CN105175327B - A kind of synthetic method of quinoline - Google Patents
A kind of synthetic method of quinoline Download PDFInfo
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- CN105175327B CN105175327B CN201510687848.0A CN201510687848A CN105175327B CN 105175327 B CN105175327 B CN 105175327B CN 201510687848 A CN201510687848 A CN 201510687848A CN 105175327 B CN105175327 B CN 105175327B
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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
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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
- C07D215/18—Halogen atoms or nitro radicals
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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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- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F17/00—Metallocenes
- C07F17/02—Metallocenes of metals of Groups 8, 9 or 10 of the Periodic System
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Abstract
The invention belongs to technical field of organic synthesis, and in particular to a kind of synthetic method of quinoline.The present invention in molar ratio 1：1~1.4：1.3~4 add aromatic amine, aldehyde and alcohol into reaction vessel successively, add solvent, it is subsequently added into catalyst AgOTf, additive HOTf, addition is respectively the 0.8%~2% of aromatic amine mole, 1.8%~4%, and 15~24h is reacted under the conditions of 100~120 DEG C of oil baths, room temperature is cooled to, extraction, it is concentrated under reduced pressure, product is purified by column chromatography, obtains quinoline.Products collection efficiency of the present invention is high, purity is high, selectivity is good, easily separated purifying; reaction pollution is few; operating procedure is simple; protection and the deprotection synthesis step of functional group can be omitted; low cost, in terms of target product quinoline is widely used in the part, pharmaceutical intermediate and photoelectric material of organic chemical reactionses.
Description
Technical field
The invention belongs to technical field of organic synthesis, and in particular to a kind of synthetic method of quinoline.
Background technology
Quinoline derivatives are the important heterocyclic compounds of a class, are widely used in drug screening, chemical analysis, dye
Expect the fields such as industry.The chemical method of quinoline is typically the beta-unsaturated aldehyde using amino benzenes compounds as initiation material and α
Or that Michael additions, cyclization, dehydrogenation etc. occur under conditions of the concentrated sulfuric acid or concentrated hydrochloric acid is a series of anti-for ketone or derivatives thereof
Synthesis of quinoline analog derivative should be carried out.But, there are many shortcomings in these synthetic methods：Severe reaction conditions, reaction temperature is high, pressure
Power is high, and accessory substance is more, and product separation is difficult, and course of reaction needs the amount of acid too big, it is easy to etching apparatus, the requirement to equipment
Height, reaction it is substrate limiting relatively strong, the structure of the quinoline of synthesis is single, and the quinoline of synthesis substituent has
Limit, it is difficult to synthesize the quinoline of 2 and 4 substitutions.
Although transition metal-catalyzed method avoids the use of the inorganic acids such as the concentrated sulfuric acid or concentrated hydrochloric acid, raw material alkynes
Normal foul smelling smell, endangers operator's health, and environmental pollution is serious, and is gas less than the alkynes of 4 carbon atoms, reacts
Journey needs HTHP, and course of reaction is complicated and safety factor is difficult to control to, moreover, the limited activity of catalyst, separates and return
Receive difficult, further result in the operation difficulty increase of preparation process.
Chinese patent CN104151235A discloses a kind of quinoline preparation method, is urged using silver trifluoromethanesulfonate
Change the aniline and ketenes or olefine aldehydr derivative synthesis of quinoline derivatives of substituent, the patent procedure is simple, can be applied not only to
Substantial amounts of functional group, and yield is high, and product is single, is easy to separate and purifies, safety is cheap, it is small to pollute.But the patent is still
So there are some shortcomings：Such as reaction substrate ketenes or the synthesis of olefine aldehydr needs and purification, reactions steps are relative complex, and reaction bottom
The stereoeffect of thing amine is obvious, and when substitution has the functional group of steric hindrance on aromatic amine ortho position, reaction effect is bad.
The content of the invention
To overcome drawbacks described above, it is an object of the invention to provide a kind of synthetic method of quinoline.
A kind of quinoline, chemical structure of general formula is as follows：
Wherein, R1For-H, C1~C6 Chain-like alkyl, C1~C6Chain alkoxy ,-NO2、-OH、-Br、-Cl、-F、-CF3
Or ferrocenyl；R2For-H, C1~C6Chain-like alkyl, thienyl, pyrrole radicals, cyclohexyl, phenyl, aminomethyl phenyl, methoxyl group
Phenyl, bromo phenyl or nitrobenzophenone；R3For-H, C1~C6Chain-like alkyl or phenyl.
The reaction expression of synthetic method is expressed as follows：
。
To achieve the above object, the present invention is adopted the following technical scheme that：
A kind of synthetic method of quinoline, comprises the following steps：
In molar ratio 1 in reaction vessel：1~1.4：1.3~4 sequentially add aromatic amine, aldehyde and alcohol, by 1 mmol fragrance
The ratio that amine adds 3~8 mL solvent adds solvent, is subsequently added into catalyst AgOTf（Silver trifluoromethanesulfonate）, additive
HOTf（Trifluoromethanesulfonic acid）, addition is respectively the 0.8%~2% of aromatic amine mole, 1.8%~4%, 100~120 DEG C of oil baths
Under the conditions of react 12~24 h, be cooled to room temperature, extract, be concentrated under reduced pressure, product by column chromatography purifying, obtain quinoline derivatives
Thing.
According to the synthetic method of above-mentioned quinoline, described aromatic amine is aniline, adjacent fluoroaniline, m-fluoroaniline,
Para-fluoroaniline, o-chloraniline, m-chloroaniline, parachloroanilinum, o-bromoaniline, m-bromoaniline, para-bromoaniline, ortho-nitraniline,
Nitroaniline, paranitroanilinum, o-aminoanisole, m-anisidine, P-nethoxyaniline, o-toluidine, a methyl
Aniline, open-chain crown ether, o-trifluoromethyl aniline, 3-Aminotrifluorotoluene, p-trifluoromethylaniline, adjacent ferrocene aniline,
Ferrocene aniline or to ferrocene aniline.
According to the synthetic method of above-mentioned quinoline, described aldehyde is for benzaldehyde, a tolyl aldehyde, to methylbenzene
Formaldehyde, P-methoxybenzal-dehyde, paranitrobenzaldehyde, o-bromobenzaldehye, p-bromobenzaldehyde, m-methoxybenzaldehyde, a nitro
Benzaldehyde, formaldehyde, acetaldehyde, n-hexyl aldehyde, hexahydrobenzaldehyde, 2 thiophene carboxaldehyde or 2- pyrrole aldehydes.
According to the synthetic method of above-mentioned quinoline, described alcohol is benzyl carbinol, ethanol, normal propyl alcohol, n-amyl alcohol, just
Hexanol, ring propyl alcohol, cyclopentanol, cyclohexanol or suberol.
According to the synthetic method of above-mentioned quinoline, described solvent is toluene, THF or 1,2- dichloroethanes.
According to the synthetic method of above-mentioned quinoline, described column chromatography condition is：300~400 mesh silicagel columns, are washed
De- agent is the mixture of ethyl acetate and petroleum ether, and both volume ratios are 1: 10.
The positive beneficial effect of the present invention：
1. the present invention is using aromatic amine, aldehyde and alcohol come synthesis of quinoline derivatives, reaction substrate is simple, and aromatic amine source is wide
It is general, it is adapted to the aniline of various functional group's substitutions（There is the aromatic amine of functional group's substitution of steric hindrance including ortho position）, stereoeffect is to anti-
The influence answered is small；And alcohol replace traditional raw material in alkynes use, alcohol as a kind of valency it is low be easy to get and non-hazardous raw material, subtract
Lack environmental pollution, meanwhile, alcohol is in a liquid state, and operation is fairly simple；Acid consumption of the invention is few, reduces environmental pollution；
2. products collection efficiency of the present invention is high, purity is high, selectivity is good, easily separated purifying, reaction pollution is few, operating procedure letter
It is single, it is convenient to omit the protection of functional group and deprotection synthesis step, low cost, target product quinoline have been widely used in
In terms of part, pharmaceutical intermediate and the photoelectric material of chemical machine reaction.
Embodiment
With reference to some embodiments, the present invention is further described.
Embodiment 1
The synthetic method of one kind 2,4- diphenylquinolines, comprises the following steps：
The mmol of aniline 0.5 is sequentially added in reaction vessel（46.5 mg）, the mmol of benzaldehyde 0.5（53 mg）, benzene second
The mmol of alcohol 0.75（91.6 mg）, the mmol of catalyst AgOTf 0.005 (1.29 mg), the mmol (1.5 of HOTf 0.01
Mg), the mL of solvent toluene 2,20 h are reacted in 120 DEG C of oil baths, room temperature is cooled to, and add water 5 mL, is extracted with ethyl acetate 3
It is secondary, merge organic layer, be concentrated under reduced pressure, product by column chromatography purify, 300-400 mesh silicagel columns, eluant, eluent be ethyl acetate with
The mixture of petroleum ether, both volume ratios are 1:10, obtain white solid product, yield 89%, purity 99.9%.1H NMR
(500 MHz, CDCl3) ppm: 8.43 (d, J = 8.0 Hz, 1H), 8.34 (d, J = 8.0 Hz, 2H),
8.00 (d, J = 8.5 Hz, 1H), 7.92 (s, 1H), 7.80 (t, 1H), 7.51 - 7.64 (m, 9H); 13C
NMR (500 MHz, 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。
Wherein, described 2,4- diphenylquinoline chemical structure of general formula is。
Embodiment 2
A kind of synthetic method of 6- methyl -2,4- diphenylquinoline, comprises the following steps：
The mmol of open-chain crown ether 0.5 is sequentially added in reaction vessel（53.5 mg）, the mmol of benzaldehyde 0.5（53
mg）, the mmol of benzyl carbinol 0.75（91.6 mg）, the mmol of catalyst AgOTf 0.004 (1.03 mg), the mmol of HOTf 0.015
(2.25 mg), the mL of solvent toluene 2,21 h are reacted in 110 DEG C of oil baths, room temperature is cooled to, and add water 5 mL, and 3 are extracted with ether
It is secondary, merge organic layer, be concentrated under reduced pressure, product by column chromatography purify, 300-400 mesh silicagel columns, eluant, eluent be ethyl acetate with
The mixture of petroleum ether, both volume ratios are 1:10, obtain light yellow solid product, yield 89%, purity 99.9%.1H
NMR (400 MHz, CDCl3) δ ppm: 8.13 - 8.18 (q, 3H), 7.77 (s, 1H), 7.65 (s, 1H),
7.88 (s, 1H), 7.49 - 7.57 (m, 8H), 7.43 - 7.46 (m, 1H), 2.47 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ ppm: 156.1, 148.5, 147.4, 139.8, 138.7, 136.3, 131.8,
129.9, 129.6, 129.2, 128.8, 128.6, 128.3, 127.5, 125.7, 124.4, 119.6, 21.8;
HRMS (EI) Calcd. for C22H17N: [M+], 295.1361. Found: m/z 295.1364。
Wherein, the chemical structure of general formula of 6- methyl -2,4- diphenylquinoline is。
Embodiment 3
A kind of synthetic method of 6- methoxyl groups -2,4- diphenylquinoline, comprises the following steps：
The mmol of P-nethoxyaniline 0.5 is sequentially added in reaction vessel（61.5 mg）, the mmol of benzaldehyde 0.5（53
mg）, the mmol of benzyl carbinol 0.85（103.8 mg）, the mmol of catalyst AgOTf 0.005 (1.29 mg), the mmol of HOTf 0.01
(1.5 mg), solvent 1, the mL of 2- dichloroethanes 1.5 reacts 12 h in 120 DEG C of oil baths, is cooled to room temperature, and add water 5 mL, uses
Ethyl acetate is extracted 4 times, is merged organic layer, is concentrated under reduced pressure, and product is purified by column chromatography, 300-400 mesh silicagel columns, eluant, eluent
For ethyl acetate and the mixture of petroleum ether, both volume ratios are 1:10, light yellow solid product is obtained, yield 76% is pure
Degree 99.5%.1H NMR (400 MHz, CDCl3) δ ppm: 8.20 (t, 3H), 7.81 (t, 1H), 7.53 - 7.62
(m, 7H), 7.42 - 7.49 (m, 2H), 7.22 (d, J = 3.0 Hz, 1H), 3.83 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ ppm: 157.9, 154.5, 147.8, 145.1, 139.8, 138.9, 131.8,
129.5, 129.1, 128.9, 128.8, 128.4, 127.4, 126.8, 121.9, 119.6, 103.8, 55.4;
HRMS (EI) Calcd. for C22H17NO: [M+], 311.1310. Found: m/z 311.1304。
Wherein, the general structure of 6- methoxyl groups -2,4- diphenylquinoline is。
Embodiment 4
The synthetic method of above-mentioned fluoro- 2, the 4- diphenylquinolines of 6-, comprises the following steps：
The mmol of para-fluoroaniline 0.5 is added in reaction vessel（55.5 mg）, the mmol of benzaldehyde 0.6（63.7 mg）, benzene
The mmol of ethanol 0.75（91.6 mg）, the mmol of catalyst AgOTf 0.005 (1.29 mg), the mmol (1.65 of HOTf 0.011
Mg), the mL of solvent THF 4,24 h are reacted in 110 DEG C of oil baths, room temperature is cooled to, and add water 5 mL, is extracted with ethyl acetate 3
It is secondary, merge organic layer, be concentrated under reduced pressure, product by column chromatography purify, 300-400 mesh silicagel columns, eluant, eluent be ethyl acetate with
The mixture of petroleum ether, both volume ratios are 1:10, obtain light yellow solid product, yield 89%, purity 99.9%.1H
NMR (400 MHz, CDCl3) δ ppm: 8.24 (d, J = 8.8 Hz, 1H), 8.18 (d, J = 7.6 Hz,
2H), 7.93 (d, J = 8.0 Hz, 1H), 7.80 (s, 1H), 7.72 (m, 1H), 7.45 - 7.54 (m,
6H), 7.35 (d, J = 8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ ppm: 156.9, 149.1,
148.9, 139.4, 138.3, 137.0,135.6,130.0,129.6, 129.5, 129.4, 129.3, 127.5,
126.0, 125.8, 125.7, 119.2; HRMS (EI) Calcd. for C21H14NF: [M+], 299.1110.
Found: m/z 299.1111。
Wherein, the chemical structure of general formula of fluoro- 2, the 4- diphenylquinolines of 6- is。
Embodiment 5
A kind of 6- comprises the following steps to the synthetic method of trifluoromethyl -2,4- diphenylquinoline：
The mmol of p-trifluoromethylaniline 0.5 is added in reaction vessel（80.5 mg）, the mmol of benzaldehyde 0.5（53
mg）, the mmol of benzyl carbinol 0.75（91.6 mg）, the mmol of catalyst AgOTf 0.0045 (1.16 mg), the mmol of HOTf 0.01
(1.5 mg), the mL of toluene 2,16 h are reacted in 120 DEG C of oil baths, room temperature is cooled to, and add water 5 mL, is extracted with ethyl acetate 3
It is secondary, merge organic layer, be concentrated under reduced pressure, product by column chromatography purify, 300-400 mesh silicagel columns, eluant, eluent be ethyl acetate with
The mixture of petroleum ether, both volume ratios are 1:10, obtain light yellow solid product, yield 72%, purity 99.9%.1H
NMR (400 MHz, CDCl3) δ ppm: 8.32 (d, J = 8.8 Hz, 1H), 8.20 (t, 3H), 7.87 (d,J = 8.0 Hz, 2H), 7.44 - 7.55 (m, 8H); 13C NMR (100 MHz, DMSO-d 6 ) 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/z 349.1064。
Wherein, 6- is to the chemical structure of general formula of trifluoromethyl -2,4- diphenylquinoline。
Embodiment 6
A kind of 6- methyl 4-phenyls -2-（4- aminomethyl phenyls）The synthetic method of quinoline, comprises the following steps：
The mmol of open-chain crown ether 0.5 is added in reaction vessel（53.5 mg）, the mmol of p-tolyl aldehyde 0.5（60
mg）, the mmol of benzyl carbinol 0.65（79.4 mg）, the mmol of catalyst AgOTf 0.005 (1.29 mg), the mmol of HOTf 0.01
(1.5 mg), the mL of solvent THF 2,24 h are reacted in 120 DEG C of oil baths, room temperature is cooled to, and add water 5 mL, is extracted with dichloromethane
Take 2 times, merge organic layer, be concentrated under reduced pressure, product is purified by column chromatography, 300-400 mesh silicagel columns, and eluant, eluent is ethyl acetate
With the mixture of petroleum ether, both volume ratios are 1:10, obtain light yellow solid product, yield 90%, purity 99.9%.1H
NMR (400 MHz, CDCl3) δ ppm: 8.32 (d, J = 8.8 Hz, 1H), 8.20 (t, 3H), 7.87 (d,J = 8.0 Hz, 2H), 7.44 - 7.55 (m, 8H); 13C NMR (100 MHz, DMSO-d 6 ) 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/z 349.1064。
Wherein, 6- methyl 4-phenyls -2-（4- aminomethyl phenyls）The chemical structure of general formula of quinoline is。
Embodiment 7
A kind of 6- methoxyl groups -4- phenyl -2-（4- aminomethyl phenyls）The synthetic method of quinoline, comprises the following steps：
The mmol of P-nethoxyaniline 0.5 is added in reaction vessel（61.5 mg）, the mmol of p-tolyl aldehyde 0.55
（66.1 mg）, the mmol of benzyl carbinol 0.75（91.6 mg）, the mmol of catalyst AgOTf 0.0075 (1.93 mg), HOTf
0.012 mmol (1.8 mg), the mL of solvent toluene 2.24 h are reacted in 100 DEG C of oil baths, room temperature is cooled to, add water 5 mL,
It is extracted with ethyl acetate 3 times, merges organic layer, be concentrated under reduced pressure, product is purified by column chromatography, 300-400 mesh silicagel columns, elution
Agent is the mixture of ethyl acetate and petroleum ether, and both volume ratios are 1:10, obtain light yellow solid product, yield 90%,
Purity 99.4%.1H NMR (400 MHz, CDCl3) δ ppm: 8.77 (d, J = 7.2 Hz, 1H), 8.19 (d, J
= 7.6 Hz, 2H), 7.91 (m, 2H), 7.81 (s, 1H), 7.60 - 7.81 (m, 5H), 7.81 (d, J =
7.2 Hz, 2H), 3.95 (s, 3H), 2.58 (s, 3H); 13C NMR (100 MHz, CDCl3) δ ppm:
160.6, 157.6, 150.3, 147.1, 139.8, 138.9, 129.2, 128.82, 128.80, 128.75,
127.6, 126.6, 125.0, 121.7, 119.3, 118.1, 108.2, 55.6, 38.6; HRMS (EI) Calcd.
for C23H19NO: [M+], 325.1467. Found: m/z 325.1470。
Wherein, 6- methoxyl groups -4- phenyl -2-（4- aminomethyl phenyls）The chemical structure of general formula of quinoline is。
Embodiment 8
A kind of fluoro- 4- phenyl -2- of 6-（4- aminomethyl phenyls）The synthetic method of quinoline, comprises the following steps：
The mmol of para-fluoroaniline 0.5 is added in reaction vessel（55.5 mg）, the mmol of p-tolyl aldehyde 0.5（60
mg）, the mmol of benzyl carbinol 0.85（103.8 mg）, the mmol of catalyst AgOTf 0.005 (1.29 mg), HOTf 0.013
Mmol (1.95 mg), the mL of solvent toluene 3,24 h are reacted in 120 DEG C of oil baths, room temperature is cooled to, and add water 5 mL, uses ether
Extraction 3 times, merges organic layer, is concentrated under reduced pressure, and product is purified by column chromatography, 300-400 mesh silicagel columns, and eluant, eluent is acetic acid second
The mixture of ester and petroleum ether, both volume ratios are 1:10, obtain light yellow solid product, yield 80%, purity 99.7%.1H NMR (400 MHz, CDCl3) δ ppm: 8.24 (q, 1H), 8.11 (d, J = 8.5 Hz, 2H), 7.85
(s, 1H), 7.50 - 7.61 (m, 7H), 7.36 (d, J = 8.0 Hz, 2H), 2.47 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ ppm: 161.5, 159.5, 156.3, 148.6, 145.9, 139.5, 138.1,
136.6, 132.5, 129.6, 129.4, 128.8, 128.6, 127.4, 119.7, 119.4, 108.9, 21.3;
HRMS (EI) Calcd. for C22H16NF: [M+], 313.1267. Found: m/z 313.1271。
Wherein, the fluoro- 4- phenyl -2- of 6-（4- aminomethyl phenyls）The chemical structure of general formula of quinoline is。
Embodiment 9
A kind of synthetic method of 8- methyl 4-phenyls -2- phenylchinolines, comprises the following steps：
The mmol of o-toluidine 0.5 is added in reaction vessel（53.5 mg）, the mmol of benzaldehyde 0.5（53 mg）, benzene
The mmol of ethanol 0.85（103.8 mg）, the mmol of catalyst AgOTf 0.005 (1.29 mg), the mmol (1.5 of HOTf 0.01
Mg), the mL of solvent toluene 2,24 h are reacted in 120 DEG C of oil baths, room temperature is cooled to, and add water 5 mL, are extracted with ethyl acetate 4 times,
Merge organic layer, be concentrated under reduced pressure, product is purified by column chromatography, 300-400 mesh silicagel columns, eluant, eluent is ethyl acetate and oil
The mixture of ether, both volume ratios are 1:10, obtain light yellow solid product, yield 78%, purity 99.7%.1H NMR
(400 MHz, CDCl3) δ ppm: 8.27 (d, J = 8.0 Hz, 2H), 7.82 (s, 1H), 7.71 (d, J =
8.4 Hz, 2H),7.41 - 7.56 (m, 9H), 7.32 (t, 1H), 2.95 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ ppm: 155.0, 149.4, 147.8, 139.9, 139.0, 138.0, 129.7, 129.3, 128.8,
128.6, 128.3, 127.6, 126.0, 125.8, 123.7, 118.7, 18.5; HRMS (EI) Calcd. for
C22H17N: [M+], 295.1361. Found: m/z 295.1364。
A kind of chemical structure of general formula of 8- methyl 4-phenyls -2- phenylchinolines is。
Embodiment 10
A kind of synthetic method of 8- ferrocenyls -2- phenylchinolines, comprises the following steps：
The adjacent mmol of ferrocene aniline 0.5 is added in reaction vessel（142 mg）, the mmol of benzaldehyde 0.5（53 mg）, second
Alcohol 2 mmol, catalyst AgOTf 0.005 mmol (1.29 mg), the mmol of HOTf 0.013 (1.95 mg), solvent toluene 3
ML, 24 h are reacted in 120 DEG C of oil baths, room temperature is cooled to, and add water 5 mL, are extracted with ethyl acetate 3 times, are merged organic layer, are subtracted
Pressure concentration, product is purified by column chromatography, 300-400 mesh silicagel columns, and eluant, eluent is the mixture of ethyl acetate and petroleum ether, two
Person's volume ratio is 1:10, obtain light yellow solid product, yield 64%, purity 99.8%.1H NMR (400 MHz, CDCl3)δppm: 8.02 (d, J = 8.4 Hz, 1H), 7.73 (d, J = 8.4 Hz, 1H), 7.58 (t, 1H), 7.42
- 7.48 (m, 6H), 7.35 (t, 1H), 4.99 (t, 2H), 4.38 (d, 2H), 3.99 (s, 5H); 13C
NMR (100 MHz, CDCl3) δppm: 159.1, 148.8, 147.8, 138.5, 129.7, 129.5, 129.3,
128.7, 128.4, 125.7, 125.5, 125.4, 119.7, 84.1, 70.5, 69.8, 68.1; HRMS (EI)
Calcd. for C25H19FeN: [M+], 389.0867. Found: m/z 389.0865.
A kind of chemical structure of general formula of 8- ferrocenyls -2- phenylchinolines is。
Embodiment 11
A kind of synthetic method of 7- methyl -2,4- diphenylquinoline, comprises the following steps：
The mmol of m-toluidine 0.5 is added in reaction vessel（53.5 mg）, the mmol of benzaldehyde 0.55（58.4 mg）,
The mmol of benzyl carbinol 0.75（85.5 mg）, the mmol of catalyst AgOTf 0.005 (1.29 mg), the mmol (1.5 of HOTf 0.01
Mg), the mL of toluene 2,15 h are reacted in 120 DEG C of oil baths, room temperature is cooled to, and add water 5 mL, are extracted 3 times with dichloromethane, are closed
And organic layer, it is concentrated under reduced pressure, product is purified by column chromatography, 300-400 mesh silicagel columns, eluant, eluent is ethyl acetate and petroleum ether
Mixture, both volume ratios be 1:10, obtain light yellow solid product, yield 84%, purity 99.9%.1H NMR
(400 MHz, CDCl3) δ ppm: 8.11 (s, 1H), 7.99 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H),
7.38 - 7.44 (m, 4H), 7.23 - 7.29 (m, 7H), 2.58 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ ppm: 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/z 295.1364。
Wherein, the chemical structure of general formula of 7- methyl -2,4- diphenylquinoline is。
Embodiment 12
A kind of synthetic method of 7- methoxyl groups -2,4- diphenylquinoline, comprises the following steps：
The mmol of m-anisidine 0.5 is added in reaction vessel（61.5 mg）, the mmol of benzaldehyde 0.5（53 mg）,
The mmol of benzyl carbinol 0.65（79.4 mg）, the mmol of catalyst AgOTf 0.004 (1.03 mg), the mmol of HOTf 0.009
(1.35 mg), solvent 1, the mL of 2- dichloroethanes 3 reacts 24 h in 100 DEG C of oil baths, is cooled to room temperature, and add water 5 mL, uses
Ethyl acetate is extracted three times, is merged organic layer, is concentrated under reduced pressure, and product is purified by column chromatography, 300-400 mesh silicagel columns, elution
Agent is the mixture of ethyl acetate and petroleum ether, and both volume ratios are 1:10, obtain light yellow solid product, yield 82%,
Purity 99.9%.1H NMR (400 MHz, CDCl3) δ ppm: 7.92 (s, 1H), 7.66 (m, 1H), 7.45 (d,J = 6.0 Hz, 1H), 7.35 (t, 2H), 7.11 - 7.23 (m, 9H), 3.91 (s, 3H); 13C NMR (100
MHz, CDCl3) δppm: 159.5, 157.9, 148.1, 137.0, 132.8, 130.9, 130.0, 129.8,
129.2, 128.5, 128.1, 127.9, 127.8, 126.9, 126.1, 122.3, 106.7, 55.79; HRMS
(EI) Calcd. for C 22 H 17 NO: [M+], 311.1310. Found: m/z 311.1314。
Wherein, the chemical structure of general formula of 7- methoxyl groups -2,4- diphenylquinoline is。
Embodiment 13
A kind of synthetic method of fluoro- 2, the 4- diphenylquinolines of 7-, comprises the following steps：
The mmol of m-fluoroaniline 0.5 is added in reaction vessel（55.5 mg）, the mmol of benzaldehyde 0.5（53 mg）, benzene second
The mmol of alcohol 0.75（91.6 mg）, the mmol of catalyst AgOTf 0.005 (1.29 mg), the mmol (1.5 of HOTf 0.01
Mg), the mL of solvent toluene 2,22 h are reacted in 100 DEG C of oil baths, room temperature is cooled to, and add water 5 mL, is extracted with ethyl acetate 3
It is secondary, merge organic layer, be concentrated under reduced pressure, product by column chromatography purify, 300-400 mesh silicagel columns, eluant, eluent be ethyl acetate with
The mixture of petroleum ether, both volume ratios are 1:10, obtain light yellow solid product, yield 89%, purity 99.9%.1H
NMR (400 MHz, CDCl3) δ ppm: 8.16 (d, J = 8.0 Hz, 1H), 8.02 (d, J = 8.0 Hz,
2H), 7.82 (d, J = 8.4 Hz, 2H), 7.73 (s, 1H), 7.66(m, 1H), 7.38 - 7.49 (m,
6H); 13C NMR (100 MHz, CDCl3) δ ppm: 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 C21H14FN: [M+], 299.1110. Found: m/z 299.1114.
Wherein, the chemical structure of general formula of fluoro- 2, the 4- diphenylquinolines of 7- is。
Embodiment 14
A kind of synthetic method of the fluoro- 2- methyl 4-phenyls quinoline of 6-, comprises the following steps：
The mmol of para-fluoroaniline 0.5 is added in reaction vessel（55.5 mg）, the mmol of acetaldehyde 0.7（30.8 mg）, benzene second
The mmol of alcohol 0.8（97.7 mg）, the mmol of catalyst AgOTf 0.005 (1.29 mg), the mmol of HOTf 0.01 (1.5 mg),
The mL of solvent toluene 2,23 h are reacted in 110 DEG C of oil baths, room temperature is cooled to, and add water 5 mL, are extracted with ethyl acetate 3 times, are closed
And organic layer, it is concentrated under reduced pressure, product is purified by column chromatography, 300-400 mesh silicagel columns, eluant, eluent is ethyl acetate and petroleum ether
Mixture, both volume ratios be 1:10, obtain light yellow solid product, yield 84%, purity 99.4%.1H NMR (400
MHz, CDCl3) δ ppm: 7.54 (d, J = 7.2 Hz, 2H), 7.38 - 7.42 (t, 2H), 7.34 (m,
1H), 7.07 (m, 1H), 6.95 - 7.00 (m, 2H), 6.77 (s, 1H); 13C NMR (100 MHz, CDCl3)
δ ppm: 159.3, 156.9, 144.4, 142.3, 139.7, 128.7, 127.3, 127.2, 120.9, 120.6,
116.1, 115.9, 112.3, 21.7; HRMS (EI) Calcd. for C16H12FN: [M+], 237.0954.
Found: m/z 237.0952。
Wherein, the chemical structure of general formula of the fluoro- 2- methyl 4-phenyls quinoline of 6- is。
Embodiment 15
A kind of synthetic method of 4- methyl -2- phenylchinolines, comprises the following steps：
The mmol of aniline 0.5 is added in reaction vessel（46.5 mg）, the mmol of benzaldehyde 0.5（53 mg）, normal propyl alcohol 2
Mmol, catalyst AgOTf 0.005 mmol (1.29 mg), the mmol of HOTf 0.01 (1.5 mg), the mL of solvent THF 4,
22 h are reacted in 110 DEG C of oil baths, room temperature is cooled to, add water 5 mL, are extracted 3 times with dichloromethane, merge organic layer, are depressurized dense
Contracting, product is purified by column chromatography, 300-400 mesh silicagel columns, and eluant, eluent is the mixture of ethyl acetate and petroleum ether, Liang Zheti
Product is than being 1:10, obtain light yellow solid product, yield 63%, purity 99.7%.1H NMR (400 MHz, CDCl3) δ
ppm: 8.13 (d, J = 8.8 Hz, 1H), 8.01 (s, 1H), 7.77 (d, J = 8.0 Hz, 1H), 7.64 -
7.68 (m, 1H), 7.58 - 7.60 (m, 2H), 7.41 - 7.53 (m, 4H), 2.46 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ ppm: 152.4, 148.1, 145.4, 136.7, 129.9, 129.3, 128.6,
128.1, 127.5, 127.2, 126.1, 125.9, 117.7; HRMS (EI) Calcd. for C16H13N: [M+],
219.1048. Found: m/z 219.1046。
Wherein, the chemical structure of general formula of 4- methyl -2- phenylchinolines is。
Embodiment 16
A kind of 6- comprises the following steps to the synthetic method of trifluoromethyl -4- butyl -2- phenylchinolines：
The mmol of p-trifluoromethylaniline 0.5 is added in reaction vessel（80.5 mg）, the mmol of benzaldehyde 0.5（53
mg）, n-hexyl alcohol 2 mmol, catalyst AgOTf 0.005 mmol (1.29 mg), the mmol of HOTf 0.02 (3 mg), solvent
The mL of toluene 3,24 h are reacted in 120 DEG C of oil baths, room temperature is cooled to, and add water 5 mL, are extracted with ethyl acetate 3 times, are associated with
Machine layer, is concentrated under reduced pressure, and product is purified by column chromatography, 300-400 mesh silicagel columns, and eluant, eluent is mixing for ethyl acetate and petroleum ether
Compound, both volume ratios are 1:10, obtain light yellow solid product, yield 88%, purity 99.9%.1H NMR (400
MHz, CDCl3) δ ppm: 8.31 (s, 1H), 8.26 (d, J = 8.4 Hz, 1H), 8.15 - 8.17 (m,
2H), 7.86 (d, J = 8.4 Hz, 1H), 7.78 (s, 1H), 7.53 (t, J = 7.8 Hz, 2H), 7.48
(t, J = 7.5 Hz, 1H), 3.14 (t, J = 7.8 Hz, 2H), 1.77 - 1.82 (m, 2H), 1.48 -
1.52 (m, 2H),1.00 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ ppm: 159.0,
150.3, 149.5, 139.2, 131.5, 129.8, 128.9, 127.7, 125.7, 124.9, 121.4, 121.4,
119.6, 32.2, 32.0, 22.7, 13.9; HRMS (EI) Calcd. for C20H18F3N : [M+], 329.1391.
Found: m/z 329.1375。
Wherein, 6- is to the chemical structure of general formula of trifluoromethyl -4- butyl -2- phenylchinolines。
Claims (5)
1. a kind of synthetic method of quinoline, it is characterised in that comprise the following steps：
In molar ratio 1：1~1.4：1.3~4 add aromatic amine, aldehyde and alcohol into reaction vessel successively, add by 1mmol aromatic amines
The ratio for entering 3~8mL solvent adds solvent, is subsequently added into catalyst AgOTf, additive HOTf, addition is respectively fragrance
0.8%~2%, the 1.8%~4% of amine mole, reacts 12~24h, is cooled to room temperature under the conditions of 100~120 DEG C of oil baths, extract
Take, be concentrated under reduced pressure, product is purified by column chromatography, obtains quinoline；
Described alcohol is benzyl carbinol, ethanol, normal propyl alcohol, n-amyl alcohol or n-hexyl alcohol.
2. the synthetic method of quinoline according to claim 1, it is characterised in that described aromatic amine be aniline,
Adjacent fluoroaniline, m-fluoroaniline, para-fluoroaniline, o-chloraniline, m-chloroaniline, parachloroanilinum, o-bromoaniline, m-bromoaniline, to bromine
Aniline, ortho-nitraniline, meta nitro aniline, paranitroanilinum, o-aminoanisole, m-anisidine, P-nethoxyaniline,
O-toluidine, m-toluidine, open-chain crown ether, o-trifluoromethyl aniline, 3-Aminotrifluorotoluene, to trifluoromethylbenzene
Amine, adjacent ferrocene aniline, a ferrocene aniline or to ferrocene aniline.
3. the synthetic method of quinoline according to claim 1, it is characterised in that described aldehyde be benzaldehyde,
Tolyl aldehyde, p-tolyl aldehyde, P-methoxybenzal-dehyde, paranitrobenzaldehyde, o-bromobenzaldehye, p-bromobenzaldehyde,
Methoxybenzaldehyde, m-nitrobenzaldehyde, formaldehyde, acetaldehyde, n-hexyl aldehyde, hexahydrobenzaldehyde, 2 thiophene carboxaldehyde or 2- pyrroles's first
Aldehyde.
4. the synthetic method of quinoline according to claim 1, it is characterised in that described solvent is toluene, THF
Or 1,2- dichloroethanes.
5. the synthetic method of quinoline according to claim 1, it is characterised in that described column chromatography condition is：
300~400 mesh silicagel columns, eluant, eluent is the mixture of ethyl acetate and petroleum ether, and both volume ratios are 1:10.
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| CN110724094B (en) * | 2019-10-29 | 2022-06-14 | 陕西科技大学 | Quinoline compound and synthesis method thereof |
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| CN113563391B (en) * | 2021-07-19 | 2023-11-21 | 河南中烟工业有限责任公司 | Method for synthesizing ferrocenyl coumarin quinoline compound by using composite catalyst |
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| CN104151235A (en) * | 2014-08-07 | 2014-11-19 | 南阳师范学院 | Preparation method for quinoline derivatives |
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| CN104151235A (en) * | 2014-08-07 | 2014-11-19 | 南阳师范学院 | Preparation method for quinoline derivatives |
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