CN108794395A - A kind of preparation method of 2- quinolinones compounds - Google Patents
A kind of preparation method of 2- quinolinones compounds Download PDFInfo
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- CN108794395A CN108794395A CN201810733452.9A CN201810733452A CN108794395A CN 108794395 A CN108794395 A CN 108794395A CN 201810733452 A CN201810733452 A CN 201810733452A CN 108794395 A CN108794395 A CN 108794395A
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- Prior art keywords
- quinolinones
- preparation
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- zinc
- quinoline
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- 0 C*IC(C=C(C1)C=CC=[N+]1O)=CC=C Chemical compound C*IC(C=C(C1)C=CC=[N+]1O)=CC=C 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
- C07D215/227—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 2
Abstract
The present invention provides a kind of preparation methods of 2- quinolinones compounds, using Quinoline-N-oxide species compound as raw material, using zinc salt as catalyst, are reacted in organic solvent under the conditions of Xenon light shining, synthesize a series of 2- quinolinones compounds.The beneficial effects of the invention are as follows：Quinolinone compounds have been applied to the fields such as medicine, important reaction intermediate, have had a vast market application as a kind of important nitrogen-containing heterocycle compound.The present invention is using Quinoline-N-oxide as raw material, using cheap metal salt as catalyst, it is reacted in organic solvent under illumination condition, synthesizes a series of 2- quinolinones compounds, the patent of invention method and step is simple, raw material is easy to get, reaction condition is mild, meets the advantages that green chemistry principles.The present invention has larger use value and economic results in society.
Description
Technical field
The present invention relates to the preparation methods of pharmaceutical-chemical intermediate, and in particular to the synthesis side of 2- quinolinones and its derivative
Method.
Background technology
2- quinolinone compounds have been applied to as a kind of important nitrogen-containing heterocycle compound in medicine, important reaction
The fields such as mesosome, and as the reach of science, 2- quinolinones and its derivative have had been developed that a variety of synthetic methods, including pass
The Friedlander reactions of system, the C-C coupling reaction synthesizing quinolinones of the palladium chtalyst developed in recent years, synthesis in solid state, microwave
The methods of synthesis.But the problems such as these method generally existing reaction time are long, cumbersome, severe reaction conditions.Therefore, it develops
Easy, economic 2- quinolinone compounds new synthetic methods become one of the research hotspot of current organic synthesis field.
(1) Friedlander reacts
2009, J.Cejka professors et al. report to be reacted using tradition Friedlander, with 2- amino benzophenone and second
For ethyl acetoacetic acid ethyl ester when toluene is as solvent, MAP synthesizes 2- quinolinones as catalyst under being heated at 100 DEG C.[referring to：
Dominguez-Fernandez,F.；Lopez-Sanz,J.；Perez-Mayoral,E.；Bek,D.； Martin-Aranda,
R.M.；Lopez-Peinado,A.J.；Cejka,J.,Novel Basic Mesoporous Catalysts for the
Friedlander Reaction from 2-Aminoaryl Ketones: Quinolin-2(1H)-ones versus
Quinolines.Chemcatchem,2009,1(2),241-243.]
(2) the C-C coupling reaction synthesizing quinolinones of palladium chtalyst
2000, Fujiwara et al. reported the Intramolecular electrocyclization of the palladium chtalyst by adjacent alkynyl-N- anilides
2- quinolinones are synthesized, in the in the mixed solvent containing trifluoroacetic acid, in the Pd (OAc) of catalytic amount2In the presence of, arylalkyne acid esters and
Alkynes anilide just can carry out reaction in rapid molecular at room temperature, and the quinolinone of excellent yield, and the reactant are waited until in obtaining
System is equally applicable to the synthesis of cumarin.[referring to：1.Ying, B.；Xu,J.；Zhu,X.；Shen,C.；Zhang,P.,
Catalyst-Controlled Selectivity in the Synthesis of C2-and C3-Sulfonate
Esters from Quinoline N-Oxides and Aryl Sulfonyl Chlorides.Chemcatchem 2016,8
(16),2604-2608.]
(3) synthesis in solid state：
2016, it was to react bottom that Hangzhou Pedagogic University Zhang Pengfei et al. 1, which is reported with benzene sulfonyl chloride and Quinoline-N-oxide,
Object synthesizes the reaction system of 2- qualone derivatives using supported catalyst chitosan@cupric iodides as catalyst choice.?
1,2- dichloroethanes is reaction solution, and when being heated to 100 DEG C, the benzsulfamide of Quinoline-N-oxide and 2 equivalents is in potassium carbonate
It is added in reaction system and reacts as alkali, the 2- qualone derivatives for obtaining being connected with benzenesulfonyl on 2 oxygen atoms of high yield.
[referring to：Ying,B.；Xu,J.；Zhu,X.；Shen,C.； Zhang,P.,Catalyst-Controlled Selectivity
in the Synthesis of C2-and C3-Sulfonate Esters from Quinoline N-Oxides and
Aryl Sulfonyl Chlorides.Chemcatchem 2016,8 (16),2604-2608.]
Invention content
The object of the present invention is to provide a kind of catalysis of cheap metal, step is simple, raw material is easy to get, reaction condition is mild, symbol
Close the synthesizing quinolinone of Green Chemistry theory and its new method of derivative.
Technical scheme of the present invention：
A kind of preparation method of 2- quinolinones compounds is with zinc salt using Quinoline-N-oxide species compound as raw material
Catalyst reacts under the conditions of Xenon light shining, synthesizes a series of 2- quinolinones compounds, reaction equation is as follows in organic solvent：
In formula：R1Selected from hydrogen, alkoxy and nitro；
R2Selected from hydrogen, halogen and alkyl；
The one kind of the catalyst in zinc iodide, zinc oxide, zinc bromide, zinc chloride, acetic anhydride zinc, catalyst
Addition be Quinoline-N-oxide species compound 1-10mol%；
Organic solvent used is ether, toluene, DCE, 1,4- dioxane, acetone, DMF, DMSO, acetonitrile, ethyl alcohol
One or more mixing；The addition of organic solvent is 2-50 times of Quinoline-N-oxide species compound by weight；
Reaction illumination used, which is that the irradiation of full spectral region xenon lamp is lower, to be carried out.
Reaction time is 1-3 hours.
The beneficial effects of the invention are as follows：Quinolinone compounds are applied as a kind of important nitrogen-containing heterocycle compound
To fields such as medicine, important reaction intermediates.Such as：Quinolinone and its derivative, which are mainly extracted from rutaceae, to be detached
It arrives, the general angled and linear fusion structure of the product isolated.They have antibacterial, and anti-malarial, desinsection is antitumor, cell
The important biomolecules such as toxic agents, antidiuresis, anti-arrhythmia and calmness activity, and be widely used in Chinese Traditional Medicine field.
The present invention method synthetic route is short, mild condition, to meet green chemistry principles, easy to operate and yield higher.
Description of the drawings
Fig. 1 is compound 1a's1H-NMR spectrum.
Fig. 2 is compound 1b's1H-NMR spectrum.
Fig. 3 is compound 1c's1H-NMR spectrum.
Fig. 4 is compound 1d's1H-NMR spectrum.
Fig. 5 is compound 1e's1H-NMR spectrum.
Specific implementation mode
Further illustrated the present invention with reference to examples of implementation and the method for the present invention carry out mode.These examples of implementation
Merely to the present invention is further explained and the protection of non-present invention is only limitted to this.
Embodiment 1：The synthesis of 2- quinolinones (1a)
Precise reaction substrate Quinoline-N-oxide (145.2mg, 1.0mmol) and zinc iodide (5mol%, 15.9
Mg it) is added in quartz reactor, acetonitrile 2.0ml is added, under air conditions, after being placed in the lower reaction 1h of xenon lamp irradiation, utilize rotation
Turn evaporimeter and remove acetonitrile, with silica gel column chromatography separating purification (petroleum ether：Ethyl acetate=2:1) reaction product is obtained.Product
For white powdery solids, yield is 90% (130.7mg).1H NMR(400MHz,DMSO)δ11.72(s,1H),7.86(d,J
=9.5Hz, 1H), 7.70-7.57 (m, 1H), 7.54-7.41 (m, 1H), 7.29 (d, J=8.2Hz, 1H), 7.19-7.05 (m,
1H), 6.47 (d, J=9.5Hz, 1H)
Embodiment 2：The synthesis of 6- methoxyl group -2- quinolinones (1b)
Precise reaction substrate 6- methoxy quinoline-N- oxides (175.1mg, 1.0mmol) and zinc oxide (3
Mol%, 2.4mg) it is added in quartz reactor, ether 2.0ml is added, under air conditions, is placed in the lower reaction 2h of xenon lamp irradiation
Afterwards, ether is removed using Rotary Evaporators, with silica gel column chromatography separating purification (petroleum ether：Ethyl acetate=2:1) it is reacted
Product.Product is white powdery solids, and yield is 95% (166.3 mg).1H NMR(400MHz,DMSO)δ11.62(s,
1H), 7.83 (d, J=9.5Hz, 1H), 7.20 (dd, J=13.8,5.8Hz, 1H), 7.13 (dd, J=8.9,2.8Hz, 1H),
6.47 (d, J=9.5Hz, 1H), 3.76 (s, 1H)
Embodiment 3：The synthesis of the bromo- 2- quinolinones (1c) of 3-
Precise reaction substrate 3- bromoquinoline-N- oxides (223.0mg, 1.0mmol) and zinc bromide (1mol%,
It 2.3mg) is added in quartz reactor, toluene 0.5ml is added, under air conditions, after being placed in the lower reaction 3h of xenon lamp irradiation, utilize
Rotary Evaporators remove toluene, with silica gel column chromatography separating purification (petroleum ether：Ethyl acetate=2:1) reaction product is obtained.Production
Object is white powdery solids, and yield is 90% (154.4mg).1H NMR(400MHz,DMSO)δ12.28(s,1H),8.68
(d, J=2.6Hz, 1H), 8.31 (dd, J=9.1,2.6Hz, 1H), 8.11 (d, J=9.6Hz, 1H), 7.41 (d, J=
9.1Hz, 1H), 6.65 (dd, J=9.6,1.5Hz, 1H)
Embodiment 4：The synthesis of 4- methyl -2- quinolinones (1d)
Precise reaction substrate 4- methylquinoline-N- oxides (159.1mg, 1.0mmol) and zinc chloride (10
Mol%, 13.4mg) it is added in quartz reactor, Isosorbide-5-Nitrae-dioxane 20.0ml is added, under air conditions, is placed in xenon lamp photograph
After penetrating lower reaction 3h, Isosorbide-5-Nitrae-dioxane is removed using Rotary Evaporators, with silica gel column chromatography separating purification (petroleum ether：Acetic acid
Ethyl ester=2:1) reaction product is obtained.Product is white powdery solids, and yield is 90% (143.2mg).1H NMR
(400MHz, DMSO) δ 11.59 (s, 1H), 7.70 (d, J=8.0Hz, 1H), 7.49 (t, J=7.7Hz, 1H), 7.30 (d, J=
8.1Hz, 1H), 7.19 (dd, J=7.9,7.2Hz, 1H), 6.39 (s, 1H), 2.42 (s, 1H)
Embodiment 5：The synthesis of 6- nitro -2- quinolinones (1e)
Precise reaction substrate 6- nitroquinoline-N- oxides (190.0mg, 1.0mmol) and zinc acetate (10
Mol%, 18.4mg) it is added in quartz reactor, acetone 5.0ml is added, under air conditions, is placed in the lower reaction 3h of xenon lamp irradiation
Afterwards, acetone is removed using Rotary Evaporators, with silica gel column chromatography separating purification (petroleum ether：Ethyl acetate=2:1) it is reacted
Product.Product is white powdery solids, and yield is 88% (167.2 mg).1H NMR(400 MHz,DMSO)δ12.23(s,
1H), 8.46 (d, J=11.6 Hz, 1H), 7.72-7.57 (m, 1H), 7.55-7.46 (m, 1H), 7.29 (dd, J=11.7,
7.4 Hz,1H),7.22–7.14(m, 1H)。
Claims (8)
1. a kind of preparation method of 2- quinolinones compounds, which is characterized in that steps are as follows：With Quinoline-N-oxide species
Conjunction object is that raw material is reacted using zinc salt as catalyst under the conditions of Xenon light shining in organic solvent, synthesizes a series of 2- quinolinones
Compound, reaction equation are as follows：
In formula：R1Selected from hydrogen, alkoxy and nitro；
R2Selected from hydrogen, halogen and alkyl；
The addition of the catalyst is the 1-10mol% of Quinoline-N-oxide species compound；
The addition of the organic solvent is 2-50 times of Quinoline-N-oxide species compound by weight.
2. the preparation method of 2- quinolinones compounds according to claim 1, which is characterized in that the catalyst choosing
One kind from zinc iodide, zinc oxide, zinc bromide, zinc chloride, acetic anhydride zinc.
3. the preparation method of 2- quinolinones compounds according to claim 1 or 2, which is characterized in that described is organic
Solvent is one or more kinds of mixing of ether, toluene, DCE, 1,4- dioxane, acetone, DMF, DMSO, acetonitrile, ethyl alcohol.
4. the preparation method of 2- quinolinones compounds according to claim 1 or 2, which is characterized in that reaction is used up
Lower carry out is irradiated according to for full spectral region xenon lamp.
5. the preparation method of 2- quinolinones compounds according to claim 3, which is characterized in that reacting illumination used is
Full spectral region xenon lamp irradiation is lower to be carried out.
6. the preparation method of the 2- quinolinones compounds according to claim 1,2 or 5, which is characterized in that the reaction time
It is 1-3 hours.
7. the preparation method of 2- quinolinones compounds according to claim 3, which is characterized in that reaction time 1-3
Hour.
8. the preparation method of 2- quinolinones compounds according to claim 4, which is characterized in that reaction time 1-3
Hour.
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040181064A1 (en) * | 2002-05-17 | 2004-09-16 | Chong-Qing Sun | Bicyclic modulators of androgen receptor function |
| WO2006027684A1 (en) * | 2004-09-10 | 2006-03-16 | Pfizer Products Inc. | Therapeutic diphenyl ether ligands |
| CN1759108A (en) * | 2003-02-14 | 2006-04-12 | 施万制药 | Biphenyl derivatives |
| CN103200820A (en) * | 2010-10-08 | 2013-07-10 | N30医药品公司 | Novel substituted quinoline compounds as S-nitrosoglutathione reductase inhibitors |
| CN104628643A (en) * | 2015-02-17 | 2015-05-20 | 大连理工大学 | Preparation method of isoquinolone and derivatives thereof |
| CN107098855A (en) * | 2017-04-05 | 2017-08-29 | 上海诺星医药科技有限公司 | A kind of method for preparing the quinolinone of 7 hydroxyl 2 |
-
2018
- 2018-07-06 CN CN201810733452.9A patent/CN108794395B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040181064A1 (en) * | 2002-05-17 | 2004-09-16 | Chong-Qing Sun | Bicyclic modulators of androgen receptor function |
| CN1759108A (en) * | 2003-02-14 | 2006-04-12 | 施万制药 | Biphenyl derivatives |
| WO2006027684A1 (en) * | 2004-09-10 | 2006-03-16 | Pfizer Products Inc. | Therapeutic diphenyl ether ligands |
| CN103200820A (en) * | 2010-10-08 | 2013-07-10 | N30医药品公司 | Novel substituted quinoline compounds as S-nitrosoglutathione reductase inhibitors |
| CN104628643A (en) * | 2015-02-17 | 2015-05-20 | 大连理工大学 | Preparation method of isoquinolone and derivatives thereof |
| CN107098855A (en) * | 2017-04-05 | 2017-08-29 | 上海诺星医药科技有限公司 | A kind of method for preparing the quinolinone of 7 hydroxyl 2 |
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