CN107602461A - A kind of synthetic method of quinolines - Google Patents
A kind of synthetic method of quinolines Download PDFInfo
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- CN107602461A CN107602461A CN201710872970.4A CN201710872970A CN107602461A CN 107602461 A CN107602461 A CN 107602461A CN 201710872970 A CN201710872970 A CN 201710872970A CN 107602461 A CN107602461 A CN 107602461A
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- quinolines
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Abstract
The present invention relates to a kind of synthetic method of quinolines, following steps are specifically included：Amino benzenes compounds are taken, as raw material, to add water with alkyls compound and acetic acid is reacted to obtain quinolines.The present invention is directed to the synthetic method of quinolines under conditions of non-metal catalyst, reacted by solvent of water, its reaction raw materials is more environmentally friendly to be easy to get, experimental cost is lower, the quinolines yield obtained in the process of the present invention simultaneously reaches as high as 98%, and it is above the yield of quinolines acquired in conventional method.
Description
Technical field
The invention belongs to chemosynthesis technical field, more particularly to a kind of synthetic method of quinolines.
Background technology
Quinolines are a kind of important hexa-atomic nitrogen-containing heterocycle compounds of benzo, are widely present in natural products,
With important biology, pharmaceutical activity；Simultaneously as a kind of multi-functional organic synthesis intermediate, quinolines are in organic conjunction
Obtained a wide range of applications into the field such as chemistry, pharmaceutical synthesis chemistry, materials chemistry.Specific its is widely present in alkaloid
And show the bioactivity of highly significant, have anti-asthma, it is antibacterial, antiviral, enhancing memory, anti-hypertension, antidepression, resist
Allergy, anti-malarial and antitumor and other effects.In addition, they or important fine chemical material, are widely used in medicine, dyestuff
Learn auxiliary agent, the synthesis of agricultural chemicals and the preparation of photosensitive material, be also used as solvent and extractant, applied to plating, METAL EXTRACTION,
The industries such as smelting.
Urged in the prior art in the preparation of quinolines, more and toxicity high using metal or remaining cost are big
Agent catalysed aniline is prepared with the reaction of ethyl benzene-like compounds, such as application publication number is
CN101555225A patent of invention discloses a kind of preparation method of poly-substituted quinoline compound, with phenyl amines
Compound and 2- alkenyls aldehyde or 2- alkenyl ketones are that raw material adds catalyst green vitriol, the heating reflux reaction 2- in sulfuric acid
20 hours, after reaction system is cooled into room temperature, post-processed, substd quinolines compound is made.It is known to be directed to seven hydration sulphur
Sour ferrous irritant to respiratory tract, suction causes cough and shortness of breath.It is irritant to eyes, skin and mucous membrane.Wrongly take and cause
Weak, stomachache, nausea, have blood in stool, lung and liver are impaired, shock, stupor etc., severe patient can be lethal.In addition, also have for environment certain
Harm.
Deficiency of the prior art can be based on, there is provided a kind of synthetic method of quinolines, avoid using metal
Catalyst or poisoned catalyst, and environmental protection is easy to get, and reduces experimental cost, improves the yield of product, turn into those skilled in the art
Technical barrier urgently to be resolved hurrily.
The content of the invention
The present invention is directed to above-mentioned technical problem, a kind of synthetic method of quinolines is proposed, without metal catalytic
Under the conditions of agent, reacted by solvent of water, greatly reduce the environmental pollution in building-up process, at the same reduce experiment into
This.
In order to achieve the above object, the technical solution adopted by the present invention is：
A kind of synthetic method of quinolines, its course of reaction are as follows：
Amino benzenes compounds shown in structure formula (I) and the alkyls compound shown in structure formula (II) are taken as raw material,
Add water and acetic acid is reacted to obtain the quinolines shown in structure formula (III)；
Wherein R1For hydrogen, methyl or halogen, R2For phenyl or tolyl；The R1In the ortho position of amino or contraposition.
As preferred：The mol ratio of the amino benzenes compounds, alkyls compound and acetic acid is 20:40:1；Institute in water
The initial concentration for stating amino benzenes compounds is 0.25~0.4mol/L.
As preferred：Its reaction condition is：Reacted 15~24 hours under the conditions of 110~120 DEG C.
As preferred：Described halogen is chlorine.
As preferred：The amino benzenes compounds are aniline, o-toluidine, parachloroanilinum or open-chain crown ether.
As preferred：The alkyls compound be ethylo benzene or 4- methyl-ethyl benzenes described in alkyls compound be ethylo benzene
Or 4- ethyltoluenes.
As preferred：The alkyls compound is 4- methyl-ethyl benzenes；The amino benzenes compounds are for aniline or to methyl
Aniline.
As preferred：Take aniline, 4- methyl-ethyl benzenes, acetic acid and water, the mol ratio of the aniline, 4- methyl-ethyl benzenes and acetic acid
For 20:40:1, the concentration of open-chain crown ether described in water is 0.333mol/L；Reacted in closing space under the conditions of 110 DEG C
18 hours, the compound shown in structure formula (IV) is obtained through column chromatography for separation,
As preferred：Take open-chain crown ether, 4- methyl-ethyl benzenes, acetic acid and water, the open-chain crown ether, 4- methyl-ethyl benzenes and
The mol ratio of acetic acid is 20:40:1, the concentration of open-chain crown ether described in water is 0.333mol/L；In 110 in closing space
Reacted 19 hours under the conditions of DEG C, the compound shown in structure formula (V) obtained through column chromatography for separation,
Compared with prior art, the advantages and positive effects of the present invention are：
1st, the present invention enters for the synthetic method of quinolines under conditions of non-metal catalyst by solvent of water
Row reaction, its reaction raw materials environmental protection are easy to get, and experimental cost is lower, while the products collection efficiency obtained in the process of the present invention reaches as high as
98%, it is above the yield acquired in conventional method.
2nd, for the synthetic method for being used to prepare quinolines conventional in art technology, typically it is required to add
Catalyst, and the application adds acetic acid and water in reaction raw materials, wherein acetic acid during the course of the reaction act as catalyst, water
During the course of the reaction act as solvent so that obtain quinolines yield it is higher.
Embodiment
The technical scheme in the embodiment of the present invention will be clearly and completely described below, it is clear that described implementation
Example only part of the embodiment of the present invention, rather than whole embodiments.It is common based on the embodiment in the present invention, this area
The every other embodiment that technical staff is obtained under the premise of creative work is not made, belong to the model that the present invention protects
Enclose.
The embodiments of the invention provide a kind of synthetic method of quinolines, its course of reaction are as follows：
Amino benzenes compounds shown in structure formula (I) and the alkyls compound shown in structure formula (II) are taken as raw material,
Add water and acetic acid is reacted to obtain the quinolines shown in structure formula (III)；
Wherein R1For hydrogen, methyl or halogen, R2For phenyl or tolyl；The R1In the ortho position of amino or contraposition.
Solvent screening is tested, and it is small to react 15~24 under the conditions of 120 DEG C according to reaction raw materials shown in table 1 and solvent successively
When, detect products collection efficiency.From the data in table 1, it can be seen that preferred solvent is acetic acid.Its yield can reach 93%.
The solvent screening laboratory test results of table 1
| Aniline (mmol) | Ethylo benzene (mmol) | Solvent(ml) | T(℃) | Yield |
| 2 | 2 | DMSO | 120 | Do not react |
| 2 | 2 | DMF | 120 | 5% |
| 2 | 2 | 1,4- dioxane | 120 | Do not react |
| 2 | 2 | Dichloromethane | 120 | Do not react |
| 2 | 2 | Tetrahydrofuran | 120 | Do not react |
| 2 | 2 | Ethyl acetate | 120 | 10% |
| 2 | 2 | Acetonitrile | 120 | Do not react |
| 2 | 2 | Chloroform | 120 | Do not react |
| 2 | 2 | Water | 120 | 90% |
From the data in table 1, it can be seen that preferred water can further improve reaction of the present invention as solvent in reaction raw materials of the present invention
Reaction efficiency, to improve products collection efficiency, simultaneous reactions condition is gentleer.
In an alternative embodiment, the mol ratio of the amino benzenes compounds, alkyls compound and acetic acid is 20:40:
1；The initial concentration of amino benzenes compounds described in water is 0.25~0.4mol/L.
In an alternative embodiment, its reaction condition is：Reacted 15~24 hours under the conditions of 110~120 DEG C.
In an alternative embodiment, described halogen is chlorine.
In an alternative embodiment, the amino benzenes compounds are aniline, o-toluidine, parachloroanilinum or to methylbenzene
Amine.
In an alternative embodiment：The alkyls compound is alkyls compound described in ethylo benzene or 4- methyl-ethyl benzenes
For ethylo benzene or 4- ethyltoluenes.
In an alternative embodiment：The alkyls compound is 4- methyl-ethyl benzenes；The amino benzenes compounds are aniline
Or open-chain crown ether.
In an alternative embodiment：Take aniline, 4- methyl-ethyl benzenes, acetic acid and water, the aniline, 4- methyl-ethyl benzenes and second
The mol ratio of acid is 20:40:1, the concentration of open-chain crown ether described in water is 0.333mol/L；In 110 DEG C in closing space
Under the conditions of react 18 hours, obtain the compound shown in structure formula (IV) through column chromatography for separation,
In an alternative embodiment：Take open-chain crown ether, 4- methyl-ethyl benzenes, acetic acid and water, the open-chain crown ether, 4- first
The mol ratio of base ethylbenzene and acetic acid is 20:40:1, the concentration of open-chain crown ether described in water is 0.333mol/L；In closing space
It is interior to be reacted 19 hours under the conditions of 110 DEG C, the compound shown in structure formula (V) is obtained through column chromatography for separation,
In order to become apparent from introducing a kind of synthetic method for quinolines that the embodiment of the present invention is provided in detail, under
Face will be described in conjunction with specific embodiments.
Embodiment 1
A kind of synthetic method of quinolines, comprises the following steps：Take 1.0mmol aniline, 1.0 mmol second
Base benzene, 0.05mmol acetic acid and 3.0mL water, add in reaction bulb, reaction bulb is closed, it is small that 15 are reacted under the conditions of 110 DEG C
When, reaction finishes obtains the compound shown in structure formula (VI), yield 93% through column chromatography for separation.
Nuclear magnetic data：1H NMR(400MHz,CDCl3,ppm):δ=9.20-9.19 (d, J=2.4Hz, 1H), 8.33-
8.31 (d, J=2.0Hz, 1H), 8.16-8.12 (d, J=8.4Hz, 1 H), 7.90-7.86 (d, J=8Hz, 1H), 7.76-
7.71(m,3H),7.62-7.50(m,3H), 7.49-7.43(m,1H)；13C NMR(100MHz,CDCl3,ppm):δ=
149.96, 147.32,137.87,133.85,133.21,129.35,129.21,129.15,128.13, 128.02,
127.41,127.02.
Embodiment 2
A kind of synthetic method of quinolines, comprises the following steps：Take 1.0mmol o-toluidine, 2.0mmol
Ethylo benzene, 0.05mmol acetic acid and 3.0mL water, add in reaction bulb, reaction bulb closed, reacted under the conditions of 120 DEG C
24 hours, reaction finishes obtained the compound shown in structure formula (VII), yield 95% through column chromatography for separation.
Nuclear magnetic data：1H NMR(400MHz,CDCl3,ppm):δ=9.04 (d, J=2.0 Hz, 1H), 8.23 (d, J=
2.0Hz, 1H), 8.04-8.00 (d, J=9.2Hz, 1H), 7.75-7.68 (m, 2H), 7.55-7.51 (m, 2H), 7.44-7.40
(m, 1H), 7.39-7.35 (m, 1H), 7.14-7.12 (d, J=2.4Hz, 1H), 3.96 (s, 3H)；13C NMR(100 MHz,
CDCl3,ppm):δ=158.15,147.43,143.50,138.06,134.11,132.09,130.60,129.11,
128.05,127.43,122.17,105.30,55.59.
Embodiment 3
A kind of synthetic method of quinolines, comprises the following steps：1.0mmol parachloroanilinum is taken, 1.0mmol's
Ethylo benzene, 0.05mmol acetic acid and 3.0mL water, add in reaction bulb, reaction bulb is closed, reacts 15 under the conditions of 110 DEG C
Hour, reaction finishes obtains the compound shown in structure formula (VIII), yield 97% through column chromatography for separation.
Nuclear magnetic data：1H NMR(400MHz,CDCl3,ppm):δ=9.16 (d, J=2.0 Hz, 1H), 8.20 (d, J=
2.0Hz, 1H), 8.08-8.06 (d, J=8.8Hz, 1H), 7.86 (d, J=2.4Hz, 1H), 7.71-7.69 (m, 2H), 7.66-
7.63 (m, 1H), 7.55-7.51 (m, 2H), 7.47-7.45 (d, J=7.6Hz, 1H)；13C NMR(100 MHz,CDCl3,
ppm):δ=150.21,145.72,137.42,134.75,132.77,132.17,130.89,130.28,129.26,
128.87,128.70,128.42,127.46, 126.58.
Embodiment 4
A kind of synthetic method of quinolines, comprises the following steps：Take 1.0mmol aniline, 2.0 mmol 4-
Methyl-ethyl benzene, 0.05mmol acetic acid and 3.0mL water, add in reaction bulb, reaction bulb is closed, reacted under the conditions of 110 DEG C
18 hours, reaction finishes obtained the compound shown in structure formula (IV), yield 96% through column chromatography for separation.
Nuclear magnetic data：1H NMR(400MHz,CDCl3,ppm):δ=9.18-9.16 (d, J=2.4Hz, 1H), 8.28-
8.25 (d, J=2.0Hz, 1H), 8.14-8.11 (d, J=8.4Hz, 1H), 7.87-7.85 (d, J=8.0Hz, 1H), 7.72-
7.69 (m, 1H), 7.68-7.67 (d, J=1.6Hz, 2H), 7.62-7.55 (m, 1H), 7.34-7.31 (d, J=8.0Hz,
2H), 2.42(s,3H)；13C NMR(100MHz,CDCl3,ppm):δ=149.98,147.23,138.07,134.99,
133.77,132.79,129.88,129.21,129.16,128.09, 127.90,127.21,126.91,21.13.
Embodiment 5：
A kind of synthetic method of quinolines, comprises the following steps：Take 1.0mmol open-chain crown ether, 2.0mmol
4- methyl-ethyl benzenes, 0.05mmol acetic acid and 3.0mL water, add in reaction bulb, reaction bulb closed, under the conditions of 110 DEG C
Reaction 19 hours, reaction finishes obtains the compound shown in structure formula (V), yield 98% through column chromatography for separation.
Nuclear magnetic data：1H NMR(400MHz,CDCl3,ppm):δ=9.10 (d, J=2.4 Hz, 1H), 8.18-8.16 (d,
J=2.0Hz, 1H), 8.04-8.01 (d, J=8.4Hz, 1H), 7.60-7.57 (m, 3H), 7.53-7.50 (m, 1H), 7.33-
7.30 (d, J=7.6Hz, 2H), 2.54 (s, 3H), 2.42 (s, 3H)；13C NMR(100MHz,CDCl3,ppm):δ=
149.05,145.84,137.92,136.77,135.11,133.70,132.18,131.51, 129.84,128.82,
128.11,127.21,126.71,21.60,21.15。
Claims (9)
- A kind of 1. synthetic method of quinolines, it is characterised in that：Its course of reaction is as follows：The amino benzenes compounds shown in structure formula (I) are taken, as raw material, to be added with the alkyls compound shown in structure formula (II) Water and acetic acid are reacted to obtain the quinolines shown in structure formula (III)；Wherein R1For hydrogen, methyl or halogen, R2For phenyl or tolyl；The R1In the ortho position of amino or contraposition.
- 2. the synthetic method of quinolines according to claim 1, it is characterised in that：The amino benzenes compounds, Alkyls compound and the mol ratio of acetic acid are 20:40:1；The initial concentration of amino benzenes compounds described in water be 0.25~ 0.4mol/L。
- 3. the synthetic method of quinolines according to claim 1, it is characterised in that：Its reaction condition is：110~ Reacted 15~24 hours under the conditions of 120 DEG C.
- 4. the synthetic method of quinolines according to claim 1, it is characterised in that：Described halogen is chlorine.
- 5. the synthetic method of quinolines according to claim 1, it is characterised in that：The amino benzenes compounds are Aniline, o-toluidine, parachloroanilinum or open-chain crown ether.
- 6. the synthetic method of quinolines according to claim 1, it is characterised in that：The alkyls compound is Ethylo benzene or 4- methyl-ethyl benzenes.
- 7. the synthetic method of quinolines according to claim 6, it is characterised in that：The alkyls compound is 4- methyl-ethyl benzenes；The amino benzenes compounds are aniline or open-chain crown ether.
- 8. the synthetic method of quinolines according to claim 7, it is characterised in that：Specifically include following steps： Aniline, 4- methyl-ethyl benzenes, acetic acid and water are taken, the mol ratio of the aniline, 4- methyl-ethyl benzenes and acetic acid is 20:40:1, institute in water The concentration for stating open-chain crown ether is 0.333mol/L；Reacted 18 hours under the conditions of 110 DEG C in closing space, through column chromatography point From obtaining the compound shown in structure formula (IV),
- 9. the synthetic method of quinolines according to claim 7, it is characterised in that：Specifically include following steps： Open-chain crown ether, 4- methyl-ethyl benzenes, acetic acid and water are taken, the mol ratio of the open-chain crown ether, 4- methyl-ethyl benzenes and acetic acid is 20: 40:1, the concentration of open-chain crown ether described in water is 0.333mol/L；Reaction 19 is small under the conditions of 110 DEG C in closing space When, the compound shown in structure formula (V) is obtained through column chromatography for separation,
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|---|---|---|---|---|
| CN1847225A (en) * | 2005-04-14 | 2006-10-18 | 中国科学院化学研究所 | Quinoline compound and its prepn process |
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| CN102464613A (en) * | 2010-11-10 | 2012-05-23 | 中国石油大学(北京) | Synthetic method of quinoline derivative |
| CN103467373A (en) * | 2013-09-05 | 2013-12-25 | 南京欧信医药技术有限公司 | Synthetic method of quinoline compounds |
| CN105175327A (en) * | 2015-10-21 | 2015-12-23 | 南阳师范学院 | Synthesis method of quinoline derivatives |
| CN106674101A (en) * | 2016-12-12 | 2017-05-17 | 湖南大学 | Method for constructing quinoline compound by means of functionalization of organic antimony catalyzed C-H bond |
-
2017
- 2017-09-25 CN CN201710872970.4A patent/CN107602461A/en not_active Withdrawn
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1847225A (en) * | 2005-04-14 | 2006-10-18 | 中国科学院化学研究所 | Quinoline compound and its prepn process |
| CN101851195A (en) * | 2008-08-27 | 2010-10-06 | 中国科学院上海有机化学研究所 | Quinoline compound and synthetic method and application thereof in synthesizing camptothecin alkaloid |
| CN102464613A (en) * | 2010-11-10 | 2012-05-23 | 中国石油大学(北京) | Synthetic method of quinoline derivative |
| CN103467373A (en) * | 2013-09-05 | 2013-12-25 | 南京欧信医药技术有限公司 | Synthetic method of quinoline compounds |
| CN105175327A (en) * | 2015-10-21 | 2015-12-23 | 南阳师范学院 | Synthesis method of quinoline derivatives |
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Application publication date: 20180119 |