DEG C~120 DEG C, more preferably 100
℃；
The time of reaction is 6h~for 24 hours, preferably 10h.
In the embodiment of the present invention, the molar ratio of formula (I) compound and formula (II) compound is (1~3): (3~1), preferably
For 1:2.The molar ratio of formula (II) compound and metallic catalyst is 1:1~3:1, preferably 2:1 or 1:1.
In the embodiment of the present invention, atent solvent is selected from toluene, tetrahydrofuran, Isosorbide-5-Nitrae-dioxane, N, N '-dimethyl formyl
Amine, N, N '-dimethyl acetamide, N-Methyl pyrrolidone, dimethyl sulfoxide, acetonitrile or 1,2- dichloroethanes, preferably toluene.
The molar ratio of atent solvent and formula (I) compound is 1:10~10:1, more preferably 1:2.
In the embodiment of the present invention, after being reacted, before obtaining formula (III) compound, further includes:
Reaction product is cooled to room temperature, is filtered using diatomite, then is concentrated to give crude product；
Crude product is subjected to thin layer chromatography separation using the silica gel plate of preparation.
The solvent or eluant, eluent of thin layer chromatography separation are petroleum ether and ethyl acetate, the volume of petroleum ether and ethyl acetate
Than for 100:1~10:1, preferably 20:1.
Preparation method raw material of the present invention is simple and easy to get, and safe operation is simple, and wide application range of substrates chooses, and prepares ɑ, β
Beta-unsaturated ketone compound it is high-efficient.
The present invention also provides ɑ made from above-mentioned technical proposal preparation method, beta unsaturated ketone compounds.
The present invention also provides ɑ made from above-mentioned technical proposal preparation method, beta unsaturated ketone compound in drug and/or
Application in materials synthesis.
ɑ, beta unsaturated ketone compound are a kind of organic matters with multiple reaction site, are easy to subsequent further conversion, tool
There is very good Atom economy, can be used for preparing has the active molecule of potential source biomolecule, is applied to medicine and Material Field.
For a further understanding of the present invention, the present invention will be described in detail combined with specific embodiments below.
Embodiment 1
The present embodiment carries out the preparation of (E) -3- (4- bromophenyl) -1- phenyl propyl- 2- alkene -1- ketone (3a), and reaction equation is such as
Shown in lower:
Under an atmospheric air atmosphere, sequentially added into 15mL Schlenk reaction tube propiophenone 1a (26.8mg,
0.20mmol), 4- bromobenzeneboronic acid 2a (80.1mg, 0.40mmol), cuprous oxide (2.8mg, 0.02mmol), tert-butyl hydroperoxide
Hydrogen (72.1mg, 0.80mmol), 2,2,6,6- tetramethyl piperidine oxides (9.4mg, 0.06mmol) and toluene (toluene,
1.5mL), 16h reaction is carried out at 80 DEG C, is cooled to room temperature after reaction, after suction filtered through kieselguhr, is concentrated to get thick production
Object.The silica gel plate of crude product preparation carries out thin layer chromatography separation, and solvent or eluant, eluent are petroleum ether and ethyl acetate, petroleum
The volume ratio of ether and ethyl acetate is 20:1, obtains product (E) -3- (4- bromophenyl) -1- phenyl propyl- 2- alkene -1- ketone (3a), is produced
Object is yellow-brown solid, and product yield is 79% (45.4mg).
The measurement of nuclear magnetic resonance spectroscopy is carried out to (E) -3- (4- bromophenyl) -1- phenyl propyl- 2- alkene -1- ketone (3a), as a result
Are as follows:1H NMR(400MHz,CDCl3) δ 8.00 (d, J=7.2Hz, 2H), 7.72 (d, J=15.6Hz, 1H), 7.56-7.53 (m,
2H), 7.48 (d, J=9.2Hz, 1H), 7.46-7.42 (m, 3H), 7.33-7.28 (m, 2H)；
The measurement of carbon-13 nmr spectra is carried out to (E) -3- (4- bromophenyl) -1- phenyl propyl- 2- alkene -1- ketone (3a), as a result
Are as follows:13C NMR(100MHz,CDCl3) δ 189.6,142.6,137.6,136.5,134.7,132.8,130.0,129.9,
128.4,128.3,127.7,126.5,122.9.
Product (E) -3- (4- the bromophenyl) -1- phenyl propyl- 2- alkene -1- ketone (3a) that the embodiment of the present invention is prepared can be with
Compatible with the functional group such as carbonyl, C-C double bond, halogen bromine etc. for facilitating conversion, for the product subsequent transformation become drug and/
Or material compound is provided convenience.
Embodiment 2
The present embodiment carries out the preparation of (E) -1- (4- methoxyphenyl) -3- phenyl propyl- 2- alkene -1- ketone (3b), reaction
Formula is as follows:
Under an atmospheres oxygen atmosphere, sequentially added into 15mL Schlenk reaction tube to methoxybenzene acetone 1b
(32.8mg, 0.20mmol), phenyl boric acid 2b (36.6mg, 0.30mmol), cuprous oxide (2.8mg, 0.02mmol), tert-butyl mistake
Hydrogen oxide (72.1mg, 0.80mmol), 2,2,6,6- tetramethyl piperidine oxides (9.4mg, 0.06mmol) and toluene
(toluene, 2.0mL) carries out 14h reaction at 90 DEG C, is cooled to room temperature after reaction, after suction filtered through kieselguhr, concentration
Obtain crude product.The silica gel plate of crude product preparation carries out thin layer chromatography separation, and solvent or eluant, eluent are petroleum ether and acetic acid
The volume ratio of ethyl ester, petroleum ether and ethyl acetate is 20:1, obtains product (E) -1- (4- methoxyphenyl) -3- phenyl propyl- 2-
Alkene -1- ketone (3b), product are light yellow solid, and product yield is 79% (37.6mg).
The measurement of nuclear magnetic resonance spectroscopy is carried out to (E) -1- (4- methoxyphenyl) -3- phenyl propyl- 2- alkene -1- ketone (3b),
As a result are as follows:1H NMR(400MHz,CDCl3) δ 8.04 (dd, J=2.0Hz, 6.8Hz, 2H), 7.80 (d, J=15.6Hz, 1H),
7.65-7.63 (m, 2H), 7.64 (d, J=16.0Hz, 1H), 7.43-7.40 (m, 3H), 6.98 (dd, J=1.6Hz, 6.8Hz,
2H), 3.89 (s, 3H).
The measurement of carbon-13 nmr spectra is carried out to (E) -1- (4- methoxyphenyl) -3- phenyl propyl- 2- alkene -1- ketone (3b),
As a result are as follows:13C NMR (100MHz, CDCl3) δ 188.7,163.4,143.9,135.1,131.1,130.8,130.2,128.9,
128.3,121.9,113.8,55.5.
Product (E) -1- (4- methoxyphenyl) -3- phenyl propyl- 2- alkene -1- ketone (3b) that the embodiment of the present invention is prepared
Medicine can be become compatible with the functional group such as carbonyl, C-C double bond, methoxyl group etc. for facilitating conversion for the product subsequent transformation
Object and/or material compound are provided convenience.
Embodiment 3
The present embodiment carries out the preparation of (E) -3- (anthracene -9- base) -1- phenyl propyl- 2- alkene -1- ketone (3c), and reaction equation is as follows
It is shown:
Under an atmospheres oxygen atmosphere, sequentially added into 15mL Schlenk reaction tube propiophenone 1c (33.5mg,
0.25mmol), 9- anthracene boric acid 2c (88.8mg, 0.40mmol), cuprous oxide (7.0mg, 0.05mmol), tert-butyl hydroperoxide
(101.3mg, 1.125mmol), 2,2,6,6- tetramethyl piperidine oxides (7.9mg, 0.05mmol) and toluene (toluene,
2.5mL), 12h reaction is carried out at 100 DEG C, is cooled to room temperature after reaction, after suction filtered through kieselguhr, is concentrated to get thick production
Object.The silica gel plate of crude product preparation carries out thin layer chromatography separation, and solvent or eluant, eluent are petroleum ether and ethyl acetate, petroleum
The volume ratio of ether and ethyl acetate is 50:1, obtains product (E) -3- (anthracene -9- base) -1- phenyl propyl- 2- alkene -1- ketone (3c), is produced
Object is light yellow solid, and product yield is 62% (47.8mg).
The measurement of nuclear magnetic resonance spectroscopy is carried out to (E) -3- (anthracene -9- base) -1- phenyl propyl- 2- alkene -1- ketone (3c), as a result
Are as follows:1H NMR (400MHz, CDCl3) δ 8.80 (d, J=16.0Hz, 1H), 8.47 (d, J=5.2Hz, 1H), 8.31 (d, J=
8.4Hz, 2H), 8.10 (d, J=7.6Hz, 2H), 8.04-8.02 (m, 2H), 7.64-7.58 (m, 2H), 7.53 (d, J=
6.0Hz,3H),7.52-7.49(m,3H)。
The measurement of carbon-13 nmr spectra is carried out to (E) -3- (anthracene -9- base) -1- phenyl propyl- 2- alkene -1- ketone (3c), as a result
Are as follows:13C NMR(100MHz,CDCl3) δ 189.7,141.9,137.9,133.0,131.3,131.0,130.1,129.6,
128.9,128.73,128.70,128.4,126.4,125.4,125.3。
Product (E) -3- (anthracene -9- base) -1- phenyl propyl- 2- alkene -1- ketone (3c) that the embodiment of the present invention is prepared is compatible
Complicated condensed ring, increases ɑ, the diversity of beta unsaturated ketone compound.
Embodiment 4
The system of the present embodiment progress (E) -3- (3A, 3A-1- pyrene -1- base) -1- (thiophene -2- base) propyl- 2- alkene -1- ketone (3d)
Standby, reaction equation is as follows:
Under an atmospheres oxygen atmosphere, 2- propionyl thiophene 1d is sequentially added into 15mL Schlenk reaction tube
(70.1mg, 0.50mmol), 1- pyrene boric acid 2d (61.1mg, 0.50mmol), cuprous oxide (7.0mg, 0.05mmol), tert-butyl
Hydrogen peroxide (182.2mg, 2.0mmol), 2,2,6,6- tetramethyl piperidine oxides (1.6mg, 0.01mmol) and toluene
(toluene, 3.0mL) carries out 8h reaction at 130 DEG C, is cooled to room temperature after reaction, after suction filtered through kieselguhr, concentration
Obtain crude product.The silica gel plate of crude product preparation carries out thin layer chromatography separation, and solvent or eluant, eluent are petroleum ether and acetic acid
The volume ratio of ethyl ester, petroleum ether and ethyl acetate is 50:1, obtains product (E) -3- (3A, 3A-1- pyrene -1- base) -1- (thiophene -
2- yl) propyl- 2- alkene -1- ketone (3d), product is light yellow solid, and product yield is 50% (84.5mg).
Hydrogen nuclear magnetic resonance is carried out to (E) -3- (3A, 3A-1- pyrene -1- base) -1- (thiophene -2- base) propyl- 2- alkene -1- ketone (3d)
The measurement of spectrum, as a result are as follows:1H NMR(400MHz,CDCl3) δ 8.95 (d, J=15.2Hz, 1H), 8.48 (d, J=9.2Hz, 1H),
8.35 (d, J=8.4Hz, 1H), 8.18 (d, J=7.6Hz, 2H), 8.15-8.12 (m, 3H), 8.11-8.08 (m, 1H), 8.03-
7.99 (m, 2H), 7.77 (d, J=15.6Hz, 1H), 7.63 (t, J=7.2Hz, 1H), 7.58-7.55 (m, 1H).
Nuclear magnetic resonance carbon is carried out to (E) -3- (3A, 3A-1- pyrene -1- base) -1- (thiophene -2- base) propyl- 2- alkene -1- ketone (3d)
The measurement of spectrum, as a result are as follows:13C NMR (100MHz, CDCl3) δ 190.2,141.4,138.4,132.9,132.8,131.2,
130.6,130.3,128.7,128.6,127.2,126.2,126.0,125.8,124.9,124.5,124.1,123.8,
122.5。
Product (E) -3- (3A, 3A-1- pyrene -1- base) -1- (thiophene -2- base) propyl- 2- that the embodiment of the present invention is prepared
Alkene -1- ketone (3d) has heterocycle thiophene and condensed ring pyrene, and the subsequent conversion that exists for of C-C double bond provides conveniently.
Embodiment 5
The present embodiment carries out the preparation of (E) -3- (furans -2- base) -1- (thiophene -2- base) propyl- 2- alkene -1- ketone (3e),
Reaction equation is as follows:
Under an atmospheres oxygen atmosphere, 1- (2- thienyl) -1- is sequentially added into 15mL Schlenk reaction tube
Acetone 1e (70.2mg, 0.50mmol), 2- furan boronic acid 2e (44.7mg, 0.40mmol), cuprous oxide (21.3mg,
0.17mmol), tert-butyl hydroperoxide (182.2mg, 2.0mmol), 2,2,6,6- tetramethyl piperidine oxides (1.6mg,
0.01mmol) with toluene (toluene, 2.0mL), 20h reaction is carried out at 60 DEG C, is cooled to room temperature after reaction, through silicon
After diatomaceous earth filters, it is concentrated to get crude product.The silica gel plate of crude product preparation carries out thin layer chromatography separation, solvent or eluant, eluent
For petroleum ether and ethyl acetate, the volume ratio of petroleum ether and ethyl acetate is 20:1, obtains product (E) -3- (furans -2- base) -
1- (thiophene -2- base) propyl- 2- alkene -1- ketone (3e), product are light yellow solid, and product yield is 59% (60.2mg).
The survey of nuclear magnetic resonance spectroscopy is carried out to (E) -3- (furans -2- base) -1- (thiophene -2- base) propyl- 2- alkene -1- ketone (3e)
It is fixed, as a result are as follows:1H NMR(400MHz,CDCl3) δ 7.81 (d, J=3.6Hz, 1H), 7.62 (d, J=4.8Hz, 1H), 7.58 (d,
J=15.2Hz, 1H), 7.50 (s, 1H), 7.30 (d, J=15.6Hz, 1H), 7.13 (t, J=4.4Hz, 1H), 6.68 (d, J=
3.2Hz, 1H), 6.67 (dd, J=1.6Hz, 3.2Hz, 1H).
The survey of carbon-13 nmr spectra is carried out to (E) -3- (furans -2- base) -1- (thiophene -2- base) propyl- 2- alkene -1- ketone (3e)
It is fixed, as a result are as follows:13C NMR(100MHz,CDCl3)δ181.4,151.2,145.4,144.8,133.6,131.5,129.6,
128.0,118.8,116.1,112.5。
The embodiment of the present invention can efficiently obtain the ɑ with thiophene and furan structure, alpha, beta-unsaturated ketone compound, Ke Yiliang
Good carry out next step conversion, and then obtain the drug with heterocycle structure and/or material compound.
Embodiment 6
The present embodiment carries out the preparation of amyl- 2, the 4- diene -1- ketone (3f) of (2E, 4E) -1,5- diphenyl, and reaction equation is as follows
It is shown:
Under an atmospheres oxygen atmosphere, propiophenone 1f is sequentially added into 15mL Schlenk reaction tube
(120.4mg, 0.6mmol), phenethyl boric acid 2f (60.0mg, 0.40mmol), cuprous oxide (25.2mg, 0.18mmol), uncle
Butylhydroperoxide (270.3mg, 3.0mmol), 2,2,6,6- tetramethyl piperidine oxides (17.1mg, 0.12mmol) and toluene
(toluene, 3.0mL) carries out 10h reaction at 100 DEG C, is cooled to room temperature after reaction, after suction filtered through kieselguhr, concentration
Obtain crude product.The silica gel plate of crude product preparation carries out thin layer chromatography separation, and solvent or eluant, eluent are petroleum ether and acetic acid
The volume ratio of ethyl ester, petroleum ether and ethyl acetate is 20:1, obtains amyl- 2, the 4- diene -1- of product (2E, 4E) -1,5- diphenyl
Ketone (3f), product are light yellow solid, and product yield is 56% (78.2mg).
The measurement of nuclear magnetic resonance spectroscopy is carried out to amyl- 2, the 4- diene -1- ketone of (2E, 4E) -1,5- diphenyl (3f), as a result
Are as follows:1H NMR (400MHz, CDCl3) δ 7.98 (d, J=7.2Hz, 2H), 7.64-7.55 (m, 2H), 7.51-7.47 (m, 4H),
7.39-7.31 (m, 3H), 7.09 (d, J=14.8Hz, 1H), 7.03-7.01 (m, 2H).
The measurement of carbon-13 nmr spectra is carried out to amyl- 2, the 4- diene -1- ketone of (2E, 4E) -1,5- diphenyl (3f), as a result
Are as follows:13C NMR(100MHz,CDCl3)δ190.4,144.8,141.8,138.2,136.1,132.6,129.2,128.8,
128.5,128.3,127.2,126.9,125.4。
The embodiment of the present invention can efficiently obtain the ɑ of multiple dehydrogenation, and alpha, beta-unsaturated ketone compound has unsaturation to be subsequent
The conversion of the beta-unsaturated ketone medical compounds of the long-chain branch of degree provides precursor.
Embodiment 7
The present embodiment progress (1E, 3E, 7E, 8E) -1,1'- diphenyl -1,3, the preparation of 3,8- tetraene -5- ketone (3g),
Reaction equation is as follows:
Under an atmospheres oxygen atmosphere, 3 ketone 1g of 1- phenyl hept- is sequentially added into 15mL Schlenk reaction tube
(57.1mg, 0.30mmol), phenethyl boric acid 2g (30.0mg, 0.20mmol), cuprous oxide (12.6mg, 0.09mmol), uncle
Butylhydroperoxide (135.2mg, 1.5mmol), 2,2,6,6- tetramethyl piperidine oxides (9.4mg, 0.06mmol) and toluene
(toluene, 2.0mL) carries out 8h reaction at 130 DEG C, is cooled to room temperature after reaction, after suction filtered through kieselguhr, concentration
Obtain crude product.The silica gel plate of crude product preparation carries out thin layer chromatography separation, and solvent or eluant, eluent are petroleum ether and acetic acid
The volume ratio of ethyl ester, petroleum ether and ethyl acetate is 20:1, obtains product (1E, 3E, 7E, 8E) -1,1'- diphenyl -1,3,3,
8- tetraene -5- ketone (3g), product are light yellow solid, and product yield is 55% (47.3mg).
To (1E, 3E, 7E, 8E) -1,1'- diphenyl -1,3,3,8- tetraene -5- ketone (3g) carry out the survey of nuclear magnetic resonance spectroscopy
It is fixed, as a result are as follows:1H NMR(400MHz,CDCl3) δ 7.51-7.45 (m, 6H), 7.39-7.30 (m, 6H), 7.01-6.91 (m,
4H), 6.56 (d, J=13.6Hz, 2H).
To (1E, 3E, 7E, 8E) -1,1'- diphenyl -1,3,3,8- tetraene -5- ketone (3g) carry out the survey of carbon-13 nmr spectra
It is fixed, as a result are as follows:13C NMR(100MHz,CDCl3)δ188.8,142.9,141.4,136.1,129.1,129.0,128.8,
127.2,127.0。
The embodiment of the present invention can efficiently obtain the ɑ of multiple dehydrogenation, and alpha, beta-unsaturated ketone has high degree of unsaturation to be subsequent
Drug molecule conversion provide precursor.
The above is only a preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, various improvements and modifications may be made without departing from the principle of the present invention, these improvements and modifications are also answered
It is considered as protection scope of the present invention.
Claims (10)
1. a kind of ɑ, the preparation method of beta unsaturated ketone compound, which comprises the following steps:
Formula (I) compound and formula (II) compound are dissolved in atent solvent, under the action of metallic catalyst and oxidant, into
Row reaction, obtains formula (III) compound；
Wherein,R2-B(OH)2Formula (II),
R1Selected from saturated or unsaturated alkyl, substituted hydrocarbon radical or heterocycle, R2Selected from saturated or unsaturated alkyl, replace hydrocarbon
Base, heterocycle, substituted heterocyclic radical or saturations or undersaturated straight chain alkyl or cyclic hydrocarbon radical containing functional group；
The oxidant includes tetramethyl piperidine nitrogen oxides.
2. preparation method according to claim 1, which is characterized in that the functional group is selected from halogen, ester group, carbonyl, ammonia
Base, nitro, cyano, sulfuryl or acyl group.
3. preparation method according to claim 1, which is characterized in that the metallic catalyst is selected from copper acetate, fluoroform
Sulfonic acid copper, cuprous halide or copper halide.
4. preparation method according to claim 1, which is characterized in that the oxidant further includes tert-butyl hydroperoxide
And/or tert-butyl peroxide.
5. preparation method according to claim 1, which is characterized in that the reaction is also added into additive；
The additive is selected from silver acetate, silver carbonate, silver nitrate, sodium acetate, lithium carbonate, potassium carbonate, cesium carbonate or potassium acetate.
6. preparation method according to claim 1, which is characterized in that the temperature of the reaction is 60 DEG C~120 DEG C；
The time of the reaction is 6h~for 24 hours.
7. preparation method according to claim 1, which is characterized in that formula (I) compound and the formula (II) chemical combination
The molar ratio of object is (1~3): (3~1).
8. preparation method according to claim 1, which is characterized in that the atent solvent is selected from toluene, tetrahydrofuran, 1,
4- dioxane, N, N '-dimethyl formamide, N, N '-dimethyl acetamide, N-Methyl pyrrolidone, dimethyl sulfoxide, acetonitrile or
1,2- dichloroethanes.
9. ɑ made from preparation method described in claim 1 to claim 8 any one, beta unsaturated ketone compound.
10. ɑ made from preparation method described in claim 1 to claim 8 any one, beta unsaturated ketone compound is in drug
And/or the application in materials synthesis.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910138125.3A CN110194713A (en) | 2019-02-25 | 2019-02-25 | A kind of ɑ, beta unsaturated ketone compound and its preparation method and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910138125.3A CN110194713A (en) | 2019-02-25 | 2019-02-25 | A kind of ɑ, beta unsaturated ketone compound and its preparation method and application |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110194713A true CN110194713A (en) | 2019-09-03 |
Family
ID=67751722
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910138125.3A Pending CN110194713A (en) | 2019-02-25 | 2019-02-25 | A kind of ɑ, beta unsaturated ketone compound and its preparation method and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110194713A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1854128A (en) * | 2001-04-24 | 2006-11-01 | 麻省理工学院 | Copper-catalyzed formation of carbon-heteroatom and carbon-carbon bonds |
| CN107216307A (en) * | 2017-05-26 | 2017-09-29 | 中国科学院上海有机化学研究所 | A kind of method for efficiently synthesizing 1,1 diaryl alkane hydro carbons compounds |
-
2019
- 2019-02-25 CN CN201910138125.3A patent/CN110194713A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1854128A (en) * | 2001-04-24 | 2006-11-01 | 麻省理工学院 | Copper-catalyzed formation of carbon-heteroatom and carbon-carbon bonds |
| CN107216307A (en) * | 2017-05-26 | 2017-09-29 | 中国科学院上海有机化学研究所 | A kind of method for efficiently synthesizing 1,1 diaryl alkane hydro carbons compounds |
Non-Patent Citations (6)
| Title |
|---|
| N.A. SHAKIL: "Microwave synthesis, characterization and bio-efficacy evaluation of novel chalcone based 6-carbethoxy-2-cyclohexen-1-one and 2H-indazol-3-ol derivatives", 《EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY》 * |
| SHANG Y,P: "Dehydrogenative desaturation-relay via formation of multicenter-stabilized radical intermediates", 《NATURE COMMUNICATIONS》 * |
| TIANZHANG WANG: "Intermolecular Multiple Dehydrogenative Cross‐Couplings of Ketones with Boronic Acids and Amines via Copper Catalysis", 《ADVANCED SYNTHESIS & CATALYSIS》 * |
| XIAOMING JIE: "Cu-Catalyzed Sequential Dehydrogenation–Conjugate Addition for β-Functionalization of Saturated Ketones Scope and Mechanism", 《J. AM. CHEM. SOC.》 * |
| Y. TERAO: "Multiple arylation of alkyl aryl ketones and α,β-unsaturated carbonyl compounds via palladium catalysis", 《TETRAHEDRON》 * |
| 王天璋: "铜盐/TEMPO体系催化氧化串联反应研究", 《中国优秀博硕士学位论文全文数据库(硕士)工程科技Ⅰ辑》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN115947668A (en) | Preparation method of polysubstituted indene derivative | |
| CN109134372A (en) | A kind of preparation method of pyrido indene compounds | |
| CN109942616A (en) | A kind of aryl amide analog derivative and its preparation method and application containing alkynyl | |
| Meshram et al. | Bismuthtriflate-catalyzed Reaction of N-Alkylisatins with Allyltrimethylsilane | |
| CN111072605B (en) | Preparation method of fluoroalkyl-substituted benzofuran derivative or indole derivative | |
| CN110194713A (en) | A kind of ɑ, beta unsaturated ketone compound and its preparation method and application | |
| CN109879788B (en) | Method for preparing N-substituted indole derivative | |
| CN109879792B (en) | Polysubstituted isoindole compound and preparation method thereof | |
| CN105085563B (en) | A kind of branch allyl compound, preparation method and application | |
| CN108440384B (en) | Process for the preparation of trifluoromethylated derivatives of isoindolones | |
| KR100733023B1 (en) | Dialdehyde compound, preparation method thereof, and synthetic method of carotenoids using the same | |
| Kong et al. | Synthesis of spiro dienones from internal acetylene and cyclic 3-iodo enones in the presence of nickel bromide and zinc powder | |
| CN115650914A (en) | Preparation method of indenoquinoline derivative | |
| CN110317170B (en) | Green synthesis method of 3-phenanthridinyl propyl formate compound | |
| CN108689892A (en) | 3- sulfonylations-indane ketone compounds and preparation method thereof | |
| CN110305156B (en) | Alkyne derivative containing nitrogen-oxygen bond and preparation method and application thereof | |
| CN109942615B (en) | Aryl amine derivative containing alkynyl and preparation method and application thereof | |
| CN114656314B (en) | Preparation method of internal alkyne compound | |
| JPWO2005085204A1 (en) | Method for producing nitrogen-containing 5-membered ring compound | |
| CN109796399A (en) | One kind ɑ containing N-, beta unsaturated ketone compound and its preparation method and application | |
| CN106866348B (en) | A kind of polycyclic aromatic hydrocarbon compounds, synthetic method and purposes | |
| CN110256480A (en) | A kind of nitogen-contained heterocycle derivant and its preparation method and application containing alkynyl | |
| Matsushita et al. | Optical activation of racemic. ALPHA.-substituted carbonyl compounds using optically active amines. | |
| CN104327025A (en) | Preparation method of 4-aryltetralin lactone derivatives | |
| CN109867691A (en) | A kind of aryl amine derivant and its preparation method and application |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20190903 |