CN109879806A - A kind of isoquinolin indenes ether derivant and preparation method thereof - Google Patents
A kind of isoquinolin indenes ether derivant and preparation method thereof Download PDFInfo
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- CN109879806A CN109879806A CN201910223871.2A CN201910223871A CN109879806A CN 109879806 A CN109879806 A CN 109879806A CN 201910223871 A CN201910223871 A CN 201910223871A CN 109879806 A CN109879806 A CN 109879806A
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Abstract
The present invention provides a kind of isoquinolin indenes ether derivants and preparation method thereof, and four acetylene compounds are reacted in toluene with isoquinolone, obtain isoquinolin indenes ether derivant.Compared with prior art, the present invention provides a kind of preparation method of completely new isoquinolin indone, a series of new isoquinolin indenes ether derivants are generated.The isoquinolin indenes ether derivant of synthesis has compared with high atom economy, the more complicated multiplicity of structure, has certain utilization prospect.
Description
Technical field
The present invention relates to organic compound fields, more particularly to a kind of isoquinolin indenes ether derivant and preparation method thereof.
Background technique
Isoquinolin can manufacture drug and efficient pesticides, can be made into picolinic acid after oxidation, its derivative can be used for making
Colour motion picture films and dyestuff are made, the intermediate and GC stationary liquid of synthetic drug, dyestuff, insecticide are also used as.Therefore,
Isoquinolin can be used for the production of the products such as pesticide, medicine, rubber accelerator, colour motion picture films sensitizer, dyestuff；As medicine,
The raw material of dyestuff, insecticide, anion exchange resin etc., the preservative of iron, the fixative etc. of resol resin；Isoquinolin
The additive compound formed with metal can be used for the qualitative determination of nickel, the quantitative determination of cadmium and noble metal；It is reacted in benzoylation
In the polymerization reaction of alpha-olefin, isoquinolin can also make catalyst use.
Summary of the invention
The purpose of the present invention is to provide a kind of preparation methods of isoquinolin indenes ether derivant, and preparation method is mild, simple,
Efficiently.
Another object of the present invention is to provide a kind of isoquinolin indenes ether derivant, the more complicated multiplicity of structure has wide
It is wealthy to use prospect.
Specific technical solution of the present invention is as follows:
A kind of preparation method of isoquinolin indenes ether derivant, comprising the following steps:
Four acetylene compounds are reacted in toluene with isoquinolone, isoquinolin indenes ether derivant is obtained.
Further, the molar ratio of four acetylene compound, isoquinolone and toluene is 1:1:28-66；
The reaction refers to be carried out under conditions of 100-110 DEG C, reaction time at least 12h.
Further, purifies and separates are carried out after reaction, specifically: products therefrom is washed with water, then ethyl acetate extracts
It takes, crystallizing at room temperature, produces and obtain white powder with petroleum ether to get isoquinolin indenes ether derivant.
Further, the four acetylene compounds structural formulaR is straight chained alkyl, branched alkane
Base or unsaturated hydrocarbons；R1For hydrogen, halogen, straight chained alkyl, branched alkyl, ester group or alkoxy.
Four acetylene compound the preparation method comprises the following steps:
1) using sodium hydride as catalyst, malonate is added to ice-water bath in anhydrous acetonitrile with propargyl bromide and is reacted, so
Purifies and separates afterwards obtain compound 1；
2) compound 1 of step 1) preparation and phenylacetylene bromide or substituted phenylacetylene bromide are blended in Pd (PPh3)2Cl2In the anhydrous and oxygen-free catalyst system of/CuI, alkali is made with triethylamine, using anhydrous acetonitrile as solvent, is stirred to react at room temperature, is purified
After separation, four acetylene compounds are obtained.
Further, the molar ratio of sodium hydride in step 1), malonate, propargyl bromide and anhydrous acetonitrile is 4-5:1:
2.2-3.2:20-23；The malonate is selected from diethyl malonate or Diisopropyl malonate.
In step 1) under the conditions of ice-water bath reaction temperature at 0-5 DEG C；Reaction time was at 5 hours or more；
Purifies and separates described in step 1) specifically: product adds water washing, is extracted with ethyl acetate, and decompression is spin-dried for, volume
Than the ethyl acetate for 1:80: petroleum ether column chromatography obtains white solid product, i.e. compound 1.
The structural formula of compound 1 described in step 1)R is straight chained alkyl, branched alkyl or not
Saturated hydrocarbons；
Compound 1 and phenylacetylene bromide or substituted phenylacetylene bromide, Pd (PPh in step 2)3)2Cl2/ CuI, triethylamine
The mass ratio of the material with anhydrous acetonitrile is 1:2.2-3.2:0.03-0.04:4-5:30-45；
Step 2) is described to be stirred to react, and the reaction time was at 10 hours or more；
Step 2) the substituted phenylacetylene bromide is selected to methylbenzene acetylenebromide；
Purifies and separates described in step 2) specifically: product is washed with water, and is extracted with ethyl acetate, and decompression is spin-dried for, and uses body
Product is than the ethyl acetate for 1:80: petroleum ether column chromatography for separation obtains four acetylene compounds.
Pd (PPh described in step 2)3)2Cl2The anhydrous and oxygen-free catalyst system of/CuI, molar ratio Pd (PPh3)2Cl2: CuI=
3:1。
A kind of isoquinolin indenes ether derivant provided by the invention, is prepared, structural formula using the above method are as follows:
Wherein E is CO2R；R is straight chained alkyl, branched alkyl or unsaturated hydrocarbons；R1And R2For hydrogen, halogen, straight chained alkyl, branch
Alkyl group, ester group or alkoxy.
Preferably, the isoquinolin indenes ether structure formula are as follows:
Reaction mechanism of the invention are as follows: it is that four alkynes itself occur HDDA and react to form benzyne intermediate first, then benzyne
Intermediate reacts nucleophilic addition with isoquinolone and forms product.Compared with prior art, the present invention provides a kind of completely new
Isoquinolin indone preparation method, generate a series of new isoquinolin indenes ether derivants.The isoquinolin indenes ether derivant of synthesis
With compared with high atom economy, the more complicated multiplicity of structure has certain utilization prospect.
Detailed description of the invention
Fig. 1 is the structural formula of isoquinolin indenes ether derivant；
Fig. 2 is the structural formula of isoquinolin indenes ether derivant prepared by embodiment 1；
Fig. 3 is the structural formula of isoquinolin indenes ether derivant prepared by embodiment 2；
Fig. 4 is the nuclear magnetic resonance spectroscopy of isoquinolin indenes ether derivant prepared by embodiment 1；
Fig. 5 is the carbon-13 nmr spectra of isoquinolin indenes ether derivant prepared by embodiment 1；
Fig. 6 is the nuclear magnetic resonance spectroscopy of isoquinolin indenes ether derivant prepared by embodiment 2；
Fig. 7 is the carbon-13 nmr spectra of isoquinolin indenes ether derivant prepared by embodiment 2；
Fig. 8 is 1 preparation process equation of embodiment；
Fig. 9 is 2 preparation process equation of embodiment；
Figure 10 is 1 step 3) reaction mechanism of embodiment；
Figure 11 is 2 step 3) reaction mechanism of embodiment.
Specific embodiment
Embodiment 1
A kind of isoquinolin indenes ether derivant, structural formula are as follows:
The preparation method of above-mentioned isoquinolin indenes ether, comprising the following steps:
1) using 830mmol sodium hydride as alkali, 200mmol Diisopropyl malonate and 440mmol propargyl bromide are added to
Ice-water bath in 210mL anhydrous acetonitrile is stirred to react 8.5 hours, and product adds water washing, is extracted with ethyl acetate, and decompression is spin-dried for, column
Chromatography (volume ratio ethyl acetate: petroleum ether=1:80) obtains white solid product, i.e. compound 1；
2) 80mmol compound 1 is mixed into Pd (PPh with 200mmol phenylacetylene bromide3)2Cl2/CuI(2.56mmol/
In anhydrous and oxygen-free catalyst system 0.85mmol), molar ratio Pd (PPh3)2Cl2: CuI=3:1 makees alkali with 336mmol triethylamine,
It using 150mL anhydrous acetonitrile as solvent, is stirred to react at room temperature 11 hours, product is washed with water, and is extracted with ethyl acetate, decompression rotation
Dry, column chromatography (volume ratio ethyl acetate: petroleum ether=1:80) obtains faint yellow solid product, i.e. compound 2.
3) under conditions of 105 DEG C, by step 2) preparation 2mmol compound 2 in 10mL toluene with 2mmol isoquinoline promise
Reactive ketone 12 hours, obtain compound 3, the i.e. crude product of isoquinolin indenes ether, crude product with water washing, ethyl acetate extraction, room temperature
Crystallization is produced with petroleum ether, obtains white powder, i.e. isoquinolin indenes ether derivant, yield is about 85.8%.
Products therefrom white powder product structure passes through；1H NMR；13C NMR is measured, as a result as follows:
1H NMR(400MHz,CDCl3) δ 8.48 (d, J=8.0Hz, 1H), 8.02-7.67 (m, 6H), 7.47-7.38 (m,
5H), 7.37-7.22 (m, 5H), 5.11-5.05 (m, 2H), 3.90 (s, 2H), 3.52 (s, 2H), 1.26 (d, J=4.0Hz,
6H), 1.24 (d, J=4.0Hz, 6H).
13C NMR(125MHz,CDCl3)δ171.34,159.92,149.80,149.77,146.53,144.84,
140.41,140.39,140.13,138.98,132.10,131.80,131.45,129.84,128.66,128.49,128.25,
127.90,127.71,126.76,124.69,124.02,122.14,119.91,117.02,95.81,87.49,77.71,
77.45,77.20,69.76,69.74,60.13,41.66,38.83,21.94.ppm。
Embodiment 2
A kind of isoquinolin indenes ether derivant, structural formula are as follows:
The preparation method of above-mentioned isoquinolin indenes ether, comprising the following steps:
1) using 830mmol sodium hydride as alkali, 200mmol diethyl malonate and 440mmol propargyl bromide are added to
Ice-water bath in 210mL anhydrous acetonitrile is stirred to react 8.5 hours, and product adds water washing, is extracted with ethyl acetate, and decompression is spin-dried for, column
Chromatography (volume ratio ethyl acetate: petroleum ether=1:80) obtains white solid product, i.e. compound 1；
2) by 80mmol compound 1 with to 200mmol methylbenzene acetylenebromide mixing Pd (PPh3)2Cl2/CuI
In the anhydrous and oxygen-free catalyst system of (2.56mmol/0.85mmol), molar ratio Pd (PPh3)2Cl2: CuI=3:1, with 336mmol
Triethylamine makees alkali, using 150mL anhydrous acetonitrile as solvent, is stirred to react at room temperature 11 hours, product is washed with water, and uses ethyl acetate
Extraction, decompression are spin-dried for, and column chromatography (volume ratio ethyl acetate: petroleum ether=1:80) obtains faint yellow solid product, i.e. compound
2。
3) under conditions of 108 DEG C, 2mmol compound 2 prepared by step 2) in 10mL toluene with 2mmol isoquinoline promise
Reactive ketone 12 hours, obtain compound 3, the i.e. crude product of isoquinolin indenes ether.Crude product with water washing, ethyl acetate extraction, room temperature
Crystallization, produces and obtains white powder i.e. isoquinolin indenes ether with petroleum ether, yield is about 87.3%.
White powder product structure passes through；1H NMR；13C NMR is measured.
1H NMR(400MHz,CDCl3) δ 8.48 (d, J=12.0Hz, 1H), 8.01-7.63 (m, 6H), 7.37-7.29 (m,
4H), 7.26-7.14 (m, 4H), 4.23 (q, J=8.0Hz, 4H), 3.92 (s, 2H), 3.53 (s, 2H), 2.43 (s, 3H), 2.38
(s, 3H), 1.28 (q, J=4.0Hz, 6H).
13C NMR(100MHz,CDCl3)δ171.45,159.55,149.15,145.87,144.31,139.80,
138.54,138.22,137.20,137.11,131.31,131.26,131.01,129.27,129.03,128.59,127.28,
126.35,124.31,121.70,120.61,119.51,116.58,115.19,95.65,86.56,77.37,77.06,
76.74,61.89,59.71,41.36,38.53,21.56,21.30,14.05ppm。
Claims (10)
1. a kind of preparation method of isoquinolin indenes ether derivant, which is characterized in that the preparation method comprises the following steps:
Four acetylene compounds are reacted in toluene with isoquinolone, isoquinolin indenes ether derivant is obtained.
2. preparation method according to claim 1, which is characterized in that four acetylene compound, isoquinolone and toluene
Molar ratio be 1:1:28-66.
3. preparation method according to claim 1 or 2, which is characterized in that the reaction refers to the condition at 100-110 DEG C
Lower progress, reaction time at least 12h.
4. preparation method according to claim 1 or 2, which is characterized in that the four acetylene compounds structural formulaR is straight chained alkyl, branched alkyl or unsaturated hydrocarbons；R1For hydrogen, halogen, straight chained alkyl, branched alkane
Base, ester group or alkoxy.
5. preparation method according to claim 1 or 4, which is characterized in that four acetylene compound the preparation method comprises the following steps:
1) using sodium hydride as catalyst, malonate is added to ice-water bath in anhydrous acetonitrile with propargyl bromide and is reacted, it is then pure
Change separation, obtains compound 1；
2) compound 1 of step 1) preparation and phenylacetylene bromide or substituted phenylacetylene bromide are blended in Pd (PPh3)2Cl2/
In the anhydrous and oxygen-free catalyst system of CuI, alkali is made with triethylamine, using anhydrous acetonitrile as solvent, is stirred to react at room temperature, purifies and separates
Afterwards, four acetylene compounds are obtained.
6. preparation method according to claim 5, which is characterized in that sodium hydride, malonate, propargyl bromide in step 1)
Molar ratio with anhydrous acetonitrile is 4-5:1:2.2-3.2:20-23.
7. preparation method according to claim 5 or 6, which is characterized in that the malonate is selected from diethyl malonate
Or Diisopropyl malonate.
8. preparation method according to claim 5 or 6, which is characterized in that in step 2) compound 1 and phenylacetylene bromide or
Substituted phenylacetylene bromide, Pd (PPh3)2Cl2The mass ratio of the material of/CuI, triethylamine and anhydrous acetonitrile are 1:2.2-3.2:
0.03-0.04:4-5:30-45.
9. preparation method according to claim 5, which is characterized in that compound 1 and phenylacetylene bromide or taken in step 2)
The phenylacetylene bromide in generation, Pd (PPh3)2Cl2The mass ratio of the material of/CuI, triethylamine and anhydrous acetonitrile are 1:2.2-3.2:0.03-
0.04:4-5:30-45.
10. a kind of isoquinolin indenes ether derivant is prepared, structural formula using any one of claim 1-9 the method are as follows:
Wherein E is CO2R；R is straight chained alkyl, branched alkyl or unsaturated hydrocarbons；R1And R2For hydrogen, halogen, straight chained alkyl, branched alkane
Base, ester group or alkoxy.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110330485A (en) * | 2019-07-25 | 2019-10-15 | 中国科学技术大学 | A kind of indenoisoquinoline class compound and preparation method thereof |
| CN114014779A (en) * | 2021-12-14 | 2022-02-08 | 安徽师范大学 | Bisaryl oxime ether compound and preparation method thereof |
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| CN108774189A (en) * | 2018-06-08 | 2018-11-09 | 安徽师范大学 | Yi Zhong oxazine phenylate derivatives and preparation method thereof |
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| US4927838A (en) * | 1987-07-10 | 1990-05-22 | Hoffman-La Roche Inc. | Pyridine compounds which are useful in treating a disease state characterized by an excess of platelet activating factors |
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| CN114014779A (en) * | 2021-12-14 | 2022-02-08 | 安徽师范大学 | Bisaryl oxime ether compound and preparation method thereof |
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Application publication date: 20190614 |