CN108840881A - A kind of tetra- substituted benzene of 1,2,3,5- and its synthetic method of the silicon substrate containing 3- - Google Patents
A kind of tetra- substituted benzene of 1,2,3,5- and its synthetic method of the silicon substrate containing 3- Download PDFInfo
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- CN108840881A CN108840881A CN201810294930.0A CN201810294930A CN108840881A CN 108840881 A CN108840881 A CN 108840881A CN 201810294930 A CN201810294930 A CN 201810294930A CN 108840881 A CN108840881 A CN 108840881A
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- 0 CCOC(COC1C(*c2ccc(C)cc2)=CC(CC=C(C)C)=CC1*)=O Chemical compound CCOC(COC1C(*c2ccc(C)cc2)=CC(CC=C(C)C)=CC1*)=O 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic System
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/0803—Compounds with Si-C or Si-Si linkages
- C07F7/0825—Preparations of compounds not comprising Si-Si or Si-cyano linkages
- C07F7/083—Syntheses without formation of a Si-C bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic System
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/20—Purification, separation
Abstract
The present invention disclose it is a kind of using 3- containing silicon group simple aryne precursor synthesis the silicon substrate containing 3- 1,2,3,5- tetra- substituted benzenes and its synthetic method, structure it is as shown in the figure.The synthetic method of tetra- substituted benzene of 1,2,3,5- of the silicon substrate containing 3- includes two steps of synthesis of the 3- aryne alkynes precursors containing silicon group and 3,3- dimethyl-allyl phenylsulfone.Using the 3- simple aryne precursors and 3 containing silicon group, 3- dimethyl-allyl phenylsulfone and bromoacetate are treated different things alike and are reacted, and the 1 of the available silicon substrate containing 3-, 2,3,5- tetra- substituted benzenes.The solution have the advantages that the compound and its synthetic method have broad application prospects in organic synthesis and pharmaceutical synthesis field；Secondly, the method simple synthetic method, can largely prepare.
Description
Technical field
The present invention proposes that a kind of simple aryne precursor for containing silicon group using No. 3 positions synthesizes the 1 of a kind of silicon substrate containing 3-,
The new method of tetra- substituted benzene of 2,3,5-.
Background technique
Benzene with multiple substituent groups is widely present in the nuclear structure of natural products and drug molecule and numerous
The core skeleton of organic functional material.How the method being simple and efficient to be used to prepare polysubstituted benzene derivate, is all the time
One important research direction of synthetic organic chemistry.
In recent years, aryne chemistry has received widespread attention, and three keys for being primarily due to Aryne intermediates have very high work
Property, it can be reacted with many close aryne reagents, while introducing Liang Ge functional group at the ortho position of aromatic ring.But also just because of virtue
The characteristics of three key of alkynes intermediate can only provide two reaction sites makes aryne when participating in chemical reaction, can only be at aromatic ring ortho position
Bifunctionalized reaction occurs, is difficult to realize the functionalization in aromatic ring other positions simultaneously.To solve the above-mentioned problems, Li is in 2016
It reports in year and the reaction of simple aryne is reset into the chemical conversion process being connected in series with Claisen, successfully synthesize aromatic ring ortho position three
Functionalized products, referring specifically to " Aryne 1,2,3-Trifunctionalization with Aryl Allyl
Sulfoxides " (1,2, the 3- trifunctional of aromatic ring that phenyl allyl sulfoxide participates in), Yuanyuan Li；Dachuan Qiu；
Rongrong Gu；Junli Wang；Jiarong Shi；Yang Li*.J.Am.Chem.Soc.,2016,138, 10814–
10817.But in synthesis containing there are three when the above substituent group benzene, this method is also helpless.This is also field technical staff
Thirst for and insurmountable technical problem always.
Summary of the invention
Problem in view of the above technology, the invention proposes a kind of the 1 of silicon substrate containing 3-, 2,3,5- tetra- substituted benzene and its synthesis sides
Method, this method have the characteristic of 1,2,3,5- tetra- substituted benzenes of one-step synthesis silicon substrate containing 3-.
In order to solve above-mentioned technical problem, the present invention provides a kind of ground 1,2,3,5- tetra- substituted benzene structure of silicon substrate containing 3- such as
Under：
The synthetic method of tetra- substituted benzene of 1,2,3,5- of the silicon substrate containing 3- of the invention includes following rapid：
Step 1, the 3- preparations containing silicon substrate aryne precursor
No. 3 positions are that the simple aryne precursor of silicon group is known compound, and specific synthesis step is referring to document
“Aryne Trifunctionalization Enabled by 3-Silylaryne as a 1,2-Benzdiyne
Equivalent " (the aromatic ring trifunctional for using 3- silicon substrate aryne to realize as 1,2- benzene diine precursor) Chunjie Lv；
Caiwen Wan；Song Liu；Yu Lan*and Yang Li*.Org.Lett.,2018,DOI:10.1021/
acs.orglett.8b00469；
Step 2, the preparation of 3,3- dimethyl-allyl phenylsulfones
3,3- dimethyl-allyl phenylsulfones be known compound, specific synthesis step referring to document " Aryne 1,
2,3-Trifunctionalization with Aryl Allyl the Sulfoxides " (aromatic ring that phenyl allyl sulfoxide participates in
1,2,3- trifunctional), Yuanyuan Li；Dachuan Qiu；Rongrong Gu；Junli Wang；Jiarong Shi；
Yang Li*.J.Am.Chem. Soc.,2016,138,10814–10817；
Step 3,1 of the silicon substrate containing 3-, the synthesis of 2,3,5- tetra- substituted benzenes
In glove box, by No. 3 positions be silicon group aryne precursor quantitative weighing in a round bottom flask, then thereto
3,3- dimethyl-allyl phenylsulfone, bromoacetate, cesium fluoride is added, above-mentioned reaction flask is removed out of glove box,
Argon gas protection is lower to be added acetonitrile as solvents, the stir about 6 hours under the conditions of 80 DEG C；Saturation food is added thereto after complete reaction
Salt water is extracted with ethyl acetate, and obtains sterling A using concentration and column chromatography.
Compared with prior art, the present invention has the following technical effect that：This method has the 1 of one-step synthesis silicon substrate containing 3-,
The characteristic of tetra- substituted benzene of 2,3,5-；Reaction condition is mild, and raw material is easily prepared.This is in the synthesis of drug molecule and native compound
With important potential using value.
Specific embodiment：
Below in conjunction with specific reaction, the present invention is further illustrated.Product structure of the invention is as follows
By taking No. 3 positions are the product structure of trimethyl silicon substrate (TMS) as an example.
Step 1, the preparation of 3,3- dimethyl-allyl phenylsulfones
Methylbenzene phenyl-sulfhydrate (8mmol, 1equiv) will be dissolved in 100ml pear shape bottle in the dry tetrahydrofuran of 30ml,
And pear shape bottle is placed in ice-water bath and is stirred.After mixing to drug and solvent, 60%NaH is slowly added at 0 DEG C
(12mmol, 1.5equiv) stirs 30min.Take 3,3- dimethallyl bromide (8.8mmol, 1.1equiv) slow with syringe
It is added in solution, filtering is spin-dried for obtaining colourless oil liquid after fully reacting.
The product that the first step is obtained is dissolved in 30ml dehydrated alcohol, is stirred at room temperature.3- chlorine peroxide benzene first is added afterwards
Sour (4mmol, 0.5equiv) reacts 2 hours.Dehydrated alcohol is directly spin-dried for after after fully reacting, is isolated with column chromatography
Product 677mg.Referring to document " Aryne 1,2,3-Trifunctionalization with Aryl Allyl
Sulfoxides " (the 1,2,3- trifunctional for the aromatic ring that phenyl allyl sulfoxide participates in), Yuanyuan Li；Dachuan
Qiu； Rongrong Gu；Junli Wang；Jiarong Shi；Yang Li*.J.Am.Chem. Soc.,2016,138,
10814–10817。
Step 2,3- are the preparation of trimethyl silicon substrate (TMS) aryne precursor
It weighs and is placed in ice-water bath simultaneously in 2,6- dibromophenol (1.98mmol, 1.0equiv) addition 30ml tetrahydrofuran
It stirs evenly.It weighs and is stirred 20 minutes in the slow solubilization liquid of 60%NaH (2.78mmol, 1.5equiv), with injection at 0 DEG C
Tolerance takes trim,ethylchlorosilane (2.78 mmol, 1.5equiv) to be slowly added to stir into solution, after complete reaction will reaction
Temperature is down to -78 DEG C, measures n-BuLi (2.78mmol, 1.5equiv) addition with syringe and maintains temperature 30 to divide into solution
Clock.10% sodium bicarbonate solution is slowly added dropwise at low temperature later, obtains colourless liquid with after being spin-dried for after pure petroleum ether extraction
438mg。
It weighs above-mentioned raw materials (1.23mmol, 1.0equiv) and is placed in 0 DEG C in 30ml tetrahydrofuran and stir evenly.It weighs
60%NaH (1.85mmol, 1.5equiv) is slowly added to stir 20 minutes in solution.Trimethyl is measured with syringe at 0 DEG C
Chlorosilane (1.85mmol, 1.5 equiv) is slowly added into solution stirring 40 minutes.N-BuLi is measured with syringe
(1.85 mmol, 1.5equiv) are slowly added dropwise into solution, are to slowly warm up to use injection tolerance at -10 DEG C after complete reaction
It takes trifluoromethanesulfanhydride anhydride (1.85mmol, 1.5equiv) to be added into solution, is post-processed after complete reaction.In low temperature
The sodium bicarbonate solution of lower dropwise addition 10%, afterwards with pure petroleum ether extraction, the organic phase anhydrous sodium sulfate drying extracted is spin-dried for
Obtain colourless liquid 364mg.Referring to document " Aryne Trifunctionalization Enabled by 3-
Silylaryne as a 1,2-Benzdiyne Equivalent " (realizes three officials of aromatic ring with 3- silicon substrate -1,2- aryne precursor
Energyization) Chunjie Lv；Caiwen Wan；Song Liu；Yu Lan*and Yang Li*.Org. Lett.,2018,DOI:
10.1021/acs.orglett.8b00469。
Step 3,1 of the silicon substrate containing 3-, the synthesis of 2,3,5- trisubstituted benzenes
Firstly, weighing the aryne precursor that No. 3 positions are trimethyl silicon substrate with assay balance in the environment of anhydrous and oxygen-free
(74.0mg, 0.2mmol, 1.0equiv), 3,3- dimethyl-allyl phenylsulfones (124.0mg, 0.6mmol, 3.0equiv),
Bromoacetate (100.2mg, 0.6 mmol, 3.0equiv) and cesium fluoride (128.0mg, 0.8mmol, 4.0equiv), and will
It is dissolved in acetonitrile (10ml), reacts 6 hours under conditions of temperature is 80 DEG C.
Post-processing：After reaction terminates, extra villiaumite is washed away with saturated salt solution, afterwards plus ethyl acetate extracts, then uses
Anhydrous sodium sulfate is dry, is most concentrated afterwards through Rotary Evaporators, and silica gel chromatograph column separating purification obtains 1 of the silicon substrate containing 3-, and 2,3,5-
Four substituted benzenes.
Detailed description of the invention：
Fig. 1 is four substituted benzene product structure of 3- silicon substrate -1,2,3,5-
Fig. 2 is the synthetic route of specific synthesis four substituted benzene of 3- silicon substrate -1,2,3,5-
Fig. 3 is four substituted benzene product structure of 3- trimethyl silicon substrate -1,2,3,5-
The drug used
Nuclear magnetic data hydrogen spectrum, carbon spectrum, infrared, high resolution mass spectrum is as follows：
1H NMR(400MHz,CDCl3) δ 7.33 (d, J=8.1Hz, 2H), 7.16 (d, J=8.0 Hz, 2H), 6.96 (s,
1H), 6.95 (s, 1H), 5.60 (t, J=6.7Hz, 1H), 4.59 (d, J=6.7Hz, 2H), 2.36 (s, 3H), 1.80 (s,
3H),1.74(s,3H),0.31(s,9H)ppm. 13C NMR(126MHz,CDCl3)δ168.99,168.89,160.36,
158.69,138.37, 138.06,137.76,134.00,133.59,132.98,132.80,130.39,130.38,69.68,
61.29,33.66,25.79,21.36,17.88,14.41,-0.16ppm,IR(thin flim)3077, 2953,2952,
2856,2653,1640,1550,1491,1459,1367,1256,1227, 1113,965,HRMS-MALDI(m/z)calcd
for[C25H34NaO3SSi+] 465.1890,found 465.1891
Claims (2)
1. the 1 of a kind of silicon substrate containing 3-, 2,3,5- tetra- substituted benzenes, structural formula is as follows：
2. 1 of the silicon substrate containing 3- according to claim 1, the synthetic method of 2,3,5- tetra- substituted benzenes, characterized in that including following
Step：
Step 1, the 3- preparations containing silicon substrate aryne precursor
No. 3 positions are that the simple aryne precursor of silicon group is known compound, and specific synthesis step is referring to document " Aryne
Trifunctionalization Enabled by 3-Silylaryne as a 1,2-Benzdiyne Equivalent”
(the aromatic ring trifunctional for using 3- silicon substrate aryne to realize as 1,2- benzene diine precursor) Chunjie Lv；Caiwen Wan；Song
Liu；Yu Lan*and Yang Li*.Org.Lett.,2018,DOI:10.1021/acs.orglett.8b00469；
Step 2, the preparation of 3,3- dimethyl-allyl phenylsulfones
3,3- dimethyl-allyl phenylsulfones are known compound, and specific synthesis step is referring to document " Aryne 1,2,3-
Trifunctionalization with Aryl Allyl Sulfoxides " (aromatic ring 1,2 that phenyl allyl sulfoxide participates in,
3- trifunctional), Yuanyuan Li；Dachuan Qiu；Rongrong Gu；Junli Wang；Jiarong Shi；Yang
Li*.J.Am.Chem.Soc.,2016,138,10814–10817；
Step 3,1 of the silicon substrate containing 3-, the synthesis of 2,3,5- tetra- substituted benzenes
In glove box, by No. 3 positions be trimethyl silicon substrate (TMS) aryne precursor quantitative weighing in a round bottom flask, then
3,3- dimethyl-allyl phenylsulfone, bromoacetate, cesium fluoride are added thereto, above-mentioned reaction flask is moved out of glove box
Out, acetonitrile as solvents is added under protection of argon gas, the stir about 6 hours under the conditions of 80 DEG C；It is added thereto after complete reaction
Saturated salt solution is extracted with ethyl acetate, and obtains sterling A using concentration and column chromatography.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111675721A (en) * | 2020-06-30 | 2020-09-18 | 许昌学院 | Method for synthesizing polysubstituted aryl compound by using 1, 2-diaryl alkyne precursor |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106316900A (en) * | 2016-08-18 | 2017-01-11 | 重庆大学 | 1, 2, 3-tri-substituted benzene and method for synthesizing same |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106316900A (en) * | 2016-08-18 | 2017-01-11 | 重庆大学 | 1, 2, 3-tri-substituted benzene and method for synthesizing same |
Non-Patent Citations (2)
| Title |
|---|
| CHUNJIE LV ET AL.: "Aryne Trifunctionalization Enabled by 3-Silylaryne as a 1,2-Benzdiyne Equivalent", 《ORG. LETT.》 * |
| YUANYUAN LI ET AL.: "Aryne 1,2,3-Trifunctionalization with Aryl Allyl Sulfoxides", 《J. AM. CHEM. SOC.》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111675721A (en) * | 2020-06-30 | 2020-09-18 | 许昌学院 | Method for synthesizing polysubstituted aryl compound by using 1, 2-diaryl alkyne precursor |
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