CN109575034A - The method of level-one amine guiding building 6- Phenylindole simultaneously [1,2-a] quinoxaline - Google Patents
The method of level-one amine guiding building 6- Phenylindole simultaneously [1,2-a] quinoxaline Download PDFInfo
- Publication number
- CN109575034A CN109575034A CN201811576551.7A CN201811576551A CN109575034A CN 109575034 A CN109575034 A CN 109575034A CN 201811576551 A CN201811576551 A CN 201811576551A CN 109575034 A CN109575034 A CN 109575034A
- Authority
- CN
- China
- Prior art keywords
- quinoxaline
- indoles
- reaction
- aniline
- base
- 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.)
- Withdrawn
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Indole Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The present invention relates to a kind of level-one amine to be oriented to building 6- Phenylindole simultaneously [1,2-a] quinoxaline method.In reaction tube, 2- (1 is addedHIndoles -1- base) aniline, benzoyl formic acid be raw material, 6- Phenylindole simultaneously [1,2- is obtained by acylation/cyclizationa] quinoxaline.The method of the present invention synthesizing mean is novel, avoids the use of the additives such as alkali, raw materials required for the reaction is cheap and easy to get, mild condition and easy to operate, selective single, separation yield height, be conducive to industrialized production, have in the research and development of drug and the synthesis of natural products and have been widely used.
Description
Technical field
The present invention relates to medication chemistry synthesis technical fields, and in particular to a kind of level-one amine guiding building 6- Phenylindole
And the method for [1,2-a] quinoxaline.
Background technique
Organometallic Chemistry has obtained unprecedented development in recent years, becomes building carbon-carbon bond and the important hand of carbon-heterodesmic
Section.The C-H function dough reaction of homing device auxiliary has obtained the wide of scientists because of its good selectivity and reactivity
General concern.A series of nitrogenous guiding bases are reacted by Successful utilization in C-H function dough after decades of development, they include
Level-one amine, pyridine, amide, imines, oxime, enamine and various nitrogen-containing heterocycles.It is worth noting that, level-one amine is realized as guiding base
The report of C-H functionalization is considerably less, because level-one amine has very strong sequestering power, it is easy to catalyst poisoning be caused to be lost
It is living, it is achieved that the C-H functionalization of level-one amine guiding has very big challenge.Currently, utilizing transition metal-catalyzed level-one
Amine guiding strategy is successfully realized alkenyl, alkynyl, arylation and cyclization (Lazareva, A.;Daugulis
O.Org.Lett.,2006,8,5211-5213;Liang,D.;Hu,Z.;Peng,J.;et al.Chem.Commun.,2013,
49,173-175;Liang,Z.;Feng,R.;Yin,H.;et al.Org.Lett.,2013,15,4544-4547;Bai,P.;
Huang X.-F.;Xu,G.-D.;et al.Org.Lett.,2016,18,3058-3061;Suzuki,C.;Hirano,K.;
Satoh,T.;et al.Org.Lett.,2013,15,3990-3993;Liang,Z.;Ju,L.;Xie,Y.;et
al.Chem.Eur.J.,2012,18,15816-15821;Jiang,G.;Hu,W.;Zhu,C.;etal.Chem.Commun.,
2018,54,1746-1749.);But level-one amine is used to realize that acylation/cyclization strategy never has for seamless guiding base
It is reported.Therefore, realize that acylation/cyclization of level-one amine guiding has very important researching value.
Quinoxaline derivant is important nitrogenous compound, the activity with antitumor, antimycotic and AntiHIV1 RT activity etc.,
It can also be used as angiotensin receptor inhibitor (Patel, M.;Mc Hugh,R.J.;Cordova,B.C.;Klabe,R.M.;
Erickson-Vitanen,S.;Trainor,G.L.;Rodger,J.D.Bioorg.Med.Chem.Lett.2000,10,
1729-1731;Guillon,J.;Dallemagne,P.;Pfeiffer,B.;Renard,P.;Manechez,D.;Kervran,
A.;Rault,S.Eur.J.Med.Chem.1998,33,293-308;Ramamohan,M.;Sridhar,R.;
Raghavendrarao,K.;Paradesi,N.;Chandrasekhar,K.B.;Jayaprakash,S.Synlett,2015,
26,1096-1100), at the same they be also some natural products important component.Because of the importance of this kind of compound,
Scientists have put into a large amount of energy and have carried out synthesizing quinoxaline derivant, after decades of development, achieve plentiful and substantial research
Achievement, but simultaneously its synthetic method is very limited as important quinoxaline derivant for [1,2-a] quinoxaline compounds for indoles.
(Xie,C.;Feng,L.;Li,W.;Ma,X.;Ma,X.;Liu,Y.;Ma,C.Org.Biomol.Chem.2016,14,8529-
8535;Rubio-Presa,R.;Pedrosa,M.;Fernández-Rodríguez,Arnáiz,F.;Sanz,
R.Org.Lett.2017,19,5470-5473;Ramamohan,M.;Sridhar,R.;Raghavendrarao,K.;
Paradesi,N.;Chandrasekhar,K.B.;Jayaprakash,S.Synlett,2015,26,1096-1100).And
There are reaction temperatures in reaction known to these, and high, substrate was difficult in place of the deficiencies of preparing.Here, we have invented a kind of palladiums
It is catalyzed the new method of level-one amine guiding synthesis 6- Phenylindole simultaneously [1,2-a] quinoxaline.This method reaction condition is simple, required original
Expect cheap and easy to get, preparation condition is mild, and easy to operate, selectivity is single, and separation yield is high, is conducive to industrialized production, in medicine
Have in the research and development of object and the synthesis of natural products and has been widely used.
Summary of the invention
The object of the present invention is to provide a kind of methods that level-one amine is oriented to building 6- Phenylindole simultaneously [1,2-a] quinoxaline.
Thinking of the invention: using 2- (1H- indoles -1- base) aniline, benzoyl formic acid as raw material, persulfate is oxidation
Under the catalysis of palladium salt acylation/cyclization occurs for agent, and one-step synthesis has the 6- Phenylindole simultaneously [1,2- of pharmaceutical activity
A] quinoxaline.This method avoid the uses of the additives such as alkali, and raw materials required for the reaction is cheap and easy to get, and reaction condition is mild, operation
Simplicity, selectivity is single, and step economy is high, has potential practical value.
Specific steps are as follows:
2- (1H- indoles -1- base) aniline and benzoyl formic acid are sequentially added in reaction flask, are oxidation with persulfate
Agent, using organic solvent as solvent, is stirred 10~24 hours at 70~90 DEG C, is cooled down after reaction using palladium salt as catalyst
To room temperature, filtering reacting liquid, after vacuum rotary steam crude product, obtain 6- Phenylindole simultaneously [1,2-a] quinoline through column chromatographic purifying
Quinoline.
The molar ratio of 2- (1H- indoles -1- base) aniline and benzoyl formic acid is 1:1~2.
The oxidant is potassium peroxydisulfate, sodium peroxydisulfate or ammonium persulfate;The amount and 2- (1H- indoles -1- of oxidant is added
Base) aniline molar ratio be 1~2:1.
The catalyst is palladium acetate, palladium trifluoroacetate, two (triphenylphosphine) palladium chlorides or palladium chloride;Catalyst and 2-
The molar ratio of (1H- indoles -1- base) aniline is 0.05:1.
The solvent is 1,4- dioxane or diethylene glycol dimethyl ether.
The column chromatography eluent is the mixed solvent of petroleum ether and ethyl acetate, the volume ratio of petroleum ether and ethyl acetate
For 100~10:1.
The present invention has the following advantages that compared with the prior art and effect:
The method that the present invention synthesizes 6- Phenylindole simultaneously [1,2-a] quinoxaline, it is raw materials used nontoxic and cheap and easy to get;Reaction
Without inert gas shielding, selectivity is single;In addition, reaction also has step economy high, easy to operate, safety reacts item
The advantages of part is mild, high income.The strategy provides effectively for the synthesis of functional molecular 6- Phenylindole simultaneously [1,2-a] quinoxaline
Synthetic method.
Detailed description of the invention
Fig. 1 is the synthesis equation of 6- Phenylindole simultaneously [1,2-a] quinoxaline in the present invention.
Fig. 2 be 6- Phenylindole made from the embodiment of the present invention 14 simultaneously [1,2-a] quinoxaline hydrogen spectrum.
Fig. 3 be 6- Phenylindole made from the embodiment of the present invention 14 simultaneously [1,2-a] quinoxaline carbon spectrum.
Specific embodiment
The invention is further described below by specific embodiment.
Embodiment 1:
0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of palladium chloride, 0.4 is sequentially added in reaction tube
MM potassium peroxydisulfate and 0.4 mM of benzoyl formic acid.It is solvent that 2 milliliters of Isosorbide-5-Nitrae-dioxane, which are then added, in 78 DEG C of items
Stop reaction after being stirred to react under part 12 hours, be cooled to room temperature and filter, filtrate is extracted with ethyl acetate 3 times, merges organic
It is dried, filtered mutually and using 0.5g anhydrous magnesium sulfate, vacuum rotary steam obtains crude product, most afterwards through column chromatographic isolation and purification, column used
Chromatographic eluate is the petroleum ether of volume ratio 30:1: ethyl acetate mixed solvent.Obtain pure 6- Phenylindole simultaneously [1,2-a]
Quinoxaline, yield 36%.
Embodiment 2:
0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of palladium acetate, 0.4 is sequentially added in reaction tube
MM potassium peroxydisulfate and 0.4 mM of benzoyl formic acid.It is solvent that 2 milliliters of Isosorbide-5-Nitrae-dioxane, which are then added, in 78 DEG C of items
Stop reaction after being stirred to react under part 12 hours, be cooled to room temperature and filter, filtrate is extracted with ethyl acetate 3 times, merges organic
It is dried, filtered mutually and using 0.5g anhydrous magnesium sulfate, vacuum rotary steam obtains crude product, most afterwards through column chromatographic isolation and purification, column used
Chromatographic eluate is the petroleum ether of volume ratio 30:1: ethyl acetate mixed solvent.Obtain pure 6- Phenylindole simultaneously [1,2-a]
Quinoxaline, yield 56%.
Embodiment 3:
Sequentially added in reaction tube 0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of palladium trifluoroacetate,
0.4 mM of potassium peroxydisulfate and 0.4 mM of benzoyl formic acid.It is solvent that 2 milliliters of Isosorbide-5-Nitrae-dioxane, which are then added, at 78 DEG C
Under the conditions of be stirred to react 12 hours after stop reaction, be cooled to room temperature and filter, filtrate is extracted with ethyl acetate 3 times, is associated with
Machine phase is simultaneously dried, filtered using 0.5g anhydrous magnesium sulfate, and vacuum rotary steam obtains crude product, used most afterwards through column chromatographic isolation and purification
Column chromatographic eluate is the petroleum ether of volume ratio 30:1: ethyl acetate mixed solvent.Obtain pure 6- Phenylindole simultaneously [1,2-
A] quinoxaline, yield 43%.
Embodiment 4:
0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of four triphenylphosphine is sequentially added in reaction tube
Palladium, 0.4 mM of potassium peroxydisulfate and 0.4 mM of benzoyl formic acid.It is solvent that 2 milliliters of Isosorbide-5-Nitrae-dioxane, which are then added,
Stop reaction after being stirred to react under the conditions of 78 DEG C 12 hours.TLC (thin-layered chromatography) detection reaction, does not detect 6- phenyl Yin
The generation of diindyl simultaneously [1,2-a] quinoxaline.
Embodiment 5:
0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of two (triphen of dichloro are sequentially added in reaction tube
Base phosphine) palladium, 0.4 mM of potassium peroxydisulfate and 0.4 mM of benzoyl formic acid.It is molten that 2 milliliters of 1,4- dioxane, which are then added,
Agent stops reaction, is cooled to room temperature and filters, filtrate is extracted with ethyl acetate 3 after being stirred to react under the conditions of 78 DEG C 12 hours
It is secondary, merge organic phase and dried, filtered using 0.5g anhydrous magnesium sulfate, vacuum rotary steam obtains crude product, most afterwards through column chromatography for separation
Purifying, column chromatographic eluate used are the petroleum ether of volume ratio 30:1: ethyl acetate mixed solvent.Obtain pure 6- phenyl Yin
Diindyl simultaneously [1,2-a] quinoxaline, yield 22%.
Embodiment 6:
0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of palladium acetate, 0.4 is sequentially added in reaction tube
MM copper acetate and 0.4 mM of benzoyl formic acid.It is solvent that 2 milliliters of Isosorbide-5-Nitrae-dioxane, which are then added, in 78 DEG C of conditions
Under be stirred to react 12 hours after stop reaction.TLC (thin-layered chromatography) detection reaction, is only able to detect trace 6- Phenylindole simultaneously
The generation of [1,2-a] quinoxaline, can not be isolated.
Embodiment 7:
0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of palladium acetate, 0.4 is sequentially added in reaction tube
MM silver acetate and 0.4 mM of benzoyl formic acid.It is solvent that 2 milliliters of Isosorbide-5-Nitrae-dioxane, which are then added, in 78 DEG C of conditions
Under be stirred to react 12 hours after stop reaction.TLC (thin-layered chromatography) detection reaction, is only able to detect trace 6- Phenylindole simultaneously
The generation of [1,2-a] quinoxaline, can not be isolated.
Embodiment 8:
0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of palladium acetate, 0.4 is sequentially added in reaction tube
MM 1,4-benzoquinone and 0.4 mM of benzoyl formic acid.It is solvent that 2 milliliters of Isosorbide-5-Nitrae-dioxane, which are then added, in 78 DEG C of conditions
Under be stirred to react 12 hours after stop reaction.TLC (thin-layered chromatography) detection reaction, is only able to detect trace 6- Phenylindole simultaneously
The generation of [1,2-a] quinoxaline, can not be isolated.
Embodiment 9:
0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of palladium acetate, 0.4 is sequentially added in reaction tube
MM ammonium persulfate and 0.4 mM of benzoyl formic acid.It is solvent that 2 milliliters of Isosorbide-5-Nitrae-dioxane, which are then added, in 78 DEG C of items
Stop reaction after being stirred to react under part 12 hours, be cooled to room temperature and filter, filtrate is extracted with ethyl acetate 3 times, merges organic
It is dried, filtered mutually and using 0.5g anhydrous magnesium sulfate, vacuum rotary steam obtains crude product, most afterwards through column chromatographic isolation and purification, column used
Chromatographic eluate is the petroleum ether of volume ratio 30:1: ethyl acetate mixed solvent.Obtain pure 6- Phenylindole simultaneously [1,2-a]
Quinoxaline, yield 64%.
Embodiment 10:
0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of palladium acetate, 0.4 is sequentially added in reaction tube
MM sodium peroxydisulfate and 0.4 mM of benzoyl formic acid.It is solvent that 2 milliliters of Isosorbide-5-Nitrae-dioxane, which are then added, in 78 DEG C of items
Stop reaction after being stirred to react under part 12 hours, be cooled to room temperature and filter, filtrate is extracted with ethyl acetate 3 times, merges organic
It is dried, filtered mutually and using 0.5g anhydrous magnesium sulfate, vacuum rotary steam obtains crude product, most afterwards through column chromatographic isolation and purification, column used
Chromatographic eluate is the petroleum ether of volume ratio 30:1: ethyl acetate mixed solvent.Obtain pure 6- Phenylindole simultaneously [1,2-a]
Quinoxaline, yield 47%.
Embodiment 11:
0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of palladium acetate, 0.4 is sequentially added in reaction tube
MM ammonium persulfate and 0.4 mM of benzoyl formic acid.It is solvent that 2 milliliters of DMSO, which are then added, is stirred under the conditions of 78 DEG C
Stop reaction after reaction 12 hours.TLC (thin-layered chromatography) detection reaction, does not detect 6- Phenylindole simultaneously [1,2-a] quinoline
The generation of quinoline.
Embodiment 12:
0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of palladium acetate, 0.4 is sequentially added in reaction tube
MM ammonium persulfate and 0.4 mM of benzoyl formic acid.It is solvent that 2 milliliters of DMF, which are then added, is stirred under the conditions of 78 DEG C anti-
Stop reaction after answering 12 hours.TLC (thin-layered chromatography) detection reaction, does not detect 6- Phenylindole simultaneously [1,2-a] quinoline
The generation of quinoline.
Embodiment 13:
0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of palladium acetate, 0.4 is sequentially added in reaction tube
MM ammonium persulfate and 0.4 mM of benzoyl formic acid.It is solvent that 2 milliliters of toluene, which are then added, is stirred under the conditions of 78 DEG C
Stop reaction after reaction 12 hours.TLC (thin-layered chromatography) detection reaction, does not detect 6- Phenylindole simultaneously [1,2-a] quinoline
The generation of quinoline.
Embodiment 14:
0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of palladium acetate, 0.4 is sequentially added in reaction tube
MM ammonium persulfate and 0.4 mM of benzoyl formic acid.It is solvent that 2 milliliters of diethylene glycol dimethyl ethers, which are then added, at 78 DEG C
Under the conditions of be stirred to react 12 hours after stop reaction, be cooled to room temperature and filter, filtrate is extracted with ethyl acetate 3 times, is associated with
Machine phase is simultaneously dried, filtered using 0.5g anhydrous magnesium sulfate, and vacuum rotary steam obtains crude product, used most afterwards through column chromatographic isolation and purification
Column chromatographic eluate is the petroleum ether of volume ratio 30:1: ethyl acetate mixed solvent.Obtain pure 6- Phenylindole simultaneously [1,2-
A] quinoxaline, yield is up to 81%.
Simultaneously the hydrogen spectrum of [1,2-a] quinoxaline and carbon compose as shown in Figures 2 and 3, structure indicator respectively to gained 6- Phenylindole
Data are as follows:
Yellow solid;mp 171-172℃;IR: ν=3959,2922,2851,1672,1608,1529,1476,
1443,1214,1127,745,702,561cm-1;1H NMR(400MHz,CDCl3) δ 8.49 (t, J=9.2Hz, 2H), 8.10
(dd, J=7.9,1.3Hz, 1H), 8.06-8.01 (m, 2H), 7.92 (d, J=8.0Hz, 1H), 7.63-7.53 (m, 5H),
7.47-7.41(m,2H),7.24(s,1H);13C NMR(100MHz,CDCl3)δ156.2,138.2,136.2,133.0,
130.5,130.2,130.0,129.2,129.1,128.6,128.6,128.3,124.3,124.2,122.8,122.6,
114.6,114.5,102.5;HRMS(ESI)m/z:calcd for C21H15N2[M+H]+,295.1230;found
295.1231.
The structure of 6- Phenylindole simultaneously [1,2-a] quinoxaline is as follows:
Embodiment 15:
0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of palladium acetate, 0.4 is sequentially added in reaction tube
MM ammonium persulfate and 0.4 mM of benzoyl formic acid.It is solvent that 2 milliliters of diethylene glycol dimethyl ethers, which are then added, at 70 DEG C
Under the conditions of be stirred to react 12 hours after stop reaction, be cooled to room temperature and filter, filtrate is extracted with ethyl acetate 3 times, is associated with
Machine phase is simultaneously dried, filtered using 0.5g anhydrous magnesium sulfate, and vacuum rotary steam obtains crude product, used most afterwards through column chromatographic isolation and purification
Column chromatographic eluate is the petroleum ether of volume ratio 30:1: ethyl acetate mixed solvent.Obtain pure 6- Phenylindole simultaneously [1,2-
A] quinoxaline, yield 71%.
Embodiment 16:
0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of palladium acetate, 0.4 is sequentially added in reaction tube
MM ammonium persulfate and 0.4 mM of benzoyl formic acid.It is solvent that 2 milliliters of diethylene glycol dimethyl ethers, which are then added, at 85 DEG C
Under the conditions of be stirred to react 12 hours after stop reaction, be cooled to room temperature and filter, filtrate is extracted with ethyl acetate 3 times, is associated with
Machine phase is simultaneously dried, filtered using 0.5g anhydrous magnesium sulfate, and vacuum rotary steam obtains crude product, used most afterwards through column chromatographic isolation and purification
Column chromatographic eluate is the petroleum ether of volume ratio 30:1: ethyl acetate mixed solvent.Obtain pure 6- Phenylindole simultaneously [1,2-
A] quinoxaline, yield 69%.
Embodiment 17:
0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of palladium acetate, 0.4 is sequentially added in reaction tube
MM ammonium persulfate and 0.4 mM of benzoyl formic acid.It is solvent that 2 milliliters of diethylene glycol dimethyl ethers, which are then added, and nitrogen is protected
Shield stops reaction, is cooled to room temperature and filters, filtrate is extracted with ethyl acetate 3 after being stirred to react under the conditions of 78 DEG C 12 hours
It is secondary, merge organic phase and dried, filtered using 0.5g anhydrous magnesium sulfate, vacuum rotary steam obtains crude product, most afterwards through column chromatography for separation
Purifying, column chromatographic eluate used are the petroleum ether of volume ratio 30:1: ethyl acetate mixed solvent.Obtain pure 6- phenyl Yin
Diindyl simultaneously [1,2-a] quinoxaline, yield 76%.
Embodiment 18:
0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of palladium acetate, 0.4 is sequentially added in reaction tube
MM ammonium persulfate and 0.2 mM of benzoyl formic acid.It is solvent that 2 milliliters of diethylene glycol dimethyl ethers, which are then added, at 78 DEG C
Under the conditions of be stirred to react 12 hours after stop reaction, be cooled to room temperature and filter, filtrate is extracted with ethyl acetate 3 times, is associated with
Machine phase is simultaneously dried, filtered using 0.5g anhydrous magnesium sulfate, and vacuum rotary steam obtains crude product, used most afterwards through column chromatographic isolation and purification
Column chromatographic eluate is the petroleum ether of volume ratio 30:1: ethyl acetate mixed solvent.Obtain pure 6- Phenylindole simultaneously [1,2-
A] quinoxaline, yield 53%.
Embodiment 19:
0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of palladium acetate, 0.2 is sequentially added in reaction tube
MM ammonium persulfate and 0.4 mM of benzoyl formic acid.It is solvent that 2 milliliters of diethylene glycol dimethyl ethers, which are then added, at 78 DEG C
Under the conditions of be stirred to react 12 hours after stop reaction, be cooled to room temperature and filter, filtrate is extracted with ethyl acetate 3 times, is associated with
Machine phase is simultaneously dried, filtered using 0.5g anhydrous magnesium sulfate, and vacuum rotary steam obtains crude product, used most afterwards through column chromatographic isolation and purification
Column chromatographic eluate is the petroleum ether of volume ratio 30:1: ethyl acetate mixed solvent.Obtain pure 6- Phenylindole simultaneously [1,2-
A] quinoxaline, yield 39%.
Embodiment 20:
0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of palladium acetate, 0.4 is sequentially added in reaction tube
MM ammonium persulfate and 0.4 mM of benzoyl formic acid.It is solvent that 2 milliliters of diethylene glycol dimethyl ethers, which are then added, at 78 DEG C
Under the conditions of be stirred to react 6 hours after stop reaction, be cooled to room temperature and filter, filtrate is extracted with ethyl acetate 3 times, merge it is organic
It is dried, filtered mutually and using 0.5g anhydrous magnesium sulfate, vacuum rotary steam obtains crude product, most afterwards through column chromatographic isolation and purification, column used
Chromatographic eluate is the petroleum ether of volume ratio 30:1: ethyl acetate mixed solvent.Obtain pure 6- Phenylindole simultaneously [1,2-a]
Quinoxaline, yield 51%.
Embodiment 21:
0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of palladium acetate, 0.4 is sequentially added in reaction tube
MM ammonium persulfate and 0.4 mM of benzoyl formic acid.It is solvent that 2 milliliters of diethylene glycol dimethyl ethers, which are then added, at 78 DEG C
Under the conditions of be stirred to react 24 hours after stop reaction, be cooled to room temperature and filter, filtrate is extracted with ethyl acetate 3 times, is associated with
Machine phase is simultaneously dried, filtered using 0.5g anhydrous magnesium sulfate, and vacuum rotary steam obtains crude product, used most afterwards through column chromatographic isolation and purification
Column chromatographic eluate is the petroleum ether of volume ratio 30:1: ethyl acetate mixed solvent.Obtain pure 6- Phenylindole simultaneously [1,2-
A] quinoxaline, yield 68%.Test result in above-described embodiment is shown in Table 1.
Table 1: the conditional FP tree of reactiona
aReaction condition: 0.2 mM of aniline of 2- (1H- indoles -1- base), 0.4 mM of benzoyl formic acid, catalyst
0.01 mM, 0.4 mM and 2.0 milliliters of solvent of oxidant sequentially adds in test tube, and 12 hours are reacted in 78 DEG C (without lazy
Property gas shield);bSeparation yield, n.d. representative do not detect product;cReaction temperature is 70 DEG C;dReaction temperature is 85 DEG C;eNitrogen
Gas shielded;fBenzoyl formic acid dosage is 0.2 mM;gThe dosage of ammonium persulfate is 0.2 mM;hReaction time is 6 hours
;iReaction time is 24 hours.
The present invention realizes 6- Phenylindole, and simultaneously [1,2-a] quinoxaline efficiently synthesizes.Reaction condition is simply in air
It can complete;It is raw materials used nontoxic and cheap and easy to get;The reaction has stronger selectivity to oxidant and solvent, and (persulfate is
Best oxidant, diethylene glycol dimethyl ether are best reaction dissolvents);Step economy is high, selectivity is single, easy to operate
Safety, mild condition, high income are the major advantages of reaction, the strategy for 6- Phenylindole simultaneously [1,2-a] quinoxaline synthesis
Provide new approaches.
Claims (2)
1. a kind of level-one amine guiding constructs 6- Phenylindole simultaneously [1,2-a] quinoxaline method, it is characterised in that: in reaction flask
In, 2- (1 is addedHIndoles -1- base) aniline and benzoyl formic acid be that raw material is with organic solvent using persulfate as oxidant
Solvent, 70 ~ 90oIt stirs 10 ~ 24 hours, is cooled to room temperature after reaction, filtering reacting liquid under C, obtained slightly after vacuum rotary steam
Product obtains 6- Phenylindole simultaneously [1,2- through column chromatographic purifyinga] quinoxaline;
The 2- (1HIndoles -1- base) molar ratio of aniline and benzoyl formic acid is 1:1 ~ 2;
The oxidant is potassium peroxydisulfate, sodium peroxydisulfate and ammonium persulfate;Oxidant and 2- (1HIndoles -1- base) aniline rubs
You are than being 1 ~ 2:1;
The catalyst is palladium acetate, palladium trifluoroacetate, two (triphenylphosphine) palladium chlorides or palladium chloride.
2. catalyst and 2- (1HIndoles -1- base) aniline molar ratio be 0.05:1;
The solvent is 1,4- dioxane or diethylene glycol dimethyl ether;
The column chromatographs eluent as the mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether and ethyl acetate is
100~10:1。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201811576551.7A CN109575034A (en) | 2018-12-22 | 2018-12-22 | The method of level-one amine guiding building 6- Phenylindole simultaneously [1,2-a] quinoxaline |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201811576551.7A CN109575034A (en) | 2018-12-22 | 2018-12-22 | The method of level-one amine guiding building 6- Phenylindole simultaneously [1,2-a] quinoxaline |
Publications (1)
Publication Number | Publication Date |
---|---|
CN109575034A true CN109575034A (en) | 2019-04-05 |
Family
ID=65931355
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201811576551.7A Withdrawn CN109575034A (en) | 2018-12-22 | 2018-12-22 | The method of level-one amine guiding building 6- Phenylindole simultaneously [1,2-a] quinoxaline |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN109575034A (en) |
-
2018
- 2018-12-22 CN CN201811576551.7A patent/CN109575034A/en not_active Withdrawn
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN108299423B (en) | Synthesis method of dihydropyrrolo-2-aminoquinoline compound | |
CN107235923B (en) | Preparation method of 3-aryl quinoxalinone derivatives | |
CN104892547B (en) | A kind of method that catalysis of carbonyl is combined to alpha-keto amide compound | |
CN111233852B (en) | NON type chiral bisoxazoline ligand and synthetic method and application thereof | |
Pan et al. | One-pot synthesis of 3-trifluoromethylbenzo [b][1, 4] oxazines from CF 3-imidoyl sulfoxonium ylides with 2-bromophenols | |
CN102977017B (en) | Method for catalytically preparing 6(5H)-phenanthridine ketone by copper component | |
CN109438451A (en) | The method of level-one amine guiding building 6- (2- bromophenyl) indoles simultaneously [1,2-a] quinoxaline | |
CN109503603A (en) | The method of level-one amine guiding building 6- (4- n-butylphenyl) indoles simultaneously [1,2-a] quinoxaline | |
CN105732648B (en) | The nitrogen-containing heterocycle compound and synthetic method of a kind of pyrrolo- furans | |
CN109575034A (en) | The method of level-one amine guiding building 6- Phenylindole simultaneously [1,2-a] quinoxaline | |
CN109438453A (en) | The method of level-one amine guiding building 6- (furans -2- base) indoles simultaneously [1,2-a] quinoxaline | |
CN109608466A (en) | The method of the level-one amine guiding building fluoro- 6- Phenylindole of 9- simultaneously [1,2-a] quinoxaline | |
CN109503597A (en) | The method of level-one amine guiding building 6- (4- methoxyphenyl) indoles simultaneously [1,2-a] quinoxaline | |
CN109575033A (en) | The method of level-one amine guiding building 6- (2- aminomethyl phenyl) indoles simultaneously [1,2-a] quinoxaline | |
CN109627249A (en) | The method of level-one amine guiding building 6- (naphthalene -1- base) indoles simultaneously [1,2-a] quinoxaline | |
CN109627247A (en) | The method of level-one amine guiding building 8- benzyloxy -6- Phenylindole simultaneously [1,2-a] quinoxaline | |
CN109438452A (en) | The method of level-one amine guiding building 6- (2- fluorophenyl) indoles simultaneously [1,2-a] quinoxaline | |
CN109575032A (en) | The method of level-one amine guiding building 6- (3- fluorophenyl) indoles simultaneously [1,2-a] quinoxaline | |
CN109485650A (en) | The method of level-one amine guiding building 8,10- dimethyl -6- Phenylindole simultaneously [1,2-a] quinoxaline | |
CN109503599A (en) | The method of level-one amine guiding building 6- (3- methoxyphenyl) indoles simultaneously [1,2-a] quinoxaline | |
CN109503598A (en) | The method of level-one amine guiding building 6- (4- chlorphenyl) indoles simultaneously [1,2-a] quinoxaline | |
CN109627246A (en) | The method of level-one amine guiding building 7- methyl -6- Phenylindole simultaneously [1,2-a] quinoxaline | |
CN109503601A (en) | The method of level-one amine guiding building 6- (4- bromophenyl) indoles simultaneously [1,2-a] quinoxaline | |
CN109608467A (en) | The method of level-one amine guiding building 8- chloro-6-phenyl indoles simultaneously [1,2-a] quinoxaline | |
CN109503596A (en) | The method of level-one amine guiding building 2- chloro-6-phenyl indoles simultaneously [1,2-a] quinoxaline |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
WW01 | Invention patent application withdrawn after publication |
Application publication date: 20190405 |
|
WW01 | Invention patent application withdrawn after publication |