CN105693632A - Preparation method of polysubstitution quinoxalin derivatives - Google Patents

Preparation method of polysubstitution quinoxalin derivatives Download PDF

Info

Publication number
CN105693632A
CN105693632A CN201610028051.4A CN201610028051A CN105693632A CN 105693632 A CN105693632 A CN 105693632A CN 201610028051 A CN201610028051 A CN 201610028051A CN 105693632 A CN105693632 A CN 105693632A
Authority
CN
China
Prior art keywords
solvent
preparation
derivatives
aryl
alkoxyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN201610028051.4A
Other languages
Chinese (zh)
Other versions
CN105693632B (en
Inventor
崔秀灵
沈金海
程国林
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Huaqiao University
Original Assignee
Huaqiao University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Huaqiao University filed Critical Huaqiao University
Priority to CN201610028051.4A priority Critical patent/CN105693632B/en
Publication of CN105693632A publication Critical patent/CN105693632A/en
Application granted granted Critical
Publication of CN105693632B publication Critical patent/CN105693632B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
    • C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
    • C07D241/40—Benzopyrazines
    • C07D241/42—Benzopyrazines with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
    • C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Electroluminescent Light Sources (AREA)

Abstract

The invention discloses a preparation method of polysubstitution quinoxalin derivatives. The method has the reaction equation as follows (please see the equation in the description). By means of the method, quinoxalin derivatives which are not easy to obtain through other methods and have various substituent groups can be synthesized.

Description

A kind of preparation method of polysubstituted quinoxaline derivant
Technical field
The invention belongs to technical field of organic synthesis, the preparation method being specifically related to a kind of polysubstituted quinoxaline derivant。
Background technology
Quinoxaline derivant be a class important there is benzopyrazines heterocyclic compounds, there is biological activity widely, in antitumor, antidepressant, antiinflammatory and anti HIV-1 virus medicine, be respectively provided with important using value。Therefore, the novel synthesis research of quinoxaline compounds and the like has important applying value, receives the concern of association area researcher。
The synthesis of tradition quinoxaline compounds obtains mainly through double; two dehydration condensations of o-phenylenediamine Yu 1,2-dicarbonyl compound。In the method, when asymmetric o-phenylenediamine and asymmetric 1,2-dicarbonyl compound reaction, the regioselectivity of reaction is uncontrollable, generally yields isomer, but not single product。
Summary of the invention
It is an object of the invention to overcome prior art defect, it is provided that the preparation method of a kind of polysubstituted quinoxaline derivant。
The concrete technical scheme of the present invention is as follows:
A kind of preparation method of polysubstituted quinoxaline derivant, the structural formula of prepared polysubstituted quinoxaline derivant is as follows:
Wherein, R1For hydrogen, halogen, alkyl, aryl, substituted aryl, acyl group, amino, nitro or alkoxyl；
R2For hydrogen, halogen, alkyl, aryl, substituted aryl, acyl group, amino, nitro or alkoxyl；
R3For hydrogen, halogen, alkyl, aryl, substituted aryl, acyl group, amino, nitro or alkoxyl；
R4For hydrogen, halogen, alkyl, aryl, substituted aryl, acyl group, amino, nitro or alkoxyl；
R5For hydrogen, halogen, alkyl, aryl, substituted aryl, acyl group, amino, nitro or alkoxyl；
R6For hydrogen, halogen, alkyl, aryl, substituted aryl, acyl group, amino, nitro or alkoxyl；
The reaction equation of the method is as follows:
Described solvent one is water, methanol, ethanol, isopropanol, toluene；Described solvent two is dimethyl sulfoxide, DMF, N,N-dimethylacetamide or METHYLPYRROLIDONE。
Comprise the steps: in a preferred embodiment of the invention
(1) corresponding acetylenic ketone or derivatives thereof, corresponding o-phenylenediamine or derivatives thereof and solvent one are placed in reaction vessel, react 4～22h in 48～85 DEG C；
(2) solvent one in step (1) gained material is evaporated, adds alkali and solvent two, react 1～6h in 20～55 DEG C, add suitable quantity of water after having reacted or sodium chloride solution terminates reaction；
(3) by after the product diluted ethyl acetate of step (2), then through washing, organic facies is obtained；
(4) by step (3) gained organic facies drying, filtration, concentration and column chromatography purification, described polysubstituted quinoxaline derivant is obtained；
Wherein, the mol ratio of corresponding acetylenic ketone or derivatives thereof, corresponding o-phenylenediamine or derivatives thereof and alkali is 1:1～1.5:1.5～2.5, every mole of corresponding acetylenic ketone or derivatives thereof correspondence 2～12L solvent one and 2～12L solvent two。
In a preferred embodiment of the invention, corresponding acetylenic ketone or derivatives thereof is 1:1.2 with the mol ratio of corresponding o-phenylenediamine or derivatives thereof。
In a preferred embodiment of the invention, every mole of corresponding acetylenic ketone or derivatives thereof correspondence 3～10L solvent one and 3～10L solvent two。
In a preferred embodiment of the invention, described alkali is sodium hydroxide, potassium hydroxide, potassium tert-butoxide, sodium tert-butoxide, Feldalat NM or cesium carbonate。
In a preferred embodiment of the invention, the reaction temperature of described step (1) is 50～80 DEG C, and the response time is 5～20h。
In a preferred embodiment of the invention, the reaction temperature of described step (2) is 20～50 DEG C, and the response time is 1～5h。
The invention has the beneficial effects as follows:
1, the present invention can synthesize the quinoxaline derivant with multiple substituent group that additive method is difficult to obtain；
2, the method for the present invention is raw materials used is easy to get, and yield is high, and reaction condition is gentle, and the response time is short, and substrate spectrum is wide, and reaction specificity is strong, and post processing is easy and green。
Detailed description of the invention
Below by way of detailed description of the invention technical scheme it is further detailed and describes。
Embodiment 1
The preparation of 2,3-diphenylquinoxaline
1,3-diphenylprop-2-alkynes-1-ketone 0.5mmol, o-phenylenediamine 0.6mmol, methanol 5mL is added in the reaction tube of 10mL, be placed in the oil bath of 50 DEG C, react 24h；Boil off methanol, add potassium hydroxide 1mmol, dimethyl sulfoxide 3mL, be placed in the oil bath of 20 DEG C, react 5h。Add suitable quantity of water or sodium chloride solution stopped reaction, be cooled to room temperature。Reactant liquor diluted ethyl acetate, washes three times, organic facies anhydrous Na2SO4Dry, to filter, concentration, column chromatography purification obtains 112.8mg target product, and yield is 80%。The nuclear-magnetism of this compound is characterized as below:1HNMR(400MHz,CDCl3) δ 8.23 8.11 (m, 2H), 7.80 7.74 (m, 2H), 7.57 7.48 (m, 4H), 7.39 7.30 (m, 6H)；13CNMR(100MHz,CDCl3)δ153.4,141.2,139.0,129.9,129.8,129.2,128.7,128.2.。
Embodiment 2
The preparation of 5-methyl-2,3-diphenylquinoxaline
1,3-diphenylprop-2-alkynes-1-ketone 0.5mmol, 3-methyl-o-phenylenediamine 0.6mmol, ethanol 3mL is added in the reaction tube of 10mL, be placed in the oil bath of 80 DEG C, react 24h；Boil off ethanol, add potassium hydroxide 1mmol, N-Methyl pyrrolidone 2mL, be placed in the oil bath of 30 DEG C, react 5h。Add suitable quantity of water or sodium chloride solution stopped reaction, be cooled to room temperature。Reactant liquor diluted ethyl acetate, washes three times, organic facies anhydrous Na2SO4Dry, to filter, concentration, column chromatography purification obtains 91.8mg target product, and yield is 62%。The nuclear-magnetism of this compound is characterized as below:1HNMR(400MHz,CDCl3) δ 8.00 (d, J=8.2Hz, 1H), 7.69 7.48 (m, 6H), 7.33 (dd, J=12.4,5.1Hz, 6H), 2.86 (s, 3H)；13CNMR(100MHz,CDCl3)δ152.8,151.7,141.1,140.4,139.4,139.3,137.6,130.1,129.8,129.7,128.7,128.3,128.1,126.9,17.1。
Embodiment 3
The preparation of 5-methyl-2,3-diphenylquinoxaline
1,3-diphenylprop-2-alkynes-1-ketone 0.5mmol, 4-methyl-o-phenylenediamine 0.6mmol, isopropanol 5mL is added in the reaction tube of 10mL, be placed in the oil bath of 60 DEG C, react 18h；Boil off isopropanol, add potassium tert-butoxide 1mmol, dimethyl sulfoxide 3mL, be placed in the oil bath of 25 DEG C, react 2h。Add suitable quantity of water or sodium chloride solution stopped reaction, be cooled to room temperature。Reactant liquor diluted ethyl acetate, washes three times, organic facies anhydrous Na2SO4Dry, to filter, concentration, column chromatography purification obtains 93.2mg target product, and yield is 63%。The nuclear-magnetism of this compound is characterized as below:1HNMR(400MHz,CDCl3) δ 8.06 (d, J=8.5Hz, 1H), 7.95 (s, 1H), 7.60 (dd, J=8.6,1.8Hz, 1H), 7.54 7.46 (m, 4H), 7.38 7.30 (m, 6H), 2.61 (s, 3H)；13CNMR(100MHz,CDCl3)δ153.3,152.6,141.3,140.5,139.7,139.2,132.3,129.8,129.8,128.7,128.7,128.6,128.2,128.0,21.9。
Embodiment 4
The preparation of the fluoro-2,3-diphenylquinoxaline of 6-
1,3-diphenylprop-2-alkynes-1-ketone 0.5mmol, 4-fluorine o-phenylenediamine 0.6mmol, methanol 1.5mL is added in the reaction tube of 10mL, be placed in the oil bath of 60 DEG C, react 18h；Boil off methanol, add potassium tert-butoxide 1mmol, DMF 5mL, be placed in the oil bath of 30 DEG C, react 5h。Add suitable quantity of water or sodium chloride solution stopped reaction, be cooled to room temperature。Reactant liquor diluted ethyl acetate, washes three times, organic facies anhydrous Na2SO4Dry, to filter, concentration, column chromatography purification obtains 108.0mg target product, and yield is 72%。The nuclear-magnetism of this compound is characterized as below:1HNMR(400MHz,CDCl3) δ 8.17 (dd, J=9.2,5.7Hz, 1H), 7.80 (dd, J=9.2,2.8Hz, 1H), 7.60 7.48 (m, 5H), 7.43 7.29 (m, 6H).13CNMR(100MHz,CDCl3) δ 164.1,161.6,154.2,152.8 (d, J=3.2Hz), 141.9 (d, J=13.3Hz), 138.8, (138.7,138.4 d, J=0.6Hz), 131.2 (d, J=10.1Hz), 129.8,129.8,129.0128.9,128.3,120.3 (d, J=26.1Hz), 112.6 (d, J=21.5Hz)。
Embodiment 5
The preparation of the chloro-2,3-diphenylquinoxaline of 6-
1,3-diphenylprop-2-alkynes-1-ketone 0.5mmol, 4-chlorine o-phenylenediamine 0.6mmol, water 4mL is added in the reaction tube of 10mL, be placed in the oil bath of 80 DEG C, react 18h；Boil off water, add sodium tert-butoxide 1mmol, DMF 5mL, be placed in the oil bath of 20 DEG C, react 5h。Add suitable quantity of water or sodium chloride solution stopped reaction, be cooled to room temperature。Reactant liquor diluted ethyl acetate, washes three times, organic facies anhydrous Na2SO4Dry, to filter, concentration, column chromatography purification obtains 91.6mg target product, and yield is 58%。The nuclear-magnetism of this compound is characterized as below:1HNMR(400MHz,CDCl3) δ 8.17 (d, J=2.2Hz, 1H), 8.10 (d, J=8.9Hz, 1H), 7.70 (dd, J=8.9,2.3Hz, 1H), 7.57 7.46 (m, 4H), 7.43 7.26 (m, 6H)；13CNMR(100MHz,CDCl3)δ154.2,153.6,141.4,139.7,138.7,138.6,135.6,131.0,130.4,129.8,129.8,129.1,129.0,128.3,128.3,128.0。
Embodiment 6
The preparation of the 6-tert-butyl group-2,3-diphenylquinoxaline
1,3-diphenylprop-2-alkynes-1-ketone 0.5mmol, 4-tert-butyl o phenylenediamine 0.6mmol, ethanol 2mL is added in the reaction tube of 10mL, be placed in the oil bath of 40 DEG C, react 24h；Boil off ethanol, add Feldalat NM 1mmol, dimethyl sulfoxide 5mL, be placed in the oil bath of 40 DEG C, react 1h。Add suitable quantity of water or sodium chloride solution stopped reaction, be cooled to room temperature。Reactant liquor diluted ethyl acetate, washes three times, organic facies anhydrous Na2SO4Dry, to filter, concentration, column chromatography purification obtains 131.8mg target product, and yield is 78%。The nuclear-magnetism of this compound is characterized as below:1HNMR(400MHz,CDCl3) δ 8.13 (dd, J=9.5,5.4Hz, 2H), 7.87 (dd, J=8.9,2.1Hz, 1H), 7.58 7.43 (m, 4H), 7.42 7.26 (m, 6H), 1.47 (s, 9H)；13CNMR(100MHz,CDCl3)δ153.5,153.3,152.8,141.1,139.6,139.2,139.2,129.8,129.7,128.9,128.6,128.6,128.5,128.2,128.2,124.4,35.3,31.1。
Embodiment 7
The preparation of 2,3-diphenyl benzo [g] quinoxaline
1,3-diphenylprop-2-alkynes-1-ketone 0.5mmol, 2,3-neighbour naphthylenediamine 0.6mmol, methanol 5mL is added in the reaction tube of 10mL, be placed in the oil bath of 80 DEG C, react 5h；Boil off methanol, add potassium tert-butoxide 1mmol, dimethyl sulfoxide 5mL, be placed in the oil bath of 50 DEG C, react 1h。Add suitable quantity of water or sodium chloride solution stopped reaction, be cooled to room temperature。Reactant liquor diluted ethyl acetate, washes three times, organic facies anhydrous Na2SO4Dry, to filter, concentration, column chromatography purification obtains 76.4mg target product, and yield is 46%。The nuclear-magnetism of this compound is characterized as below:1HNMR(400MHz,CDCl3) δ 8.73 (s, 2H), 8.10 (dd, J=6.4,3.3Hz, 2H), 7.61 7.52 (m, 6H), 7.41 7.32 (m, 6H)；13CNMR(100MHz,CDCl3)δ154.1,139.1,137.9,134.0,129.8,129.0,128.5,128.2,127.5,126.7。
Embodiment 8
The preparation of 2-phenyl-3-p-methylphenyl quinoxaline
3-phenyl-1-p-methylphenyl-propyl-2-alkynes-1-ketone 0.5mmol, o-phenylenediamine 0.6mmol, methanol 5mL is added in the reaction tube of 10mL, be placed in the oil bath of 80 DEG C, react 5h；Boil off methanol, add sodium hydroxide 1mmol, N,N-dimethylacetamide 5mL, be placed in the oil bath of 20 DEG C, react 5h。Add suitable quantity of water or sodium chloride solution stopped reaction, be cooled to room temperature。Reactant liquor diluted ethyl acetate, washes three times, organic facies anhydrous Na2SO4Dry, to filter, concentration, column chromatography purification obtains 115.4mg target product, and yield is 78%。The nuclear-magnetism of this compound is characterized as below:1HNMR(400MHz,CDCl3) δ 8.23 8.07 (m, 2H), 7.74 (dd, J=6.3,3.6Hz, 2H), 7.57 7.50 (m, 2H), 7.41 (d, J=8.1Hz, 2H), 7.37 7.29 (m, 3H), 7.13 (d, J=7.9Hz, 2H), 2.35 (s, 3H)；13CNMR(100MHz,CDCl3)δ153.4,153.4,141.2,141.0,139.2,138.8,136.1,129.8,129.8,129.7,129.70,129.1,128.9,128.7,128.2,21.2。
Embodiment 9
The preparation of 2-p-methoxyphenyl-3-phenyl quinoxaline
3-phenyl-1-p-methoxyphenyl-propyl-2-alkynes-1-ketone 0.5mmol, o-phenylenediamine 0.6mmol, isopropanol 3mL is added in the reaction tube of 10mL, be placed in the oil bath of 70 DEG C, react 18h；Boil off isopropanol, add potassium hydroxide 1mmol, DMF 1.5mL, be placed in the oil bath of 20 DEG C, react 4h。Add suitable quantity of water or sodium chloride solution stopped reaction, be cooled to room temperature。Reactant liquor diluted ethyl acetate, washes three times, organic facies anhydrous Na2SO4Dry, to filter, concentration, column chromatography purification obtains 118.6mg target product, and yield is 76%。The nuclear-magnetism of this compound is characterized as below:1H NMR(400MHz,CDCl3) δ 8.19 8.12 (m, 2H), 7.78 7.70 (m, 2H), 7.57 7.52 (m, 2H), 7.51 7.45 (m, 2H), 7.36 (dd, J=5.4,1.7Hz, 3H), 6.89 6.82 (m, 2H), 3.81 (s, 3H)；13CNMR(100MHz,CDCl3)δ160.2,153.4,153.0,141.3,141.0,139.4,131.3,131.3,129.8,129.7,129.6,129.1,129.0,128.7,128.3,113.7,55.3。
Embodiment 10
The 2-preparation to fluorophenyl-3-phenyl quinoxaline
Fluorophenyl-propyl-2-alkynes-1-ketone 0.5mmol, o-phenylenediamine 0.6mmol, methanol 4mL is added by 3-phenyl-1-in the reaction tube of 10mL, be placed in the oil bath of 50 DEG C, react 24h；Boil off methanol, add potassium tert-butoxide 1mmol, DMF 5mL, react 2h。Add suitable quantity of water or sodium chloride solution stopped reaction, be cooled to room temperature。Reactant liquor diluted ethyl acetate, washes three times, organic facies anhydrous Na2SO4Dry, to filter, concentration, column chromatography purification obtains 99.0mg target product, and yield is 66%。The nuclear-magnetism of this compound is characterized as below:
Embodiment 11
The preparation of 2-(2-naphthyl)-3-phenyl quinoxaline
3-phenyl-1-(2-naphthyl)-propyl-2-alkynes-1-ketone 0.5mmol, o-phenylenediamine 0.6mmol, ethanol 4mL is added in the reaction tube of 10mL, be placed in the oil bath of 80 DEG C, react 15h；Boil off ethanol, add sodium tert-butoxide 1mmol, dimethyl sulfoxide 3mL, be placed in the oil bath of 40 DEG C, react 3h。Add suitable quantity of water or sodium chloride solution stopped reaction, be cooled to room temperature。Reactant liquor diluted ethyl acetate, washes three times, organic facies anhydrous Na2SO4Dry, to filter, concentration, column chromatography purification obtains 134.5mg target product, and yield is 81%。The nuclear-magnetism of this compound is characterized as below:1HNMR(400MHz,CDCl3) δ 8.24 8.16 (m, 2H), 8.14 (s, 1H), 7.77 (ddd, J=18.9,13.0,7.9Hz, 5H), 7.58 7.43 (m, 5H), 7.37 7.26 (m, 3H)；13CNMR(100MHz,CDCl3)δ153.5,153.2,141.3,141.2,139.0,136.5,133.2,133.1,130.0,129.8,129.8,129.2,129.2,128.8,128.6,128.3,127.6,127.6,127.0, 126.8,126.2。
Embodiment 12
The preparation of 2-(2-furyl)-3-phenyl quinoxaline
3-phenyl-1-(2-furyl)-propyl-2-alkynes-1-ketone 0.5mmol, o-phenylenediamine 0.6mmol, toluene 1.5mL is added in the reaction tube of 10mL, be placed in the oil bath of 50 DEG C, react 24h；Boil off toluene, add sodium hydroxide 1mmol, dimethyl sulfoxide 2mL, be placed in the oil bath of 30 DEG C, react 3h。Add suitable quantity of water or sodium chloride solution stopped reaction, be cooled to room temperature。Reactant liquor diluted ethyl acetate, washes three times, organic facies anhydrous Na2SO4Dry, to filter, concentration, column chromatography purification obtains 78.9mg target product, and yield is 58%。The nuclear-magnetism of this compound is characterized as below:1HNMR(400MHz,CDCl3) δ 8.21 (dd, J=8.1,1.2Hz, 1H), 8.11 (dd, J=8.1,1.3Hz, 1H), 7.80 7.71 (m, 2H), 7.62 7.46 (m, 6H), 6.36 (dd, J=3.5,1.7Hz, 1H), 6.15 (d, J=3.4Hz, 1H)；13CNMR(100MHz,CDCl3)δ152.5,150.9,144.7,143.1,141.0,140.3,139.3,130.3,129.9,129.2,129.1,129.0,128.8,128.6,114.8,111.7。
Embodiment 13
The preparation of 2-cyclohexyl-3-phenyl quinoxaline
3-phenyl-1-cyclohexyl-propyl-2-alkynes-1-ketone 0.5mmol, o-phenylenediamine 0.6mmol, methanol 5mL is added in the reaction tube of 10mL, be placed in the oil bath of 80 DEG C, react 24h；Boil off methanol, add potassium tert-butoxide 1mmol, DMF 5mL, be placed in the oil bath of 50 DEG C, react 2h。Add suitable quantity of water or sodium chloride solution stopped reaction, be cooled to room temperature。Reactant liquor diluted ethyl acetate, washes three times, organic facies anhydrous Na2SO4Dry, to filter, concentration, column chromatography purification obtains 102.2mg target product, and yield is 71%。The nuclear-magnetism of this compound is characterized as below:1HNMR(400MHz,CDCl3) δ 8.09 (dd, J=7.5,2.3Hz, 2H), 7.74 7.66 (m, 2H), 7.58 (dt, J=8.1,2.1Hz, 2H), 7.55 7.47 (m, 3H), 3.18 3.07 (m, 1H), 1.82 (dd, J=14.7,5.9Hz, 6H), 1.38 1.19 (m, 4H)；13CNMR(100MHz,CDCl3)δ159.9,154.7,141.7,140.4,139.2,129.4,129.1,129.0,128.8,128.7,128.6,128.4,42.3,32.4,26.3,25.8。
Embodiment 14
The preparation of 5-methyl-3-(2-naphthyl)-2-phenyl quinoxaline
3-phenyl-1-(2-naphthyl)-propyl-2-alkynes-1-ketone 0.5mmol, 3-methyl-o-phenylenediamine 0.6mmol, methanol 3mL is added in the reaction tube of 10mL, be placed in the oil bath of 60 DEG C, react 18h；Boil off methanol, add sodium tert-butoxide 1mmol, N-Methyl pyrrolidone 2mL, be placed in the oil bath of 25 DEG C, react 2h。Add suitable quantity of water or sodium chloride solution stopped reaction, be cooled to room temperature。Reactant liquor diluted ethyl acetate, washes three times, organic facies anhydrous Na2SO4Dry, to filter, concentration, column chromatography purification obtains 84.0mg target product, and yield is 48%。The nuclear-magnetism of this compound is characterized as below:1HNMR(400MHz,CDCl3) δ 8.13 (s, 1H), 8.03 (d, J=8.1Hz, 1H), 7.83 7.73 (m, 3H), 7.70 7.59 (m, 3H), 7.56 (dd, J=7.9,1.5Hz, 2H), 7.51 7.44 (m, 2H), 7.37 7.28 (m, 3H), 2.89 (s, 3H)；13CNMR(100MHz,CDCl3)δ152.9,151.6,141.1,140.5,139.4,137.6,136.8,133.2,133.1,130.0,129.8,129.8,129.7,128.7,128.6,128.6,127.6,127.5,127.4,126.9,126.7,126.3,17.2。
Embodiment 4
The preparation of 5-methyl-3-(2-furyl)-2-phenyl quinoxaline
3-phenyl-1-(2-furyl)-propyl-2-alkynes-1-ketone 0.5mmol, 3-methyl-o-phenylenediamine 0.6mmol, isopropanol 4mL is added in the reaction tube of 10mL, be placed in the oil bath of 80 DEG C, react 22h；Boil off isopropanol, add potassium tert-butoxide 1mmol, DMF 3mL, be placed in the oil bath of 50 DEG C, react 2h。Add suitable quantity of water or sodium chloride solution stopped reaction, be cooled to room temperature。Reactant liquor diluted ethyl acetate, washes three times, organic facies anhydrous Na2SO4Dry, to filter, concentration, column chromatography purification obtains 80.1mg target product, and yield is 56%。The nuclear-magnetism of this compound is characterized as below:1HNMR(400MHz,CDCl3) δ 7.94 (d, J=8.3Hz, 1H), 7.72 7.59 (m, 3H), 7.54 (d, J=7.0Hz, 1H), 7.52 7.42 (m, 3H), 7.39 (d, J=5.0Hz, 1H), 6.95 6.85 (m, 1H), 6.79 (d, J=3.7Hz, 1H), 2.79 (s, 3H)；13CNMR(101MHz,CDCl3)δ151.0,146.3,142.9,141.0,139.7,139.7,137.5,129.8,129.6,129.5,129.0,128.9,128.4,127.6,126.6,17.1
Embodiment 16
The preparation of 5-methyl-3-cyclohexyl-2-phenyl quinoxaline
3-phenyl-1-cyclohexyl-propyl-2-alkynes-1-ketone 0.5mmol, 3-methyl-o-phenylenediamine 0.6mmol, ethanol 5mL is added in the reaction tube of 10mL, be placed in the oil bath of 60 DEG C, react 24h；Boil off ethanol, add potassium tert-butoxide 1mmol, N,N-dimethylacetamide 3mL, be placed in the oil bath of 30 DEG C, react 2h。Add suitable quantity of water or sodium chloride solution stopped reaction, be cooled to room temperature。Reactant liquor diluted ethyl acetate, washes three times, organic facies anhydrous Na2SO4Dry, to filter, concentration, column chromatography purification obtains 96.6mg target product, and yield is 64%。The nuclear-magnetism of this compound is characterized as below:1HNMR(400MHz,CDCl3) δ 7.92 (dd, J=7.8,1.4Hz, 1H), 7.62 7.44 (m, 7H), 3.16 3.04 (m, 1H), 2.83 (s, 3H), 1.87 1.77 (m, 6H), 1.74 1.67 (m, 1H), 1.42 1.18 (m, 4H)；13CNMR(100MHz,CDCl3)δ158.4,154.0,140.7,140.4,139.4,137.1,129.2,128.8,128.7,128.5,128.4,126.8,42.35(s),32.8,26.3,25.9,17.0。
Those of ordinary skill in the art are it can be seen that when technical scheme changes in following ranges, remain able to obtain same as the previously described embodiments or close technique effect:
The structural formula of prepared polysubstituted quinoxaline derivant is as follows:
Wherein, R1For hydrogen, halogen, alkyl, aryl, substituted aryl, acyl group, amino, nitro or alkoxyl；
R2For hydrogen, halogen, alkyl, aryl, substituted aryl, acyl group, amino, nitro or alkoxyl；
R3For hydrogen, halogen, alkyl, aryl, substituted aryl, acyl group, amino, nitro or alkoxyl；
R4For hydrogen, halogen, alkyl, aryl, substituted aryl, acyl group, amino, nitro or alkoxyl；
R5For hydrogen, halogen, alkyl, aryl, substituted aryl, acyl group, amino, nitro or alkoxyl；
R6For hydrogen, halogen, alkyl, aryl, substituted aryl, acyl group, amino, nitro or alkoxyl；
The reaction equation of the method is as follows:
Described solvent one is water, methanol, ethanol, isopropanol, toluene；Described solvent two is dimethyl sulfoxide, DMF, N,N-dimethylacetamide or METHYLPYRROLIDONE。
The method specifically includes following steps:
(1) corresponding acetylenic ketone or derivatives thereof, corresponding o-phenylenediamine or derivatives thereof and solvent one are placed in reaction vessel, react 4～22h (preferably 50～80 DEG C of reaction 5～20h) in 48～85 DEG C；
(2) solvent one in step (1) gained material is evaporated, adds alkali and solvent two, react 1～6h (preferably 20～50 DEG C of reaction 1～5h) in 20～55 DEG C, add suitable quantity of water after having reacted or sodium chloride solution terminates reaction,
(3) by after the product diluted ethyl acetate of step (2), then through washing, organic facies is obtained；
(4) by step (3) gained organic facies drying, filtration, concentration and column chromatography purification, described polysubstituted quinoxaline derivant is obtained；
Wherein, the mol ratio of corresponding acetylenic ketone or derivatives thereof, corresponding o-phenylenediamine or derivatives thereof and alkali is 1:1～1.5:1.5～2.5, every mole of corresponding acetylenic ketone or derivatives thereof correspondence 2～12L solvent one and 2～12L solvent two。
Every mole of corresponding acetylenic ketone or derivatives thereof correspondence 3～10L solvent one and 3～10L solvent two。
Described alkali is sodium hydroxide, potassium hydroxide, potassium tert-butoxide, sodium tert-butoxide, Feldalat NM or cesium carbonate。
The above, be only presently preferred embodiments of the present invention, therefore can not limit scope of the invention process according to this, and the equivalence namely made according to the scope of the claims of the present invention and description changes and modifies, and all should still belong in the scope that the present invention contains。

Claims (7)

1. the preparation method of a polysubstituted quinoxaline derivant, it is characterised in that: the structural formula of prepared polysubstituted quinoxaline derivant is as follows:
Wherein, R1For hydrogen, halogen, alkyl, aryl, substituted aryl, acyl group, amino, nitro or alkoxyl；
R2For hydrogen, halogen, alkyl, aryl, substituted aryl, acyl group, amino, nitro or alkoxyl；
R3For hydrogen, halogen, alkyl, aryl, substituted aryl, acyl group, amino, nitro or alkoxyl；
R4For hydrogen, halogen, alkyl, aryl, substituted aryl, acyl group, amino, nitro or alkoxyl；
R5For hydrogen, halogen, alkyl, aryl, substituted aryl, acyl group, amino, nitro or alkoxyl；
R6For hydrogen, halogen, alkyl, aryl, substituted aryl, acyl group, amino, nitro or alkoxyl；
The reaction equation of the method is as follows:
Described solvent one is water, methanol, ethanol, isopropanol, toluene；Described solvent two is dimethyl sulfoxide, DMF, N,N-dimethylacetamide or METHYLPYRROLIDONE。
2. preparation method as claimed in claim 1, it is characterised in that: comprise the steps:
(1) corresponding acetylenic ketone or derivatives thereof, corresponding o-phenylenediamine or derivatives thereof and solvent one are placed in reaction vessel, react 4～22h in 48～85 DEG C；
(2) solvent one in step (1) gained material is evaporated, adds alkali and solvent two, react 1～6h in 20～55 DEG C, add suitable quantity of water after having reacted or sodium chloride solution terminates reaction；
(3) by after the product diluted ethyl acetate of step (2), then through washing, organic facies is obtained；
(4) by step (3) gained organic facies drying, filtration, concentration and column chromatography purification, described polysubstituted quinoxaline derivant is obtained；
Wherein, the mol ratio of corresponding acetylenic ketone or derivatives thereof, corresponding o-phenylenediamine or derivatives thereof and alkali is 1:1～1.5:1.5～2.5, every mole of corresponding acetylenic ketone or derivatives thereof correspondence 2～12L solvent one and 2～12L solvent two。
3. preparation method as claimed in claim 2, it is characterised in that: the mol ratio of corresponding acetylenic ketone or derivatives thereof and corresponding o-phenylenediamine or derivatives thereof is 1:1.2。
4. preparation method as claimed in claim 2, it is characterised in that: every mole of corresponding acetylenic ketone or derivatives thereof correspondence 3～10L solvent one and 3～10L solvent two。
5. preparation method as claimed in claim 2, it is characterised in that: described alkali is sodium hydroxide, potassium hydroxide, potassium tert-butoxide, sodium tert-butoxide, Feldalat NM or cesium carbonate。
6. preparation method as claimed in claim 2, it is characterised in that: the reaction temperature of described step (1) is 50～80 DEG C, and the response time is 5～20h。
7. preparation method as claimed in claim 2, it is characterised in that: the reaction temperature of described step (2) is 20～50 DEG C, and the response time is 1～5h。
CN201610028051.4A 2016-01-15 2016-01-15 A kind of preparation method of polysubstituted quinoxaline derivant Active CN105693632B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201610028051.4A CN105693632B (en) 2016-01-15 2016-01-15 A kind of preparation method of polysubstituted quinoxaline derivant

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201610028051.4A CN105693632B (en) 2016-01-15 2016-01-15 A kind of preparation method of polysubstituted quinoxaline derivant

Publications (2)

Publication Number Publication Date
CN105693632A true CN105693632A (en) 2016-06-22
CN105693632B CN105693632B (en) 2018-04-17

Family

ID=56227415

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201610028051.4A Active CN105693632B (en) 2016-01-15 2016-01-15 A kind of preparation method of polysubstituted quinoxaline derivant

Country Status (1)

Country Link
CN (1) CN105693632B (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108752325A (en) * 2018-08-06 2018-11-06 青岛科技大学 A kind of preparation method of -2 (1H) -one class compound of 3- oxyalkyls quinoxaline
CN109810112A (en) * 2019-02-01 2019-05-28 华侨大学 A kind of preparation method of indoles simultaneously [2,1-a] phthalazine derivatives
CN110698426A (en) * 2019-11-04 2020-01-17 陕西师范大学 Method for preparing 1, 3-benzothiazole derivative by efficient catalysis of potassium tert-butoxide

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104177241A (en) * 2014-06-23 2014-12-03 华东师范大学 Alkynyl diketone compound and synthetic method thereof

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104177241A (en) * 2014-06-23 2014-12-03 华东师范大学 Alkynyl diketone compound and synthetic method thereof

Non-Patent Citations (9)

* Cited by examiner, † Cited by third party
Title
DONGDONG LIANG，等: "A Metal-Free Tandem Demethylenation/C(sp2)-H Cycloamination Process of N‑Benzyl-2-aminopyridines via C-C and C-N Bond Cleavage", 《ORGANIC LETTERS》 *
E. A. KOKAREVA，等: "Synthesis of (2,3-Diphenyl)pyrazinotribenzoporphyrazine", 《RUSSIAN JOURNAL OF ORGANIC CHEMISTRY》 *
HUI LIU，等: "Transition-Metal-Free Aerobic Oxidative Cleavage of C-C Bonds in α-Hydroxy Ketones and Mechanistic Insight to the Reaction Pathway", 《ANGEW. CHEM. INT. ED.》 *
ISSA YAVARI，等: "Efficient Synthesis of Dialkyl (2Z)-2-[(E)-1-Aryl-2-(3-arylquinoxalin-2-yl)ethenyl]but-2-enedioates", 《HELVETICA CHIMICA ACTA》 *
JOYDEV K. LAHA，等: "Transition-Metal-Free Tandem Oxidative Removal of Benzylic Methylene Group by C-C and C-N Bond Cleavage Followed by Intramolecular New Aryl C-N Bond Formation under Radical Conditions", 《ORGANIC LETTERS》 *
KAREN C. COLLINS，等: "Dissecting AI-2-mediated quorum sensing through C5-analogue synthesis and biochemical analysis", 《TETRAHEDRON》 *
SANDIP A. PUJARI，等: "A Mild and Efficient CH2-Extrusion Reaction for the Enantiospecific Synthesis of Highly Configurationally Stable Troger Bases", 《ANGEW. CHEM. INT. ED.》 *
SOTA OKUMURA，等: "Hypervalent iodine(III)-induced oxidative [4+2] annulation of o-phenylenediamines and electrondeficient alkynes: direct synthesis of quinoxalines from alkyne substrates under metal-free conditions", 《CHEMCOMM》 *
YUESI FANG，等: "Formation of Acridones by Ethylene Extrusion in the Reaction of Arynes with β-Lactams and Dihydroquinolinones", 《J. ORG. CHEM.》 *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108752325A (en) * 2018-08-06 2018-11-06 青岛科技大学 A kind of preparation method of -2 (1H) -one class compound of 3- oxyalkyls quinoxaline
CN108752325B (en) * 2018-08-06 2021-03-23 曲阜师范大学 Preparation method of 3-oxyalkyl quinoxaline-2 (1H) -ketone compound
CN109810112A (en) * 2019-02-01 2019-05-28 华侨大学 A kind of preparation method of indoles simultaneously [2,1-a] phthalazine derivatives
CN109810112B (en) * 2019-02-01 2021-03-23 华侨大学 Preparation method of indolo [2,1-a ] phthalazine derivative
CN110698426A (en) * 2019-11-04 2020-01-17 陕西师范大学 Method for preparing 1, 3-benzothiazole derivative by efficient catalysis of potassium tert-butoxide
CN110698426B (en) * 2019-11-04 2022-08-23 陕西师范大学 Method for preparing 1, 3-benzothiazole derivative by efficient catalysis of potassium tert-butoxide

Also Published As

Publication number Publication date
CN105693632B (en) 2018-04-17

Similar Documents

Publication Publication Date Title
JP7038843B2 (en) Methods and Intermediates for Preparing Therapeutic Compounds Useful in the Treatment of Retroviridae Virus Infections
CN110204486B (en) Synthesis method of quinoline derivative
CN105801575B (en) A kind of synthetic method of imidazo [1,2-a] pyridine
CN104803964B (en) Multi-substituent isocoumarin derivative and preparation method thereof
CN104447686B (en) Polysubstituted 2-pyrroles's pyridine derivate and preparation method thereof
CN104744348A (en) Polysubstituted pyridine derivative and preparation method thereof
CN105693632A (en) Preparation method of polysubstitution quinoxalin derivatives
CN106946972B (en) A kind of ursolic acid derivative with anti-tumor activity and preparation method thereof
CN106117216B (en) A kind of method of atmospheric synthesis 6H- iso-indoles [2,1-a] indoles -6- ketone compounds
CN104649857B (en) Trifluoromethyl-substituted azide, amine and heterocycle compounds and preparing methods thereof
CN105481752B (en) A kind of preparation method of the trifluoromethyl oxidized indole compounds of 3 fluorine alkenyl Oxoindole spiral shell 3,3 '
CN112209876B (en) Preparation method of 3-trifluoromethyl isoquinolinone derivative
CN109776407B (en) Preparation method of 2-methyl-4-hydroxymethyl quinoline and derivatives thereof
CN114573512B (en) Method for synthesizing C2-difluoro alkyl benzimidazole derivative
CN106588921B (en) A kind of synthetic method of the methyl formate of 7 azaindole 3
CN111978167B (en) One-step synthesis method of polysubstituted cyclohex-2-enone
CN106866511A (en) A kind of preparation method of polysubstituted pyridine derivative
CN105693778A (en) N-methoxyl formamide-orientated method for synthesizing ferrocene and pyridone derivative
CN108218758B (en) Preparation method of 2, 4-disubstituted pyrrole derivative
CN105218477A (en) A kind of polysubstituted benzo [b] [Isosorbide-5-Nitrae] oxygen azatropylidene piperidine derivatives and preparation method thereof
CN104860864B (en) The synthetic method of the alkynyl azole compounds of 2 carbonyl 5
BR112021011084A2 (en) PROCESS FOR PREPARING 1-[(3R,4S)-4-CYANOTETRAHYDROPYRAN-3-IL]-3-[(2-FLUORO-6-METOXY-4-PYRIDYL)AMINO]PYRAZOLE-4-CARBOXAMIDE
CN112538059B (en) Reaction method for selectively synthesizing oxazole-4-carboxylic ester
CN107382899A (en) A kind of polysubstituted benzo-oxazine derivative of 2 hydroxyl 1,4
CN114349684B (en) Synthetic method of benzo [ c, d ] indole imine derivative

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant