CN108558635A - The preparation method of 3- aryl propiolic acid classes and 3- aryl propiolic acid ester type compounds - Google Patents
The preparation method of 3- aryl propiolic acid classes and 3- aryl propiolic acid ester type compounds Download PDFInfo
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Abstract
The present invention relates to a kind of preparation methods of 3 aryl propiolic acid class compound：In the presence of alkali by phenylacetylene class compound shown in formula (I) and carbon dioxide, it is reacted at 40 70 DEG C in solvent dimethyl sulfoxide, obtain 3 aryl propiolic acid class compound shown in formula (II), the above reaction carries out under normal pressure and in anhydrous, anaerobic inert atmosphere, and reaction route is as follows：Wherein, R1Selected from hydrogen, alkyl, alkoxy, phenyl, nitro or halogen.Invention further provides a kind of preparation methods of 3 aryl propiolic acid ester type compound：Using 3 aryl propiolic acid class compound shown in above method formula (II), halogenated hydrocarbons or p-methyl benzenesulfonic acid ester are then added thereto, 3 aryl propiolic acid ester type compound shown in formula (III) is obtained after reaction in-situ：Wherein, R2Selected from alkyl, benzyl or allyl.The method of the present invention is good without transition metal or rare-earth metal catalyst, synthesis under normal pressure, mild condition, substrate universality.
Description
Technical field
The present invention relates to organic synthesis field more particularly to a kind of 3- aryl propiolic acid class and 3- aryl propiolic acid esters
Close the preparation method of object.
Background technology
3- aryl propiolic acid class compounds are as important intermediate in drug molecule, bioactive molecule and conductive polymer
It is had a wide range of applications in the preparation of son.Propiolic acid in order to obtain, the first traditional synthetic route are with corresponding end alkynes
For starting material, is then aoxidized by formaldehyde addition and obtain target product.Second method is metallized in carbon monoxide, alcoxyl
Propiolate is obtained under the action of object and oxidant, then hydrolysis obtains corresponding propiolic acid.The third, is inserted using carbon dioxide
Enter the direct carboxylation reaction of terminal alkyne also comparative maturity, be that Grignard Reagent or lithium reagent is made in end-group alkyne, then again with
Carbon dioxide reaction.First two has selected formaldehyde and carbon monoxide as C respectively in these methods1Building block, and the cost of formaldehyde
Relatively high and toxic, carbon monoxide also has toxicity, therefore constrains the development of both methods.It is all C1Building block, dioxy
Change carbon then have many advantages, such as it is nontoxic, be easy to get with it is renewable.But Grignard Reagent or lithium reagent method are maximum the disadvantage is that can not be straight
It connects and prepares the propiolic acid with other susceptible groups, need to increase the step of protecting and being deprotected.So development condition
Mildly, easy to operate, the high terminal alkyne and carbon dioxide of Atom economy carboxylation reaction be very it is necessary to.
It is mainly the following at present about the report for preparing 3- aryl propiolic acid class compounds：
(1) 2010 year, Goo β en seminars realized end-group alkyne c h bond two for the first time using the cuprous complex of phenanthrolene
Carbonoxide intercalation reaction.They have found previously prepared alkynyl copper and quantitative carbon dioxide reaction can obtain propiolic acid copper
Close object, but (35 DEG C) have occurred violent decomposition at a lower temperature, and the addition of Cu (I) complex can obtain it is higher
Yield, it was demonstrated that Cu (I) complex can effectively inhibit the generation of reverse decarboxylic reaction.In addition, they also found it is excessively high anti-
Answer temperature (>50 DEG C) yield can be caused to decline (Goossen L.J., RodriguezN., Manjolinho F., Lange
P.P.,Adv.Synth.Catal.2010,352,2913-2917.)。
(2) the same year, Yugen Zhang seminars are prepared for a kind of N-heterocyclic carbine copper complex, the catalyst have compared with
High catalytic activity.Reaction can carry out under conditions of room temperature (25 DEG C), an atmospheric pressure carbon dioxide, and can obtain substantially
Satisfactory yield, but the aromatic series end-group alkyne yield with electron-withdrawing substituent is not very ideal.Adjusting azepine
When the feed molar ratio of ring carbenes and stannous chloride, they be surprised to find that excessive stannous chloride can cause yield drastically under
Drop, this show free Cabbeen play the role of in the reaction it is vital (Yu D., Zhang Y.,
P.Natl.Acad.Sci.USA.2010,107(47),20184-20189,S20184/1-S20184/6.)。
(3) 2011 years, the research of Wen-Zhen Zhang seminars found that AgI can also play similar effect.The one of AgI
Big advantage is exactly can be to avoid using complicated and expensive ligand.Its reaction condition is more mild, can obtain medium supreme
Yield, but only drawback is that need 2 atmospheric pressure carbon dioxide.In addition, they compare different anions silver salt,
As a result show that yield does not change significantly, it was demonstrated that Ag+It is the key that ensure reaction (Zhang X., Zhang W.Z., Ren
X.,Zhang L.L.,Lu X.B.,Org.Lett.2011,13(9),2402-2405.)。
(4) 2012 years, Goo β en seminars screened on Wen-Zhen Zhang working foundations obtain activity it is higher
AgBF4, it is reduced to 1bar, catalyst amount to reduce to 500ppm, still than before pressure carbon dioxide by condition optimizing
It can obtain satisfied yield.But such reaction system has higher dependence for solvent, in addition to DMSO, in other solvents
Only down to moderate yield (Arndt M., Risto E., Krause T., Goossen L.J., ChemCatChem.2012,
4,484-487.)。
(5) 2015 years, the catalyst of metal centered on rare earth metal was probed at this by Zhao Bei seminars of University Of Suzhou
Application in reaction.They have synthesized a kind of cyclohexyl bridging amide groups ytterbium, and have studied this catalyst and holding
Catalytic activity in base alkynes carboxylation reaction, discovery can obtain third under conditions of 40 DEG C and an atmospheric pressure with outstanding yield
Alkynes acid compounds.But it cannot further obtain corresponding acetylenic acid ester (Cheng H., Zhao B., Yao using the above method
Y.,Lu C.,Green Chem.2015,17,1675-1682.)。
As the derivative of propiolic acid, 3- aryl propiolate is equally used as intermediate in drug molecule or bioactivity point
It is widely used in the synthesis of son.It is mainly the following at present about the report of preparation method：
(1) 2012 year, Kiyofumi Inamoto team was using CuI and Phosphine ligands as catalyst, 3 equivalent Cs2CO3,
DMA realizes end-group alkyne, carbon dioxide and the coupling life of three component of halogenated hydrocarbons as solvent under conditions of one atmospheric pressure and room temperature
At propiolate (K.Inamoto, N.Asano, K.Kobayashi, M.Yonemoto, Y.Kondo,
Org.Bio.Chem.2012,10,1514-1516.)。
(2) the same year, Wen-Zhen Zhang team are sent out in end-group alkyne and carbon dioxide carboxylation reaction before using them
The AgI catalyst systems of exhibition, also achieve end-group alkyne, CO2And the coupling of halogenated hydrocarbons, but its pressure carbon dioxide is up to 15
Atmospheric pressure, requirement to consersion unit it is very high (X.Zhang, W.Z.Zhang, L.L.Shi, C.Zhu, J.L.Jiang, X.B.Lu,
Tetrahedron 2012,68,9085-9089.)。
(3) 2013 years, Liang-Nian He team equally used CuI catalyst systems, but they replace with solvent
More environment-friendly ethylene carbonate (EC), in 1.2 equivalent Cs2CO3, high yield has also been obtained under the conditions of an atmospheric pressure and 80 DEG C
Rate (B.Yu, Z.F.Diao, C.X.Guo, C.L.Zhong, L.N.He, Y.-N.Zhao, Q.-W.Song, A.-H.Liu,
J.Q.Wang,Green Chem.2013,15,2401-2407.)。
(4) 2015 years, Liang-Nian He team also found, the ionic liquid of Cu (I) structure can be in room temperature and normal pressure
The coupling of lower catalysis end-group alkyne, carbon dioxide and halogenated hydrocarbons, shows very high catalytic activity.(J.N.Xie,B.Yu,
Z.H.Zhou,H.C.Fu,N.Wang,L.N.He,Tetrahedron Lett.2015,56,7059-7062.)
To sum up, although these catalyst system and catalyzings can be effectively synthesized 3- aryl propiolic acid and its ester type compound, these
Also there are many problems in system, such as：Reaction process need to use catalyst, the less varieties of used transition catalyst, rare earth
Metallic catalyst structure is more complex, reaction system high pressure, and the expansion range of substrate is small etc..Therefore, a kind of no catalyst is found
Participation, the preparation method that reaction condition is mild, substrate universality is good to synthesize 3- aryl propiolic acid and its esters in high yield
Object is closed to be of great significance.
Invention content
In order to solve the above technical problems, the object of the present invention is to provide a kind of 3- aryl propiolic acid class and 3- aryl propiolic acids
The preparation method of ester type compound, this method efficiently and can one kettle way prepare above compound, be not necessarily to transition metal or rare earth
The catalysis of metallic catalyst, reacts under normal pressure, mild condition, and substrate universality is good.
To achieve the above object, the present invention adopts the following technical scheme that：
On the one hand, the present invention provides a kind of preparation method of 3- aryl propiolic acid class compound, include the following steps：
By phenylacetylene class compound shown in formula (I) and carbon dioxide (CO2) in the presence of alkali, in solvent dimethyl sulfoxide
(DMSO) 12-24h is reacted at 40-70 DEG C in, it is organic base to obtain 3- aryl propiolic acid class compound, alkali shown in formula (II)
And/or inorganic weak bases, the above reaction carry out under normal pressure and in anhydrous, anaerobic inert atmosphere, reaction route is as follows：
Wherein, R1Selected from hydrogen, alkyl, alkoxy, phenyl, nitro or halogen.
Preferably, alkyl C1-C4Alkyl；Alkoxy is C1-C4Alkoxy.
Further, halogen is fluorine, chlorine, bromine or iodine.
Further, organic base 1, it is 11 carbon -7- alkene (DBU) of 8- diazabicylos [5.4.0], potassium tert-butoxide, two different
One or more of propyl amido lithium (LDA) and n-BuLi.
Further, inorganic weak bases are cesium carbonate (Cs2CO3)。
Further, alkali is organic base and inorganic weak bases, and organic base 1,11 carbon of 8- diazabicylos, inorganic weak bases are
Cesium chloride (CsCl) or cesium carbonate.
Preferably, alkali DBU, Cs2CO3, DBU and Cs2CO3, DBU and CsCl, potassium tert-butoxide, LDA or n-BuLi.
Further, phenylacetylene class compound and the molar ratio of alkali shown in formula (I) are 1:1-4.Preferably, formula (I) institute
The molar ratio of the phenylacetylene class compound and alkali shown is 1:2.
Preferably, reaction temperature is 60-70 DEG C.
In the present invention, under the promotion of alkali, the target product in 60 degree of maximum outputs derived above is reacted, illustrates to be heated to 60
Degree disclosure satisfy that the requirement of the activation energy of substrate alkynes molecule, reactivity reach best.
On the other hand, the present invention also provides a kind of preparation methods of 3- aryl propiolic acid ester type compound, using one
Pot method, includes the following steps：
Using 3- aryl propiolic acid class compound shown in above method formula (II), then before not separation product
It puts, halogenated hydrocarbons or p-methyl benzenesulfonic acid ester is added thereto, 3- aryl propiolates shown in formula (III) are obtained after reaction in-situ
Class compound：
3- aryl propiolic acid ester type compound shown in formula (III) is obtained after being reacted by 3- aryl propiolic acid class compounds
Reaction route is as follows：
Wherein, R1Selected from hydrogen, alkyl, alkoxy, phenyl, nitro or halogen, R2Selected from alkyl, benzyl or allyl.
Preferably, alkyl C1-C4Alkyl；Alkoxy is C1-C4Alkoxy.
Further, halogen is fluorine, chlorine, bromine or iodine.
Further, R1Selected from hydrogen, R2Selected from C1-C4Alkyl, benzyl or allyl.Preferably, R2Selected from normal-butyl, benzyl
Or allyl.
Further, halogenated hydrocarbons C1-C4Halogenated alkyl hydrocarbon, cylite or 3- bromopropenes.Preferably, C1-C4Halogenated alkyl
Hydrocarbon is C4N-butyl chloride, n-butyl bromide or n-butyl iodide specifically may be selected in halogenated alkyl hydrocarbon.
Further, p-methyl benzenesulfonic acid ester is p-methyl benzenesulfonic acid N-butyl, ethyl p-toluenesulfonate, propyl p-toluenesulfonate
Or p-methyl benzenesulfonic acid isopropyl ester.
Further, phenylacetylene class compound shown in formula (I) and the molar ratio of halogenated hydrocarbons or p-methyl benzenesulfonic acid ester are 1:
1.2-2.Preferably, the two molar ratio is 1:1.2、1:1.5 or 1:2.
In the present invention, reaction carries out under normal pressure, refers specifically to, and reacts used CO2Pressure be an air
Pressure.
In the present invention, reaction in-situ refer to intermediate during prepare compound or catalyst without purifying and
It is directly used in and reacts in next step.
According to the above aspect of the present invention, the present invention has at least the following advantages：
1, the present invention use carbon dioxide as reactant, carbon dioxide have many advantages, such as it is nontoxic, be easy to get with it is renewable, and
The reaction condition of one atmospheric pressure is easy to experimental implementation.
2, present invention reaction is participated in without transition metal or rare-earth metal catalyst, and at low cost and reaction is efficient, also keeps away
Possible heavy-metal residual in product is exempted from.
3, present invention reaction uses organic base and/or inorganic weak bases, mild condition to be resistant to alkali-sensitive substrate,
Yield may be up to 98%.
4,3- aryl propiolate is prepared by one kettle way, without detaching intermediate product, high-efficient simple.
Above description is only the general introduction of technical solution of the present invention, in order to better understand the technical means of the present invention,
And can be implemented in accordance with the contents of the specification, below with presently preferred embodiments of the present invention and after coordinating detailed description such as.
Specific implementation mode
With reference to embodiment, the embodiment of the present invention is furthur described in detail.Following embodiment is used for
Illustrate the present invention, but is not limited to the scope of the present invention.
In following embodiment, solvent for use has carried out removing water process in advance, whole there are when more water in reaction system
A reaction process can be hindered, influences yield；CO used2Gas is an atmospheric pressure, and reaction carries out under normal pressure.
Comparative example 1：At 60 DEG C, phenylacetylene and carbon dioxide reaction：
110 μ L (1mmol, 1equiv.) phenylacetylenes are added in anhydrous and oxygen-free, argon gas protection under confined conditions, in reaction bulb,
5mL DMSO, CO is added in syringe2Air in gas displacement reaction system stirs for 24 hours in 60 DEG C of constant temperature baths.After reaction
Sky is exposed, is cooled down with ice-water bath after room temperature end is cold.10mL deionized waters are added, add 20mL 6mol/L HCl solutions to fill
Divide acidification, extracted with 3 × 10mL anhydrous ethers, merges organic phase, organic phase saturated common salt water washing.Separate organic be added to
Anhydrous Na2SO4It is dry, it depressurizes after removing solvent without product.
Embodiment 1：At 60 DEG C, phenylacetylene and carbon dioxide reaction that cesium carbonate participates in：
Anhydrous and oxygen-free, argon gas protection weigh 0.6516g Cs under confined conditions, in reaction bulb2CO3(2mmol,
2equiv.), 110 μ L (1mmol, 1equiv.) phenylacetylenes are added in micro syringe, and 5mL DMSO, CO is added in syringe2Gas
The air in reaction system is displaced, 60 DEG C of reactions are for 24 hours.Sky is exposed after reaction, is cooled down with ice-water bath after room temperature end is cold.Add
Enter 10mL deionized waters, add 20mL 6mol/L HCl solutions to be fully acidified, extracted with 3 × 10mL anhydrous ethers, is merged
Organic phase, organic phase saturated common salt water washing.It separates and organic is added to anhydrous Na2SO4Dry, decompression obtains target except solvent
Product, separation yield 94%.The structure of target product is as follows：
Nuclear magnetic data：1H NMR(400MHz,CDCl3):δ10.64(s,1H),7.66-7.59(m,2H),7.53-7.46
(m,1H),7.43-7.37(m,2H)。
By comparative example 1 and embodiment 1 as can be seen that when embodiment 1 is using cesium carbonate, under the same reaction conditions,
Its ultimate yield is greatly improved than reaction (comparative example 1) yield without using cesium carbonate.
In following example 2-35 of the present invention, the preparation method of different 3- aryl propiolic acid class compounds is provided：
Embodiment 2：At 40 DEG C, phenylacetylene and carbon dioxide reaction that cesium carbonate participates in：
Anhydrous and oxygen-free, argon gas protection weigh 0.6516g Cs under confined conditions, in reaction bulb2CO3(2mmol,
2equiv.), 110 μ L (1mmol, 1equiv.) phenylacetylenes are added in micro syringe, and 5mL DMSO, CO is added in syringe2Gas
The air in reaction system is displaced, 40 DEG C of reactions are for 24 hours.Sky is exposed after reaction, is cooled down with ice-water bath after room temperature end is cold.Add
Enter 10mL deionized waters, add 20mL 6mol/L HCl solutions to be fully acidified, extracted with 3 × 10mL anhydrous ethers, is merged
Organic phase, organic phase saturated common salt water washing.It separates and organic is added to anhydrous Na2SO4Dry, decompression obtains target except solvent
Product, separation yield 51%.
Embodiment 3：At 50 DEG C, phenylacetylene and carbon dioxide reaction that cesium carbonate participates in：
Anhydrous and oxygen-free, argon gas protection weigh 0.6516g Cs under confined conditions, in reaction bulb2CO3(2mmol,
2equiv.), 110 μ L (1mmol, 1equiv.) phenylacetylenes are added in micro syringe, and 5mL DMSO, CO is added in syringe2Gas
The air in reaction system is displaced, 50 DEG C of reactions are for 24 hours.Sky is exposed after reaction, is cooled down with ice-water bath after room temperature end is cold.Add
Enter 10mL deionized waters, add 20mL 6mol/L HCl solutions to be fully acidified, extracted with 3 × 10mL anhydrous ethers, is merged
Organic phase, organic phase saturated common salt water washing.It separates and organic is added to anhydrous Na2SO4Dry, decompression obtains target except solvent
Product, separation yield 70%.
Embodiment 4：At 55 DEG C, phenylacetylene and carbon dioxide reaction that cesium carbonate participates in：
Anhydrous and oxygen-free, argon gas protection weigh 0.6516g Cs under confined conditions, in reaction bulb2CO3(2mmol,
2equiv.), 110 μ L (1mmol, 1equiv.) phenylacetylenes are added in micro syringe, and 5mL DMSO, CO is added in syringe2Gas
The air in reaction system is displaced, 55 DEG C of reactions are for 24 hours.Sky is exposed after reaction, is cooled down with ice-water bath after room temperature end is cold.Add
Enter 10mL deionized waters, add 20mL 6mol/L HCl solutions to be fully acidified, extracted with 3 × 10mL anhydrous ethers, is merged
Organic phase, organic phase saturated common salt water washing.It separates and organic is added to anhydrous Na2SO4Dry, decompression obtains target except solvent
Product, separation yield 84%.
Embodiment 5：At 70 DEG C, phenylacetylene and carbon dioxide reaction that cesium carbonate participates in：
Anhydrous and oxygen-free, argon gas protection weigh 0.6516g Cs under confined conditions, in reaction bulb2CO3(2mmol,
2equiv.), 110 μ L (1mmol, 1equiv.) phenylacetylenes are added in micro syringe, and 5mL DMSO, CO is added in syringe2Gas
The air in reaction system is displaced, 70 DEG C of reactions are for 24 hours.Sky is exposed after reaction, is cooled down with ice-water bath after room temperature end is cold.Add
Enter 10mL deionized waters, add 20mL 6mol/L HCl solutions to be fully acidified, extracted with 3 × 10mL anhydrous ethers, is merged
Organic phase, organic phase saturated common salt water washing.It separates and organic is added to anhydrous Na2SO4Dry, decompression obtains target except solvent
Product, separation yield 93%.
Embodiment 6：At 60 DEG C, phenylacetylene and carbon dioxide reaction that cesium carbonate participates in：
Anhydrous and oxygen-free, argon gas protection weigh 0.6516g Cs under confined conditions, in reaction bulb2CO3(2mmol,
2equiv.), 110 μ L (1mmol, 1equiv.) phenylacetylenes are added in micro syringe, and 5mL DMSO, CO is added in syringe2Gas
Displace the air in reaction system, 60 DEG C of reaction 12h.Sky is exposed after reaction, is cooled down with ice-water bath after room temperature end is cold.Add
Enter 10mL deionized waters, add 20mL 6mol/L HCl solutions to be fully acidified, extracted with 3 × 10mL anhydrous ethers, is merged
Organic phase, organic phase saturated common salt water washing.It separates and organic is added to anhydrous Na2SO4Dry, decompression obtains target except solvent
Product, separation yield 90%.
Embodiment 7：At 60 DEG C, phenylacetylene and carbon dioxide reaction that cesium carbonate participates in：
Anhydrous and oxygen-free, argon gas protection weigh 0.6516g Cs under confined conditions, in reaction bulb2CO3(2mmol,
2equiv.), 110 μ L (1mmol, 1equiv.) phenylacetylenes are added in micro syringe, and 5mL EtOH (ethyl alcohol) are added in syringe,
CO2The air in reaction system is fallen in gas displacement, and 60 DEG C of reactions are for 24 hours.Sky is exposed after reaction, and ice-water bath is used after room temperature end is cold
It is cooling.10mL deionized waters are added, add 20mL 6mol/L HCl solutions to be fully acidified, are extracted with 3 × 10mL anhydrous ethers
It takes, merges organic phase, organic phase saturated common salt water washing.It separates and organic is added to anhydrous Na2SO4Dry, decompression removes solvent not
Obtain target product.
Embodiment 8：At 60 DEG C, phenylacetylene and carbon dioxide reaction that cesium carbonate participates in：
Anhydrous and oxygen-free, argon gas protection weigh 0.6516g Cs under confined conditions, in reaction bulb2CO3(2mmol,
2equiv.), 110 μ L (1mmol, 1equiv.) phenylacetylenes are added in micro syringe, and 5mL THF (tetrahydrochysene furans are added in syringe
Mutter), CO2The air in reaction system is fallen in gas displacement, and 60 DEG C of reactions are for 24 hours.Sky is exposed after reaction, and ice is used after room temperature end is cold
Water-bath cooling.10mL deionized waters are added, add 20mL 6mol/L HCl solutions to be fully acidified, with the anhydrous second of 3 × 10mL
Ether extracts, and merges organic phase, organic phase saturated common salt water washing.It separates and organic is added to anhydrous Na2SO4Dry, decompression is except molten
Agent does not obtain target product.
Embodiment 9：At 60 DEG C, phenylacetylene and carbon dioxide reaction that cesium carbonate participates in：
Anhydrous and oxygen-free, argon gas protection weigh 0.6516g Cs under confined conditions, in reaction bulb2CO3(2mmol,
2equiv.), 110 μ L (1mmol, 1equiv.) phenylacetylenes are added in micro syringe, and 5mL toluene, CO is added in syringe2Gas is set
The air in reaction system is changed, 60 DEG C of reactions are for 24 hours.Sky is exposed after reaction, is cooled down with ice-water bath after room temperature end is cold.It is added
10mL deionized waters, add 20mL 6mol/L HCl solutions to be fully acidified, and are extracted, are associated with 3 × 10mL anhydrous ethers
Machine phase, organic phase saturated common salt water washing.It separates and organic is added to anhydrous Na2SO4Dry, decompression does not obtain target except solvent
Product.
Embodiment 10：At 60 DEG C, phenylacetylene and carbon dioxide reaction that cesium carbonate participates in：
Anhydrous and oxygen-free, argon gas protection weigh 0.6516g Cs under confined conditions, in reaction bulb2CO3(2mmol,
2equiv.), 110 μ L (1mmol, 1equiv.) phenylacetylenes are added in micro syringe, and 5mL CHCl are added in syringe3(three chloromethanes
Alkane), CO2The air in reaction system is fallen in gas displacement, and 60 DEG C of reactions are for 24 hours.Sky is exposed after reaction, and ice is used after room temperature end is cold
Water-bath cooling.10mL deionized waters are added, add 20mL 6mol/L HCl solutions to be fully acidified, with the anhydrous second of 3 × 10mL
Ether extracts, and merges organic phase, organic phase saturated common salt water washing.It separates and organic is added to anhydrous Na2SO4Dry, decompression is except molten
Agent does not obtain target product.
Embodiment 11：At 60 DEG C, phenylacetylene and carbon dioxide reaction that cesium carbonate participates in：
Anhydrous and oxygen-free, argon gas protection weigh 0.6516g Cs under confined conditions, in reaction bulb2CO3(2mmol,
2equiv.), 110 μ L (1mmol, 1equiv.) phenylacetylenes are added in micro syringe, and 5mL DMF (N, N- diformazans are added in syringe
Base formamide), CO2The air in reaction system is fallen in gas displacement, and 60 DEG C of reactions are for 24 hours.Sky is exposed after reaction, and room temperature end is cold
It is cooled down afterwards with ice-water bath.10mL deionized waters are added, add 20mL 6mol/L HCl solutions to be fully acidified, with 3 × 10mL
Anhydrous ether extracts, and merges organic phase, organic phase saturated common salt water washing.It separates and organic is added to anhydrous Na2SO4It is dry, subtract
Pressure obtains target product, separation yield 14% except solvent.
Comparative example 7-11 and embodiment 1, under identical condition, when only using DMSO as reaction dissolvent, production
Rate is just up to 94%, and uses other solvents, and reaction yield is relatively low, or even cannot get target product.
Embodiment 12：At 60 DEG C, phenylacetylene and carbon dioxide reaction that potassium carbonate participates in：
Anhydrous and oxygen-free, argon gas protection weigh 0.2764g K under confined conditions, in reaction bulb2CO3(2mmol,
2equiv.), 110 μ L (1mmol, 1equiv.) phenylacetylenes are added in micro syringe, and 5mL DMSO, CO is added in syringe2Gas
The air in reaction system is displaced, 60 DEG C of reactions are for 24 hours.Sky is exposed after reaction, is cooled down with ice-water bath after room temperature end is cold.Add
Enter 10mL deionized waters, add 20mL 6mol/L HCl solutions to be fully acidified, extracted with 3 × 10mL anhydrous ethers, is merged
Organic phase, organic phase saturated common salt water washing.It separates and organic is added to anhydrous Na2SO4Dry, decompression obtains target except solvent
Product, separation yield 8%.
Embodiment 13：At 60 DEG C, phenylacetylene and carbon dioxide reaction that sodium carbonate participates in：
Anhydrous and oxygen-free, argon gas protection weigh 0.2120g Na under confined conditions, in reaction bulb2CO3(2mmol,
2equiv.), 110 μ L (1mmol, 1equiv.) phenylacetylenes are added in micro syringe, and 5mL DMSO, CO is added in syringe2Gas
The air in reaction system is displaced, 60 DEG C of reactions are for 24 hours.Sky is exposed after reaction, is cooled down with ice-water bath after room temperature end is cold.Add
Enter 10mL deionized waters, add 20mL 6mol/L HCl solutions to be fully acidified, extracted with 3 × 10mL anhydrous ethers, is merged
Organic phase, organic phase saturated common salt water washing.It separates and organic is added to anhydrous Na2SO4Dry, decompression does not obtain mesh except solvent
Mark product.
Embodiment 14：At 60 DEG C, phenylacetylene and carbon dioxide reaction that cesium chloride participates in：
Anhydrous and oxygen-free, argon gas protection weigh under confined conditions, in reaction bulb 0.3367g CsCl (2mmol,
2equiv.), 110 μ L (1mmol, 1equiv.) phenylacetylenes are added in micro syringe, and 5mL DMSO, CO is added in syringe2Gas
The air in reaction system is displaced, 60 DEG C of reactions are for 24 hours.Sky is exposed after reaction, is cooled down with ice-water bath after room temperature end is cold.Add
Enter 10mL deionized waters, add 20mL 6mol/L HCl solutions to be fully acidified, extracted with 3 × 10mL anhydrous ethers, is merged
Organic phase, organic phase saturated common salt water washing.It separates and organic is added to anhydrous Na2SO4Dry, decompression does not obtain mesh except solvent
Mark product.
Embodiment 15：At 60 DEG C, phenylacetylene and carbon dioxide reaction that NaOH is participated in：
Anhydrous and oxygen-free, argon gas protection weigh under confined conditions, in reaction bulb 0.0800g NaOH (2mmol,
2equiv.), 110 μ L (1mmol, 1equiv.) phenylacetylenes are added in micro syringe, and 5mL DMSO, CO is added in syringe2Gas
The air in reaction system is displaced, 60 DEG C of reactions are for 24 hours.Sky is exposed after reaction, is cooled down with ice-water bath after room temperature end is cold.Add
Enter 10mL deionized waters, add 20mL 6mol/L HCl solutions to be fully acidified, extracted with 3 × 10mL anhydrous ethers, is merged
Organic phase, organic phase saturated common salt water washing.It separates and organic is added to anhydrous Na2SO4Dry, decompression does not obtain except solvent obtains
Target product.
Embodiment 16：At 60 DEG C, K2CO3The phenylacetylene and carbon dioxide reaction that+CsCl is participated in：
Anhydrous and oxygen-free, argon gas protection weigh 0.2764g K under confined conditions, in reaction bulb2CO3(2mmol,2equiv.)
With 0.3367g CsCl (2mmol, 2equiv.), 110 μ L (1mmol, 1equiv.) phenylacetylenes, syringe is added in micro syringe
5mL DMSO, CO is added2The air in reaction system is fallen in gas displacement, and 60 DEG C of reactions are for 24 hours.Sky is exposed after reaction, at room temperature
It is cooled down with ice-water bath after slightly cold.10mL deionized waters are added, add 20mL 6mol/L HCl solutions to be fully acidified, with 3 ×
10mL anhydrous ethers extract, and merge organic phase, organic phase saturated common salt water washing.It separates and organic is added to anhydrous Na2SO4It is dry
Dry, decompression obtains target product except solvent, and separation yield is<1%.
The result of integrated embodiment 13-16, it is possible to find, when using above-mentioned inorganic base, target product can hardly be obtained.
Embodiment 17：At 60 DEG C, phenylacetylene and carbon dioxide reaction that DBU is participated in：
300 μ L DBU (2mmol, 2equiv.) are added in anhydrous and oxygen-free, argon gas protection under confined conditions, in reaction bulb, micro-
It measures syringe and 110 μ L (1mmol, 1equiv.) phenylacetylenes is added, 5mL DMSO, CO is added in syringe2Reactant is fallen in gas displacement
Air in system, 60 DEG C of reactions are for 24 hours.Sky is exposed after reaction, is cooled down with ice-water bath after room temperature end is cold.10mL deionizations are added
Water, adds 20mL 6mol/L HCl solutions to be fully acidified, and is extracted with 3 × 10mL anhydrous ethers, merges organic phase, organic
Mutually use saturated common salt water washing.It separates and organic is added to anhydrous Na2SO4Dry, decompression obtains target product except solvent, detaches
Yield is 45%.
Embodiment 18：At 60 DEG C, DBU+Cs2CO3The phenylacetylene and carbon dioxide reaction of participation：
Anhydrous and oxygen-free, argon gas protection be added under confined conditions, in reaction bulb 300 μ L DBU (2mmol, 2equiv.) and
0.6516g Cs2CO3110 μ L (1mmol, 1equiv.) phenylacetylenes, syringe is added in (2mmol, 2equiv.), micro syringe
5mL DMSO, CO is added2The air in reaction system is fallen in gas displacement, and 60 DEG C of reactions are for 24 hours.Sky is exposed after reaction, at room temperature
It is cooled down with ice-water bath after slightly cold.10mL deionized waters are added, add 20mL 6mol/L HCl solutions to be fully acidified, with 3 ×
10mL anhydrous ethers extract, and merge organic phase, organic phase saturated common salt water washing.It separates and organic is added to anhydrous Na2SO4It is dry
Dry, decompression obtains target product, separation yield 98% except solvent.
Embodiment 19：At 60 DEG C, phenylacetylene and carbon dioxide reaction that DBU+CsCl is participated in：
Anhydrous and oxygen-free, argon gas protection be added under confined conditions, in reaction bulb 300 μ L DBU (2mmol, 2equiv.) and
110 μ L (1mmol, 1equiv.) phenylacetylenes are added in 0.3367g CsCl (2mmol, 2equiv.), micro syringe, and syringe adds
Enter 5mL DMSO, CO2The air in reaction system is fallen in gas displacement, and 60 DEG C of reactions are for 24 hours.Empty, room temperature end is exposed after reaction
It is cooled down with ice-water bath after cold.10mL deionized waters are added, add 20mL 6mol/L HCl solutions to be fully acidified, with 3 ×
10mL anhydrous ethers extract, and merge organic phase, organic phase saturated common salt water washing.It separates and organic is added to anhydrous Na2SO4It is dry
Dry, decompression obtains target product, separation yield 43% except solvent.
Embodiment 20：At 60 DEG C, phenylacetylene and carbon dioxide reaction that triethylamine participates in：
Anhydrous and oxygen-free, argon gas protection be added under confined conditions, in reaction bulb 0.23mL triethylamines (2mmol,
2equiv.), 110 μ L (1mmol, 1equiv.) phenylacetylenes are added in micro syringe, and 5mL DMSO, CO is added in syringe2Gas
The air in reaction system is displaced, 60 DEG C of reactions are for 24 hours.Sky is exposed after reaction, is cooled down with ice-water bath after room temperature end is cold.Add
Enter 10mL deionized waters, add 20mL 6mol/L HCl solutions to be fully acidified, extracted with 3 × 10mL anhydrous ethers, is merged
Organic phase, organic phase saturated common salt water washing.It separates and organic is added to anhydrous Na2SO4Dry, decompression does not obtain mesh except solvent
Mark product.
Embodiment 21：At 60 DEG C, phenylacetylene and carbon dioxide reaction that pyridine participates in：
Under confined conditions, 0.16mL pyridines (2mmol, 2equiv.) are added in anhydrous and oxygen-free, argon gas protection in reaction bulb,
110 μ L (1mmol, 1equiv.) phenylacetylenes are added in micro syringe, and 5mL DMSO, CO is added in syringe2Reaction is fallen in gas displacement
Air in system, 60 DEG C of reactions are for 24 hours.Sky is exposed after reaction, is cooled down with ice-water bath after room temperature end is cold.Be added 10mL go from
Sub- water, adds 20mL 6mol/L HCl solutions to be fully acidified, and is extracted with 3 × 10mL anhydrous ethers, merges organic phase, has
Machine mutually uses saturated common salt water washing.It separates and organic is added to anhydrous Na2SO4Dry, decompression does not obtain target product except solvent.
Embodiment 22：At 60 DEG C, phenylacetylene and carbon dioxide reaction that sodium ethoxide participates in：
Anhydrous and oxygen-free, argon gas protection be added under confined conditions, in reaction bulb 0.1361g sodium ethoxides (2mmol,
2equiv.), 110 μ L (1mmol, 1equiv.) phenylacetylenes are added in micro syringe, and 5mL DMSO, CO is added in syringe2Gas
The air in reaction system is displaced, 60 DEG C of reactions are for 24 hours.Sky is exposed after reaction, is cooled down with ice-water bath after room temperature end is cold.Add
Enter 10mL deionized waters, add 20mL 6mol/L HCl solutions to be fully acidified, extracted with 3 × 10mL anhydrous ethers, is merged
Organic phase, organic phase saturated common salt water washing.It separates and organic is added to anhydrous Na2SO4Dry, decompression does not obtain mesh except solvent
Mark product.
Integrated embodiment 20-22, it can be seen that when alkali selects above-mentioned organic base, cannot obtain target product.
Embodiment 23：At 60 DEG C, phenylacetylene and carbon dioxide reaction that potassium tert-butoxide participates in：
Anhydrous and oxygen-free, argon gas protection be added under confined conditions, in reaction bulb 0.2244g potassium tert-butoxides (2mmol,
2equiv.), 110 μ L (1mmol, 1equiv.) phenylacetylenes are added in micro syringe, and 5mL DMSO, CO is added in syringe2Gas
The air in reaction system is displaced, 60 DEG C of reactions are for 24 hours.Sky is exposed after reaction, is cooled down with ice-water bath after room temperature end is cold.Add
Enter 10mL deionized waters, add 20mL 6mol/L HCl solutions to be fully acidified, extracted with 3 × 10mL anhydrous ethers, is merged
Organic phase, organic phase saturated common salt water washing.It separates and organic is added to anhydrous Na2SO4Dry, decompression obtains target except solvent
Product, separation yield 96%.
Embodiment 24：At 60 DEG C, phenylacetylene and carbon dioxide reaction that LDA is participated in：
Under confined conditions, 2mmol brand-new LDA solids (2equiv.) are added in anhydrous and oxygen-free, argon gas protection in reaction bulb,
110 μ L (1mmol, 1equiv.) phenylacetylenes are added in micro syringe, and 5mL DMSO, CO is added in syringe2Reaction is fallen in gas displacement
Air in system, 60 DEG C of reactions are for 24 hours.Sky is exposed after reaction, is cooled down with ice-water bath after room temperature end is cold.Be added 10mL go from
Sub- water, adds 20mL 6mol/L HCl solutions to be fully acidified, and is extracted with 3 × 10mL anhydrous ethers, merges organic phase, has
Machine mutually uses saturated common salt water washing.It separates and organic is added to anhydrous Na2SO4Dry, decompression obtains target product except solvent, point
It is 91% from yield.
Embodiment 25：At 60 DEG C, phenylacetylene and carbon dioxide reaction that n-BuLi participates in：
Under confined conditions, the hexane solution of 0.73mL n-BuLis is added in anhydrous and oxygen-free, argon gas protection in reaction bulb
110 μ L (1mmol, 1equiv.) phenylacetylenes are added in (2.7634mol/L, 2mmol, 2equiv.), micro syringe, and syringe adds
Enter 5mL DMSO, CO2The air in reaction system is fallen in gas displacement, and 60 DEG C of reactions are for 24 hours.Empty, room temperature end is exposed after reaction
It is cooled down with ice-water bath after cold.10mL deionized waters are added, add 20mL 6mol/L HCl solutions to be fully acidified, with 3 ×
10mL anhydrous ethers extract, and merge organic phase, organic phase saturated common salt water washing.It separates and organic is added to anhydrous Na2SO4It is dry
Dry, decompression obtains target product, separation yield 98% except solvent.
Embodiment 26：At 60 DEG C, phenylacetylene and carbon dioxide reaction that cesium carbonate participates in：
Anhydrous and oxygen-free, argon gas protection weigh 0.3258g Cs under confined conditions, in reaction bulb2CO3(1mmol,
1equiv.), 110 μ L (1mmol, 1equiv.) phenylacetylenes are added in micro syringe, and 5mL DMSO, CO is added in syringe2Gas
The air in reaction system is displaced, 60 DEG C of reactions are for 24 hours.Sky is exposed after reaction, is cooled down with ice-water bath after room temperature end is cold.Add
Enter 10mL deionized waters, add 20mL 6mol/L HCl solutions to be fully acidified, extracted with 3 × 10mL anhydrous ethers, is merged
Organic phase, organic phase saturated common salt water washing.It separates and organic is added to anhydrous Na2SO4Dry, decompression obtains target except solvent
Product, separation yield 77%.
Embodiment 27：At 60 DEG C, phenylacetylene and carbon dioxide reaction that cesium carbonate participates in：
Anhydrous and oxygen-free, argon gas protection weigh 0.4887g Cs under confined conditions, in reaction bulb2CO3(1.5mmol,
1.5equiv.), 110 μ L (1mmol, 1equiv.) phenylacetylenes are added in micro syringe, and 5mLDMSO, CO is added in syringe2Gas
The air in reaction system is displaced, 60 DEG C of reactions are for 24 hours.Sky is exposed after reaction, is cooled down with ice-water bath after room temperature end is cold.Add
Enter 10mL deionized waters, add 20mL 6mol/L HCl solutions to be fully acidified, extracted with 3 × 10mL anhydrous ethers, is merged
Organic phase, organic phase saturated common salt water washing.It separates and organic is added to anhydrous Na2SO4Dry, decompression obtains target except solvent
Product, separation yield 91%.
Embodiment 28：At 60 DEG C, 4- fluorobenzene acetylene and carbon dioxide reaction that cesium carbonate participates in：
Anhydrous and oxygen-free, argon gas protection weigh 0.6516g Cs under confined conditions, in reaction bulb2CO3(2mmol,
2equiv.), 115 μ L (1mmol, 1equiv.) 4- fluorobenzene acetylene are added in micro syringe, and 5mLDMSO, CO is added in syringe2Gas
Body displaces the air in reaction system, and 60 DEG C of reactions are for 24 hours.Sky is exposed after reaction, is cooled down with ice-water bath after room temperature end is cold.
10mL deionized waters are added, add 20mL 6mol/L HCl solutions to be fully acidified, are extracted with 3 × 10mL anhydrous ethers, close
And organic phase, organic phase saturated common salt water washing.It separates and organic is added to anhydrous Na2SO4Dry, decompression obtains mesh except solvent
Mark product, separation yield 98%.The structure of target product is as follows：
Nuclear magnetic data：1H NMR(400MHz,CDCl3):δ8.27(s,1H),7.67-7.57(m,2H),7.16-7.03(m,
2H)。
Embodiment 29：At 60 DEG C, 3- fluorobenzene acetylene and carbon dioxide reaction that cesium carbonate participates in：
Anhydrous and oxygen-free, argon gas protection weigh 0.6516g Cs under confined conditions, in reaction bulb2CO3(2mmol,
2equiv.), 116 μ L (1mmol, 1equiv.) 3- fluorobenzene acetylene are added in micro syringe, and 5mLDMSO, CO is added in syringe2Gas
Body displaces the air in reaction system, and 60 DEG C of reactions are for 24 hours.Sky is exposed after reaction, is cooled down with ice-water bath after room temperature end is cold.
10mL deionized waters are added, add 20mL 6mol/L HCl solutions to be fully acidified, are extracted with 3 × 10mL anhydrous ethers, close
And organic phase, organic phase saturated common salt water washing.It separates and organic is added to anhydrous Na2SO4Dry, decompression obtains mesh except solvent
Mark product, separation yield 99%.The structure of target product is as follows：
Nuclear magnetic data：1H NMR(400MHz,CDCl3):δ9.99(s,1H),7.45-7.34(m,2H),7.33-7.28(m,
1H),7.23-7.16(m,1H)。
Embodiment 30：At 60 DEG C, 4- methyl phenylacetylene and carbon dioxide reaction that cesium carbonate participates in：
Anhydrous and oxygen-free, argon gas protection weigh 0.6516g Cs under confined conditions, in reaction bulb2CO3(2mmol,
2equiv.), 127 μ L (1mmol, 1equiv.) 4- methyl phenylacetylenes are added in micro syringe, and 5mL DMSO are added in syringe,
CO2The air in reaction system is fallen in gas displacement, and 60 DEG C of reactions are for 24 hours.Sky is exposed after reaction, and ice-water bath is used after room temperature end is cold
It is cooling.10mL deionized waters are added, add 20mL 6mol/L HCl solutions to be fully acidified, are extracted with 3 × 10mL anhydrous ethers
It takes, merges organic phase, organic phase saturated common salt water washing.It separates and organic is added to anhydrous Na2SO4Dry, decompression is obtained except solvent
To target product, separation yield 82%.The structure of target product is as follows：
Nuclear magnetic data：1H NMR(400MHz,CDCl3):δ 9.92 (s, 1H), 7.51 (d, J=8.1Hz, 2H), 7.20 (d, J
=8.0Hz, 2H), 2.39 (s, 3H).
Embodiment 31：At 60 DEG C, 3- methyl phenylacetylene and carbon dioxide reaction that cesium carbonate participates in：
Anhydrous and oxygen-free, argon gas protection weigh 0.6516g Cs under confined conditions, in reaction bulb2CO3(2mmol,
2equiv.), 129 μ L (1mmol, 1equiv.) 3- methyl phenylacetylenes are added in micro syringe, and 5mLDMSO, CO is added in syringe2
The air in reaction system is fallen in gas displacement, and 60 DEG C of reactions are for 24 hours.Sky is exposed after reaction, it is cold with ice-water bath after room temperature end is cold
But.10mL deionized waters are added, add 20mL 6mol/L HCl solutions to be fully acidified, are extracted with 3 × 10mL anhydrous ethers
It takes, merges organic phase, organic phase saturated common salt water washing.It separates and organic is added to anhydrous Na2SO4Dry, decompression is obtained except solvent
To target product, separation yield 91%.The structure of target product is as follows：
Nuclear magnetic data：1H NMR(400MHz,CDCl3):δ 8.85 (s, 1H), 7.47-7.38 (m, 2H), 7.29 (dd, J=
4.5,1.5Hz,2H),2.36(s,3H)。
Embodiment 32：At 60 DEG C, 4- Methoxy-phenylacetylenes and carbon dioxide reaction that cesium carbonate participates in：
Anhydrous and oxygen-free, argon gas protection weigh 0.6516g Cs under confined conditions, in reaction bulb2CO3(2mmol,
2equiv.), 130 μ L (1mmol, 1equiv.) 4- Methoxy-phenylacetylenes are added in micro syringe, and 5mL DMSO are added in syringe,
CO2The air in reaction system is fallen in gas displacement, and 60 DEG C of reactions are for 24 hours.Sky is exposed after reaction, and ice-water bath is used after room temperature end is cold
It is cooling.10mL deionized waters are added, add 20mL 6mol/L HCl solutions to be fully acidified, are extracted with 3 × 10mL anhydrous ethers
It takes, merges organic phase, organic phase saturated common salt water washing.It separates and organic is added to anhydrous Na2SO4Dry, decompression is obtained except solvent
To target product, separation yield 81%.The structure of target product is as follows：
Nuclear magnetic data：1H NMR(400MHz,CDCl3):δ 9.39 (s, 1H), 7.51 (d, J=8.1Hz, 2H), 7.20 (d, J
=8.0Hz, 2H), 2.39 (s, 3H).
Embodiment 33：At 60 DEG C, 4- nitrobenzene acetylenes and carbon dioxide reaction that cesium carbonate participates in：
Anhydrous and oxygen-free, argon gas protection weigh 0.6516g Cs under confined conditions, in reaction bulb2CO3(2mmol,
2equiv.), 0.1471g (1mmol, 1equiv.) 4- nitrobenzene acetylenes are added in micro syringe, and 5mLDMSO is added in syringe,
CO2The air in reaction system is fallen in gas displacement, and 60 DEG C of reactions are for 24 hours.Sky is exposed after reaction, and ice-water bath is used after room temperature end is cold
It is cooling.10mL deionized waters are added, add 20mL 6mol/L HCl solutions to be fully acidified, are extracted with 3 × 10mL anhydrous ethers
It takes, merges organic phase, organic phase saturated common salt water washing.It separates and organic is added to anhydrous Na2SO4Dry, decompression is obtained except solvent
To target product, separation yield 91%.The structure of target product is as follows：
Nuclear magnetic data：1H NMR (400MHz, DMSO) δ 8.27 (d, J=8.8Hz, 2H), 7.89 (d, J=8.8Hz, 2H).
Embodiment 34：At 60 DEG C, 3- nitrobenzene acetylenes and carbon dioxide reaction that cesium carbonate participates in：
Anhydrous and oxygen-free, argon gas protection weigh 0.6516g Cs under confined conditions, in reaction bulb2CO3(2mmol,
2equiv.), 0.1471g (1mmol, 1equiv.) 3- nitrobenzene acetylenes are added in micro syringe, and 5mLDMSO is added in syringe,
CO2The air in reaction system is fallen in gas displacement, and 60 DEG C of reactions are for 24 hours.Sky is exposed after reaction, and ice-water bath is used after room temperature end is cold
It is cooling.10mL deionized waters are added, add 20mL 6mol/L HCl solutions to be fully acidified, are extracted with 3 × 10mL anhydrous ethers
It takes, merges organic phase, organic phase saturated common salt water washing.It separates and organic is added to anhydrous Na2SO4Dry, decompression is obtained except solvent
To target product, separation yield 95%.The structure of target product is as follows：
Nuclear magnetic data：1H NMR(400MHz,DMSO)δ6.92-6.84(m,2H),6.62-6.52(m,1H),6.28(t,J
=8.0Hz, 1H).
Embodiment 35：At 60 DEG C, 4- acetenyls biphenyl and carbon dioxide reaction that cesium carbonate participates in：
Anhydrous and oxygen-free, argon gas protection weigh 0.6516g Cs under confined conditions, in reaction bulb2CO3(2mmol,
2equiv.), 0.1782g (1mmol, 1equiv.) 4- acetenyl biphenyl is added in micro syringe, and 5mL DMSO are added in syringe,
CO2The air in reaction system is fallen in gas displacement, and 60 DEG C of reactions are for 24 hours.Sky is exposed after reaction, and ice-water bath is used after room temperature end is cold
It is cooling.10mL deionized waters are added, add 20mL 6mol/L HCl solutions to be fully acidified, are extracted with 3 × 10mL anhydrous ethers
It takes, merges organic phase, organic phase saturated common salt water washing.It separates and organic is added to anhydrous Na2SO4Dry, decompression is obtained except solvent
To target product, separation yield 86%.The structure of target product is as follows：
Nuclear magnetic data：1H NMR(400MHz,DMSO):δ 13.86 (s, 1H), 7.89-7.60 (m, 6H), 7.44 (dd, J=
24.8,6.9Hz,3H)。
Following example 3 6-41 of the present invention provides the method that one kettle way prepares 3- aryl propiolic acid ester type compounds：
Embodiment 36：3- phenyl propiolic acids cesium salt and n-butyl chloride reaction in-situ
Anhydrous and oxygen-free, argon gas protection weigh 0.6516g Cs under confined conditions, in reaction bulb2CO3(2equiv.), it is micro
110 μ L (1mmol, 1equiv.) phenylacetylenes are added in syringe, and 5mL DMSO, CO is added in syringe2Reaction system is fallen in gas displacement
In air, 60 DEG C reaction for 24 hours.Then 125 μ L (1.2mmol, 2equiv.) n-butyl chlorides are added, 60 DEG C of temperature is kept to continue
Reaction is for 24 hours.Empty, cooled to room temperature, addition 20mL deionized waters are exposed after reaction.It is extracted with 3 × 10mL ethyl acetate,
Merge organic phase, with a little saturated common salt water washing 3 times.What is obtained organic is added to suitable anhydrous MgSO4It is dry, filtering,
Decompression obtains crude product except solvent.EA:PE=1:100 are used as solvent, column chromatography to purify to obtain product, and separation yield is
57%.The structure of target product it is following (nBu refers to normal-butyl)：
Nuclear magnetic data：1H NMR(400MHz,CDCl3):δ7.62-7.50(m,2H),7.47-7.28(m,3H),4.22(t,
J=6.7Hz, 2H), 1.68 (dt, J=14.6,6.8Hz, 2H), 1.48-1.36 (m, 2H), 0.94 (t, J=7.4Hz, 3H)
Embodiment 37：3- phenyl propiolic acids cesium salt and n-butyl bromide reaction in-situ
Anhydrous and oxygen-free, argon gas protection weigh 0.6516g Cs under confined conditions, in reaction bulb2CO3(2equiv.), it is micro
110 μ L (1mmol, 1equiv.) phenylacetylenes are added in syringe, and 5mL DMSO, CO is added in syringe2Reaction system is fallen in gas displacement
In air, 60 DEG C reaction for 24 hours.Then 129 μ L (1.2mmol, 2equiv.) n-butyl bromides are added, 60 DEG C of temperature is kept to continue
Reaction is for 24 hours.Empty, cooled to room temperature, addition 20mL deionized waters are exposed after reaction.It is extracted with 3 × 10mL ethyl acetate,
Merge organic phase, with a little saturated common salt water washing 3 times.What is obtained organic is added to suitable anhydrous MgSO4It is dry, filtering,
Decompression obtains crude product except solvent.EA:PE=1:100 are used as solvent, column chromatography to purify to obtain product, and separation yield is
98%.The structure of target product is as follows：
Nuclear magnetic data：1H NMR(400MHz,CDCl3):δ7.62-7.50(m,2H),7.47-7.28(m,3H),4.22(t,
J=6.7Hz, 2H), 1.68 (dt, J=14.6,6.8Hz, 2H), 1.48-1.36 (m, 2H), 0.94 (t, J=7.4Hz, 3H)
Embodiment 38：3- phenyl propiolic acids cesium salt and n-butyl iodide reaction in-situ
Anhydrous and oxygen-free, argon gas protection weigh 0.6516g Cs under confined conditions, in reaction bulb2CO3(2equiv.), it is micro
110 μ L (1mmol, 1equiv.) phenylacetylenes are added in syringe, and 5mL DMSO, CO is added in syringe2Reaction system is fallen in gas displacement
In air, 60 DEG C reaction for 24 hours.Then 137 μ L (1.2mmol, 2equiv.) n-butyl iodides are added, 60 DEG C of temperature is kept to continue
Reaction is for 24 hours.Empty, cooled to room temperature, addition 20mL deionized waters are exposed after reaction.It is extracted with 3 × 10mL ethyl acetate,
Merge organic phase, with a little saturated common salt water washing 3 times.What is obtained organic is added to suitable anhydrous MgSO4It is dry, filtering,
Decompression obtains crude product except solvent.EA:PE=1:100 are used as solvent, column chromatography to purify to obtain product, and separation yield is
90%.The structure of target product is as follows：
Nuclear magnetic data：1H NMR(400MHz,CDCl3):δ7.62-7.50(m,2H),7.47-7.28(m,3H),4.22(t,
J=6.7Hz, 2H), 1.68 (dt, J=14.6,6.8Hz, 2H), 1.48-1.36 (m, 2H), 0.94 (t, J=7.4Hz, 3H)
Embodiment 39：3- phenyl propiolic acids cesium salt and p-methyl benzenesulfonic acid N-butyl reaction in-situ
Anhydrous and oxygen-free, argon gas protection weigh 0.6516g Cs under confined conditions, in reaction bulb2CO3(2equiv.), it is micro
110 μ L (1mmol, 1equiv.) phenylacetylenes are added in syringe, and 5mL DMSO, CO is added in syringe2Reaction system is fallen in gas displacement
In air, 60 DEG C reaction for 24 hours.Then 245 μ L (1.2mmol, 2equiv.) p-methyl benzenesulfonic acid N-butyls are added, are kept for 60 DEG C
The reaction was continued for temperature for 24 hours.Empty, cooled to room temperature, addition 20mL deionized waters are exposed after reaction.With 3 × 10mL acetic acid
Ethyl ester extracts, and merges organic phase, with a little saturated common salt water washing 3 times.What is obtained organic is added to suitable anhydrous MgSO4It is dry
Dry, filtering, decompression obtains crude product except solvent.EA:PE=1:100 are used as solvent, column chromatography to purify to obtain product, and separation is received
Rate is 87%.The structure of target product is as follows：
Nuclear magnetic data：1H NMR(400MHz,CDCl3):δ7.62-7.50(m,2H),7.47-7.28(m,3H),4.22(t,
J=6.7Hz, 2H), 1.68 (dt, J=14.6,6.8Hz, 2H), 1.48-1.36 (m, 2H), 0.94 (t, J=7.4Hz, 3H)
Embodiment 40：3- phenyl propiolic acids cesium salt and cylite reaction in-situ
Anhydrous and oxygen-free, argon gas protection weigh 0.6516g Cs under confined conditions, in reaction bulb2CO3(2equiv.), it is micro
110 μ L (1mmol, 1equiv.) phenylacetylenes are added in syringe, and 5mL DMSO, CO is added in syringe2Reaction system is fallen in gas displacement
In air, 60 DEG C reaction for 24 hours.Then 143 μ L (1.2mmol, 2equiv.) cylites are added, keep 60 DEG C of temperature to continue anti-
It should for 24 hours.Empty, cooled to room temperature, addition 20mL deionized waters are exposed after reaction.It is extracted, is closed with 3 × 10mL ethyl acetate
And organic phase, with a little saturated common salt water washing 3 times.What is obtained organic is added to suitable anhydrous MgSO4Dry, filtering subtracts
Pressure obtains crude product except solvent.EA:PE=1:100 are used as solvent, column chromatography to purify to obtain product, separation yield 97%.
The structure of target product is following (Bz refers to benzyl)：
Nuclear magnetic data：1H NMR(400MHz,CDCl3):δ 7.54 (dd, J=5.3,3.3Hz, 2H), 7.47-7.24 (m,
8H),5.25(s,2H).
Embodiment 41：3- phenyl propiolic acids cesium salt and 3- bromopropene reaction in-situs
Anhydrous and oxygen-free, argon gas protection weigh 0.6516g Cs under confined conditions, in reaction bulb2CO3(2equiv.), it is micro
110 μ L (1mmol, 1equiv.) phenylacetylenes are added in syringe, and 5mL DMSO, CO is added in syringe2Reaction system is fallen in gas displacement
In air, 60 DEG C reaction for 24 hours.Then 104 μ L (1.2mmol, 2equiv.) 3- bromopropenes are added, 60 DEG C of temperature is kept to continue
Reaction is for 24 hours.Empty, cooled to room temperature, addition 20mL deionized waters are exposed after reaction.It is extracted with 3 × 10mL ethyl acetate,
Merge organic phase, with a little saturated common salt water washing 3 times.What is obtained organic is added to suitable anhydrous MgSO4It is dry, filtering,
Decompression obtains crude product except solvent.EA:PE=1:100 are used as solvent, column chromatography to purify to obtain product, and separation yield is
83%.The structure of target product is as follows：
Nuclear magnetic data：1H NMR(400MHz,CDCl3):δ 7.57 (dt, J=8.5,1.7Hz, 2H), 7.47-7.40 (m,
1H), 7.39-7.32 (m, 2H), 5.97 (ddt, J=16.3,10.4,5.9Hz, 1H), 5.45-5.26 (m, 2H), 4.72 (dt, J
=5.9,1.2Hz, 2H)
Integrated embodiment 36-41 is it is found that method using the present invention, under the promotion of alkali, can in high yield, one kettle way is normal
Pressure prepares 3- aryl propiolic acid ester type compounds, and the yield of product may be up to 98%.Compared to using catalyst and high compacting
The method of standby 3- aryl propiolic acid ester type compounds, method of the invention is easier, and condition is milder, and yield is higher.
The above is only a preferred embodiment of the present invention, it is not intended to restrict the invention, it is noted that for this skill
For the those of ordinary skill in art field, without departing from the technical principles of the invention, can also make it is several improvement and
Modification, these improvements and modifications also should be regarded as protection scope of the present invention.
Claims (10)
1. a kind of preparation method of 3- aryl propiolic acid class compound, which is characterized in that include the following steps：
In the presence of alkali by phenylacetylene class compound shown in formula (I) and carbon dioxide, in 40-70 in solvent dimethyl sulfoxide
It is reacted at DEG C, obtains 3- aryl propiolic acid class compound shown in formula (II), the alkali is organic base and/or inorganic weak
Alkali, the above reaction carry out under normal pressure and in anhydrous, anaerobic inert atmosphere, and reaction route is as follows：
Wherein, R1Selected from hydrogen, alkyl, alkoxy, phenyl, nitro or halogen.
2. according to the method described in claim 1, it is characterized in that：The organic base is 1,8- diazabicylos [5.4.0] ten
One or more of one carbon -7- alkene, potassium tert-butoxide, lithium diisopropyl amido and n-BuLi.
3. according to the method described in claim 1, it is characterized in that：The inorganic weak bases are cesium carbonate.
4. according to the method described in claim 1, it is characterized in that：The alkali is organic base and inorganic weak bases, the organic base
For 1,8- diazabicylos, 11 carbon, the inorganic weak bases are cesium chloride or cesium carbonate.
5. according to the method described in claim 1, it is characterized in that：Mole of phenylacetylene class compound and alkali shown in formula (I)
Than being 1:1-4.
6. a kind of preparation method of 3- aryl propiolic acid ester type compound, which is characterized in that include the following steps：
Using 3- aryl propiolic acid class compound shown in the method formula (II) as described in any one of claim 1-5,
Then halogenated hydrocarbons or p-methyl benzenesulfonic acid ester are added thereto, 3- aryl propiolates shown in formula (III) are obtained after reaction in-situ
Class compound：
Wherein, R1Selected from hydrogen, alkyl, alkoxy, phenyl, nitro or halogen, R2Selected from alkyl, benzyl or allyl.
7. according to the method described in claim 6, it is characterized in that：R1Selected from hydrogen, R2Selected from C1-C4Alkyl, benzyl or allyl.
8. according to the method described in claim 6, it is characterized in that：The halogenated hydrocarbons is C1-C4Halogenated alkyl hydrocarbon, cylite or
3- bromopropenes.
9. according to the method described in claim 6, it is characterized in that：The p-methyl benzenesulfonic acid ester be p-methyl benzenesulfonic acid N-butyl,
Methyl tosylate, ethyl p-toluenesulfonate, propyl p-toluenesulfonate or p-methyl benzenesulfonic acid isopropyl ester.
10. according to the method described in claim 6, it is characterized in that：Phenylacetylene class compound shown in formula (I) and halogenated hydrocarbons or
The molar ratio of p-methyl benzenesulfonic acid ester is 1:1.2-2.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111423345A (en) * | 2020-04-11 | 2020-07-17 | 黄河水利职业技术学院 | α -methyl sulfoxide methyl ester compound and preparation method thereof |
| CN113149827A (en) * | 2021-04-19 | 2021-07-23 | 华南理工大学 | Method for synthesizing alkynoic acid by using terminal alkyne and carbon dioxide |
| CN114957012A (en) * | 2022-05-20 | 2022-08-30 | 湖南工程学院 | Preparation method for synthesizing unsaturated organic carboxylic ester by carbon dioxide and alkyne |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102958888A (en) * | 2009-12-17 | 2013-03-06 | 新加坡科技研究局 | Carboxylation of terminal alkynes |
| CN103168022A (en) * | 2010-08-20 | 2013-06-19 | 巴斯夫欧洲公司 | Process for preparing a propiolic acid or a derivative thereof |
| WO2013110998A1 (en) * | 2012-01-25 | 2013-08-01 | Council Of Scientific & Industrial Research (An Indian Registered Body Incorporated Under The Registration Of Societies Act (Act Xxi Of 1860) | A process for preparation of alkynyl carboxylic acids |
| WO2015075087A1 (en) * | 2013-11-21 | 2015-05-28 | Basf Se | Process for selective chlorination of salicylic acid derivatives |
-
2018
- 2018-06-01 CN CN201810556447.5A patent/CN108558635B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102958888A (en) * | 2009-12-17 | 2013-03-06 | 新加坡科技研究局 | Carboxylation of terminal alkynes |
| CN103168022A (en) * | 2010-08-20 | 2013-06-19 | 巴斯夫欧洲公司 | Process for preparing a propiolic acid or a derivative thereof |
| WO2013110998A1 (en) * | 2012-01-25 | 2013-08-01 | Council Of Scientific & Industrial Research (An Indian Registered Body Incorporated Under The Registration Of Societies Act (Act Xxi Of 1860) | A process for preparation of alkynyl carboxylic acids |
| WO2015075087A1 (en) * | 2013-11-21 | 2015-05-28 | Basf Se | Process for selective chlorination of salicylic acid derivatives |
Non-Patent Citations (2)
| Title |
|---|
| MISATO YONEMOTO-KOBAYASHI 等: "Carboxylation of alkynylsilanes with carbon dioxide mediated by cesium fluoride in DMSO", 《ORG. BIOMOL. CHEM.》 * |
| YU DINGYI 等: "The direct carboxylation of terminal alkynes with carbon dioxide", 《GREEN CHEM.》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111423345A (en) * | 2020-04-11 | 2020-07-17 | 黄河水利职业技术学院 | α -methyl sulfoxide methyl ester compound and preparation method thereof |
| CN113149827A (en) * | 2021-04-19 | 2021-07-23 | 华南理工大学 | Method for synthesizing alkynoic acid by using terminal alkyne and carbon dioxide |
| CN114957012A (en) * | 2022-05-20 | 2022-08-30 | 湖南工程学院 | Preparation method for synthesizing unsaturated organic carboxylic ester by carbon dioxide and alkyne |
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