CN108516956A - A kind of environment-friendly preparation method thereof of bis- quinoline ethylene compounds of 1,2- - Google Patents
A kind of environment-friendly preparation method thereof of bis- quinoline ethylene compounds of 1,2- Download PDFInfo
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- CN108516956A CN108516956A CN201810744768.8A CN201810744768A CN108516956A CN 108516956 A CN108516956 A CN 108516956A CN 201810744768 A CN201810744768 A CN 201810744768A CN 108516956 A CN108516956 A CN 108516956A
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- quinoline
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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
-
- 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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- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The present invention relates to a kind of environment-friendly preparation method thereofs of 1,2 2 quinoline ethylene compounds.Prepared 1,2 two quinoline ethylene compounds structural formulas are as shown in Fig. 1, wherein R1、R2、R3、R4、R5For hydrogen atom, alkyl, alkoxy, halogen, trifluoromethyl, trifluoromethoxy, cyano.Preparation method：2 methylquinoline class compounds, alkali and solvent are in room temperature to 150oIt is stirred 1 48 hours under C.It is quenched after reaction, organic solvent extraction, concentration, purification obtain 1,2 two quinoline ethylene compounds, yield is 28~82%.The features such as present invention has reaction temperature low, and reaction condition is mild, synthesis technology is simple, easy to operate.
Description
Technical field
The present invention relates to a kind of environment-friendly preparation method thereofs of bis- quinoline ethylene compounds of 1,2-.
Background technology
2- methylquinoline analog derivatives are a kind of important nitrogen-containing heterocycle compound, many derivatives containing quinoline ring structure
Object has significant antiulcer, anti-malarial, anticancer and antiviral isoreactivity.People are just isolated from plant very early can
2- substituted chinoline derivatives for treating cutaneous Leishmaniasis（Journal of Natural Products,1993,
56:1547-1552）；2007, the researchers such as Zeng also detected that proliferative induction can be carried out to Rat Mesenchymal Stem Cells
The positions 2- have vinyl substituent quinoline（Journal of Applied Crystallography,2007,
40:471-475）.Report also seldom, involved method about the synthesis of 1,2-, bis- quinoline ethylene compounds both at home and abroad at present
2- methylquinolines are oxidized to 2- quinoline aldehydes by mainly two-step synthesis method with oxidant first, then with 2- methylquinolines
Carry out coupling reaction.2011, Cao seminars just reported 2- methylquinolines SeO first2It is oxidized to 2- quinoline first
Aldehyde, then using 2- methylquinolines and 2- quinoline aldehydes as substrate, under the action of acetic anhydride, 2- first of the high―temperature nuclei containing vinyl
Base quinoline dimer method (Angewandte Chemie International Edition,2011, 50:10216-
10220).But this method is complicated for operation, and post-processing is cumbersome and needs hot conditions, does not meet Atom economy and green is feasible
Property.And the present invention is directly using 2- methylquinoline class compounds as raw material, in a mild condition can a step prepare 1,2-, bis- quinoline
Ethylene compounds.Therefore in comparison, the present invention has reaction temperature low, and reaction condition is mild, synthesis technology is simple, operation
The features such as simple.
Invention content
Present invention aims at provide a kind of environment-friendly preparation method thereof of bis- quinoline ethylene compounds of 1,2-.
To achieve the above object, 1,2-, bis- quinoline ethylene compounds structures provided by the invention are as shown in Figure 1, wherein
R1、R2、R3、R4、R5For hydrogen atom, alkyl, alkoxy, halogen, trifluoromethyl, trifluoromethoxy, cyano.System provided by the invention
Preparation Method has main steps that：2- methylquinoline classes compound, alkali and solvent are in room temperature to 150oIt is stirred 1-48 hours under C.Instead
It is quenched after answering, organic solvent extraction, concentration, purification obtain 1,2-, bis- quinoline ethylene compounds, yield is 28~82%.
Gained compound is through nmr spectrum（1H-NMR and13C-NMR）Confirm, structure is errorless.
The present invention can directly commercially using substituted or unsubstituted 2- methylquinolines class compound.
The alkali that the present invention uses is cesium carbonate, potassium tert-butoxide, sodium hydroxide, potassium hydroxide, sodium hydride, sodium methoxide, hydrogen-oxygen
Change lithium, double trimethyl silane potassamides, n-BuLi.
The solvent that the present invention uses is dimethyl sulfoxide (DMSO), hexamethylphosphoramide, n,N-Dimethylformamide, toluene.
Eluant, eluent used in the column chromatography of the present invention is petroleum ether or alkane etc..
Description of the drawings
Fig. 1 is the structure chart of bis- quinoline ethylene compounds of 1,2-；
Fig. 2 is the detailed process figure of reaction.
Specific implementation mode
Its reaction process is as shown in Fig. 2, in Fig. 2 reaction equations：Wherein R1、R2、R3、R4、R5For hydrogen atom, alkyl, alkoxy,
Halogen, trifluoromethyl, trifluoromethoxy, cyano.
Specific preparation method citing one：0.2 mM of 2- methylquinoline, 0.4 mM of potassium tert-butoxide and 1 milliliter six
Methyl phosphoric triamide mixes, and reaction 48 hours is sufficiently stirred at 40 DEG C.Saturated ammonium chloride is used after reaction
Aqueous solution is quenched, organic solvent extraction, dry, filters, concentration, and column chromatography purification obtains 2- [2- (quinoline -2- bases) ethylene
Base]-quinoline, yield 82%.Nuclear magnetic resonance spectroscopy1HNMR (400MHz, CDCl3) δ: 8.18 (d, 2H, J = 8.5
Hz), 8.12 (d, 2H, J = 8.4 Hz), 7.95 (s, 2H), 7.82-7.78 (m, 4H), 7.73 (t, 2H,
J = 7.6 Hz), 7.53 (t, 2H, J = 7.4 Hz);Carbon-13 nmr spectra13C NMR (100 MHz, CDCl3) δ:
155.4, 148.3, 136.5, 134.6, 129.8, 129.4, 127.6, 127.5, 126.6, 119.5。
Specific preparation method citing two：0.2 mM of 2,6- dimethyl quinoline, 0.4 mM of potassium tert-butoxide and 1 milli
It rises hexamethylphosphoramide to mix, reaction 48 hours is sufficiently stirred at 40 DEG C.After reaction with saturation chlorine
Change aqueous ammonium to be quenched, organic solvent extraction is dry, filters, concentration, and column chromatography purification obtains 2- [2- (6- methylquinolines -2-
Base) vinyl]-quinoline, yield 46%.Nuclear magnetic resonance spectroscopy1H NMR (400 MHz,CDCl3) δ: 8.09 (d, 2H, J
= 8.6 Hz), 8.00 (d, 2H, J = 8.4 Hz), 7.90 (s, 2H), 7.80 (d, 2H, J = 8.6 Hz),
7.56 (d, 4H, J = 9.2 Hz), 2.55 (s, 6H);Carbon-13 nmr spectra13C NMR (100 MHz, CDCl3)
δ: 154.7, 146.9, 136.6, 135.8, 134.3, 132.1, 129.1, 127.6, 126.4, 119.4,
21.6。
Specific preparation method citing three：0.2 mM of 6- methoxyl group -2- methylquinoline, 0.4 mM of potassium tert-butoxide
（Alkali）It is mixed with 1 milliliter of hexamethylphosphoramide, reaction 48 hours is sufficiently stirred at 40 DEG C.Reaction terminates
It is quenched afterwards with saturated aqueous ammonium chloride, organic solvent extraction is dry, filters, concentration, and 2- [2- (6- first is arrived in column chromatography purification
Phenoxyl quinoline -2- bases) vinyl]-quinoline, yield 79%.Nuclear magnetic resonance spectroscopy1H NMR (400 MHz,CDCl3) δ:
8.06 (d, 2H, J = 8.5 Hz), 8.00 (d, 2H, J = 9.3 Hz), 7.85 (s, 2H), 7.78 (d,
2H, J = 8.5Hz), 7.38 (dd, 2H, J = 2.2 Hz, J = 9.1 Hz), 7.08 (d, 2H, J = 2.0
Hz), 3.95 (s, 6H);Carbon-13 nmr spectra13C NMR (100 MHz, CDCl3) δ: 171.1, 157.9,
153.3, 135.2, 133.6, 130.8, 128.6, 122.4, 119.7, 105.2, 55.6。
The present invention relates to the environment-friendly preparation method thereofs of 1,2- of one kind, bis- quinoline ethylene compounds, with 2- methylquinoline class chemical combination
The features such as object is raw material, has reaction temperature low, and reaction condition is mild, synthesis technology is simple, easy to operate.Above-mentioned specific implementation
Citing is only the preferred embodiments of the present invention, is not that the invention has other forms of limitations.
Claims (5)
1. a kind of green synthesis method of structure 1,2-, bis- quinoline ethylene compounds as shown in Figure 1, has main steps that：
A) 2- methylquinoline class compounds and alkali and organic solvent are added in reaction tube, room temperature to 150o1- is reacted under C
48 hours；
B) it is quenched after reaction with saturated aqueous ammonium chloride, organic solvent extraction is dry, filters, concentration；
C) column chromatography purifies, and eluant, eluent is petroleum ether or alkane etc., obtains 1,2-, bis- quinoline ethylene compounds.
2. preparation method according to claim 1, it is characterised in that：The alkali is cesium carbonate, potassium tert-butoxide, hydroxide
Sodium, potassium hydroxide, sodium hydride, sodium methoxide, lithium hydroxide, double trimethyl silane potassamides, n-BuLi.
3. preparation method according to claim 2, it is characterised in that：The best alkali is potassium tert-butoxide.
4. preparation method according to claim 1, it is characterised in that：The reaction dissolvent is dimethyl sulfoxide (DMSO), pregnancy
Base phosphoric triamide, n,N-Dimethylformamide, toluene；Optimum solvent is hexamethylphosphoramide.
5. preparation method according to claim 1, it is characterised in that：The 2- methylquinoline class compounds and alkali is rubbed
You are than being 0.1: 1-1:0.1.
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107118586A (en) * | 2016-02-24 | 2017-09-01 | 中国科学技术大学 | The purposes of the vinyl compound of nitrogen heterocycle substitution |
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- 2018-07-09 CN CN201810744768.8A patent/CN108516956A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107118586A (en) * | 2016-02-24 | 2017-09-01 | 中国科学技术大学 | The purposes of the vinyl compound of nitrogen heterocycle substitution |
Non-Patent Citations (1)
| Title |
|---|
| HE, LIN ET AL.: "Titania Supported Iridium Subnanoclusters as an Efficient Heterogeneous Catalyst for Direct Synthesis of Quinolines from Nitroarenes and Aliphatic Alcohols", 《ANGEW. CHEM. INT. ED.》 * |
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Application publication date: 20180911 |