CN105175328A - Method for synthesizing quinoline derivative by utilizing arylamine, aromatic aldehyde and ketone - Google Patents
Method for synthesizing quinoline derivative by utilizing arylamine, aromatic aldehyde and ketone Download PDFInfo
- Publication number
- CN105175328A CN105175328A CN201510699601.0A CN201510699601A CN105175328A CN 105175328 A CN105175328 A CN 105175328A CN 201510699601 A CN201510699601 A CN 201510699601A CN 105175328 A CN105175328 A CN 105175328A
- Authority
- CN
- China
- Prior art keywords
- ketone
- formula
- aromatic amine
- aromatic
- aldehyde
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
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
- C07D215/04—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 only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms
- C07D215/06—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 only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms having only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to the ring nitrogen atom
-
- 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
- C07D215/12—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 substituted hydrocarbon radicals attached to ring carbon atoms
- C07D215/14—Radicals substituted by oxygen atoms
-
- 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
- C07D215/18—Halogen atoms or nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/06—Ring systems of three rings
- C07D221/16—Ring systems of three rings containing carbocyclic rings other than six-membered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
Abstract
The invention provides a method for synthesizing a quinoline derivative by utilizing arylamine, aromatic aldehyde and ketone, and belongs to the technical field of the synthesis of the quinoline derivative. According to the method for synthesizing a quinoline derivative by utilizing arylamine, aromatic aldehyde and ketone, in the existence of silver trifluoromethanesulfonate and trifluoromethanesulfonic acid, the quinoline derivative is synthesized by virtue of the reaction of an arylamine compound, an aromatic aldehyde compound and ketone compound. A reaction general formula is as shown in the specification. Compared with the prior art, the method is not only applicable to a great amount of functional groups, but also is simple in operation, high in yield, single in product structure, convenient to separate and purify, safe, low in price and small in pollution.
Description
Technical field
The invention belongs to the synthesis technical field of quinoline, be specifically related to a kind of method utilizing aromatic amine, aromatic aldehyde, ketone synthesis of quinoline derivatives.
Background technology
Along with the progress of human society, making rapid progress of science and technology, the expectation of people to life and quality of life is more and more higher, people are more and more stronger to health care consciousness, this has also promoted the develop rapidly of medicine industry, thus develop more how more effective novel drugs, wherein synthesize by chemical process the important channel that new medicine is research and development novel drugs.
Quinoline is the compound of the very important nitrogen heterocyclic structure of a class.This compounds has the biological activitys such as good antibacterial, antitumor and antituberculosis, is one of focus of novel drugs development research.The synthetic method of quinoline is a lot, and such as, the adjacent aminobenzyl alcohol of ruthenium catalysis and reactive ketone prepare the synthesis method of quinoline; O-Aminobenzaldehyde and reactive ketone prepare the method for quinoline.But these methods also exist a lot of shortcoming: severe reaction conditions, and temperature of reaction is high, what have needs High Temperature High Pressure, separation difficulty, reaction substrate limiting comparatively strong, therefore, utilizes a kind of method to synthesize substituent quinoline very limited.In addition, utilize in metal-catalyzed processes, the limited activity of catalyzer, these shortcomings cause the operation easier of preparation process to increase, and harm operator ' s health, environmental pollution is serious.But, the method ubiquity of existing synthesis of quinoline derivatives: need active reaction substrate, react the shortcomings such as the form too single (causing synthesized product to have significant limitation) that rate is low, the reaction times is longer, how difficult by product is and react.Given this, the preparation method of the quinoline that research and development are novel seems particularly important.Chinese patent CN104151235A discloses a kind of quinoline preparation method, utilize the substituent aniline of silver trifluoromethanesulfonate catalysis and ketenes or olefine aldehydr derivative synthesis of quinoline derivatives, this patent procedure is simple, a large amount of functional groups can be applicable to, and productive rate is high, product is single, be convenient to isolation andpurification, safety cheap, pollute little.But still there are some shortcomings in this patent: need synthesis as reaction substrate ketenes or olefine aldehydr and purify, reactions steps relative complex, and the stereoeffect of reaction substrate amine is obvious, aromatic amine ortho position replaces when having a functional group of steric hindrance, reaction effect is bad.
Summary of the invention
Technical problem to be solved by this invention is, for the deficiencies in the prior art, provide a kind of substrate source extensive, product purity is high, is convenient to the method utilizing aromatic amine, aromatic aldehyde, ketone synthesis of quinoline derivatives of isolation andpurification.
For solving the problems of the technologies described above, the technical solution adopted in the present invention is:
A kind of method utilizing aromatic amine, aromatic aldehyde, ketone synthesis of quinoline derivatives, under the existence of silver trifluoromethanesulfonate (AgOTf) and trifluoromethanesulfonic acid (HOTf), by the quinoline shown in the Aromatic aldehyde compound shown in the aromatic amine compound shown in formula I, formula II and the ketone compound Reactive Synthesis formula IV shown in formula III, formula I:
; Formula II:
; Formula III:
;
Formula IV:
;
Wherein,
R
1be selected from the one in hydrogen, halogen, nitro, methyl, methoxyl group, ethanoyl, substituting group is positioned at ortho position, a position or contraposition, wherein, and R
1any CH, CH in methyl in substituting group, methoxyl group or ethanoyl
2or CH
3group is optionally at described CH, CH
2or CH
3the following substituting group that group may be the same or different with 1,2 or 3: halogen or nitro;
R
2be selected from the one in hydrogen, halogen, nitro, methoxyl group, methyl, substituting group is positioned at ortho position, a position or contraposition;
R
3be selected from C
1~ C
5one in alkyl, cycloalkyl, thienyl, phenyl; Wherein, R
3any CH, CH in substituting group
2or CH
3group is optionally at described CH, CH
2or CH
3the following substituting group that group may be the same or different with 1,2 or 3: halogen, methyl or methoxy, substituting group can be positioned at ortho position, a position or contraposition;
R
4be selected from hydrogen or methyl;
Or R
3with R
4form cyclic ketone;
Halogen is the substituting group of fluorine, chlorine, bromine or iodine.
The reaction expression of synthesis of quinoline derivatives of the present invention is as follows:
。
Preferably, the aromatic amine compound shown in described formula I is aniline, p-Nitroaniline, open-chain crown ether, m-toluidine, m-fluoroaniline, p-trifluoromethylaniline or 3-Aminotrifluorotoluene.
Preferably, the Aromatic aldehyde compound shown in described formula II is phenyl aldehyde, p-tolyl aldehyde or aubepine.
Preferably, the ketone compound shown in described formula III is acetone, acetyl cyclohexane, methyl phenyl ketone, Propiophenone, 2-acetyl thiophene, cyclobutanone or cyclopentanone.
Preferably, utilize aromatic amine, aromatic aldehyde, the method of ketone synthesis of quinoline derivatives, concrete steps are as follows: in reaction vessel, 1:1:1.5 adds the aromatic amine compound shown in formula I successively in molar ratio, ketone compound shown in Aromatic aldehyde compound shown in formula II and formula III, then solvent 2 ~ 6mL/mmol aromatic amine is added, then catalyzer silver trifluoromethanesulfonate and trifluoromethanesulfonic acid is added, the add-on of catalyzer is respectively 0.8 ~ 2% and 1.8 ~ 3% of aromatic amine compound molar weight, react 18 ~ 24 hours in 115 ~ 125 DEG C of oil baths, be cooled to room temperature, extraction, concentrating under reduced pressure, product is through column chromatography purification, obtain quinoline product.
Preferably, described solvent is toluene, DMSO, DMF or dioxane.
Preferably, described solvent is toluene.
Preferably, the condition of described column chromatography purification is, eluent is the mixture of sherwood oil and ethyl acetate, and the volume ratio of sherwood oil and ethyl acetate is 10:1.
Compared with prior art, beneficial effect of the present invention is as follows: the present invention utilizes aromatic amine, aldehyde and alcohol derivate synthesis of quinoline derivatives, reaction substrate wide material sources, and acquiring way is various, does not limit by experiment condition; Reaction conditions is gentleer, and without the need to high temperature high pressure process, experiment equipment used is normal experiment equipment, and cost is lower; Reaction product is easy to separation and purification, and operation steps is simple, and purity is high.Simultaneously, synthetic method of the present invention is than common synthesis 3, the dibasic quinoline of 4-is compared, present method can utilize liquid ketone to substitute the alkynes of gaseous state, not only low price, and easy and simple to handle, safe, quinolines can be prepared efficiently, target product quinoline is widely used in the part of organic chemical reactions, pharmaceutical intermediate and photoelectric material aspect.
Embodiment
In order to understand the present invention better, set forth content of the present invention below in conjunction with embodiment is clear further, but protection content of the present invention is not only confined to the following examples.In the following description, a large amount of concrete details is given to provide more thorough understanding of the invention.But, it will be apparent to one skilled in the art that the present invention can be implemented without the need to these details one or more.In other example, in order to avoid obscuring with the present invention, technical characteristics more well known in the art are not described.
In following embodiment, AgOTf represents silver trifluoromethanesulfonate, is its english abbreviation; HOTf represents trifluoromethanesulfonic acid, is its english abbreviation.
Embodiment 1
2, the synthetic method of 4-diphenylquinoline is as follows: in reaction vessel, add aniline 0.5mmol (46.5mg), phenyl aldehyde 0.5mmol (53mg), methyl phenyl ketone 0.75mmol (90.1mg), catalyst A gOTf0.005mmol (1.29mg), HOTf0.01mmol (1.5mg), toluene 2mL.React 24 hours in 120 DEG C of oil baths, be cooled to room temperature, the cancellation that adds water is reacted, wash three times by ethyl acetate, separatory, merge organic layer, activated carbon decolorizing, filters, anhydrous sodium sulfate drying, concentrating under reduced pressure, product is through column chromatography purification, and eluent is sherwood oil: ethyl acetate=10:1 (v/v), obtains white solid product, productive rate 94%, purity is 99.9%.
1HNMR(500MHz，CDCl
3)ppm：8.43(d，
J=8.0Hz，1H)，8.34(d，
J=8.0Hz，2H)，8.00(d，
J=8.5Hz，1H)，7.92(s，1H)，7.80(t，1H)，7.51-7.64(m，9H)；
13CNMR(500MHz，CDCl
3)：156.90，149.23，149.05，139.77，138.56，130.35，129.70，129.60，129.50，128.96，128.72，128.52，127.75，126.47，125.92，125.75，119.39；HRMS(EI)Calcd.forC
21H
15N：[M
+]，281.1207；Found：281.1204.
For embodiment 1, toluene is solvent; Change solvent, all the other conditions are constant, take DMSO as solvent, and products collection efficiency is 54%, and purity is 99.0%; Take DMF as solvent, products collection efficiency 67%, purity is 99.5%; Take dioxane as solvent, products collection efficiency 26%, purity is 99.1%.
Embodiment 2
6-trifluoromethyl-2, the synthetic method of 4-diphenylquinoline is as follows: in reaction vessel, add p-trifluoromethylaniline 0.5mmol (80.6mg), phenyl aldehyde 0.5mmol (53mg), methyl phenyl ketone 0.75mmol (90.1mg), catalyst A gOTf0.005mmol (1.29mg), HOTf0.01mmol (1.5mg), toluene 2mL.React 24 hours in 120 DEG C of oil baths, be cooled to room temperature, the cancellation that adds water is reacted, wash three times by ethyl acetate, separatory, merge organic layer, activated carbon decolorizing, filters, anhydrous sodium sulfate drying, concentrating under reduced pressure, product is through column chromatography purification, and eluent is sherwood oil: ethyl acetate=5:1 (v/v), obtains white solid product, productive rate 82%, purity is 99.8%.
1HNMR(400MHz，CDCl
3)
δppm：8.32(d，
J=8.8Hz，1H)，8.20(t，3H)，7.87(d，
J=8.0Hz，2H)，7.44-7.55(m，8H)；
13CNMR(100MHz，CDCl
3)
δppm：158.9，150.2，150.0，139.0，137.5，131.4，130.1，129.6，129.0，128.7，128.5，128.1，127.8，125.3，125.0，123.7，120.4；HRMS(EI)Calcd.forC
22H
14F
3N：[M
+]，349.1078.Found：m/z349.1064.
Embodiment 3
6-methyl-2, the synthetic method of 4-diphenylquinoline is as follows: in reaction vessel, add open-chain crown ether 0.5mmol (53.5mg), phenyl aldehyde 0.5mmol (53mg), methyl phenyl ketone 0.75mmol (90.1mg), catalyst A gOTf0.005mmol (1.29mg), HOTf0.01mmol (1.5mg), toluene 2mL.React 24 hours in 120 DEG C of oil baths, be cooled to room temperature, the cancellation that adds water is reacted, wash three times by ethyl acetate, separatory, merge organic layer, activated carbon decolorizing, filters, anhydrous sodium sulfate drying, concentrating under reduced pressure, product is through column chromatography purification, and eluent is sherwood oil: ethyl acetate=10:1 (v/v), obtains white solid product, productive rate 96%, purity is 99.9%.
1HNMR(500MHz，CDCl
3)ppm：8.85(d，
J=9.0Hz，1H)，8.15(t，2H)，7.97(d，
J=3.5Hz，2H)，7.88(s，1H)，7.62-7.73(m，8H)，2.61(s，3H)；
13CNMR(500MHz，DMSO-
d 6 )：155.7，153.4，140.0，139.4，136.2，136.1，132.9，132.7，130.5，130.2，129.8，129.6，129.5，125.9，125.5，123.1，121.8，21.8；HRMS(EI)Calcd.forC
22H
17N：[M
+]，295.1357；Found：295.1361.
Embodiment 4
The synthetic method of 2-p-methoxyphenyl-6-methyl 4-phenyl quinoline is as follows: in reaction vessel, add open-chain crown ether 0.5mmol (53.5mg), aubepine 0.5mmol (68mg), methyl phenyl ketone 0.75mmol (90.1mg), catalyst A gOTf0.005mmol (1.29mg), HOTf0.01mmol (1.5mg), toluene 2mL.React 24 hours in 120 DEG C of oil baths, be cooled to room temperature, the cancellation that adds water is reacted, wash three times by ethyl acetate, separatory, merge organic layer, activated carbon decolorizing, filters, anhydrous sodium sulfate drying, concentrating under reduced pressure, product is through column chromatography purification, and eluent is sherwood oil: ethyl acetate=10:1 (v/v), obtains white solid product, productive rate 98%, purity is 99.9%.
1HNMR(500MHz，CDCl
3)ppm：8.19-8.21(d，
J=8.5Hz，2H)，7.91-7.92(t，2H)，7.81(s，1H)，7.68-7.69(d，
J=3.5Hz，3H)，7.61-7.62(m，2H)，7.18-7.21(t，3H)，3.95(s，3H)，2.58(s，3H)；
13CNMR(500MHz，DMSO-
d 6 )：163.4，155.7，152.8，139.6，138.7，136.14，131.6，130.5，130.2，129.5，129.3，128.6，125.6，124.4，122.4，121.4，115.4，56.2，21.8；HRMS(EI)Calcd.forC
23H
19NO：[M
+]，325.1468；Found：325.1467.
Embodiment 5
7-methyl-2, the synthetic method of 4-diphenylquinoline is as follows: in reaction vessel, add m-toluidine 0.5mmol (53.5mg), phenyl aldehyde 0.5mmol (53mg), methyl phenyl ketone 0.75mmol (90.1mg), catalyst A gOTf0.005mmol (1.29mg), HOTf0.01mmol (1.5mg), toluene 2mL.React 24 hours in 120 DEG C of oil baths, be cooled to room temperature, the cancellation that adds water is reacted, wash three times by ethyl acetate, separatory, merge organic layer, activated carbon decolorizing, filters, anhydrous sodium sulfate drying, concentrating under reduced pressure, product is through column chromatography purification, and eluent is sherwood oil: ethyl acetate=10:1 (v/v), obtains white solid product, productive rate 88%, purity is 99.7%.
1HNMR(400MHz，CDCl
3)
δppm：8.11(s，1H)，7.99(s，1H)，7.75(d，
J=8.4Hz，1H)，7.38-7.44(m，4H)，7.23-7.29(m，7H)，2.58(s，3H)；
13CNMR(100MHz，CDCl
3)
δppm：158.3，147.6，140.6，140.2，140.0，137.4，133.7，130.1，130.0，129.8，129.1，128.4，128.2，127.9，127.2，127.1，125.3，22.0；HRMS(EI)Calcd.forC
22H
17N：[M
+]，295.1361.Found：m/z295.1364.
Embodiment 6
7-fluoro-2, the synthetic method of 4-diphenylquinoline is as follows: in reaction vessel, add m-fluoroaniline 0.5mmol (55.5mg), phenyl aldehyde 0.5mmol (53mg), methyl phenyl ketone 0.75mmol (90.1mg), catalyst A gOTf0.005mmol (1.29mg), HOTf0.01mmol (1.5mg), toluene 2mL.React 24 hours in 120 DEG C of oil baths, be cooled to room temperature, the cancellation that adds water is reacted, wash three times by ethyl acetate, separatory, merge organic layer, activated carbon decolorizing, filters, anhydrous sodium sulfate drying, concentrating under reduced pressure, product is through column chromatography purification, and eluent is sherwood oil: ethyl acetate=10:1 (v/v), obtains white solid product, productive rate 84%, purity is 99.9%.
1HNMR(400MHz，CDCl
3)
δppm：8.10(d，
J=7.6Hz，2H)，7.77-7.84(m，2H)，7.71(s，1H)，7.40-7.47(m，6H)，7.27(d，
J=4.4Hz，3H)；
13CNMR(100MHz，CDCl
3)
δppm：158.0，150.0，149.4，139.3，138.2，131.7，130.4，129.7，129.5，128.9，128.7，128.6，128.0，127.6，127.5，127.4，122.9；HRMS(EI)Calcd.forC
21H
14FN：[M
+]，299.1110.Found：m/z299.1114.
Embodiment 7
7-trifluoromethyl-2, the synthetic method of 4-diphenylquinoline is as follows: in reaction vessel, add 3-Aminotrifluorotoluene 0.5mmol (80.5mg), phenyl aldehyde 0.5mmol (53mg), methyl phenyl ketone 0.75mmol (90.1mg), catalyst A gOTf0.005mmol (1.29mg), HOTf0.01mmol (1.5mg), toluene 2mL.React 24 hours in 120 DEG C of oil baths, be cooled to room temperature, the cancellation that adds water is reacted, wash three times by ethyl acetate, separatory, merge organic layer, activated carbon decolorizing, filters, anhydrous sodium sulfate drying, concentrating under reduced pressure, product is through column chromatography purification, and eluent is sherwood oil: ethyl acetate=10:1 (v/v), obtains white solid product, productive rate 78%, purity is 99.5%.
1HNMR(400MHz，CDCl
3)
δppm：8.16(d，
J=8.0Hz，1H)，8.02(d，
J=8.0Hz，2H)，7.82(d，
J=8.4Hz，2H)，7.73(s，1H)，7.66(m，1H)，7.38-7.49(m，6H)；
13CNMR(100MHz，CDCl
3)
δppm：156.9，149.1，148.8，139.5，138.5，136.8，130.0，129.6，129.5，129.3，128.6，128.4，127.6，127.5，126.2，125.6，119.3；HRMS(EI)Calcd.forC
22H
14F
3N：[M
+]，349.1078.Found：m/z349.1074.
Embodiment 8
The synthetic method of 4-methyl-2-phenylquinoline is as follows: in reaction vessel, add aniline 0.5mmol (46.5mg), phenyl aldehyde 0.5mmol (53mg), acetone 2mmol (11.6mg), catalyst A gOTf0.005mmol (1.29mg), HOTf0.01mmol (1.5mg), toluene 2mL.React 24 hours in 100 DEG C of oil baths, be cooled to room temperature, the cancellation that adds water is reacted, wash three times by ethyl acetate, separatory, merge organic layer, activated carbon decolorizing, filters, anhydrous sodium sulfate drying, concentrating under reduced pressure, product is through column chromatography purification, and eluent is sherwood oil: ethyl acetate=10:1 (v/v), obtains white solid product, productive rate 74%, purity is 99.8%.
1HNMR(400MHz，CDCl
3)
δppm：8.13(d，
J=8.8Hz，1H)，8.01(s，1H)，7.77(d，
J=8.0Hz，1H)，7.64-7.68(m，1H)，7.58-7.60(m，2H)，7.41-7.53(m，4H)，2.46(s，3H)；
13CNMR(100MHz，CDCl
3)
δppm：160.6，146.7，140.9，136.8，129.3，129.2，128.9，128.8，128.3，128.2，127.6，126.7，126.4，20.7；HRMS(EI)Calcd.forC
16H
13N：[M
+]，219.1048.Found：m/z219.1046.
Embodiment 9
3-methyl-2, the synthetic method of 4-diphenylquinoline is as follows: in reaction vessel, add aniline 0.5mmol (46.5mg), phenyl aldehyde 0.5mmol (53mg), Propiophenone 0.75mmol (100mg), catalyst A gOTf0.005mmol (1.29mg), HOTf0.01mmol (1.5mg), toluene 2mL.React 24 hours in 120 DEG C of oil baths, be cooled to room temperature, the cancellation that adds water is reacted, wash three times by ethyl acetate, separatory, merge organic layer, activated carbon decolorizing, filters, anhydrous sodium sulfate drying, concentrating under reduced pressure, product is through column chromatography purification, and eluent is sherwood oil: ethyl acetate=10:1 (v/v), obtains white solid product, productive rate 82%, purity is 99.5%.
1HNMR(400MHz，CDCl
3)
δppm：8.26(d，
J=8.4Hz，1H)，7.66-7.71(m，3H)，7.51-7.60(m，5H)，7.42-7.50(m，3H)，7.36(t，2H)，2.21(s，3H)；
13CNMR(100MHz，CDCl
3)
δppm：160.9，147.9，146.3，141.5，137.8，129.41，129.35，129.0，128.7，128.6，128.3，128.1，127.9，127.1，126.8，126.3，126.0，18.6；HRMS(EI)Calcd.forC
22H
17N：[M
+]，295.1361.Found：m/z295.1360.
Embodiment 10
2-p-methylphenyl-3, the synthetic method of 6-dimethyl-4-phenylquinoline is as follows: in reaction vessel, add open-chain crown ether 0.5mmol (53.5mg), p-tolyl aldehyde 0.5mmol (60mg), Propiophenone 0.75mmol (100mg), catalyst A gOTf0.005mmol (1.29mg), HOTf0.01mmol (1.5mg), toluene 2mL.React 24 hours in 120 DEG C of oil baths, be cooled to room temperature, the cancellation that adds water is reacted, wash three times by ethyl acetate, separatory, merge organic layer, activated carbon decolorizing, filters, anhydrous sodium sulfate drying, concentrating under reduced pressure, product is through column chromatography purification, and eluent is sherwood oil: ethyl acetate=10:1 (v/v), obtains white solid product, productive rate 87%, purity is 99.7%.
1HNMR(400MHz，CDCl
3)
δppm：8.12(d，
J=8.4Hz，1H)，7.51-7.56(m，6H)，7.33-7.35(m，4H)，7.18(s，1H)，2.46(s，3H)，2.43(s，3H)，2.18(s，3H)；
13CNMR(100MHz，CDCl
3)
δppm：160.0，147.1，145.0，138.8，138.0，137.7，136.0，130.7，129.4，129.2，128.97，128.95，128.7，127.7，127.0，126.7，124.7，21.8，21.3，18.7；HRMS(EI)Calcd.forC
24H
21N：[M
+]，323.1674.Found：m/z323.1675.
Embodiment 11
The synthetic method of 2-p-methylphenyl-3-methyl-6-nitro-4-phenylquinoline is as follows: in reaction vessel, add p-Nitroaniline 0.5mmol (94mg), p-tolyl aldehyde 0.5mmol (60mg), Propiophenone 0.75mmol (100mg), catalyst A gOTf0.005mmol (1.29mg), HOTf0.01mmol (1.5mg), toluene 2mL.React 24 hours in 120 DEG C of oil baths, be cooled to room temperature, the cancellation that adds water is reacted, wash three times by ethyl acetate, separatory, merge organic layer, activated carbon decolorizing, filters, anhydrous sodium sulfate drying, concentrating under reduced pressure, product is through column chromatography purification, and eluent is sherwood oil: ethyl acetate=5:1 (v/v), obtains white solid product, productive rate 77%, purity is 99.6%.
1HNMR(500MHz，CDCl
3)δppm：8.42(q，1H)，8.37(d，
J=1.6，1H)，8.28(d，
J=9.0，1H)，7.61-7.64(t，2H)，7.59-7.60(t，3H)，7.34-7.37(m，4H)，2.47(s，3H)，2.25(s，3H)；
13CNMR(100MHz，CDCl
3)
δppm：164.4，149.7，148.4，145.4，138.8，137.8，136.2，131.2，129.2，129.12，129.08，128.8，128.7，128.0，126.1，123.0，122.0，21.3，18.9；HRMS(EI)Calcd.forC
23H
18N
2O
2：[M
+]，354.1368.Found：m/z354.1366.
Embodiment 12
2-p-methylphenyl-6-methyl-3, the synthetic method of 4-diphenylquinoline is as follows: in reaction vessel, add open-chain crown ether 0.5mmol (53.5mg), p-tolyl aldehyde 0.5mmol (60mg), Propiophenone 0.75mmol (100mg), catalyst A gOTf0.005mmol (1.29mg), HOTf0.01mmol (1.5mg), toluene 2mL.React 24 hours in 120 DEG C of oil baths, be cooled to room temperature, the cancellation that adds water is reacted, wash three times by ethyl acetate, separatory, merge organic layer, activated carbon decolorizing, filters, anhydrous sodium sulfate drying, concentrating under reduced pressure, product is through column chromatography purification, and eluent is sherwood oil: ethyl acetate=7:1 (v/v), obtains white solid product, productive rate 87%, purity is 99.9%.
1HNMR(400MHz，CDCl
3)
δppm：8.18(d，
J=8.4Hz，1H)，7.58(d，
J=10.0Hz，1H)，7.29-7.34(m，6H)，7.14-7.16(m，2H)，7.03-7.04(m，5H)，6.91-6.93(m，2H)，2.45(s，3H)，2.31(s，3H)；
13CNMR(100MHz，CDCl
3)
δppm：158.0，147.0，146.0，138.7，138.3，137.2，136.3，132.9，131.6，131.4，130.4，129.9，129.4，128.4，127.7，127.3，127.1，126.5，126.2，125.3，113.8，21.9，21.2；HRMS(EI)Calcd.forC
29H
23N：[M
+]，385.1830.Found：m/z385.1827.
Embodiment 13
The synthetic method of 4-cyclohexyl-2-phenylquinoline is as follows: in reaction vessel, add aniline 0.5mmol (46.5mg); phenyl aldehyde 0.5mmol (53mg); acetyl cyclohexane 0.75mmol (94.7mg); catalyst A gOTf0.005mmol (1.29mg); HOTf0.01mmol (1.5mg), toluene 2mL.React 24 hours in 110 DEG C of oil baths, be cooled to room temperature, the cancellation that adds water is reacted, wash three times by ethyl acetate, separatory, merge organic layer, activated carbon decolorizing, filters, anhydrous sodium sulfate drying, concentrating under reduced pressure, product is through column chromatography purification, and eluent is sherwood oil: ethyl acetate=10:1 (v/v), obtains white solid product, productive rate 89%, purity is 99.8%.
1HNMR(400MHz，CDCl
3)
δppm：8.01(d，
J=8.8Hz，1H)，7.60(s，1H)，7.47-7.53(m，7H)，7.22(s，1H)，2.90-2.96(m，1H)，1.87-1.94(m，2H)，1.68-1.80(m，2H)，1.59-1.66(m，2H)，1.31-1.52(m，4H)；
13CNMR(100MHz，CDCl
3)
δppm：165.6，148.0，146.8，138.8，135.5，131.4，129.8，129.6，129.0，128.5，128.2，124.4，119.9，47.6，33.0，29.6，26.1；HRMS(EI)Calcd.forC
21H
21N：[M
+]，287.1674.Found：m/z287.1675.
Embodiment 14
The synthetic method of 6-methyl-4-(2-thienyl)-2-phenylquinoline is as follows: in reaction vessel, add open-chain crown ether 0.5mmol (53.5mg); phenyl aldehyde 0.5mmol (53mg); 2-acetyl thiophene 0.75mmol (94.6mg); catalyst A gOTf0.005mmol (1.29mg); HOTf0.01mmol (1.5mg), toluene 2mL.React 24 hours in 110 DEG C of oil baths, be cooled to room temperature, the cancellation that adds water is reacted, wash three times by ethyl acetate, separatory, merge organic layer, activated carbon decolorizing, filters, anhydrous sodium sulfate drying, concentrating under reduced pressure, product is through column chromatography purification, and eluent is sherwood oil: ethyl acetate=5:1 (v/v), obtains white solid product, productive rate 91%, purity is 99.9%.
1HNMR(400MHz，CDCl
3)
δppm：8.12-8.18(q，2H)，8.02(s，1H)，7.89(s，1H)，7.71-7.73(m，1H)，7.51-7.60(m，5H)，7.43-7.48(m，2H)，2.54(s，3H)；
13CNMR(100MHz，CDCl
3)
δppm：156.3，147.2，145.1，137.9，135.2，133.3，132.4，130.4，129.8，129.6，129.4，129.3，129.2，128.8，125.6，125.4，125.8，22.02；HRMS(EI)Calcd.forC
20H
15NS：[M
+]，301.0925.Found：m/z301.0928.
Embodiment 15
6-methyl-2-phenyl-3, the synthetic method of 4-dihydro cyclobutyl [c] quinoline is as follows: in reaction vessel, add open-chain crown ether 0.5mmol (53.5mg), phenyl aldehyde 0.5mmol (53mg), cyclobutanone 1mmol (70mg), catalyst A gOTf0.005mmol (1.29mg), HOTf0.01mmol (1.5mg), toluene 2mL.React 24 hours in 120 DEG C of oil baths, be cooled to room temperature, the cancellation that adds water is reacted, wash three times by ethyl acetate, separatory, merge organic layer, activated carbon decolorizing, filters, anhydrous sodium sulfate drying, concentrating under reduced pressure, product is through column chromatography purification, and eluent is sherwood oil: ethyl acetate=5:1 (v/v), obtains white solid product, productive rate 77%, purity is 99.8%.
1HNMR(400MHz，CDCl
3)
δppm：8.20(d，
J=7.6Hz，2H)，8.04(d，
J=8.4Hz，1H)，7.42-7.53(m，
5H)，3.64(s，2H)，3.50(m，2H)，2.53(s，3H)；
13CNMR(100MHz，CDCl
3)
δppm：151.8，150.2，146.3，138.0，136.4，136.2，130.9，130.7，129.3，128.7，127.5，124.0，120.8，31.2，29.3，21.7；HRMS(EI)Calcd.forC
18H
15N：[M
+]，245.1204.Found：m/z245.1205.
Embodiment 16
6-methyl-2-phenyl-3, the synthetic method of 4-dihydro cyclopentyl [c] quinoline is as follows: in reaction vessel, add open-chain crown ether 0.5mmol (53.5mg), phenyl aldehyde 0.5mmol (53mg), cyclopentanone 1mmol (84mg), catalyst A gOTf0.005mmol (1.29mg), HOTf0.01mmol (1.5mg), toluene 2mL.React 24 hours in 120 DEG C of oil baths, be cooled to room temperature, the cancellation that adds water is reacted, wash three times by ethyl acetate, separatory, merge organic layer, activated carbon decolorizing, filters, anhydrous sodium sulfate drying, concentrating under reduced pressure, product is through column chromatography purification, and eluent is sherwood oil: ethyl acetate=5:1 (v/v), obtains white solid product, productive rate 79%, purity is 99.7%.
1HNMR(400MHz，CDCl
3)
δppm：8.08(d，
J=8.4Hz，1H)，7.56(s，1H)，7.46-7.50(q，2H)，7.14-7.19(m，
4H)，3.26-3.29(t，2H)，3.19-3.23(t，2H)，2.54(s，3H)，2.19-2.29(m，2H)；
13CNMR(100MHz，CDCl
3)
δppm：155.2，150.6，146.0，140.7，136.0，135.0，130.9，129.6，128.9，128.8，128.5，128.4，123.1，33.7，31.2，25.1，21.8；HRMS(EI)Calcd.forC
19H
17N：[M
+]，259.1361.Found：m/z259.1364。
Claims (8)
1. one kind utilizes the method for aromatic amine, aromatic aldehyde, ketone synthesis of quinoline derivatives, it is characterized in that: under the existence of silver trifluoromethanesulfonate and trifluoromethanesulfonic acid, by the quinoline shown in the Aromatic aldehyde compound shown in the aromatic amine compound shown in formula I, formula II and the ketone compound Reactive Synthesis formula IV shown in formula III
Formula I:
; Formula II:
; Formula III:
;
Formula IV:
;
Wherein, R
1be selected from the one in hydrogen, halogen, nitro, methyl, methoxyl group, ethanoyl, substituting group is positioned at ortho position, a position or contraposition, wherein, and R
1any CH, CH in methyl in substituting group, methoxyl group or ethanoyl
2or CH
3group is optionally at described CH, CH
2or CH
3the following substituting group that group may be the same or different with 1,2 or 3: halogen or nitro;
R
2be selected from the one in hydrogen, halogen, nitro, methoxyl group, methyl, substituting group is positioned at ortho position, a position or contraposition;
R3 is selected from C
1~ C
5one in alkyl, cycloalkyl, thienyl, phenyl; Wherein, R
3any CH, CH in substituting group
2or CH
3group is optionally at described CH, CH
2or CH
3the following substituting group that group may be the same or different with 1,2 or 3: halogen, methyl or methoxy, substituting group can be positioned at ortho position, a position or contraposition;
R
4be selected from hydrogen or methyl;
Or R
3with R
4form cyclic ketone;
Halogen is the substituting group of fluorine, chlorine, bromine or iodine.
2. utilize the method for aromatic amine, aromatic aldehyde, ketone synthesis of quinoline derivatives as claimed in claim 1, it is characterized in that: the aromatic amine compound shown in described formula I is aniline, p-Nitroaniline, open-chain crown ether, m-toluidine, m-fluoroaniline, p-trifluoromethylaniline or 3-Aminotrifluorotoluene.
3. utilize the method for aromatic amine, aromatic aldehyde, ketone synthesis of quinoline derivatives as claimed in claim 1, it is characterized in that: the Aromatic aldehyde compound shown in described formula II is phenyl aldehyde, p-tolyl aldehyde or aubepine.
4. utilize the method for aromatic amine, aromatic aldehyde, ketone synthesis of quinoline derivatives as claimed in claim 1, it is characterized in that: the ketone compound shown in described formula III is acetone, acetyl cyclohexane, methyl phenyl ketone, Propiophenone, 2-acetyl thiophene, cyclobutanone or cyclopentanone.
5. utilize aromatic amine as claimed in claim 1, aromatic aldehyde, the method of ketone synthesis of quinoline derivatives, it is characterized in that, concrete steps are as follows: in reaction vessel, 1:1:1.5 adds the aromatic amine compound shown in formula I successively in molar ratio, ketone compound shown in Aromatic aldehyde compound shown in formula II and formula III, then solvent 2 ~ 6mL/mmol aromatic amine is added, then catalyzer silver trifluoromethanesulfonate and trifluoromethanesulfonic acid is added, the add-on of catalyzer is respectively 0.8 ~ 2% and 1.8 ~ 3% of aromatic amine compound molar weight, react 18 ~ 24 hours in 115 ~ 125 DEG C of oil baths, be cooled to room temperature, extraction, concentrating under reduced pressure, product is through column chromatography purification, obtain quinoline product.
6. utilize the method for aromatic amine, aromatic aldehyde, ketone synthesis of quinoline derivatives as claimed in claim 5, it is characterized in that: described solvent is toluene, DMSO, DMF or dioxane.
7. utilize the method for aromatic amine, aromatic aldehyde, ketone synthesis of quinoline derivatives as claimed in claim 6, it is characterized in that: described solvent is toluene.
8. utilize the method for aromatic amine, aromatic aldehyde, ketone synthesis of quinoline derivatives as claimed in claim 5, it is characterized in that: the condition of described column chromatography purification is, eluent is the mixture of sherwood oil and ethyl acetate, and the volume ratio of sherwood oil and ethyl acetate is 10:1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510699601.0A CN105175328B (en) | 2015-10-26 | 2015-10-26 | It is a kind of using aromatic amine, aromatic aldehyde, ketone synthesis of quinoline derivatives method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510699601.0A CN105175328B (en) | 2015-10-26 | 2015-10-26 | It is a kind of using aromatic amine, aromatic aldehyde, ketone synthesis of quinoline derivatives method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105175328A true CN105175328A (en) | 2015-12-23 |
| CN105175328B CN105175328B (en) | 2017-12-19 |
Family
ID=54897849
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510699601.0A Expired - Fee Related CN105175328B (en) | 2015-10-26 | 2015-10-26 | It is a kind of using aromatic amine, aromatic aldehyde, ketone synthesis of quinoline derivatives method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105175328B (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107628996A (en) * | 2017-11-08 | 2018-01-26 | 沅江华龙催化科技有限公司 | A kind of synthetic method of poly-substituted quinoline |
| CN107652229A (en) * | 2017-11-08 | 2018-02-02 | 沅江华龙催化科技有限公司 | A kind of method by acetophenone and amino benzenes compounds oxidative cyclization synthesis of quinoline derivatives |
| CN107793354A (en) * | 2017-11-08 | 2018-03-13 | 沅江华龙催化科技有限公司 | A kind of method of intermolecular cyclization synthesis of quinoline derivatives |
| CN110041231A (en) * | 2019-05-21 | 2019-07-23 | 东华理工大学 | A kind of preparation method of N, O- acetal compound |
| CN110204486A (en) * | 2019-06-21 | 2019-09-06 | 江南大学 | A kind of synthetic method of quinoline |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107892668B (en) * | 2017-11-08 | 2019-08-16 | 沅江华龙催化科技有限公司 | A kind of synthetic method of quinoline |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104151235A (en) * | 2014-08-07 | 2014-11-19 | 南阳师范学院 | Preparation method for quinoline derivatives |
| CN104151236A (en) * | 2014-08-07 | 2014-11-19 | 南阳师范学院 | Method for efficiently synthesizing quinoline |
-
2015
- 2015-10-26 CN CN201510699601.0A patent/CN105175328B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104151235A (en) * | 2014-08-07 | 2014-11-19 | 南阳师范学院 | Preparation method for quinoline derivatives |
| CN104151236A (en) * | 2014-08-07 | 2014-11-19 | 南阳师范学院 | Method for efficiently synthesizing quinoline |
Non-Patent Citations (5)
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107628996A (en) * | 2017-11-08 | 2018-01-26 | 沅江华龙催化科技有限公司 | A kind of synthetic method of poly-substituted quinoline |
| CN107652229A (en) * | 2017-11-08 | 2018-02-02 | 沅江华龙催化科技有限公司 | A kind of method by acetophenone and amino benzenes compounds oxidative cyclization synthesis of quinoline derivatives |
| CN107793354A (en) * | 2017-11-08 | 2018-03-13 | 沅江华龙催化科技有限公司 | A kind of method of intermolecular cyclization synthesis of quinoline derivatives |
| CN107793354B (en) * | 2017-11-08 | 2019-09-03 | 沅江华龙催化科技有限公司 | A kind of method of intermolecular cyclization synthesis of quinoline derivatives |
| CN110041231A (en) * | 2019-05-21 | 2019-07-23 | 东华理工大学 | A kind of preparation method of N, O- acetal compound |
| CN110041231B (en) * | 2019-05-21 | 2021-04-09 | 东华理工大学 | Preparation method of N, O-acetal compound |
| CN110204486A (en) * | 2019-06-21 | 2019-09-06 | 江南大学 | A kind of synthetic method of quinoline |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105175328B (en) | 2017-12-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105175328A (en) | Method for synthesizing quinoline derivative by utilizing arylamine, aromatic aldehyde and ketone | |
| CN108047261B (en) | Preparation method of clitorium | |
| CN105175327B (en) | A kind of synthetic method of quinoline | |
| CN105801575B (en) | A kind of synthetic method of imidazo [1,2-a] pyridine | |
| CN107973778B (en) | A kind of ruthenium catalysis aromatic ketone replaces the methods and application of naphthalene derivatives with the more virtues of tolans cyclization preparation | |
| CN107501156A (en) | A kind of three components series connection synthetic method of polysubstituted pyrrole | |
| CN106243105B (en) | Methylene-bridged 1,8- naphthyridines ligand and copper (I) complex, preparation method and application | |
| CN103113293B (en) | Polysubstituted quinoline derivative and preparation method thereof | |
| CN108610304B (en) | Synthetic method of diaryl sultam compound | |
| CN110437124B (en) | Preparation method of indoloquinone derivative | |
| CN110003011B (en) | Preparation method of nitroolefin derivative by taking nitrate as nitro source | |
| CN109232363B (en) | Synthetic method of 3-selenocyanoindole compound | |
| CN104910104A (en) | Method for synthesizing dihydrofuran derivatives under catalytic action of copper | |
| CN112500339B (en) | Synthesis method of 8-acylquinoline derivative | |
| CN102863361A (en) | Chiral catalytic synthesis method of thiamphenicol | |
| CN111995554A (en) | Method for preparing asymmetric organic selenium ether compound by metal-free chemical oxidation method | |
| CN105198806B (en) | A kind of method using aromatic amine, diketone synthesis of quinoline derivatives | |
| JPWO2016125845A1 (en) | Cross coupling method and method for producing organic compound using the cross coupling method | |
| CN112812084B (en) | Synthetic method of benzofuran compound | |
| CN112194608B (en) | Synthesis method of visible light promoted 3-methyl-3-difluoroethyl-2-oxindole compound | |
| CN107382819A (en) | A kind of preparation method of 3 thioindole class compound | |
| CN108409743A (en) | A kind of preparation method of pyrrolo- [1,2-a] quinoxaline compounds of alkyl nitrile substitution | |
| CN107129464B (en) | A kind of 2,3,5,6- tetra- replaces the preparation method of symmetrical pyridine | |
| CN102336763B (en) | Synthesis method for pyranocoumarin derivatives | |
| CN112094220A (en) | Green synthesis method of 3-sulfone methyl-1H-indole compound |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20171219 Termination date: 20181026 |