CN102070520A - Method for preparing 3-aryl-subsituted quinoline by 3-oxo-2,3-diarylpropionaldehyde - Google Patents
Method for preparing 3-aryl-subsituted quinoline by 3-oxo-2,3-diarylpropionaldehyde Download PDFInfo
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- CN102070520A CN102070520A CN 201110008254 CN201110008254A CN102070520A CN 102070520 A CN102070520 A CN 102070520A CN 201110008254 CN201110008254 CN 201110008254 CN 201110008254 A CN201110008254 A CN 201110008254A CN 102070520 A CN102070520 A CN 102070520A
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Abstract
The invention discloses a method for preparing 3-aryl-subsituted quinoline by 3-oxo-2,3-diarylpropionaldehyde, and belongs to the technical field of organic compound preparation. The 3-aryl-subsituted quinoline is an intermediate of medicines and functional materials. 3-aryl quinoline with a yield of 75 to 82 percent is prepared by performing condensation and rearrangement reactions on 3-oxo-2,3-diarylpropionaldehyde serving as a raw material and o-amino benzaldehyde. The method has the advantages of readily available raw materials, simple process and high yield and is suitable for preparing the 3-aryl-subsituted quinoline.
Description
Technical field
3-aryl substd quinolines is a kind of medicine and functional materials intermediate.The present invention relates to a kind ofly with 3-oxo-2,3-diaryl propionic aldehyde prepares the method for 3-aryl substd quinolines, belongs to the technical field of organic compound preparation.
Background technology
Quinoline and derivative thereof have wide biological activity, as relieving asthma, anti-inflammatory, anti-HIV-1, inhibition Tyrosylprotein kinase etc.At medicine and as the importance of structural unit in medicine is synthetic, the chemist furthers investigate the synthetic method of different substd quinolines based on it.At least the aldehydes or ketones that contains a methylene radical as, acid (alkali) catalytic o-Aminobenzaldehyde (or adjacent aminophenyl ketone) and carbonyl alpha-position carries out condensation
Reaction is one of method of effective framework substd quinolines.In recent years, Vander M.H. group is right
Reaction improves, and adopts noble metal catalyst, as ruthenium catalytic preparation 2-replacement or 2,3-substd quinolines (Vander M.H., Eur.J.Org.Chem.2008,1625; Vander M.H., New J.Chem.2007,31,1572; Vander M.H., Tetrahedron Lett., 2008,49,6893).But, adopt
Exist precursor aryl acetaldehyde to be difficult to the synthetic shortcoming during prepared in reaction 3-aryl substd quinolines.People such as Lin have reported the method by the synthetic 3-phenyl substd quinolines of Vilsmeier-Haack reaction, but used poisonous in the reaction and easily discharged the phosphorus tribromide reagent of corrosive gases, and yield only is 64% (Y.Wang, Eur.J.Org.Chem.2009,4165).
Summary of the invention
The technical problem to be solved in the present invention is with 3-oxo-2,3-diaryl propionic aldehyde is feedstock production 3-aryl substd quinolines: 3-(4-p-methoxy-phenyl) quinoline, 3-(3-p-methoxy-phenyl) quinoline, 3-(2-p-methoxy-phenyl) quinoline, 3-(4-aminomethyl phenyl) quinoline, 3-(4-bromophenyl) quinoline or 3-(4-fluorophenyl) quinoline.
The present invention solves above-mentioned technical problem by the following technical programs.With 3-oxo-2,3-diaryl propionic aldehyde is a raw material, with o-Aminobenzaldehyde through condensation, rearrangement reaction, product 3-aryl substd quinolines.The general structure of 3-aryl substd quinolines is
Wherein, R is respectively H, p-OCH
3, m-OCH
3, o-OCH
3, p-CH
3, p-Br or p-F, reaction scheme is:
Now describe technical scheme of the present invention in detail.A kind of with 3-oxo-2,3-diaryl propionic aldehyde prepares the method for 3-aryl substd quinolines, it is characterized in that the concrete operations step:
The first step condensation
3-oxo-2 with 11.2～15.2 parts of weight, the o-Aminobenzaldehyde of 3-diaryl propionic aldehyde and 9.1 parts of weight is dissolved in the chlorobenzene of 330 parts of weight, adds the trifluoromethanesulfonic acid of 0.4 part of weight, and 90 ℃～110 ℃ following with stirring, condensation reaction 1.5 hours～3 hours makes solution;
Second step reset
The potassium tert.-butoxide that in the solution that the first step makes, adds 11 parts of weight, 80 ℃～120 ℃ following with stirring, rearrangement reaction 10 minutes～30 minutes, cooling, the water that adds 330 parts of weight, ethyl acetate extraction, dry back column chromatography purification, get the 3-aryl substd quinolines of 8.2～10.9 parts of weight, yield 75%～82%.
Compare with background technology, this method has the advantage that raw material is easy to get, technology is simple, yield is high, is suitable for being used for preparing 3-aryl substd quinolines.
Embodiment
The preparation of one of embodiment 1:3-aryl substd quinolines 3-phenylquinoline
Raw material is a 3-oxo-2, one of 3-diaryl propionic aldehyde 3-oxo-2,3-phenylbenzene propionic aldehyde.
The first step is with the 3-oxo-2 of 11.2g, and the o-Aminobenzaldehyde of 3-phenylbenzene propionic aldehyde and 9.1g is dissolved in the 330g chlorobenzene, adds the trifluoromethanesulfonic acid of 0.4g, and 90 ℃ following with stirring, and condensation reaction 1.5 hours makes solution;
Second step added the potassium tert.-butoxide of 11g in the solution that the first step makes, under 80 ℃ of stirrings, rearrangement reaction 10 minutes, cooling adds the water of 330g, ethyl acetate extraction, dry back column chromatography purification, the 3-phenylquinoline of 8.2g, yield 82%.
The preparation of one of embodiment 2:3-aryl substd quinolines 3-(4-p-methoxy-phenyl) quinoline
Raw material is a 3-oxo-2, one of 3-diaryl propionic aldehyde 3-oxo-2-(4-p-methoxy-phenyl)-3-phenylpropionaldehyde.
The first step is dissolved in 3-oxo-2-(4-the p-methoxy-phenyl)-3-phenylpropionaldehyde of 12.7g and the o-Aminobenzaldehyde of 9.1g in the 330g chlorobenzene, adds the trifluoromethanesulfonic acid of 0.4g, and 100 ℃ following with stirring, and condensation reaction 2 hours makes solution;
Second step added the potassium tert.-butoxide of 11g in the solution that the first step makes, 100 ℃ and stir down rearrangement reaction 20 minutes, cooling, the water of adding 330g, ethyl acetate extraction, drying is column chromatography purification afterwards, gets 3-(4-p-methoxy-phenyl) quinoline of 9.4g, yield 80%.
The preparation of one of embodiment 3:3-aryl substd quinolines 3-(3-p-methoxy-phenyl) quinoline
Raw material is a 3-oxo-2, one of 3-diaryl propionic aldehyde 3-oxo-2-(3-p-methoxy-phenyl)-3-phenylpropionaldehyde.
The first step is dissolved in 3-oxo-2-(3-the p-methoxy-phenyl)-3-phenylpropionaldehyde of 12.7g and the o-Aminobenzaldehyde of 9.1g in the chlorobenzene of 330g, adds the trifluoromethanesulfonic acid of 0.4g, and 110 ℃ following with stirring, and condensation reaction 3 hours makes solution;
Second step added the potassium tert.-butoxide of 11g in the solution that the first step makes, 100 ℃ and stir down rearrangement reaction 10 minutes, cooling, the water of adding 330g, ethyl acetate extraction, drying is column chromatography purification afterwards, gets 3-(3-p-methoxy-phenyl) quinoline of 8.8g, yield 75%.
The preparation of one of embodiment 4:3-aryl substd quinolines 3-(2-p-methoxy-phenyl) quinoline
Raw material is a 3-oxo-2, one of 3-diaryl propionic aldehyde 3-oxo-2-(2-p-methoxy-phenyl)-3-phenylpropionaldehyde.
The first step is dissolved in 3-oxo-2-(2-the p-methoxy-phenyl)-3-phenylpropionaldehyde of 12.7g and the o-Aminobenzaldehyde of 9.1g in the chlorobenzene of 330g, adds the trifluoromethanesulfonic acid of 0.4g, and 100 ℃ following with stirring, and condensation reaction 3 hours makes solution;
Second step added the potassium tert.-butoxide of 11g in the solution that the first step makes, 120 ℃ and stir down rearrangement reaction 10 minutes, cooling, the water of adding 330g, ethyl acetate extraction, drying is column chromatography purification afterwards, gets 3-(2-p-methoxy-phenyl) quinoline of 8.9g, yield 76%.
The preparation of one of embodiment 5:3-aryl substd quinolines 3-(4-aminomethyl phenyl) quinoline
Raw material is a 3-oxo-2, one of 3-diaryl propionic aldehyde 3-oxo-2-(4-aminomethyl phenyl)-3-phenylpropionaldehyde.
The first step is dissolved in 3-oxo-2-(4-the aminomethyl phenyl)-3-phenylpropionaldehyde of 11.9g and the o-Aminobenzaldehyde of 9.1g in the chlorobenzene of 330g, adds the trifluoromethanesulfonic acid of 0.4g, and 100 ℃ following with stirring, and condensation reaction 1.5 hours makes solution;
Second step added the potassium tert.-butoxide of 11g in the solution that the first step makes, 100 ℃ and stir down rearrangement reaction 10 minutes, cooling, the water of adding 330g, ethyl acetate extraction, drying is column chromatography purification afterwards, gets 3-(4-aminomethyl phenyl) quinoline of 8.4g, yield 77%.
The preparation of one of embodiment 6:3-aryl substd quinolines 3-(4-bromophenyl) quinoline
Raw material is a 3-oxo-2, one of 3-diaryl propionic aldehyde 3-oxo-2-(4-bromophenyl)-3-phenylpropionaldehyde.
The first step is dissolved in 3-oxo-2-(4-the bromophenyl)-3-phenylpropionaldehyde of 15.2g and the o-Aminobenzaldehyde of 9.1g in the chlorobenzene of 330g, adds the trifluoromethanesulfonic acid of 0.4g, and 100 ℃ following with stirring, and condensation reaction 2 hours makes solution;
Second step added 11 potassium tert.-butoxide in the solution that the first step makes, 80 ℃ and stir down, rearrangement reaction 10 minutes, cooling adds the water of 330g, ethyl acetate extraction, dry back column chromatography purification, 3-(4-bromophenyl) quinoline of 10.9g, yield 77%.
The preparation of one of embodiment 7:3-aryl substd quinolines 3-(4-fluorophenyl) quinoline
Raw material is a 3-oxo-2, one of 3-diaryl propionic aldehyde 3-oxo-2-(4-fluorophenyl)-3-phenylpropionaldehyde.
The first step is dissolved in 3-oxo-2-(4-the fluorophenyl)-3-phenylpropionaldehyde of 12.1g and the o-Aminobenzaldehyde of 9.1g in the chlorobenzene of 330g, adds the trifluoromethanesulfonic acid of 0.4g, and 120 ℃ following with stirring, and condensation reaction 3 hours makes solution;
Second step added the potassium tert.-butoxide of 11g in the solution that the first step makes, 100 ℃ and stir down, rearrangement reaction 30 minutes, cooling adds the water of 330g, ethyl acetate extraction, dry back column chromatography purification, 3-(4-fluorophenyl) quinoline of 8.4g, yield 75%.
Method of the present invention is particularly suitable for being used for preparing 3-aryl substd quinolines.
Claims (2)
1. one kind with 3-oxo-2, and 3-diaryl propionic aldehyde prepares the method for 3-aryl substd quinolines, it is characterized in that, with 3-oxo-2,3-diaryl propionic aldehyde is a raw material, with o-Aminobenzaldehyde through condensation, rearrangement reaction, get product 3-aryl substd quinolines, the general structure of 3-aryl substd quinolines is
Wherein, R is respectively H, p-OCH
3, m-OCH
3, o-OCH
3, p-CH
3, p-Br or p-F, reaction scheme is:
2. described with 3-oxo-2 according to claim 1,3-diaryl propionic aldehyde prepares the method for 3-aryl substd quinolines, it is characterized in that the concrete operations step:
The first step condensation
3-oxo-2 with 11.2～15.2 parts of weight, the o-Aminobenzaldehyde of 3-diaryl propionic aldehyde and 9.1 parts of weight is dissolved in the chlorobenzene of 330 parts of weight, adds the trifluoromethanesulfonic acid of 0.4 part of weight, and 90 ℃～110 ℃ following with stirring, condensation reaction 1.5 hours～3 hours makes solution;
Second step reset
The potassium tert.-butoxide that in the solution that the first step makes, adds 11 parts of weight, 80 ℃～120 ℃ following with stirring, rearrangement reaction 10 minutes～30 minutes, cooling, the water that adds 330 parts of weight, ethyl acetate extraction, dry back column chromatography purification, get the 3-aryl substd quinolines of 8.2～10.9 parts of weight, yield 75%～82%.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101103026A (en) * | 2005-01-14 | 2008-01-09 | 健亚生物科技公司 | Bicyclic heteroaryl derivatives for treating viruses |
| WO2010151740A2 (en) * | 2009-06-25 | 2010-12-29 | Amgen Inc. | Heterocyclic compounds and their uses |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101103026A (en) * | 2005-01-14 | 2008-01-09 | 健亚生物科技公司 | Bicyclic heteroaryl derivatives for treating viruses |
| WO2010151740A2 (en) * | 2009-06-25 | 2010-12-29 | Amgen Inc. | Heterocyclic compounds and their uses |
Non-Patent Citations (2)
| Title |
|---|
| 《Bioorganic & Medicinal Chemistry》 20060401 Stuart T. Hazeldine等 Synthesis and biological evaluation of conformationally constrained analogs of the antitumor agents XK469 and SH80. Part 5 2462-2467 1-2 第14卷, 第7期 * |
| 《ORGANIC LETTERS》 20101110 Makhluf J. Haddadin等 Efficient Syntheses of the Unknown Quinolino[2,3-c]cinnolines; Synthesis of Neocryptolepines 5502-5505 1-2 第12卷, 第23期 * |
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Application publication date: 20110525 |