CN108383699A - B-form DNA promotes the method that Sonogashira reactions prepare acetylenic ketone compound - Google Patents
B-form DNA promotes the method that Sonogashira reactions prepare acetylenic ketone compound Download PDFInfo
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- CN108383699A CN108383699A CN201810227021.5A CN201810227021A CN108383699A CN 108383699 A CN108383699 A CN 108383699A CN 201810227021 A CN201810227021 A CN 201810227021A CN 108383699 A CN108383699 A CN 108383699A
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- form dna
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- 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
- C07C45/45—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation
- C07C45/455—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation with carboxylic acids or their derivatives
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
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- 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
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Abstract
The invention discloses a kind of B-form DNAs to promote the method that Sonogashira reactions prepare acetylenic ketone compound, and for this method using B-form DNA as accelerating agent, pure water is solvent, and potassium carbonate is alkali, PdCl2(PPh3)2It is catalyst with CuI, under the conditions of air atmosphere, 60~70 DEG C, makes acyl chlorides and Terminal Acetylenes that Sonogashira cross-coupling reactions occur, you can to obtain acetylenic ketone compound.The method of the present invention has the following advantages that：(1) there is good substrate applicability, and target product yield is high, can be used for industrial-scale production；(2) it uses water as reaction dissolvent, avoids the use of organic solvent, it is environmentally protective；(3) this method is not necessarily to carry out water special anaerobic processing, and reaction can be catalyzed under air conditions, has good potential industrial application value.
Description
Technical field
The invention belongs to Sonogashira coupling reaction technical fields, and in particular to promote Sonogashira to B-form DNA
The method that reaction prepares acetylenic ketone compound.
Background technology
In organic chemistry and medicinal chemistry art, acetylenic ketone compound is constantly subjected to the concern of researcher, this aspect with
The structural unit appears in a kind of related in many bioactive molecules, another aspect, as important intermediate, Ke Yifang
Just multiple heterocycles compound is constructed.
Currently, can mainly be synthesized by two ways about acetylenic ketone compound：(1) organohalogen compounds are in metal derivative
Effect is lower to be obtained by the way that coupling reaction is carbonylated；(2) pass through transition metal-catalyzed method, such as palladium chtalyst Sonogashira
Cross-coupling reaction.
Sonogashira reacts at the beginning of being found, and needs under inert gas protection, could smoothly using organic solvent
It is reacted on ground.However a large amount of use of organic solvent causes the injury for being difficult to reverse for environment.In recent years, water is as reaction
Solvent has been obtained for the common concern of researchers, can utmostly reduce the pollution to environment in this way.
In order to solve the problems, such as that Sonogashira reacts the reaction in water phase, some effective strategies are suggested in succession, are wrapped
It includes and uses surfactant and phase transfer catalyst as additive, or use water soluble ligand.ChaoJun Li seminars
It was found that using lauryl sodium sulfate as additive, chlorobenzoyl chloride and Terminal Acetylenes can be made efficiently to carry out in water
Sonogashira coupling reactions (Org.Lett.2004,6,3151).Mingzhong Cai seminars find to use PEG-2000
As additive, under carbon monoxide atmosphere, chloro aryl and Terminal Acetylenes can be made to carry out carbonylation coupling reaction in water
(Green Chem.,2014,16,2515).Ruihu Wang seminars find to use 2,2- bipyridyls amine can be with as ligand
Increase palladium dissolubility in water, to promote iodobenzene and phenylacetylene in water coupling reaction (Dalton Trans., 2014,
43,2098).And strategy used at present respectively has disadvantage：It is big using conventional surfactant catalysis reaction institute expense, and surface
Activating agent itself is harmful to environment；The synthesis difficulty and applicability of water soluble ligand be not wide.Therefore carry out and synthesize alkynes in water phase
The synthetic method of ketone compound improves catalytic efficiency, can not only reduce environmental pollution, but also will produce product to industrial and agricultural production
The meaning of pole.
Invention content
Lead to Sonogashira technical problem to be solved by the present invention lies in organic matter dissolubility difference in water phase is overcome
Coupling reaction low yield and the problem of can not react in air, provide it is a kind of efficiently, the B-form DNA of green promotes
The method of Sonogashira reaction synthesis acetylenic ketone compounds.Technical solution is used by solving above-mentioned technical problem：With Type B
DNA is accelerating agent, PdCl2(PPh3)2It is catalyst with CuI, using potassium carbonate as alkali, pure water as solvent will under air atmosphere
Acyl chloride compound shown in Formulas I carries out coupling reaction with Terminal Acetylenes shown in Formula II at 60~70 DEG C, obtains shown in formula III
Acetylenic ketone compound.
R represents H, C in formula1~C4Any one in alkyl, adamantyl, aryl, heterocyclic aryl, Ar represent aryl or
Heterocyclic aryl, wherein the Aryl stands phenyl, C1~C5Alkyl-substituted phenyl, C1~C5Alkoxy substituted phenyl, halogeno-benzene
Any one in base, nitro substituted-phenyl, cyano substituted-phenyl, aldehyde radical substituted-phenyl, naphthalene, xenyl, heterocyclic aryl is
Any one in furyl, thienyl, pyridyl group.
The molar ratio of above-mentioned Terminal Acetylenes and acyl chlorides is 1:2~2.5,1~2.5mg is added by every mole of Terminal Acetylenes in B-form DNA,
PdCl2(PPh3)2Addition be the addition of 2%~5%, CuI of Terminal Acetylenes mole be the 4%~6% of Terminal Acetylenes mole,
The addition of potassium carbonate is 2.5~4 times of Terminal Acetylenes mole.
Above-mentioned b form dna is salmon sperm dna (CAS：68938-01-2), calf thymus DNA (CAS：73049-39-5), Pacific herring
Milt DNA (CAS：Any one in 100403-24-5).
The present invention is using B-form DNA as accelerating agent, and for pure water as solvent, potassium carbonate is alkali, PdCl2(PPh3)2It is catalyzed with CuI
Sonogashira cross-coupling reactions.This method has the following advantages that：(1) there is good substrate applicability, and target product
High income is suitable for industrial-scale production；(2) it uses water as reaction dissolvent, avoids the use of organic solvent, green ring
It protects；(3) this method is not necessarily to carry out water special anaerobic processing, and reaction can be catalyzed under air conditions, is had good
Potential industrial application value.
Specific implementation mode
With reference to embodiment, the present invention is described in more detail, but protection scope of the present invention is not limited only to these realities
Apply example.
Embodiment 1
Under air conditions, to addition 1mg salmon sperm dnas, 14mg (0.02mmol) PdCl in Schlenk bottles2(PPh3)2、
9.5mg (0.04mmol) CuI, 232.2 μ L (2mmol) chlorobenzoyl chlorides and 109.8 μ L (1mmol) phenylacetylenes, stir evenly, then will
414mg(3mmol)K2CO3It is dissolved in after 1mL pure water and is added in Schlenk bottles, at 65 DEG C after isothermal reaction 5 hours, be cooled to
Room temperature is extracted with ethyl acetate, pillar layer separation product, obtains following 1, the 3- hexichol -2- propargyl -1- ketone of structural formula,
Yield is 99%.
Embodiment 2
In the present embodiment, with the phenylacetylene of equimolar 4- methyl phenylacetylenes alternative embodiment 1, other steps and embodiment 1
It is identical, obtain following 1- phenyl -3- (4- the aminomethyl phenyls) -2- propargyl -1- ketone of structural formula, yield 75%.
Embodiment 3
In the present embodiment, with the phenylacetylene of equimolar 4- Methoxy-phenylacetylenes alternative embodiment 1, other steps and embodiment
1 is identical, obtains following 1- phenyl -3- (4- the methoxyphenyls) -2- propargyl -1- ketone of structural formula, yield 99%.
Embodiment 4
In the present embodiment, with the phenylacetylene of equimolar 4- amyl phenylacetylenes alternative embodiment 1, other steps and embodiment 1
It is identical, obtain structural formula following 1- phenyl -3- (4- amyls phenyl) -2- propargyl -1- ketone, yield 61%.
Embodiment 5
In the present embodiment, with the phenylacetylene of equimolar 4- chlorobenzene acetylene alternative embodiment 1, other steps and 1 phase of embodiment
Together, following 1- phenyl -3- (4- the chlorphenyls) -2- propargyl -1- ketone of structural formula, yield 98% are obtained.
Embodiment 6
In the present embodiment, with the phenylacetylene of equimolar 4- nitrobenzene acetylenes alternative embodiment 1, other steps and embodiment 1
It is identical, obtain following 1- phenyl -3- (4- the nitrobenzophenones) -2- propargyl -1- ketone of structural formula, yield 74%.
Embodiment 7
In the present embodiment, with the phenylacetylene of equimolar 4- cyano phenylacetylenes alternative embodiment 1, other steps and embodiment 1
It is identical, obtain following 1- phenyl -3- (4- the cyano-phenyls) -2- propargyl -1- ketone of structural formula, yield 98%.
Embodiment 8
In the present embodiment, with the phenylacetylene of equimolar 2- thiophene acetylenes alternative embodiment 1, other steps and embodiment 1
It is identical, obtain the following 1- phenyl -3- thienyl -2- propargyl -1- ketone of structural formula, yield 78%.
Embodiment 9
In the present embodiment, with the phenylacetylene of equimolar 4- aldehyde radical phenylacetylenes alternative embodiment 1, other steps and embodiment 1
It is identical, obtain structural formula following 1- phenyl -3- (4- aldehyde radicals phenyl) -2- propargyl -1- ketone, yield 77%.
Embodiment 10
In the present embodiment, with the chlorobenzoyl chloride of equimolar 4- methyl benzoyl chlorides alternative embodiment 1, other steps and implementation
Example 1 is identical, obtains the following 1- of structural formula (4- aminomethyl phenyls) -3- phenyl -2- propargyl -1- ketone, yield 88%.
Embodiment 11
In the present embodiment, with the chlorobenzoyl chloride of equimolar 4- chlorobenzoyl chlorides alternative embodiment 1, other steps and embodiment
1 is identical, obtains the following 1- of structural formula (4- chlorphenyls) -3- phenyl -2- propargyl -1- ketone, yield 71%.
Embodiment 12
In the present embodiment, with the chlorobenzoyl chloride of equimolar 3- methyl benzoyl chlorides alternative embodiment 1, other steps and implementation
Example 1 is identical, obtains the following 1- of structural formula (3- aminomethyl phenyls) -3- phenyl -2- propargyl -1- ketone, yield 89%.
Embodiment 13
In the present embodiment, with the chlorobenzoyl chloride of equimolar biphenyl -4- formyl chlorides alternative embodiment 1, other steps and implementation
Example 1 is identical, obtains the following 1- of structural formula (4- xenyls) -3- phenyl -2- propargyl -1- ketone, yield 89%.
Embodiment 14
In the present embodiment, with the chlorobenzoyl chloride of equimolar 1- naphthoyl chlorides alternative embodiment 1, other steps and embodiment 1
It is identical, obtain the following 1- naphthalene -3- phenyl -2- propargyl -1- ketone of structural formula, yield 60%.
Embodiment 15
In the present embodiment, with the chlorobenzoyl chloride of equimolar 1- adamantane formyl chlorides alternative embodiment 1, other steps and implementation
Example 1 is identical, obtains the following 1- adamantyl -3- phenyl -2- propargyl -1- ketone of structural formula, yield 88%.
Embodiment 16
In the present embodiment, with the chlorobenzoyl chloride of equimolar 4- methoxy benzoyl chlorides alternative embodiment 1, other steps and reality
It applies that example 1 is identical, obtains the following 1- of structural formula (4- methoxyphenyls) -3- phenyl -2- propargyl -1- ketone, yield 72%.
Specific embodiment described above is merely to illustrate the present invention rather than limits the scope of the invention.It should refer to
Go out, all deformations that those skilled in the art directly export or associate according to the present disclosure exist
In protection scope of the present invention.
Claims (8)
1. a kind of B-form DNA promotes the method that Sonogashira reactions prepare acetylenic ketone compound, it is characterised in that：It is with B-form DNA
Accelerating agent, PdCl2(PPh3)2It is catalyst with CuI, using potassium carbonate as alkali, pure water as solvent, under air atmosphere, by Formulas I institute
Terminal Acetylenes carries out coupling reaction at 60~70 DEG C shown in the acyl chloride compound and Formula II shown, obtains acetylenic ketone shown in formula III
Compound；
R represents H, C in formula1~C4Any one in alkyl, adamantyl, aryl, heterocyclic aryl, Ar represents aryl or heterocycle
Aryl.
2. B-form DNA according to claim 1 promotes the method that Sonogashira reactions prepare acetylenic ketone compound, feature
It is：The Aryl stands phenyl, C1~C5Alkyl-substituted phenyl, C1~C5Alkoxy substituted phenyl, halogenophenyl, nitro
Any one in substituted-phenyl, cyano substituted-phenyl, aldehyde radical substituted-phenyl, naphthalene, xenyl, heterocyclic aryl be furyl,
Any one in thienyl, pyridyl group.
3. B-form DNA according to claim 1 or 2 promotes the method that Sonogashira reactions prepare acetylenic ketone compound,
It is characterized in that：The molar ratio of the Terminal Acetylenes and acyl chlorides is 1:2~2.5.
4. B-form DNA according to claim 1 or 2 promotes the method that Sonogashira reactions prepare acetylenic ketone compound,
It is characterized in that：1~2.5mg is added by every mole of Terminal Acetylenes in the B-form DNA.
5. B-form DNA according to claim 1 or 2 promotes the method that Sonogashira reactions prepare acetylenic ketone compound,
It is characterized in that：The PdCl2(PPh3)2Addition be the 2%~5% of Terminal Acetylenes mole.
6. B-form DNA according to claim 1 or 2 promotes the method that Sonogashira reactions prepare acetylenic ketone compound,
It is characterized in that：The addition of the CuI is the 4%~6% of Terminal Acetylenes mole.
7. B-form DNA according to claim 1 or 2 promotes the method that Sonogashira reactions prepare acetylenic ketone compound,
It is characterized in that：The addition of the potassium carbonate is 2.5~4 times of Terminal Acetylenes mole.
8. B-form DNA according to claim 1 promotes the method that Sonogashira reactions prepare acetylenic ketone compound, feature
It is：The B-form DNA is any one in salmon sperm dna, calf thymus DNA, herring sperm dna.
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| CN201810227021.5A CN108383699B (en) | 2018-03-20 | 2018-03-20 | Method for preparing alkynone compound by promoting Sonogashira reaction through B-type DNA |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN114292304A (en) * | 2022-01-12 | 2022-04-08 | 康龙化成(宁波)科技发展有限公司 | Method for synthesizing aryl alkyne lead compound |
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| CN105859495A (en) * | 2016-05-05 | 2016-08-17 | 陕西师范大学 | Acetyenic-ketone-promoted CuI-catalyzed method for conducting Sonogashira coupled reaction |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105859495A (en) * | 2016-05-05 | 2016-08-17 | 陕西师范大学 | Acetyenic-ketone-promoted CuI-catalyzed method for conducting Sonogashira coupled reaction |
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| Title |
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| ALMUDENA GARCÍA-FERNÁNDEZ等: "DNA-Accelerated Copper Catalysis of Friedel−Crafts Conjugate Addition/Enantioselective Protonation Reactions in Water", 《J. AM. CHEM. SOC.》 * |
| LIANG CHEN等: "A Remarkably Efficient Coupling of Acid Chlorides with Alkynes in Water", 《ORG. LETT.》 * |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN114292304A (en) * | 2022-01-12 | 2022-04-08 | 康龙化成(宁波)科技发展有限公司 | Method for synthesizing aryl alkyne lead compound |
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