CN105175328B - It is a kind of using aromatic amine, aromatic aldehyde, ketone synthesis of quinoline derivatives method - Google Patents
It is a kind of using aromatic amine, aromatic aldehyde, ketone synthesis of quinoline derivatives method Download PDFInfo
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- 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
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- 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
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- 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
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- 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
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- 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 it is a kind of using aromatic amine, aromatic aldehyde, ketone synthesis of quinoline derivatives method, belong to the synthesis technical field of quinoline.It is a kind of using aromatic amine, aromatic aldehyde, ketone synthesis of quinoline derivatives method, in the presence of silver trifluoromethanesulfonate and trifluoromethanesulfonic acid, synthesis of quinoline derivatives is reacted by aromatic amine compound, Aromatic aldehyde compound and assimilation compound, reaction expression is as follows：
Description
Technical field
The invention belongs to the synthesis technical field of quinoline, and in particular to one kind is closed using aromatic amine, aromatic aldehyde, ketone
Into the method for quinoline.
Background technology
It is scientific and technological to make rapid progress with the progress of human society, people to life and the expectation more and more higher of quality of life,
People are more and more stronger to health care consciousness, and this has also promoted the rapid development of medical industry, more more effective so as to develop
Novel drugs, wherein by be chemically synthesized new medicine be research and develop novel drugs important channel.
Quinoline is the compound of a kind of highly important azepine ring structure.Such compound has good resist
The bioactivity such as bacterium, antitumor and antituberculosis, it is one of focus of novel drugs developmental research.The synthetic method of quinoline is a lot,
For example, ruthenium is catalyzed the synthetic method that adjacent aminobenzyl alcohol and reactive ketone prepare quinoline；O-Aminobenzaldehyde and reactive ketone prepare quinoline
Method.But there is also many shortcomings for these methods：Severe reaction conditions, reaction temperature is high, and some needs HTHP, separates
Difficulty, reaction it is substrate limiting relatively strong, therefore, the quinoline that substituent is synthesized using a kind of method is very limited.In addition,
Using in metal-catalyzed processes, the limited activity of catalyst, these shortcomings cause the operation difficulty of preparation process to increase, harm behaviour
Make personnel health, environmental pollution is serious.However, the method generally existing of existing synthesis of quinoline derivatives：Need active reaction
Substrate, reaction rate is low, the reaction time is longer, how difficult accessory substance is and the form of reaction excessively single (causes synthesized
Product has the shortcomings that significant limitation).In consideration of it, the preparation method of the quinoline of research and development novelty is particularly important.
Chinese patent CN104151235A discloses a kind of quinoline preparation method, is to utilize silver trifluoromethanesulfonate catalysis substituent
Aniline and ketenes or olefine aldehydr derivative synthesis of quinoline derivatives, the patent procedure is simple, can be applied to substantial amounts of functional group,
And yield is high, product is single, is easy to separate and purifies, safety is cheap, pollution is small.But the patent, which still has some, to be lacked
Point：Such as reaction substrate ketenes or the synthesis of olefine aldehydr needs and purification, reactions steps are relative complex, and the three-dimensional effect of reaction substrate amine
Should be obvious, when substitution has the functional group of steric hindrance on aromatic amine ortho position, reaction effect is bad.
The content of the invention
The technical problems to be solved by the invention are, in view of the shortcomings of the prior art, there is provided a kind of substrate source is extensive, production
Thing purity is high, be easy to separate and purify using aromatic amine, aromatic aldehyde, ketone synthesis of quinoline derivatives method.
In order to solve the above technical problems, the technical solution adopted in the present invention is：
It is a kind of using aromatic amine, aromatic aldehyde, ketone synthesis of quinoline derivatives method, in silver trifluoromethanesulfonate（AgOTf）And trifluoro
Methanesulfonic acid（HOTf）In the presence of, as the aromatic amine compound shown in formula I, the Aromatic aldehyde compound shown in formula II and the ketone shown in formula III
Quinoline shown in compound reaction synthesis type IV, formula I：；Formula II：；Formula
Ⅲ：；
Formula IV：；
Wherein,
R1One kind in hydrogen, halogen, nitro, methyl, methoxyl group, acetyl group, substituent are located at ortho position, meta or right
Position, wherein, R1Any CH, CH in methyl, methoxyl group or acetyl group in substituent2Or CH3Group is optionally in described CH, CH2
Or CH31,2 or 3 following substituent that may be the same or different is carried on group：Halogen or nitro；
R2One kind in hydrogen, halogen, nitro, methoxyl group, methyl, substituent are located at ortho position, meta or para position；
R3Selected from C1~C5One kind in alkyl, cycloalkyl, thienyl, phenyl；Wherein, R3Any CH, CH in substituent2
Or CH3Group is optionally in described CH, CH2Or CH31,2 or 3 following substituent that may be the same or different is carried on group：Halogen
Element, methyl or methoxy, substituent can be located at ortho position, meta or para position；
R4Selected from hydrogen or methyl；
Or R3With R4Form cyclic ketone；
Halogen is fluorine, chlorine, the substituent of 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 the formula I is aniline, paranitroanilinum, open-chain crown ether, a methylbenzene
Amine, m-fluoroaniline, p-trifluoromethylaniline or 3-Aminotrifluorotoluene.
Preferably, the Aromatic aldehyde compound shown in the formula II is for benzaldehyde, p-tolyl aldehyde or to methoxybenzene first
Aldehyde.
Preferably, the assimilation compound shown in the formula III is acetone, acetyl cyclohexane, acetophenone, propiophenone, 2- acetyl
Base thiophene, cyclobutanone or cyclopentanone.
Preferably, using aromatic amine, aromatic aldehyde, ketone synthesis of quinoline derivatives method, comprise the following steps that：Hold in reaction
In molar ratio 1 in device：1：1.5 sequentially add the aromatic amine compound shown in formula I, the Aromatic aldehyde compound shown in formula II and formula III
Shown assimilation compound, solvent 2 ~ 6mL/mmol aromatic amines are subsequently added into, then add catalyst silver trifluoromethanesulfonate and trifluoro
Methanesulfonic acid, the addition of catalyst is respectively the 0.8 ~ 2% and 1.8 ~ 3% of aromatic amine compound mole, in 115 ~ 125 DEG C of oil baths
Reaction 18 ~ 24 hours, is cooled to room temperature, extracts, is concentrated under reduced pressure, product purifies through column chromatography, obtains quinoline product.
Preferably, the solvent is toluene, DMSO, DMF or dioxane.
Preferably, the solvent is toluene.
Preferably, the condition of column chromatography purifying is, eluant, eluent is the mixture of petroleum ether and ethyl acetate, petroleum ether
Volume ratio with ethyl acetate is 10：1.
Compared with prior art, beneficial effects of the present invention are as follows：The present invention utilizes aromatic amine, aldehyde and 01 derivatives synthesis
Quinoline, reaction substrate wide material sources, acquiring way is various, is not limited by experiment condition；Reaction condition is gentleer, without
High temperature high pressure process, experiment device therefor is normal experiment equipment, and cost is relatively low；Reaction product is easily isolated purifying, operation
Step is simple, and purity is high.Meanwhile synthetic method of the invention is compared than common synthesis 3, the dibasic quinolines of 4-,
This method can utilize the ketone of liquid to substitute gaseous alkynes, not only cheap and easy to operate, safe, can be efficiently
Prepare quinolines, target product quinoline be widely used in the parts of organic chemical reactionses, pharmaceutical intermediate and
In terms of photoelectric material.
Embodiment
For a better understanding of the present invention, present disclosure, but this hair are further fairly set out with reference to embodiment
Bright protection content is not limited solely to the following examples.In the following description, give a large amount of concrete details so as to
More thorough understanding of the invention is provided.It will be apparent, however, to one skilled in the art that the present invention can be with
It is carried out without one or more of these details.In other examples, in order to avoid obscuring with the present invention, for
Some technical characteristics well known in the art are not described.
In following embodiments, AgOTf represents silver trifluoromethanesulfonate, is its english abbreviation；HOTf represents trifluoromethanesulfonic acid, is
Its english abbreviation.
Embodiment 1
The synthetic method of 2,4- diphenylquinolines is as follows：Aniline 0.5mmol (46.5mg), benzene are added in reaction vessel
Formaldehyde 0.5mmol (53mg), acetophenone 0.75mmol (90.1mg), the mmol of catalyst AgOTf 0.005 (1.29 mg),
The mmol of HOTf 0.01 (1.5 mg), toluene 2mL.Reacted 24 hours in 120 DEG C of oil baths, be cooled to room temperature, add water quenching to go out instead
Should, washed three times with ethyl acetate, liquid separation, merge organic layer, activated carbon decolorizing, filtering, anhydrous sodium sulfate drying, depressurize dense
Contracting, product purify by column chromatography, and eluant, eluent is petroleum ether：Ethyl acetate=10：1 (v/v), white solid product is obtained, produced
Rate 94%, purity 99.9%.1HNMR (500MHz, CDCl3)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, CDCl3)：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. for C21H15N：[M+], 281.1207；Found：281.1204.
For embodiment 1, toluene is solvent；Change solvent, remaining condition is constant, and using DMSO as solvent, products collection efficiency is
54%, purity 99.0%；Using DMF as solvent, products collection efficiency 67%, purity 99.5%；Using dioxane as solvent, products collection efficiency
26%, purity 99.1%.
Embodiment 2
The synthetic method of 6- trifluoromethyl -2,4- diphenylquinolines is as follows：Added in reaction vessel to trifluoromethylbenzene
Amine 0.5mmol (80.6mg), benzaldehyde 0.5mmol (53mg), acetophenone 0.75mmol (90.1mg), catalyst AgOTf
0.005 mmol (1.29 mg), the mmol of HOTf 0.01 (1.5 mg), toluene 2mL.Reacted 24 hours in 120 DEG C of oil baths,
Room temperature is cooled to, adds water quenching to go out reaction, is washed three times with ethyl acetate, liquid separation, merges organic layer, activated carbon decolorizing, filtering, nothing
Aqueous sodium persulfate is dried, and is concentrated under reduced pressure, and product purifies by column chromatography, and eluant, eluent is petroleum ether：Ethyl acetate=5：1 (v/v), is obtained
To white solid product, yield 82%, purity 99.8%.1HNMR (400MHz, CDCl3)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, CDCl3)δ
ppm：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. for C22H14F3N：[M+],
349.1078.Found：m/z349.1064.
Embodiment 3
The synthetic method of 6- methyl -2,4- diphenylquinolines is as follows：Open-chain crown ether 0.5mmol is added in reaction vessel
(53.5mg), benzaldehyde 0.5mmol (53mg), acetophenone 0.75mmol (90.1mg), the mmol of catalyst AgOTf 0.005
(1.29 mg), the mmol of HOTf 0.01 (1.5 mg), toluene 2mL.Reacted 24 hours in 120 DEG C of oil baths, be cooled to room temperature,
Add water quenching to go out reaction, washed three times with ethyl acetate, liquid separation, merge organic layer, activated carbon decolorizing, filtering, anhydrous sodium sulfate does
It is dry, it is concentrated under reduced pressure, product purifies by column chromatography, and eluant, eluent is petroleum ether：Ethyl acetate=10：1 (v/v), it is solid to obtain white
Body product, yield 96%, purity 99.9%.1HNMR (500MHz, CDCl3)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. for C22H17N：[M+], 295.1357；Found：295.1361.
Embodiment 4
The synthetic method of 2- p-methoxyphenyl -6- methyl 4-phenyl quinoline is as follows：Added in reaction vessel to methylbenzene
Amine 0.5mmol (53.5mg), P-methoxybenzal-dehyde 0.5mmol (68mg), acetophenone 0.75mmol (90.1mg), catalysis
The mmol of agent AgOTf 0.005 (1.29 mg), the mmol of HOTf 0.01 (1.5 mg), toluene 2mL.It is anti-in 120 DEG C of oil baths
Answer 24 hours, be cooled to room temperature, add water quenching to go out reaction, washed three times with ethyl acetate, liquid separation, merge organic layer, activated carbon takes off
Color, filtering, anhydrous sodium sulfate drying, is concentrated under reduced pressure, and product purifies by column chromatography, and eluant, eluent is petroleum ether：Ethyl acetate=
10：1 (v/v), obtain white solid product, yield 98%, purity 99.9%.1HNMR (500MHz, CDCl3)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. for C23H19NO：[M+],
325.1468；Found：325.1467.
Embodiment 5
The synthetic method of 7- methyl -2,4- diphenylquinolines is as follows：M-toluidine 0.5mmol is added in reaction vessel
(53.5mg), benzaldehyde 0.5mmol (53mg), acetophenone 0.75mmol (90.1mg), the mmol of catalyst AgOTf 0.005
(1.29 mg), the mmol of HOTf 0.01 (1.5 mg), toluene 2mL.Reacted 24 hours in 120 DEG C of oil baths, be cooled to room temperature,
Add water quenching to go out reaction, washed three times with ethyl acetate, liquid separation, merge organic layer, activated carbon decolorizing, filtering, anhydrous sodium sulfate does
It is dry, it is concentrated under reduced pressure, product purifies by column chromatography, and eluant, eluent is petroleum ether：Ethyl acetate=10：1 (v/v), it is solid to obtain white
Body product, yield 88%, purity 99.7%.1HNMR (400MHz, CDCl3)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, CDCl3)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. for
C22H17N：[M+], 295.1361.Found：m/z295.1364.
Embodiment 6
The synthetic method of fluoro- 2, the 4- diphenylquinolines of 7- is as follows：M-fluoroaniline 0.5mmol is added in reaction vessel
(55.5mg), benzaldehyde 0.5mmol (53mg), acetophenone 0.75mmol (90.1mg), the mmol of catalyst AgOTf 0.005
(1.29 mg), the mmol of HOTf 0.01 (1.5 mg), toluene 2mL.Reacted 24 hours in 120 DEG C of oil baths, be cooled to room temperature,
Add water quenching to go out reaction, washed three times with ethyl acetate, liquid separation, merge organic layer, activated carbon decolorizing, filtering, anhydrous sodium sulfate does
It is dry, it is concentrated under reduced pressure, product purifies by column chromatography, and eluant, eluent is petroleum ether：Ethyl acetate=10：1 (v/v), it is solid to obtain white
Body product, yield 84%, purity 99.9%.1HNMR (400MHz, CDCl3)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,
CDCl3)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. for C21H14FN：[M+],
299.1110.Found：m/z299.1114.
Embodiment 7
The synthetic method of 7- trifluoromethyl -2,4- diphenylquinolines is as follows：M-trifluoromethyl benzene is added in reaction vessel
Amine 0.5mmol (80.5mg), benzaldehyde 0.5mmol (53mg), acetophenone 0.75mmol (90.1mg), catalyst AgOTf
0.005 mmol (1.29 mg), the mmol of HOTf 0.01 (1.5 mg), toluene 2mL.Reacted 24 hours in 120 DEG C of oil baths,
Room temperature is cooled to, adds water quenching to go out reaction, is washed three times with ethyl acetate, liquid separation, merges organic layer, activated carbon decolorizing, filtering, nothing
Aqueous sodium persulfate is dried, and is concentrated under reduced pressure, and product purifies by column chromatography, and eluant, eluent is petroleum ether：Ethyl acetate=10：1 (v/v),
Obtain white solid product, yield 78%, purity 99.5%.1HNMR (400MHz, CDCl3)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, CDCl3)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.
for C22H14F3N：[M+], 349.1078.Found：m/z349.1074.
Embodiment 8
The synthetic method of 4- methyl -2- phenylchinolines is as follows：Aniline 0.5mmol (46.5mg) is added in reaction vessel,
Benzaldehyde 0.5mmol (53mg), acetone 2mmol (11.6mg), the mmol of catalyst AgOTf 0.005 (1.29 mg), HOTf
0.01 mmol (1.5 mg), toluene 2mL.Reacted 24 hours in 100 DEG C of oil baths, be cooled to room temperature, add water quenching to go out reaction, used
Ethyl acetate washs three times, liquid separation, merges organic layer, activated carbon decolorizing, filtering, anhydrous sodium sulfate drying, is concentrated under reduced pressure, product
Purified by column chromatography, eluant, eluent is petroleum ether：Ethyl acetate=10：1 (v/v), obtains white solid product, and yield 74% is pure
Spend for 99.8%.1HNMR (400MHz, CDCl3)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, CDCl3)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. for C16H13N：[M+],
219.1048.Found：m/z219.1046.
Embodiment 9
The synthetic method of 3- methyl -2,4- diphenylquinolines is as follows：Aniline 0.5mmol is added in reaction vessel
(46.5mg), benzaldehyde 0.5mmol (53mg), propiophenone 0.75mmol (100mg), the mmol of catalyst AgOTf 0.005
(1.29 mg), the mmol of HOTf 0.01 (1.5 mg), toluene 2mL.Reacted 24 hours in 120 DEG C of oil baths, be cooled to room temperature,
Add water quenching to go out reaction, washed three times with ethyl acetate, liquid separation, merge organic layer, activated carbon decolorizing, filtering, anhydrous sodium sulfate does
It is dry, it is concentrated under reduced pressure, product purifies by column chromatography, and eluant, eluent is petroleum ether：Ethyl acetate=10：1 (v/v), it is solid to obtain white
Body product, yield 82%, purity 99.5%.1HNMR (400MHz, CDCl3)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, CDCl3)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. for
C22H17N：[M+], 295.1361.Found：m/z295.1360.
Embodiment 10
The synthetic method of 2- p-methylphenyl -3,6- dimethyl -4- phenylchinolines is as follows：Added in reaction vessel to methyl
Aniline 0.5mmol (53.5mg), p-tolyl aldehyde 0.5mmol (60mg), propiophenone 0.75mmol (100mg), catalyst
The mmol of AgOTf 0.005 (1.29 mg), the mmol of HOTf 0.01 (1.5 mg), toluene 2mL.Reacted in 120 DEG C of oil baths
24 hours, room temperature is cooled to, adds water quenching to go out reaction, is washed three times with ethyl acetate, liquid separation, merges organic layer, activated carbon decolorizing,
Filtering, anhydrous sodium sulfate drying, is concentrated under reduced pressure, and product purifies by column chromatography, and eluant, eluent is petroleum ether：Ethyl acetate=10：1
(v/v) white solid product, yield 87%, purity 99.7%, are obtained.1HNMR (400MHz, CDCl3)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, CDCl3)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. for C24H21N：[M+], 323.1674.Found：m/z323.1675.
Embodiment 11
The synthetic method of 2- p-methylphenyl -3- methyl -6- nitro -4- phenylchinolines is as follows：The addition pair in reaction vessel
Nitroaniline 0.5mmol (94mg), p-tolyl aldehyde 0.5mmol (60mg), propiophenone 0.75mmol (100mg), catalysis
The mmol of agent AgOTf 0.005 (1.29 mg), the mmol of HOTf 0.01 (1.5 mg), toluene 2mL.It is anti-in 120 DEG C of oil baths
Answer 24 hours, be cooled to room temperature, add water quenching to go out reaction, washed three times with ethyl acetate, liquid separation, merge organic layer, activated carbon takes off
Color, filtering, anhydrous sodium sulfate drying, is concentrated under reduced pressure, and product purifies by column chromatography, and eluant, eluent is petroleum ether：Ethyl acetate=5：
1 (v/v), obtain white solid product, yield 77%, purity 99.6%.1HNMR (500MHz, CDCl3)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, CDCl3)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. for C23H18N2O2：[M+],
354.1368.Found：m/z354.1366.
Embodiment 12
The synthetic method of 2- p-methylphenyl -6- methyl -3,4- diphenylquinolines is as follows：Added in reaction vessel to methyl
Aniline 0.5mmol (53.5mg), p-tolyl aldehyde 0.5mmol (60mg), propiophenone 0.75mmol (100mg), catalyst
The mmol of AgOTf 0.005 (1.29 mg), the mmol of HOTf 0.01 (1.5 mg), toluene 2mL.Reacted in 120 DEG C of oil baths
24 hours, room temperature is cooled to, adds water quenching to go out reaction, is washed three times with ethyl acetate, liquid separation, merges organic layer, activated carbon decolorizing,
Filtering, anhydrous sodium sulfate drying, is concentrated under reduced pressure, and product purifies by column chromatography, and eluant, eluent is petroleum ether：Ethyl acetate=7：1
(v/v) white solid product, yield 87%, purity 99.9%, are obtained.1HNMR (400MHz, CDCl3)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, CDCl3)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. for C29H23N：[M+], 385.1830.Found：m/z385.1827.
Embodiment 13
The synthetic method of 4- cyclohexyl -2- phenylchinolines is as follows：Aniline 0.5mmol is added in reaction vessel
(46.5mg), benzaldehyde 0.5mmol (53mg), acetyl cyclohexane 0.75mmol (94.7mg), catalyst AgOTf 0.005
Mmol (1.29 mg), the mmol of HOTf 0.01 (1.5 mg), toluene 2mL.React 24 hours, be cooled in 110 DEG C of oil baths
Room temperature, add water quenching to go out reaction, washed three times with ethyl acetate, liquid separation, merge organic layer, activated carbon decolorizing, filtering, anhydrous slufuric acid
Sodium is dried, and is concentrated under reduced pressure, and product purifies by column chromatography, and eluant, eluent is petroleum ether：Ethyl acetate=10：1 (v/v), is obtained white
Color solid product, yield 89%, purity 99.8%.1HNMR (400MHz, CDCl3)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, CDCl3)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. for C21H21N：[M+], 287.1674.Found：m/
z287.1675.
Embodiment 14
The synthetic method of 6- methyl -4- (2- thienyls) -2- phenylchinolines is as follows：Added in reaction vessel to methyl
Aniline 0.5mmol (53.5mg), benzaldehyde 0.5mmol (53mg), 2- acetyl thiophenes 0.75mmol (94.6mg), catalysis
The mmol of agent AgOTf 0.005 (1.29 mg), the mmol of HOTf 0.01 (1.5 mg), toluene 2mL.It is anti-in 110 DEG C of oil baths
Answer 24 hours, be cooled to room temperature, add water quenching to go out reaction, washed three times with ethyl acetate, liquid separation, merge organic layer, activated carbon takes off
Color, filtering, anhydrous sodium sulfate drying, is concentrated under reduced pressure, and product purifies by column chromatography, and eluant, eluent is petroleum ether：Ethyl acetate=5：
1 (v/v), obtain white solid product, yield 91%, purity 99.9%.1HNMR (400MHz, CDCl3)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, CDCl3)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. for C20H15NS：[M+], 301.0925.Found：m/z301.0928.
Embodiment 15
The synthetic method of 6- methyl -2- phenyl -3,4- dihydro cyclobutyl [c] quinoline is as follows：The addition pair in reaction vessel
Methylaniline 0.5mmol (53.5mg), benzaldehyde 0.5mmol (53mg), cyclobutanone 1mmol (70mg), catalyst AgOTf
0.005 mmol (1.29 mg), the mmol of HOTf 0.01 (1.5 mg), toluene 2mL.Reacted 24 hours in 120 DEG C of oil baths,
Room temperature is cooled to, adds water quenching to go out reaction, is washed three times with ethyl acetate, liquid separation, merges organic layer, activated carbon decolorizing, filtering, nothing
Aqueous sodium persulfate is dried, and is concentrated under reduced pressure, and product purifies by column chromatography, and eluant, eluent is petroleum ether：Ethyl acetate=5：1 (v/v), is obtained
To white solid product, yield 77%, purity 99.8%.1HNMR (400MHz, CDCl3)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, CDCl3)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. for C18H15N：[M+],
245.1204.Found：m/z245.1205.
Embodiment 16
The synthetic method of 6- methyl -2- phenyl -3,4- dihydro cyclopenta [c] quinoline is as follows：The addition pair in reaction vessel
Methylaniline 0.5mmol (53.5mg), benzaldehyde 0.5mmol (53mg), cyclopentanone 1mmol (84mg), catalyst AgOTf
0.005 mmol (1.29 mg), the mmol of HOTf 0.01 (1.5 mg), toluene 2mL.Reacted 24 hours in 120 DEG C of oil baths,
Room temperature is cooled to, adds water quenching to go out reaction, is washed three times with ethyl acetate, liquid separation, merges organic layer, activated carbon decolorizing, filtering, nothing
Aqueous sodium persulfate is dried, and is concentrated under reduced pressure, and product purifies by column chromatography, and eluant, eluent is petroleum ether：Ethyl acetate=5：1 (v/v), is obtained
To white solid product, yield 79%, purity 99.7%.1HNMR (400MHz, CDCl3)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, CDCl3)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. for C19H17N：[M+], 259.1361.Found：m/z259.1364.
Claims (8)
1. it is a kind of using aromatic amine, aromatic aldehyde, ketone synthesis of quinoline derivatives method, it is characterised in that：In silver trifluoromethanesulfonate
In the presence of trifluoromethanesulfonic acid, as shown in the aromatic amine compound shown in formula I, the Aromatic aldehyde compound shown in formula II and formula III
Assimilation compound reaction synthesis type IV shown in quinoline,
Formula I：；Formula II：；Formula III：；
Formula IV：；
Wherein, R1One kind in hydrogen, halogen, nitro, methyl, methoxyl group, acetyl group, substituent are located at ortho position, meta or right
Position, wherein, R1Any CH, CH in methyl, methoxyl group or acetyl group in substituent2Or CH3Group is optionally in described CH, CH2
Or CH31,2 or 3 following substituent that may be the same or different is carried on group：Halogen or nitro；
R2One kind in hydrogen, halogen, nitro, methoxyl group, methyl, substituent are located at ortho position, meta or para position；
R3 is selected from C1~C5One kind in alkyl, cycloalkyl, thienyl, phenyl；Wherein, R3Any CH, CH in substituent2Or CH3
Group is optionally in described CH, CH2Or CH31,2 or 3 following substituent that may be the same or different is carried on group：Halogen, first
Base or methoxyl group, substituent can be located at ortho position, meta or para position；
R4Selected from hydrogen or methyl；
Or R3With R4Form cyclic ketone；
Halogen is fluorine, chlorine, the substituent of bromine or iodine.
2. aromatic amine, aromatic aldehyde, the method for ketone synthesis of quinoline derivatives are utilized as claimed in claim 1, it is characterised in that：Institute
State aromatic amine compound shown in formula I for aniline, paranitroanilinum, open-chain crown ether, m-toluidine, m-fluoroaniline, to three
Methyl fluoride aniline or 3-Aminotrifluorotoluene.
3. aromatic amine, aromatic aldehyde, the method for ketone synthesis of quinoline derivatives are utilized as claimed in claim 1, it is characterised in that：Institute
It is benzaldehyde, p-tolyl aldehyde or P-methoxybenzal-dehyde to state the Aromatic aldehyde compound shown in formula II.
4. aromatic amine, aromatic aldehyde, the method for ketone synthesis of quinoline derivatives are utilized as claimed in claim 1, it is characterised in that：Institute
It is acetone, acetyl cyclohexane, acetophenone, propiophenone, 2- acetyl thiophenes, cyclobutanone or ring to state the assimilation compound shown in formula III
Pentanone.
5. aromatic amine, aromatic aldehyde, the method for ketone synthesis of quinoline derivatives are utilized as claimed in claim 1, it is characterised in that tool
Body step is as follows：In molar ratio 1 in reaction vessel：1：1.5 sequentially add aromatic amine compound shown in formula I, shown in formula II
Aromatic aldehyde compound and formula III shown in assimilation compound, be subsequently added into solvent 2 ~ 6mL/mmol aromatic amines, then add catalysis
Agent silver trifluoromethanesulfonate and trifluoromethanesulfonic acid, the addition of catalyst is respectively 0.8 ~ 2% He of aromatic amine compound mole
Reacted 18 ~ 24 hours in 1.8 ~ 3%, 115 ~ 125 DEG C of oil baths, be cooled to room temperature, extracted, be concentrated under reduced pressure, product is pure through column chromatography
Change, obtain quinoline product.
6. aromatic amine, aromatic aldehyde, the method for ketone synthesis of quinoline derivatives are utilized as claimed in claim 5, it is characterised in that：Institute
Solvent is stated as toluene, DMSO, DMF or dioxane.
7. aromatic amine, aromatic aldehyde, the method for ketone synthesis of quinoline derivatives are utilized as claimed in claim 6, it is characterised in that：Institute
It is toluene to state solvent.
8. aromatic amine, aromatic aldehyde, the method for ketone synthesis of quinoline derivatives are utilized as claimed in claim 5, it is characterised in that：Institute
The condition for stating column chromatography purifying is that eluant, eluent is the volume of the mixture of petroleum ether and ethyl acetate, petroleum ether and ethyl acetate
Than for 10：1.
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| CN107652229B (en) * | 2017-11-08 | 2020-03-31 | 沅江华龙催化科技有限公司 | Method for synthesizing quinoline derivative by oxidizing and cyclizing acetophenone and aniline compounds |
| 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 |
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