CN109384755A - A kind of synthetic method of gold catalysis biphenyl - Google Patents
A kind of synthetic method of gold catalysis biphenyl Download PDFInfo
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- CN109384755A CN109384755A CN201710670342.8A CN201710670342A CN109384755A CN 109384755 A CN109384755 A CN 109384755A CN 201710670342 A CN201710670342 A CN 201710670342A CN 109384755 A CN109384755 A CN 109384755A
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- alkane
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/87—Benzo [c] furans; Hydrogenated benzo [c] furans
- C07D307/88—Benzo [c] furans; Hydrogenated benzo [c] furans with one oxygen atom directly attached in position 1 or 3
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Abstract
The invention belongs to field of pharmaceutical chemistry technology, provide a kind of synthetic method of biphenyl compound.Reaction formula is as follows, and the reaction substrate of this method is different substituted propinyl vinyl ethers and alkynes, catalyst Ph3PAuCl、Ph3PAuNTf2、NaAuCl4、Ph3PAuOTf、Ph3PAuSbF6Or IPrAuCl, the medium for reacting required are toluene, methylene chloride, 1,2- dichloroethanes or tetrahydrofuran.The implementation of reaction promotes reaction to carry out by microwave heating, cyclisation can react series connection against Diels-Alder with Diels-Alder/ under the conditions of this reaction is existing for the Au catalyst and generate a series of biphenyl compounds, have the characteristics that it is easy to operate, have a wide range of application, by-product is few, high income and reacts green.
Description
(1) technical field
The invention belongs to field of pharmaceutical chemistry technology, are related to a kind of synthetic method of gold catalysis biphenyl, and in particular to a kind of
Under the action of Au catalyst, propinyl alkene ether and alkynes occur to be cyclized isomerization/Diels-Alder/ under microwave mediation inverse
The synthetic method of Diels-Alder generation biphenol compound.
(2) background technique
Biphenol compound is a kind of important Organic Ingredients, can be used to synthesize plasticizer (Journal of
Hazardous Materials 2017,323,698-709), preservative, can be also used for manufacture fuel, engineering plastics and height
The fields such as energy fuel, it is chemical and organic in organic synthesis, pharmaceutical chemistry (J.Med.Chem.2012,55,10160), liquid crystal material
Catalysis etc. plays an important role.The simple and effective method for preparing biphenol compound is found, is always organic chemist
The emphasis (Chem.Rev.2005,105,4581) of concern.The synthetic method of biphenyl common at present has:
(1) pyrolysismethod.In high temperature coal-tar, containing about 3.0% biphenyl, it can be recycled from wash oil fraction.Nineteen twenty-six, the U.S.
Dow Chemical etc. starts to produce biphenyl by pyrolysismethod with benzene.When another source of biphenyl is that toluene heat takes off alkyl benzene
By-product.With the development of the technique, the by-product biphenyl of this process is increasingly becoming the main source of biphenyl.Under lab,
By aniline diazotising, gained diazonium salt is added in benzene, then this mixture is slowly added into sodium hydroxide solution, and stirring is anti-
It answers, temperature slowly rises to 30-35 DEG C from 5C or less, generates biphenyl after reacting 8h.
(2) catalytic coupling method: (a) Ullmann coupling reaction (Synthesis in the biphenyl
Series.Ber.1901,34,2174-2185): the reaction was found by German chemist Ullmann in 1903, i.e., in copper powder
In the presence of, halogenated aryl hydrocarbon undergoes coupling reaction to produce biphenol compound under heating conditions.Although the reflection scope of application
Wide model, but also have disadvantages that, such as: high temperature, catalyst price are higher；Certain worry is brought to the application of people.
(b) Negishi coupling reaction (J.Am.Chem.Soc.1976,98,6729-6731): the reaction by Negishi in
It reports for the first time within 1977, i.e., in the presence of palladium catalyst or Raney nickel, halogenated aryl hydrocarbon and arylzinc reagent are coupled
To biphenol compound.The reaction stereoselectivity is good, and yield is higher, but the tolerance range of functional group in this reaction is smaller,
And the catalyst used is unstable.
(c) Suzuki coupling reaction (J.Chem.Soc., Chem.Commun.1979,866-867): the reaction is
Suzuki was reported for the first time in 1979, i.e., under the action of Pd catalyst, organo-borane occurs coupling with organic halogen and obtains
Biphenol compound.The reaction is most widely used at present, and reaction condition is mild, and used borane reagent toxicity is lower, post-processing
Also simple.
(3) diazonium salt method: under conditions of weak base, using copper powder as reducing agent, since diazonium salt is left away very well, so
Symmetrical biphenyl can be generated with denitrogenation.The reaction yield is lower, and application range is very narrow.
In conclusion the synthesis for the biphenol compound being currently known, based on catalytic coupling, reaction condition is to anaerobic requirement
It is very stringent and more demanding to the tolerance of functional group, part functional group will affect reaction as a result, and each substrate need
It is prepared separately.According to the principle of economical and efficient, set out by tandem reaction by simple substrate come one-step synthesis biphenyl class chemical combination
Object is best selection, can not only reduce the process of intermediate separation, but also can reduce the generation to environment by-product.But it is existing
There is no the methods of the synthesis biphenyl of such simple and effective for technology.
(3) summary of the invention
Problem solved by the invention is to provide a kind of substrate preparation simplicity, and functional group's tolerance range is wide and efficiently synthesizes
The method of biphenyl.
The present invention is the cyclisation isomerization being catalyzed from simple substrate propinyl alkene ether and alkynes by gold, Diels-
The method of one step of the tandem reaction building biphenyl compound of Alder and inverse Diels-Alde.
The present invention obtains a good divinyl macromer skeleton to the cyclisation isomerization of propinyl alkene ether using Au catalyst,
And Diels-Alde occurs with this dienophile of alkynes and reacts, product energies are higher at this time, and the automatic inverse Diels-Alde of generation is anti-
It answers, eliminates a molecule formaldehyde and generate the lower biphenyl product of energy.In this tandem reaction, we can control in substrate three
Fragment section constructs diversified biphenol compound, realizes the approach of substrate control.
The method eliminates the cumbersome of various coupling reaction substrates preparation in coupling method, while expanding functional group's tolerance model
It encloses, post-processing is easy, can prepare the biphenyl compound that many kinds of and conventional method is not easily-synthesized.
The present invention is achieved through the following technical solutions:
The present invention relates to a kind of new methods for synthesizing biphenyl: i.e. using gold as catalyst, under microwave mediation, by propinyl alkene
Base ether and alkynes are that raw material comes synthesising target compound, reaction formula are as follows:
Wherein, R is halogen, C1-C6Alkane, C1-C6The aldehyde of alkane, C1-C6The ketone that alkane replaces, C1-C6The carboxylic acid of alkane
Ester；R1、R2For hydrogen, C1-C6Alkane, C1-C6The ester of alkane, C1-C6The aldehyde of alkane, C1-C6The ketone that alkane replaces；X, Y, Z C, O
Or carbonyl, n=0 or 1.Its preparation process are as follows:
(1) it feeds
Substrate 1 and substrate 2 that molar ratio is (1:2-1:3) are added in microwave tube, adding dosage is reactant 1
The 3-10% Au catalyst of the amount of substance.Au catalyst used in reacting is Ph3PAuCl, Ph3PAuNTf2, Ph3PAuOTf,
Ph3PAuSbF6One of.The solution for being eventually adding the amount for the 1-10 times of substance that dosage is reactant 1 is reaction medium.It is described
Reaction medium be toluene, benzene, mesitylene, one of 1,2- dichloroethanes or tetrahydrofuran.Reactant 1, reactant 2,
The addition sequence of reaction medium and Au catalyst can be exchanged arbitrarily.
(2) it reacts
It is stirred to react temperature of charge at 80-130 DEG C-120 minutes 80 minutes.With thin layer color
Spectral test reaction process.The solvent of thin-layer chromatography is petroleum ether, ethyl acetate, n-hexane, methanol, chloroform, methylene chloride, third
The mixed liquor of ketone, tetrahydrofuran or the two therein or three, such as: petroleum ether: ethyl acetate=1:1-10:1, preferably 7:
1。
(3) it post-processes
Reaction solution after cooling is subjected to rapid column chromatography separating-purifying with silica gel and obtains target product, the system of solvent
Are as follows: petroleum ether, ethyl acetate, n-hexane, methanol, chloroform, methylene chloride, acetone, tetrahydrofuran, person's the two therein or three
Mixed liquor, such as: petroleum ether: ethyl acetate=1:1-10:1, preferably 7:1.
The invention has the advantages that substrate preparation is easy, and functional group's tolerance range is wide from the point of view of chemically；From industrial angle
Degree is seen, easy to be quick, product purity height is post-processed.
(4) specific embodiment
The advantages of contacting following examples, will be better understood when the invention patent and preparation process, these embodiments are intended to
Elaboration is not intended to limit the scope of the invention.
Embodiment 1:
By substrate 1 (0.2356mmol), substrate 2 (0.4712-0.7068mmol) and Ph3PAuNTf2(0.01178mmol)
It is added in 10mL microwave tube, reaction medium toluene solution (2mL) then is added, reaction solution is heated to microwave reaction instrument
120 DEG C, 120 minutes, after reaction, target product is obtained with the method for rapid column chromatography (petroleum ether: ethyl acetate=7:1)
A-1, yield 70%.Its reaction equation are as follows:
The spectral data of product a-1 are as follows: HRMS (ESI): m/z:[M+H]+325.0719；1H NMR(600MHz,DMSO)δ
8.32 (s, 1H), 7.67 (d, J=7.4Hz, 2H), 7.59-7.41 (m, 3H), 5.70 (s, 2H), 3.91 (d, J=6.9Hz,
6H)。
Embodiment 2:
Reaction substrate 1 is changed to reaction substrate 3, other obtain target compound a-2 with embodiment 1, and reaction yield is
68%.Its reaction equation are as follows:
The spectral data of product a-2 are as follows: HRMS (ESI): m/z:[M+H]+413.1248；1H NMR(600MHz,DMSO)δ
8.38 (s, 1H), 8.09 (d, J=8.3Hz, 2H), 7.83 (d, J=8.3Hz, 2H), 5.70 (s, 2H), 5.25-5.10 (m,
1H), 3.92 (d, J=5.6Hz, 6H), 1.35 (d, J=6.2Hz, 7H).
Embodiment 3:
Reaction substrate 1 is changed to reaction substrate 4, other obtain target compound a-3 with embodiment 1, and reaction yield is
60%.Its reaction equation are as follows:
The spectral data of product a-3 are as follows: HRMS (ESI): m/z:[M+H]+343.0630；1H NMR(600MHz,DMSO)δ
8.31 (s, 1H), 7.74 (dd, J=8.8,5.3Hz, 2H), 7.40 (t, J=8.8Hz, 2H), 5.69 (s, 2H), 3.91 (d, J=
4.9Hz,6H)。
Embodiment 4:
Reaction substrate 1 is changed to reaction substrate 5, other obtain target compound a-4 with embodiment 1, and reaction yield is
40%.Its reaction equation are as follows:
The spectral data of product a-4 are as follows: HRMS (ESI): m/z:[M+H]+339.0875；1H NMR(600MHz,DMSO)δ
8.31 (s, 1H), 7.54-7.39 (m, 3H), 7.33 (d, J=6.9Hz, 1H), 5.70 (s, 2H), 3.91 (d, J=4.2Hz,
6H),2.41(s,3H)。
Embodiment 5:
Reaction substrate 1 is changed to reaction substrate 6, while being changed to reactant 2-a for 2, other obtain target with embodiment 1
Compound b-1, reaction yield 45%.Its reaction equation are as follows:
The spectral data of product b-1 are as follows: HRMS (ESI): m/z:[M+H]+325.0720；1H NMR(600MHz,DMSO)δ
8.21-8.05 (m, 2H), 8.01 (d, J=7.7Hz, 1H), 7.87 (d, J=7.7Hz, 1H), 7.84-7.71 (m, 2H), 5.63
(s, 2H), 3.90 (d, J=4.4Hz, 6H).
Embodiment 6:
Reaction substrate 1 is changed to reaction substrate 7, while being changed to reactant 2-a for 2, other obtain target with embodiment 1
Compound b-2, reaction yield 40%.Its reaction equation are as follows:
The spectral data of product b-2 are as follows: HRMS (ESI): m/z:[M+H]+301.0273；1H NMR(600MHz,DMSO)δ
7.94 (d, J=7.7Hz, 1H), 7.85 (s, 1H), 7.68 (d, J=8.5Hz, 2H), 7.61 (d, J=8.5Hz, 2H), 5.60
(s,2H),3.90(s,3H)。
Embodiment 7:
Reaction substrate 1 is changed to reaction substrate 3, while being changed to reactant 2-a for 2, other obtain target with embodiment 1
Compound b-3, reaction yield 35%.Its reaction equation are as follows:
The spectral data of product b-3 are as follows: HRMS (ESI): [M+H]+m/z:353.1032；1H NMR(600MHz,DMSO)δ
8.08 (d, J=8.3Hz, 2H), 7.99 (d, J=7.7Hz, 1H), 7.88 (d, J=7.7Hz, 1H), 7.80 (d, J=8.3Hz,
2H), 5.62 (s, 2H), 5.24-5.09 (m, 1H), 3.91 (s, 3H), 1.35 (d, J=6.2Hz, 6H).
Embodiment 8:
Reaction substrate 1 is changed to reaction substrate 3, while being changed to reactant 2-b for 2, other obtain target with embodiment 1
Compound b-4, reaction yield 44%.Its reaction equation are as follows:
The spectral data of product b-4 are as follows: HRMS (ESI): m/z:[M+H]+437.1243；1H NMR(600MHz,DMSO)δ
8.25 (d, J=16.3Hz, 1H), 8.22 (s, 1H), 8.08 (d, J=8.4Hz, 2H), 7.81 (d, J=8.4Hz, 2H), 6.25
(d, J=16.3Hz, 1H), 5.61 (s, 2H), 5.28-5.08 (m, 1H), 3.87 (s, 3H), 3.77 (s, 3H), 1.35 (d, J=
6.3Hz,6H)。
Embodiment 9:
Reaction substrate 1 is changed to reaction substrate 8, other obtain target compound c-1 with embodiment 1, and reaction yield is
45%.Its reaction equation are as follows:
The spectral data of product c-1 are as follows: HRMS (ESI): m/z:[M+H]+325.1083；1H NMR(600MHz,DMSO)δ
7.64 (s, 1H), 7.47 (dd, J=6.6,3.0Hz, 2H), 7.45-7.42 (m, 3H), 3.89 (s, 3H), 3.87 (s, 3H),
3.19–3.14(m,2H),2.72–2.68(m,2H)。
Embodiment 10:
Reaction substrate 1 is changed to reaction substrate 9, other obtain target compound c-2 with embodiment 1, and reaction yield is
62%.Its reaction equation are as follows:
The spectral data of product c-2 are as follows: HRMS (ESI): m/z:[M+H]+327.0874；1H NMR(600MHz,DMSO)δ
7.74 (s, 1H), 7.59 (dd, J=6.5,3.0Hz, 2H), 7.50-7.47 (m, 3H), 5.57 (s, 2H), 3.90 (s, 3H),
3.88(s,3H)。
Claims (10)
1. a kind of synthetic method of gold catalysis biphenyl, it is characterised in that: propinyl alkenyl ether compound 1 and alkine compounds 2 are in gold
Under the action of catalysis, reacts in microwave-medium and generate biphenyl, reaction formula are as follows:
Wherein, R is halogen, C1-C6Alkane, C1-C6The aldehyde of alkane, C1-C6The ketone that alkane replaces, C1-C6The carboxylate of alkane；R1,
R2For hydrogen, C1-C6The ester of alkane, C1-C6The aldehyde of alkane, C1-C6The ketone that alkane replaces；X, Y, Z C, O or carbonyl；N=0 or 1.
2. a kind of synthetic method of gold catalysis biphenyl as described in claim 1, it is characterised in that: the propinyl alkene ether
R is halogen, C in compound 11-C4Alkane, C1-C4The carboxylate of alkane, C1-C4The aldehyde of alkane, C1-C4The ketone that alkane replaces；X,
Y, Z forms cyclopentanone, butyrolactone；R in the alkine compounds 21、R2For hydrogen, C1-C4The ester group of alkane, C1-C4The aldehyde of alkane,
C1-C4The ketone that alkane replaces, C1-C4Alkane.
3. a kind of synthetic method of gold catalysis biphenyl as claimed in claim 1 or 2, it is characterised in that: medium is added in reaction,
The reaction medium is toluene, benzene, mesitylene, one of 1,2- dichloroethanes or tetrahydrofuran.
4. a kind of synthetic method of gold catalysis biphenyl as described in claim 1, it is characterised in that: propinyl alkenyl ether compound
1, the ratio of the amount of the substance of alkine compounds 2 is 1:2-1:3.
5. a kind of synthetic method of gold catalysis biphenyl as described in claim 1, it is characterised in that: gold catalysis used in reaction
Agent is Ph3PAuCl, Ph3PAuNTf2, Ph3PAuOTf, Ph3PAuSbF6One of.
6. a kind of synthetic method of gold catalysis biphenyl as described in claim 1, it is characterised in that: the dosage of Au catalyst is anti-
Answer the 3-10% of the amount of the substance of object 1.
7. a kind of synthetic method of gold catalysis biphenyl as described in claim 1, it is characterised in that: the reaction is in microwave
It is heated at 80-130 DEG C, is stirred to react 80-120 minutes.
8. a kind of synthetic method of gold catalysis biphenyl as described in claim 1, it is characterised in that: it is detected and is reacted with thin-layer chromatography
Process, the solvent of thin-layer chromatography are petroleum ether, ethyl acetate, n-hexane, methanol, chloroform, methylene chloride, acetone, tetrahydro furan
It mutters or both therein or three mixed liquor.
9. a kind of synthetic method of gold catalysis biphenyl as claimed in claim 8, it is characterised in that: the process for separation and purification of product
Are as follows: directly with column chromatograph method carry out separating-purifying, the system of solvent are as follows: petroleum ether, ethyl acetate, n-hexane, methanol,
The mixed liquor of chloroform, methylene chloride, acetone or the two therein or three.
10. a kind of synthetic method of gold catalysis biphenyl as described in claim 1, it is characterised in that: propinyl alkene ether chemical combination
Object 1, alkine compounds 2, reaction medium and Au catalyst addition sequence arbitrarily exchange.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113004294A (en) * | 2021-03-08 | 2021-06-22 | 温州大学新材料与产业技术研究院 | Tetrahydrofuran-1, 4-dihydroquinoline compound and preparation method and application thereof |
-
2017
- 2017-08-08 CN CN201710670342.8A patent/CN109384755A/en active Pending
Non-Patent Citations (1)
| Title |
|---|
| SHENGFEI JIN等: "Gold(I)-Initiated Cycloisomerization/Diels-Alder/Retro-Diels-Alder Cascade Strategy to Biaryls", 《THE JOURNAL OF ORGANIC CHEMISTRY》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113004294A (en) * | 2021-03-08 | 2021-06-22 | 温州大学新材料与产业技术研究院 | Tetrahydrofuran-1, 4-dihydroquinoline compound and preparation method and application thereof |
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