CN106380463A - Method for synthesis of quinoline derivatives - Google Patents
Method for synthesis of quinoline derivatives Download PDFInfo
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- CN106380463A CN106380463A CN201610785174.2A CN201610785174A CN106380463A CN 106380463 A CN106380463 A CN 106380463A CN 201610785174 A CN201610785174 A CN 201610785174A CN 106380463 A CN106380463 A CN 106380463A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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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
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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
- C07D215/20—Oxygen atoms
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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
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Abstract
The invention provides a method for synthesis of quinoline derivatives, wherein the method comprises the steps: successively adding aromatic amine and electron-withdrawing alkyne and ketone into a reaction vessel at a molar ratio of 1:1:(1.2-2), adding a solvent according to a ratio of adding 2-4 mL of the solvent to 1 mmol of aromatic amine, then adding a catalyst Cu(OTf)2 (copper(II) trifluoromethanesulfonate) and an additive HOTf (trifluoromethanesulfonic acid) with the addition amount respectively of 0.8%-5% and 1.8%-10% of the molar amount of aromatic amine, and under a condition of 100 DEG C-120 DEG C oil bath, carrying out a reaction for 10-24 h; cooling to room temperature, adding water, and extracting for three times with ethyl acetate; and merging organic layers, carrying out vacuum concentration, and carrying out column chromatography purification of the products, to obtain the quinoline derivative products. The method has the advantages of cheap reaction substrates, high yield, good selectivity, easy separation and purification, less pollution and simple steps.
Description
Technical field
The present invention relates to quinoline is and in particular to a kind of method of synthesis of quinoline derivatives.
Background technology
Quinoline and its derivates are the important organic heterocyclic molecules of a class, are widespread in nature, and widely should
For fields such as drug screening, chemical analyses, dye industries.Synthesis of quinoline derivatives method has a lot, mainly has：Skraup-
Doebner-Miller synthetic method, Friedlander-Pfitzinge-Combes synthetic method, Bischler-Napieralski
Synthetic method (Tetrahedron.Lett, 2000,41,531-533；Org.lett, 2004,6,3965-3968；
Eur.J.Org.Chem, 2008,2693-2696 and J.Org.Chem, 2003,68,3966-3975), wherein most widely used
Be Skraup-Doebner-Miller method.The synthetic method of the quinolines focus that always people study (referring to：
G.R.Humphrey, J.T.Kuethe, Chem, Rev, 2006,106,2875), industrial synthesis of quinoline is the most representative at present
Method have Skraup synthetic method, it is heated together with mild oxidizing agent with arylamine, concentrated sulphuric acid, glycerol, prepared quinoline.
During the course of the reaction, glycerol is subject to concentrated sulphuric acid effect dehydration at high temperature is acrylic aldehyde, then is dihydroquinoline with aniline condensation, finally
Oxidized obtain quinoline, conventional Nitrobenzol or arsenic acid are as catalyst method, but this reaction will high temperature be carried out in concentrated sulfuric acid.
Combes synthetic method, is condensed as quinoline ring with aromatic amine and beta-diketon in sour environment.This method is with arylamine and 1,3- dicarbapentaborane
Compound condensation obtains beta-amino-ketenes, and the latter carries out cyclization in the presence of concentrated sulphuric acid, obtains quinoline.But, when
In the presence of having electron withdraw group on arylamine ring, cloud density on phenyl ring can be made to reduce, thus being unfavorable for electrophilic substitution reaction
Carry out.As 1,3- dicarbonyl compound (R1-CO-CH2CO-R2) in R1With R2When different, then the condensation reaction of the first step has two
Plant possible, two kinds of beta-amino-ketenes can be generated, cyclised products are the mixture containing two kinds of isomerss.
Last century the eighties start to report transition metal-catalyzed terminal alkyne compound and ortho position carries the aniline of halogen
First occur coupling reaction to generate adjacent amino alkynes, then be cyclized prepare quinoline method (referring to：(a)Müller,T.E.；Beller,
M.Chem.Rev.1998,98,675；(b)Roundhill,D.M.Chem.Rev.1992,92,1.(c)Bryndza,H.E.；
Tam, W.Chem.Rev.1988,88,1163), be synthesis of quinoline analog derivative important method (referring to:(a)Hartung,
C.G.；Breindl,C.；Tillack,A.；Beller,M.Tetrahedron 2000,56,5157；(b)Kawatsura,M.；
Hartwig,J.F.J.Am.Chem.Soc.2000,122,9546；(c)Beller,M.；Trauthwein,H.；
Eichberger,M.；Breindl,C.；Müller,T.E.Eur.J.Inorg.Chem.1999,11.21；(d)
Trauthwein,H.；Tillack,A.；Beller,M.Chem.Commun.1999,2029；(e)Beller,M.；
Trauthwein,H.；Eichberger,M.；Breindl,C.；Herwig,J.；Müller,T.E.；Thiel,
O.R.Chem.Eur.J.1999,5,1306；(f)Beller,M.；Trauthwein,H.；Eichberger,M.；Breindl,
C.；Müller,T.E.；Zapf, A.J.Organomet.Chem.1998,566,277), successfully applied to natural product and
In the synthesis of bionical medicine (referring to：Z.Z.Shi,C.Zhang,S.Li,D.l.Pan,S.T.Ding,Y.X.Cui,N.Jiao,
Angew.Chem.Int.Ed.2009,48,4572).
Chinese patent CN104151235A discloses a kind of quinoline preparation method, is to be urged using silver trifluoromethanesulfonate
Change aniline and ketenes or the olefine aldehydr derivant synthesis of quinoline derivatives of substituent group, this patent is simple to operate, can be applied not only to
Substantial amounts of functional group, and yield is high, and product is single, is easy to separation and purification, safety is cheap, it is little to pollute.But this patent is still
So there are disadvantages that：2,4 upper quinolines for electrophilic ester group can not be prepared.
There are a lot of shortcomings in current synthetic method：Mainly severe reaction conditions, reaction temperature is high, and have needs high temperature
High pressure, separates difficult, reaction substrate limiting relatively strong, the quinoline that therefore a kind of method synthesizes substituent group is very limited.
In addition, utilizing in metal-catalyzed processes, the limited activity of catalyst, these shortcomings cause the operation easier of preparation process to increase,
Harm operator's health, environmental pollution is serious.The method of existing synthesis of quinoline derivatives also generally existing：Need active anti-
Answer substrate, reaction rate is low, the response time is longer, by-product is many and form that is difficult and reacting excessively single (leads to institute
The product of synthesis has the shortcomings that significant limitation).In consideration of it, the preparation method of the novel quinoline of research and development seems particularly
Important.
Content of the invention
For the defect existing for existing synthesis of quinoline derivatives, the technical problem to be solved is to provide one kind
The method of synthesis of quinoline derivatives, the method is simple to operate, and yield is high, and product is easily separated and purifies, and pollutes few.
For solving above-mentioned technical problem, the technical solution used in the present invention is：A kind of method of synthesis of quinoline derivatives,
Including following methods step：
In molar ratio 1 in reaction vessel：1:1.2～2 sequentially add aromatic amine I, electrophilic alkynes II, ketone III, press
1mmol aromatic amine adds the ratio of 2～4mL to add solvent, is subsequently added into catalyst Cu (OTf)2(copper trifluoromethanesulfcomposite) and
Additive HOTf (trifluoromethanesulfonic acid), addition is respectively the 0.8%～5% and 1.8%～10% of aromatic amine mole,
React 10～24h under the conditions of 100 DEG C～120 DEG C oil baths, be cooled to room temperature, add water, be extracted with ethyl acetate three times, merge organic
Layer, concentrating under reduced pressure, product, through column chromatography purification, obtains product quinoline, and the reaction expression of synthetic method is expressed as follows：
Its chemical structure of general formula of quinoline of the method synthesis is as follows：
Wherein, R1For H, C1～C6Chain-like alkyl, C1～C6Chain alkoxyl, NO2, OH, F, Cl or Br；R2For H, formic acid
Ester group, C1～C6Chain-like alkyl or phenyl；R3For pyridine radicals, C3～C6Alkyl, cycloalkyl, thienyl, aryl.
Described aromatic amine I is aniline, adjacent fluoroaniline, m-fluoroaniline, para-fluoroaniline, o-chloraniline, m-chloroaniline, right
Chloroaniline, o-bromoaniline, m-bromoaniline, para-bromoaniline, ortho-nitraniline, meta nitro aniline, paranitroanilinum, O-methoxy benzene
Amine, m-anisidine, P-nethoxyaniline, o-toluidine, m-toluidine, open-chain crown ether, adjacent trifluoromethyl aniline, three
Fluoroaniline or to trifluoromethyl aniline.
Described electrophilic alkynes II is dimethyl butyn, diethyl butyn, phenylpropiolic acid methyl ester, phenyl-allylene
Acetoacetic ester, Methyl propiolate, tetrolic acid methyl ester, ethyl propiolate or ethyl butyn.
Described ketone III be 2- acetylpyridine, o-fluoro acetophenone, a fluoro acetophenone, to fluoro acetophenone, o-chloroacetophenone,
M chloroacetophenone, parachloroacetophenone, bromophenyl ethyl ketone, m bromoacetophenone, parabromoacetophenone, o-methoxyacetophenone, a methoxy
Benzoylformaldoxime, acetanisole, o-methyl-benzene ethyl ketone, a methyl acetophenone, melilotal, adjacent trifluoroacetophenone,
Between trifluoroacetophenone, to trifluoroacetophenone, 1- pentanone, 1- hexanone, 1- heptanone, 2- acetyl thiophene or 2- acetyl pyrrole.
Described solvent is toluene, nitrile or THF.
Described column chromatography condition is：300～400 mesh silicagel columns, eluant is the mixture of ethyl acetate and petroleum ether,
Both volume ratios are 1:2～1:10.
The method that the present invention adopts a kind of synthesis of quinoline derivatives designed by technique scheme, its advantage is：
1. present invention acid consumption is few, decreases environmental pollution；
2. reaction substrate of the present invention is simple, wide material sources, is suitable for aniline (the big steric hindrance in inclusion ortho position that various functional groups replace
Functional group replace aniline), stereoeffect to reaction impact little；
3. portion of product of the present invention, such as：Reaction expression IV is upper to be pyridine substituents, can prepare the master of functional material
Core；
4. reaction substrate of the present invention is cheap, and yield is high, selectivity is good, easily separated purification, pollution are few, and step is simple, permissible
Omit protection and the deprotection synthesis step of functional group, target product quinoline is widely used in joining of organic chemical reactionses
Body, pharmaceutical intermediate and photoelectric material aspect.
Brief description
Fig. 1 represents compound 4- (pyridine -2- base) quinaldic acid's methyl ester1H NMR phenogram；
Fig. 2 represents compound 4- (pyridine -2- base) quinaldic acid's methyl ester13C NMR phenogram.
Specific embodiment
With reference to embodiment, to the present invention, a kind of method of synthesis of quinoline derivatives elaborates.
Embodiment 1
A kind of synthetic method of 4- (pyridine -2- base) quinaldic acid's methyl ester, comprises the following steps：
Aniline 1.0mmol (93mg), dimethyl butyn 1.0mmol (142.1mg) is sequentially added in reaction vessel,
2- acetylpyridine 1.2mmol (145.2mg), catalyst Cu (OTf)20.005mmol (1.8mg), HOTf 0.01mmol
(1.5mg), solvent nitrile 2mL, reacts 10h in 100 DEG C of oil baths, is cooled to room temperature, add water 5mL, is extracted with ethyl acetate three
Secondary, merge organic layer, concentrating under reduced pressure, product through column chromatography purification, 300-400 mesh silicagel column, eluant be ethyl acetate and
The mixture of petroleum ether, both volume ratios are 1:5, obtain white solid product 240.3mg, yield 91%, purity 99.9%.1H
NMR(400MHz,CDCl3)δppm:δ 8.86 (d, J=4.8Hz, 1H), 8.39 (d, J=8.4Hz, 1H), 8.33 (s, 1H),
8.24 (d, J=8.4Hz, 1H), 7.91-7.95 (td, 1H), 7.80-7.84 (m, 1H), 7.64-7.71 (m, 2H), 7.44-
7.47(m,1H),4.11(s,3H)；13C NMR(100MHz,CDCl3)δppm:δ165.8,156.1,149.8,148.4,
147.5,137.0,131.0,130.2,129.1,127.1,125.6,124.9,123.4,121.3,53.2；HRMS(EI)
Calcd.for C16H12N2O2:[M+],264.0899.Found:m/z 264.0897.
Wherein, described 4- (pyridine -2- base) quinaldic acid's methyl ester chemical structure of general formula is
Embodiment 2
A kind of synthetic method of 6- methyl -4- (pyridine -2- base) quinaldic acid's methyl ester, comprises the following steps：
Open-chain crown ether 1.0mmol (107mg), dimethyl butyn 1.0mmol is sequentially added in reaction vessel
(142.1mg), 2- acetylpyridine 1.2mmol (145.2mg), catalyst Cu (OTf)20.005mmol (1.8mg), HOTf
0.01mmol (1.5mg), solvent nitrile 2mL, react 10h in 100 DEG C of oil baths, are cooled to room temperature, add water 5mL, use acetic acid second
Ester extracts three times, merges organic layer, concentrating under reduced pressure, through column chromatography purification, 300-400 mesh silicagel column, eluant is second to product
Acetoacetic ester and the mixture of petroleum ether, both volume ratios are 1:5, obtain white solid product 267.0mg, yield 96%, purity
99.9%.1H NMR(400MHz,CDCl3)δppm:δ 8.85 (d, J=4.0Hz, 1H), 8.28 (d, J=9.6Hz, 1H), 8.27
(s,1H),7.90-7.95(m,2H),7.63-7.68(m,2H),7.43-7.46(m,1H),4.09(s,3H),2.53(s,3H)
；13C NMR(100MHz,CDCl3)δppm:δ165.9,156.4,149.8,146.6,146.5,139.6,137.0,132.6,
132.4,130.8,127.2,124.9,124.3,123.3,121.5,53.1,22.1；HRMS(EI)Calcd.for
C17H14N2O2:[M+],278.1055.Found:m/z 278.1057.
Wherein, described 6- methyl -4- (pyridine -2- base) quinaldic acid's methyl ester chemical structure of general formula is：
Embodiment 3
A kind of synthetic method of 6- methoxyl group -4- (pyridine -2- base) quinaldic acid's methyl ester, comprises the following steps：
P-nethoxyaniline 1.0mmol (123.1mg), dimethyl butyn is sequentially added in reaction vessel
1.0mmol (142.1mg), 2- acetylpyridine 1.2mmol (145.2mg), catalyst Cu (OTf)20.005mmol (1.8mg),
HOTf 0.01mmol (1.5mg), solvent nitrile 2mL, react 10h in 100 DEG C of oil baths, are cooled to room temperature, add water 5mL, uses second
Acetoacetic ester extracts three times, merges organic layer, concentrating under reduced pressure, product is through column chromatography purification, 300-400 mesh silicagel column, eluant
For the mixture of ethyl acetate and petroleum ether, both volume ratios are 1:5, obtain white solid product 273.5mg, yield 93%,
Purity 99.9%.1H NMR(400MHz,CDCl3)δppm:δ 8.85 (d, J=4.0Hz, 1H), 8.26-8.28 (m, 2H), 7.91-
7.94 (t, 1H), 7.70 (d, J=8.0Hz, 1H), 7.57 (s, 1H), 7.43-7.47 (m, 2H), 4.08 (s, 3H), 3.86 (s,
3H)；13C NMR(100MHz,CDCl3)δppm:δ165.9,159.9,156.6,149.7,145.4,144.9,144.6,
137.1,132.5,128.5,124.7,123.3,123.0,121.9,103.3,55.4,53.0；HRMS(EI)Calcd.for
C17H14N2O3:[M+],294.1004.Found:m/z 294.1007.
Wherein, described 6- methoxyl group -4- (pyridine -2- base) quinaldic acid's methyl ester chemical constitution
Formula is
Embodiment 4
A kind of synthetic method of 6- fluoro- 4- (pyridine -2- base) quinaldic acid's methyl ester, comprises the following steps：
Para-fluoroaniline 1.0mmol (111mg), dimethyl butyn 1.0mmol is sequentially added in reaction vessel
(142.1mg), 2- acetylpyridine 1.2mmol (145.2mg), catalyst Cu (OTf)20.005mmol (1.8mg), HOTf
0.01mmol (1.5mg), solvent nitrile 2mL, react 24h in 120 DEG C of oil baths, are cooled to room temperature, add water 5mL, use acetic acid second
Ester extracts three times, merges organic layer, concentrating under reduced pressure, through column chromatography purification, 300-400 mesh silicagel column, eluant is second to product
Acetoacetic ester and the mixture of petroleum ether, both volume ratios are 1:2, obtain white solid product 234.1mg, yield 83%, purity
99.9%.1H NMR(400MHz,CDCl3)δppm:δ 8.86 (d, J=4.8Hz, 1H), 8.37-8.41 (m, 1H), 8.34 (s,
1H), 7.92-7.97 (m, 2H), 7.70 (d, J=7.6Hz, 1H), 7.57-7.61 (m, 1H), 7.45-7.48 (m, 2H), 4.10
(s,3H)；13C NMR(100MHz,CDCl3)δppm:δ 165.6,160.9,155.8,149.9,146.9 (d, J=2.9Hz),
146.7 (d, J=6.0Hz), 145.6,137.2,133.7 (d, J=9.4Hz), 128.2 (d, J=10.5Hz), 124.7,
(d, J=26.1Hz), 123.6,121.9,120.7 109.4 (d, J=23.8Hz), 53.2；HRMS(EI)Calcd.for
C16H11FN2O2:[M+],282.0805.Found:m/z282.0807.
Wherein, the fluoro- 4- of described 6- (pyridine -2- base) quinaldic acid's methyl ester chemical constitution is led to
Formula is：
Embodiment 5
A kind of synthetic method of 6- chloro- 4- (pyridine -2- base) quinaldic acid's methyl ester, comprises the following steps：
Parachloroanilinum 1.0mmol (127mg), dimethyl butyn 1.0mmol is sequentially added in reaction vessel
(142.1mg), phenylacetylene 1.2mmol (122.4mg), catalyst Cu (OTf)20.005mmol (1.8mg), HOTf 0.01mmol
(1.5mg), solvent nitrile 2mL, reacts 12h in 120 DEG C of oil baths, is cooled to room temperature, add water 5mL, is extracted with ethyl acetate three
Secondary, merge organic layer, concentrating under reduced pressure, product through column chromatography purification, 300-400 mesh silicagel column, eluant be ethyl acetate and
The mixture of petroleum ether, both volume ratios are 1:3, obtain white solid product 241.4mg, yield 82%, purity 99.9%.δ
ppm:δ 8.87 (d, J=4.0Hz, 1H), 8.28-8.33 (m, 3H), 7.92-7.96 (t, 1H), 7.75 (d, J=9.2Hz, 1H),
7.69 (d, J=8.0Hz, 1H), 7.46-7.49 (m, 1H), 4.10 (s, 3H)；13C NMR(100MHz,CDCl3)δppm:δ
165.5,155.6,149.9,147.6,146.8,146.5,137.2,135.4,132.5,131.3,127.7,124.79,
124.76,123.6,122.1,53.3；HRMS(ESI-TOF)m/z calcd for C16H11ClN2O2[M+H]+298.0629,
found 298.0577.
Wherein, the chloro- 4- of described 6- (pyridine -2- base) quinaldic acid's methyl ester chemical constitution is led to
Formula is：
Embodiment 6
A kind of synthetic method of 6- bromo- 4- (pyridine -2- base) quinaldic acid's methyl ester, comprises the following steps：
Para-bromoaniline 1.0mmol (171mg), dimethyl butyn 1.0mmol is sequentially added in reaction vessel
(142.1mg), phenylacetylene 1.2mmol (122.4mg), catalyst Cu (OTf)20.005mmol (1.8mg), HOTf 0.01mmol
(1.5mg), solvent nitrile 2mL, reacts 12h in 120 DEG C of oil baths, is cooled to room temperature, add water 5mL, is extracted with ethyl acetate three
Secondary, merge organic layer, concentrating under reduced pressure, product through column chromatography purification, 300-400 mesh silicagel column, eluant be ethyl acetate and
The mixture of petroleum ether, both volume ratios are 1:3, obtain white solid product 287.3mg, yield 84%, purity 99.9%.1H
NMR(400MHz,CDCl3)δppm:δ 8.86 (d, J=4.0Hz, 1H), 8.45 (s, 1H), 8.32 (s, 1H), 8.24 (d, J=
9.2Hz, 1H), 7.92-7.96 (t, 1H), 7.88 (d, J=9.2Hz, 1H), 7.69 (d, J=7.6Hz, 1H), 7.46-7.49
(t,1H),4.11(s,3H)；13C NMR(100MHz,CDCl3)δppm:δ165.5,155.6,150.0,147.8,147.0,
146.5,137.3,133.9,132.6,128.2,128.1,124.8,123.9,123.7,122.1,53.3；HRMS(EI)
Calcd.for C16H11BrN2O2:[M+],342.0004.Found:m/z 342.0010.
Wherein, the bromo- 4- of described 6- (pyridine -2- base) quinaldic acid's methyl ester chemical structure of general formula is：
Embodiment 7
A kind of synthetic method of 7- methyl -4- (pyridine -2- base) quinaldic acid's methyl ester, comprises the following steps：
M-toluidine 1.0mmol (107mg), dimethyl butyn 1.0mmol is sequentially added in reaction vessel
(142.1mg), phenylacetylene 1.2mmol (122.4mg), catalyst Cu (OTf)20.005mmol (1.8mg), HOTf 0.01mmol
(1.5mg), solvent nitrile 2mL, reacts 12h in 120 DEG C of oil baths, is cooled to room temperature, add water 5mL, is extracted with ethyl acetate three
Secondary, merge organic layer, concentrating under reduced pressure, product through column chromatography purification, 300-400 mesh silicagel column, eluant be ethyl acetate and
The mixture of petroleum ether, both volume ratios are 1:5, obtain white solid product 253.1mg, yield 91%, purity 99.9%.1H
NMR(400MHz,CDCl3)δppm:δ 8.81 (d, J=2.8Hz, 1H), 8.25 (s, 1H), 8.15 (s, 1H), 8.10 (d, J=
8.4Hz, 1H), 7.85-7.88 (t, 1H), 7.65 (d, J=7.6Hz, 1H), 7.46 (d, J=8.4Hz, 1H), 7.39-7.41
(t,1H),4.08(s,3H),2.56(s,3H)；13C NMR(100MHz,CDCl3)δppm:δ165.8,156.2,149.8,
148.6,147.3,147.1,140.5,136.9,131.4,129.9,125.19,125.14,124.8,123.3,120.6,
53.0,21.6；HRMS(EI)Calcd.for C17H14N2O2:[M+],278.1055.Found:m/z 278.1058.
Wherein, described 7- methyl -4- (pyridine -2- base) quinaldic acid's methyl ester chemical structure of general formula is：
Embodiment 8
A kind of synthetic method of 7- methoxyl group -4- (pyridine -2- base) quinaldic acid's methyl ester, comprises the following steps：
M-anisidine 1.0mmol (123.1mg), dimethyl butyn is sequentially added in reaction vessel
1.0mmol (142.1mg), phenylacetylene 1.2mmol (122.4mg), catalyst Cu (OTf)20.005mmol (1.8mg), HOTf
0.01mmol (1.5mg), solvent nitrile 2mL, react 12h in 120 DEG C of oil baths, are cooled to room temperature, add water 5mL, use acetic acid second
Ester extracts three times, merges organic layer, concentrating under reduced pressure, through column chromatography purification, 300-400 mesh silicagel column, eluant is second to product
Acetoacetic ester and the mixture of petroleum ether, both volume ratios are 1:5, obtain white solid product 267.6mg, yield 91%, purity
99.9%.1H NMR(400MHz,CDCl3)δppm:δ 8.84 (d, J=4.4Hz, 1H), 8.20 (s, 1H), 8.13 (d, J=
9.2Hz, 1H), 7.89-7.93 (t, 1H), 7.69 (s, 1H), 7.68 (d, J=8.0Hz, 1H), 7.42-7.45 (t, 1H), 7.30
(d, J=9.2Hz, 1H), 4.10 (s, 3H), 3.98 (s, 3H)；13C NMR(100MHz,CDCl3)δppm:δ166.0,161.1,
156.4,150.5,149.8,147.7,147.2,137.0,126.7,124.9,123.4,122.6,122.5,119.6,
108.5,55.7,53.2；HRMS(EI)Calcd.for C17H14N2O3:[M+],294.1004.Found:m/z 294.1007.
Wherein, described 7- methoxyl group -4- (pyridine -2- base) quinaldic acid's methyl ester chemical structure of general formula is：
Embodiment 9
A kind of synthetic method of 8- methyl -4- (pyridine -2- base) quinaldic acid's methyl ester, comprises the following steps：
O-toluidine 1.0mmol (1107mg), dimethyl butyn 1.0mmol is sequentially added in reaction vessel
(142.1mg), phenylacetylene 1.2mmol (122.4mg), catalyst Cu (OTf)20.005mmol (1.8mg), HOTf 0.01mmol
(1.5mg), solvent nitrile 2mL, reacts 12h in 120 DEG C of oil baths, is cooled to room temperature, add water 5mL, is extracted with ethyl acetate three
Secondary, merge organic layer, concentrating under reduced pressure, product through column chromatography purification, 300-400 mesh silicagel column, eluant be ethyl acetate and
The mixture of petroleum ether, both volume ratios are 1:5, obtain white solid product 230.8mg, yield 83%, purity 99.9%.1H
NMR(400MHz,CDCl3)δppm:δ 8.84 (d, J=4.4Hz, 1H), 8.28 (s, 1H), 8.00 (d, J=8.4Hz, 1H),
7.88-7.92 (t, 1H), 7.66 (d, J=7.2Hz, 2H), 7.51-7.55 (t, 1H), 7.42-7.45 (t, 1H), 4.07 (s,
3H),2.95(s,3H)；13C NMR(100MHz,CDCl3)δppm:δ166.1,156.3,149.8,147.6,147.5,146.3,
139.1,136.8,130.3,128.8,127.2,125.0,123.4,123.2,121.2,52.9,18.3；HRMS(EI)
Calcd.for C17H14N2O2:[M+],278.1055.Found:m/z 278.1059.
Wherein, described 8- methyl -4- (pyridine -2- base) quinaldic acid's methyl ester chemical structure of general formula is：
Embodiment 10
A kind of 7- methoxyl group -2, the synthetic method of 4- diphenylquinoline, comprise the following steps：
M-anisidine 1.0mmol (123.1mg), phenylpropiolic acid methyl ester 1.0mmol is sequentially added in reaction vessel
(160.2mg), phenylacetylene 1.2mmol (122.4mg), catalyst Cu (OTf)20.005mmol (1.8mg), HOTf 0.01mmol
(1.5mg), solvent nitrile 2mL, reacts 8h in 100 DEG C of oil baths, is cooled to room temperature, add water 5mL, is extracted with ethyl acetate three
Secondary, merge organic layer, concentrating under reduced pressure, product through column chromatography purification, 300-400 mesh silicagel column, eluant be ethyl acetate and
The mixture of petroleum ether, both volume ratios are 1:5, obtain white solid product 296.4mg, yield 95%, purity 99.9%.1H
NMR(400MHz,CDCl3)1H NMR(400MHz,CDCl3)δppm:8.16 (d, J=7.6Hz, 2H), 7.79 (d, J=6.8Hz,
1H), 7.68 (s, 1H), 7.60 (s, 1H), 7.46-7.56 (m, 8H), 7.13 (d, J=9.2Hz, 1H), 4.00 (s, 3H)；13C
NMR(100MHz,CDCl3)δppm:160.8,157.3,150.6,149.2,139.8,138.6,129.5,129.3,128.8,
128.6,128.4,127.6,126.8,120.9,119.5,117.5,107.9,55.6；HRMS(ESI-TOF)m/z calcd
for C22H18NO[M+H]+312.0383,found 312.0383.
Wherein, described 7- methoxyl group -2,4- diphenylquinoline chemical structure of general formula is：
Embodiment 11
A kind of 7- trifluoromethyl -2, the synthetic method of 4- diphenylquinoline, comprise the following steps：
3-Aminotrifluorotoluene 1.0mmol (161.1mg), phenylpropiolic acid methyl ester is sequentially added in reaction vessel
1.0mmol (160.2mg), phenylacetylene 1.2mmol (122.4mg), catalyst Cu (OTf)20.005mmol (1.8mg), HOTf
0.01mmol (1.5mg), solvent nitrile 2mL, react 24h in 120 DEG C of oil baths, are cooled to room temperature, add water 5mL, use acetic acid second
Ester extracts three times, merges organic layer, concentrating under reduced pressure, through column chromatography purification, 300-400 mesh silicagel column, eluant is second to product
Acetoacetic ester and the mixture of petroleum ether, both volume ratios are 1:5, obtain white solid product 287.1mg, yield 82%, purity
99.9%.1H NMR(400MHz,CDCl3)δppm:8.54 (s, 1H), 8.18 (d, J=7.6Hz, 2H), 7.99 (d, J=
8.8Hz, 1H), 7.89 (s, 1H), 7.60 (d, J=8.8Hz, 1H), 7.46-7.59 (m, 8H)；13C NMR(100MHz,CDCl3)
δppm:(q, J=64.9), 158.2,149.3,147.9,138.9,137.7,131.3 129.9,129.5,129.0,128.9,
127.9 (q, J=8.6), 127.6,127.4,127.0,125.5,122.8,121.8 (q, J=5.8), 120.9；HRMS(ESI-
TOF)m/z calcd for C22H15F3N[M+H]+350.1151,found 350.1159.
Wherein, described 7- trifluoromethyl -2,4- diphenylquinoline chemical structure of general formula is：
Embodiment 12
A kind of synthetic method of 2- methyl -6- methoxyl group -4- phenylchinoline, comprises the following steps：
P-nethoxyaniline 1.0mmol (123.1mg), tetrolic acid methyl ester 1.0mmol is sequentially added in reaction vessel
(98.1mg), phenylacetylene 1.2mmol (122.4mg), catalyst Cu (OTf)20.005mmol (1.8mg), HOTf 0.01mmol
(1.5mg), solvent nitrile 2mL, reacts 8h in 100 DEG C of oil baths, is cooled to room temperature, add water 5mL, is extracted with ethyl acetate three
Secondary, merge organic layer, concentrating under reduced pressure, product through column chromatography purification, 300-400 mesh silicagel column, eluant be ethyl acetate and
The mixture of petroleum ether, both volume ratios are 1:10, obtain white solid product 182.6mg, yield 73%, purity 99.9%.1H NMR(400MHz,CDCl3)δppm:8.07-8.12(m,3H),7.68(s,1H),7.48-7.52(t,2H),7.36-7.44
(m, 2H), 7.19 (d, J=2.4Hz, 1H), 3.96 (s, 3H), 2.71 (s, 3H)；13C NMR(100MHz,CDCl3)δppm:
157.6,154.8,144.1,143.3,140.0,131.8,128.84,128.76,128.11,127.3,121.5,120.0,
101.9,55.6,19.2；HRMS(ESI-TOF)m/z calcd for C17H16NO[M+H]+250.1226,found
250.1229.
Wherein, described 2- methyl -6- methoxyl group -4- phenylchinoline chemical structure of general formula is：
Embodiment 13
A kind of synthetic method of 7,8,9,10- tetrahydrochysene phenanthridines -6- carboxylate methyl esters, comprises the following steps：
Aniline 1.0mmol (93mg), dimethyl butyn 1.0mmol (142.1mg) is sequentially added in reaction vessel,
Ketohexamethylene 1.5mmol (147.2mg), catalyst Cu (OTf)20.005mmol (1.8mg), HOTf 0.01mmol (1.5mg), molten
Agent nitrile 2mL, reacts 12h in 120 DEG C of oil baths, is cooled to room temperature, add water 5mL, is extracted with ethyl acetate three times, merges organic
Layer, concentrating under reduced pressure, through column chromatography purification, 300-400 mesh silicagel column, eluant is ethyl acetate and the mixing of petroleum ether to product
Thing, both volume ratios are 1:10, obtain white solid product 226.6mg, yield 94%, purity 99.9%.1H NMR
(400MHz,CDCl3)δppm:δ 8.15 (d, J=8.4Hz, 1H), 7.96 (d, J=8.0Hz, 1H), 7.66-7.70 (t, 1H),
7.58-7.62(t,1H),4.10(s,3H),3.18-3.19(t,2H),3.04-3.07(t,2H),1.95-1.98(m,2H),
1.85-1.90(m,2H)；13C NMR(100MHz,CDCl3)δppm:δ167.4,150.4,144.8,143.5,130.4,
128.7,128.2,128.1,127.7,127.4,52.7,26.5,25.6,22.1,21.8；HRMS(EI)Calcd.for
C15H15NO2:[M+],241.1103.Found:m/z 241.1108.
Wherein, 7,8,9,10- described tetrahydrochysene phenanthridines -6- carboxylate methyl ester chemical structure of general formula are：
Embodiment 14
A kind of 2- methyl -7, the synthetic method of 8,9,10- tetrahydrochysene phenanthridines -6- carboxylate methyl esters, comprise the following steps：
Open-chain crown ether 1.0mmol (107mg), dimethyl butyn 1.0mmol is sequentially added in reaction vessel
(142.1mg), Ketohexamethylene 1.5mmol (147.2mg), catalyst Cu (OTf)20.005mmol (1.8mg), HOTf 0.01mmol
(1.5mg), solvent nitrile 2mL, reacts 12h in 120 DEG C of oil baths, is cooled to room temperature, add water 5mL, is extracted with ethyl acetate three
Secondary, merge organic layer, concentrating under reduced pressure, product through column chromatography purification, 300-400 mesh silicagel column, eluant be ethyl acetate and
The mixture of petroleum ether, both volume ratios are 1:5, obtain white solid product 247.4mg, yield 97%, purity 99.9%.1H
NMR(400MHz,CDCl3)δppm:δ 8.03 (d, J=8.4Hz, 1H), 7.70 (s, 1H), 7.50 (d, J=8.4Hz, 1H),
4.02(s,3H),3.12-3.15(t,2H),3.03-3.06(t,2H),2.55(s,3H),1.92-1.98(m,2H),1.83-
1.88(m,2H)；13C NMR(100MHz,CDCl3)δppm:δ167.5149.3,143.4,142.8,137.9,131.0,
130.2,128.5,128.2,121.5,52.7,26.6,25.8,22.3,22.1,21.9；HRMS(EI)Calcd.for
C16H17NO2:[M+],255.1259.Found:m/z 255.1257.
Wherein, described 2- methyl -7,8,9,10- tetrahydrochysene phenanthridines -6- carboxylate methyl ester chemical structure of general formula are：
Embodiment 15
A kind of 2- trifluoromethyl -7, the synthetic method of 8,9,10- tetrahydrochysene phenanthridines -6- carboxylate methyl esters, comprise the following steps：
P-trifluoromethylaniline 1.0mmol (161mg), dimethyl butyn is sequentially added in reaction vessel
1.0mmol (142.1mg), Ketohexamethylene 1.5mmol (147.2mg), catalyst Cu (OTf)20.005mmol (1.8mg), HOTf
0.01mmol (1.5mg), solvent nitrile 2mL, react 12h in 120 DEG C of oil baths, are cooled to room temperature, add water 5mL, use acetic acid second
Ester extracts three times, merges organic layer, concentrating under reduced pressure, through column chromatography purification, 300-400 mesh silicagel column, eluant is second to product
Acetoacetic ester and the mixture of petroleum ether, both volume ratios are 1:10, obtain white solid product 268.9mg, yield 87%, purity
99.9%.1H NMR(400MHz,CDCl3)δppm:δ 8.26-8.28 (m, 2H), 7.84-7.87 (dd, J=8.8,1.6Hz,
1H),4.05(s,3H),3.21-3.24(t,2H),3.04-3.07(t,2H),1.98-2.04(m,2H),1.87-1.93(m,
2H)；13C NMR(100MHz,CDCl3)δppm:δ166.9,152.6,145.9,144.7,131.5,129.2(q),127.2
(q),125.4,124.3(q),122.7,120.6(q),52.8,26.3,25.6,21.9,21.5；HRMS(EI)Calcd.for
C16H14F3NO2:[M+],309.0977.Found:m/z 309.0964.
Wherein, described 2- trifluoromethyl -7,8,9,10- tetrahydrochysene phenanthridines -6- carboxylate methyl ester chemical structure of general formula are：
The present invention has developed aniline, electrophilic alkynes and the ketone synthesis quinoline that a kind of utilization silver trifluoromethanesulfonate is catalyzed substituent group
The method of quinoline derivant, the method is applicable not only to the aniline of supplied for electronic replacement, also has preferable product for electrophilic aniline
Rate.This method is a kind of novel method that is cheap, efficiently preparing substituted quinoline derivatives easy and simple to handle, safe.With existing
Technology is compared, and the method can be applied not only to substantial amounts of functional group, and simple to operate, yield is high, and product is single, is easy to point
From with purification, safety is cheap, it is little to pollute.
Claims (6)
1. a kind of method of synthesis of quinoline derivatives, is characterized in that including following methods step：
In molar ratio 1 in reaction vessel：1:1.2～2 sequentially add aromatic amine I, electrophilic alkynes II, ketone III, by 1mmol
Aromatic amine adds the ratio of 2～4mL to add solvent, is subsequently added into catalyst copper trifluoromethanesulfcomposite Cu (OTf)2With additive three
Fluorine methanesulfonic acid HOTf, addition is respectively the 0.8%～5% and 1.8%～10% of aromatic amine mole, 100 DEG C～120
React 10～24h under the conditions of DEG C oil bath, be cooled to room temperature, add water, be extracted with ethyl acetate three times, merge organic layer, decompression is dense
Contracting, product, through column chromatography purification, obtains product quinoline, and the reaction expression of synthetic method is expressed as follows：
Its chemical structure of general formula of quinoline of the method synthesis is as follows：
Wherein, R1For H, C1～C6Chain-like alkyl, C1～C6Chain alkoxyl, NO2, OH, F, Cl or Br；R2For H, formic acid ester group,
C1～C6Chain-like alkyl or phenyl；R3For pyridine radicals, C3～C6Alkyl, cycloalkyl, thienyl, aryl.
2. the method for a kind of synthesis of quinoline derivatives according to claim 1, is characterized in that described aromatic amine I is benzene
Amine, adjacent fluoroaniline, m-fluoroaniline, para-fluoroaniline, o-chloraniline, m-chloroaniline, parachloroanilinum, o-bromoaniline, m-bromoaniline, right
Bromaniline, ortho-nitraniline, meta nitro aniline, paranitroanilinum, o-aminoanisole, m-anisidine, to methoxybenzene
Amine, o-toluidine, m-toluidine, open-chain crown ether, adjacent trifluoromethyl aniline, a trifluoromethyl aniline or to trifluoromethyl aniline.
3. the method for a kind of synthesis of quinoline derivatives according to claim 1, is characterized in that described electrophilic alkynes II
For dimethyl butyn, diethyl butyn, phenylpropiolic acid methyl ester, ethyl phenylpropiolate, Methyl propiolate, tetrolic acid first
Ester, ethyl propiolate or ethyl butyn.
4. the method for a kind of synthesis of quinoline derivatives according to claim 1, is characterized in that described ketone III is 2- acetyl
Yl pyridines, o-fluoro acetophenone, a fluoro acetophenone, to fluoro acetophenone, o-chloroacetophenone, m chloroacetophenone, parachloroacetophenone, adjacent bromine
1-Phenylethanone., m bromoacetophenone, parabromoacetophenone, o-methoxyacetophenone, meta-methoxy 1-Phenylethanone., acetanisole, neighbour
Methyl acetophenone, a methyl acetophenone, melilotal, adjacent trifluoroacetophenone, a trifluoroacetophenone, to trifluoroacetophenone,
1- pentanone, 1- hexanone, 1- heptanone, 2- acetyl thiophene or 2- acetyl pyrrole.
5. the method for a kind of synthesis of quinoline derivatives according to claim 1, it is characterized in that described solvent be toluene,
Nitrile or THF.
6. the method for a kind of synthesis of quinoline derivatives according to claim 1, is characterized in that described column chromatography condition is：
300～400 mesh silicagel columns, eluant is the mixture of ethyl acetate and petroleum ether, and both volume ratios are 1:2～1:10.
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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 |
| CN107892668A (en) * | 2017-11-08 | 2018-04-10 | 沅江华龙催化科技有限公司 | A kind of synthetic method of quinoline |
| CN109851554A (en) * | 2017-11-30 | 2019-06-07 | 中国科学院大连化学物理研究所 | A method of preparing trifluoromethanesulfonic acid -6- quinoline ester derivant |
Citations (1)
| 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 |
-
2016
- 2016-08-30 CN CN201610785174.2A patent/CN106380463B/en active Active
Patent Citations (1)
| 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 |
Non-Patent Citations (2)
| Title |
|---|
| HONGFENG LI ET AL.: "Silver-catalyzed cascade reaction of o-aminoaryl compounds with alkynes: an aniline mediated synthesis of 2-substituted quinolines", 《TETRAHEDRON LETTERS》 * |
| SACHIN S. PATIL ET AL.: "Synthesis of Aminoindolizine and Quinoline Derivatives via Fe(acac)3/TBAOH-Catalyzed Sequential Cross-Coupling–Cycloisomerization Reactions", 《SYNLETT》 * |
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| 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 |
| CN107892668A (en) * | 2017-11-08 | 2018-04-10 | 沅江华龙催化科技有限公司 | A kind of synthetic method of quinoline |
| 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 |
| 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 |
| CN109851554A (en) * | 2017-11-30 | 2019-06-07 | 中国科学院大连化学物理研究所 | A method of preparing trifluoromethanesulfonic acid -6- quinoline ester derivant |
| CN109851554B (en) * | 2017-11-30 | 2022-05-17 | 中国科学院大连化学物理研究所 | Method for preparing trifluoromethanesulfonic acid-6-quinoline ester derivative |
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