CN109485650A - The method of level-one amine guiding building 8,10- dimethyl -6- Phenylindole simultaneously [1,2-a] quinoxaline - Google Patents
The method of level-one amine guiding building 8,10- dimethyl -6- Phenylindole simultaneously [1,2-a] quinoxaline Download PDFInfo
- Publication number
- CN109485650A CN109485650A CN201811576552.1A CN201811576552A CN109485650A CN 109485650 A CN109485650 A CN 109485650A CN 201811576552 A CN201811576552 A CN 201811576552A CN 109485650 A CN109485650 A CN 109485650A
- Authority
- CN
- China
- Prior art keywords
- dimethyl
- quinoxaline
- indoles
- reaction
- aniline
- 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- Withdrawn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)
Abstract
The invention discloses a kind of level-one amine to be oriented to building 8,10- dimethyl -6- Phenylindole simultaneously [1,2-a] quinoxaline method.In reaction tube, 2- (4,6- dimethyl -1 are addedHIndoles -1- base) aniline and benzoyl formic acid be raw material, 8,10- dimethyl -6- Phenylindole simultaneously [1,2- is made in high yield through acylation/cyclizationa] quinoxaline.The present invention realizes acylation/cyclization of level-one amine guiding, avoids the use of the additives such as acid, 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, meet the development need of green organic chemistry.
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 8,10- diformazan
The method of base -6- Phenylindole simultaneously [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 8,10- dimethyl -6- Phenylindole simultaneously [1,2-a] quinoxaline.This method reacts item
Part is simple, and required raw material is cheap and easy to get, and preparation condition is mild, easy to operate, and selectivity is single, and separation yield is high, is conducive to work
Industry metaplasia produces, and has in the research and development of drug 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 level-one amine to be oriented to building 8,10- dimethyl -6- Phenylindole simultaneously [1,2-a] quinoline
The method of quinoline.
Thinking of the invention: with 2- (4,6- dimethyl -1H- indoles -1- base) aniline, benzoyl formic acid for raw material, over cure
Hydrochlorate is oxidant, under the catalysis of palladium salt, continuous acylation/cyclization occurs, step building has pharmaceutical activity bone
The compound 8,10- dimethyl -6- Phenylindole of frame simultaneously [1,2-a] quinoxaline.This method avoid making for the additives such as acid, alkali
With raw materials required for the reaction is cheap and easy to get, and reaction condition is mild, and easy to operate, selectivity is single, and step economy is high, has latent
Practical value.
Specific steps are as follows:
2- (4,6- dimethyl -1H- indoles -1- base) aniline and benzoyl formic acid are sequentially added, in reaction flask with over cure
Hydrochlorate is oxidant, using palladium salt as catalyst, using organic solvent as solvent, is stirred 10~24 hours at 70~90 DEG C, reaction
After be cooled to room temperature, filtering reacting liquid, after vacuum rotary steam crude product, obtain compound 8,10- bis- through column chromatographic purifying
Methyl -6- Phenylindole simultaneously [1,2-a] quinoxaline.
The molar ratio of 2- (4,6- dimethyl -1H- indoles -1- base) aniline and benzoyl formic acid is 1:1~2.
The oxidant is potassium peroxydisulfate, sodium peroxydisulfate or ammonium persulfate;Oxidant and 2- (4,6- dimethyl -1H- Yin
Diindyl -1- 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 (4,6- dimethyl -1H- indoles -1- base) aniline is 0.05:1.
The solvent is 1,4- dioxane or diethylene glycol dimethyl ether.
The purification process of the product after reaction is column chromatography.The column chromatography eluent is petroleum ether and acetic acid second
The volume ratio of the mixed solvent of ester, petroleum ether and ethyl acetate is 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 8,10- dimethyl -6- Phenylindole simultaneously [1,2-a] quinoxaline, it is raw materials used nontoxic and
It is cheap and easy to get;Reaction in air atmosphere carry out can and;The strategy has single selectivity;In addition, reaction also has step
The advantages of rapid economy is high, easy to operate, safety, reaction condition is mild, high income.The strategy is 8,10- dimethyl -6- phenyl
The preparation of indoles simultaneously [1,2-a] quinoxaline provides effective synthetic method.
Detailed description of the invention
Fig. 1 is the synthesis equation of 8,10- dimethyl -6- Phenylindole simultaneously [1,2-a] quinoxaline in the present invention.
Fig. 2 be 8,10- dimethyl -6- Phenylindole made from the embodiment of the present invention 14 simultaneously [1,2-a] quinoxaline hydrogen spectrum.
Fig. 3 be 8,10- dimethyl -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- (4,6- dimethyl -1H- indoles -1- base) aniline, 0.01 mM is sequentially added in reaction tube
Palladium chloride, 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 0.5 gram of 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 50:1: ethyl acetate mixed solvent.Obtain pure 8,10- bis-
Methyl -6- Phenylindole simultaneously [1,2-a] quinoxaline, yield 34%.
Embodiment 2:
0.2 mM of 2- (4,6- dimethyl -1H- indoles -1- base) aniline, 0.01 mM is sequentially added in reaction tube
Palladium acetate, 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 0.5 gram of 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 50:1: ethyl acetate mixed solvent.Obtain pure 8,10- bis-
Methyl -6- Phenylindole simultaneously [1,2-a] quinoxaline, yield 62%.
Embodiment 3:
0.2 mM of 2- (4,6- dimethyl -1H- indoles -1- base) aniline, 0.01 mM is sequentially added in reaction tube
Palladium trifluoroacetate, 0.4 mM of potassium peroxydisulfate and 0.4 mM of benzoyl formic acid.2 milliliters of 1,4- dioxane, which are then added, is
Solvent stops reaction, is cooled to room temperature and filters, filtrate is extracted with ethyl acetate after being stirred to react under the conditions of 78 DEG C 12 hours
3 times, merge organic phase and dried, filtered using 0.5 gram of anhydrous magnesium sulfate, vacuum rotary steam obtains crude product, most afterwards through column chromatography point
From purifying, column chromatographic eluate used is the petroleum ether of volume ratio 50:1: ethyl acetate mixed solvent.Obtain pure 8,10-
Dimethyl -6- Phenylindole simultaneously [1,2-a] quinoxaline, yield 45%.
Embodiment 4:
0.2 mM of 2- (4,6- dimethyl -1H- indoles -1- base) aniline, 0.01 mM is sequentially added in reaction tube
Tetrakis triphenylphosphine palladium, 0.4 mM of potassium peroxydisulfate and 0.4 mM of benzoyl formic acid.2 milliliters of 1,4- dioxies six are then added
Ring is solvent, stops reaction after being stirred to react under the conditions of 78 DEG C 12 hours.TLC (thin-layered chromatography) detection reaction, is not examined
Measure the generation of 8,10- dimethyl -6- Phenylindole simultaneously [1,2-a] quinoxaline.
Embodiment 5:
0.2 mM of 2- (4,6- dimethyl -1H- indoles -1- base) aniline, 0.01 mM is sequentially added in reaction tube
Dichloro two (triphenylphosphine) palladium, 0.4 mM of potassium peroxydisulfate and 0.4 mM of benzoyl formic acid.2 milliliters of 1,4- bis- are then added
Six ring of oxygen is solvent, stops reaction after being stirred to react under the conditions of 78 DEG C 12 hours, is cooled to room temperature and filters, filtrate acetic acid
Ethyl ester extracts 3 times, merges organic phase and is dried, filtered using 0.5 gram of anhydrous magnesium sulfate, vacuum rotary steam obtains crude product, most passes through afterwards
Column chromatographic isolation and purification, column chromatographic eluate used are the petroleum ether of volume ratio 50:1: ethyl acetate mixed solvent.It obtains pure
8,10- dimethyl -6- Phenylindole simultaneously [1,2-a] quinoxaline, yield 19%.
Embodiment 6:
0.2 mM of 2- (4,6- dimethyl -1H- indoles -1- base) aniline, 0.01 mM is sequentially added in reaction tube
Palladium acetate, 0.4 mM of 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,
Stop reaction after being stirred to react under the conditions of 78 DEG C 12 hours.TLC (thin-layered chromatography) detection reaction, there is 8, the 10- bis- of trace
Simultaneously [1,2-a] quinoxaline generates methyl -6- Phenylindole, but can not be isolated.
Embodiment 7:
0.2 mM of 2- (4,6- dimethyl -1H- indoles -1- base) aniline, 0.01 mM is sequentially added in reaction tube
Palladium acetate, 0.4 mM of 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,
Stop reaction after being stirred to react under the conditions of 78 DEG C 12 hours.TLC (thin-layered chromatography) detection reaction, without 8,10- dimethyl -6-
The generation of Phenylindole simultaneously [1,2-a] quinoxaline.
Embodiment 8:
0.2 mM of 2- (4,6- dimethyl -1H- indoles -1- base) aniline, 0.01 mM is sequentially added in reaction tube
Palladium acetate, 0.4 mM of 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,
Stop reaction after being stirred to react under the conditions of 78 DEG C 12 hours.TLC (thin-layered chromatography) detection reaction, without 8,10- dimethyl -6-
The generation of Phenylindole simultaneously [1,2-a] quinoxaline.
Embodiment 9:
0.2 mM of 2- (4,6- dimethyl -1H- indoles -1- base) aniline, 0.01 mM is sequentially added in reaction tube
Palladium acetate, 0.4 mM of ammonium persulfate 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 0.5 gram of 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 50:1: ethyl acetate mixed solvent.Obtain pure 8,10- bis-
Methyl -6- Phenylindole simultaneously [1,2-a] quinoxaline, yield 70%.
Embodiment 10:
0.2 mM of 2- (4,6- dimethyl -1H- indoles -1- base) aniline, 0.01 mM is sequentially added in reaction tube
Palladium acetate, 0.4 mM of sodium 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 0.5 gram of 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 50:1: ethyl acetate mixed solvent.Obtain pure 8,10- bis-
Methyl -6- Phenylindole simultaneously [1,2-a] quinoxaline, yield 51%.
Embodiment 11:
0.2 mM of 2- (4,6- dimethyl -1H- indoles -1- base) aniline, 0.01 mM is sequentially added in reaction tube
Palladium acetate, 0.4 mM of ammonium persulfate and 0.4 mM of benzoyl formic acid.It is solvent that 2 milliliters of DMSO, which are then added, at 78 DEG C
Under the conditions of be stirred to react 12 hours after stop reaction.TLC (thin-layered chromatography) detection reaction, does not detect 8,10- dimethyl-
The generation of 6- Phenylindole simultaneously [1,2-a] quinoxaline.
Embodiment 12:
0.2 mM of 2- (4,6- dimethyl -1H- indoles -1- base) aniline, 0.01 mM is sequentially added in reaction tube
Palladium acetate, 0.4 mM of ammonium persulfate and 0.4 mM of benzoyl formic acid.It is solvent that 2 milliliters of DMF, which are then added, in 78 DEG C of items
Stop reaction after being stirred to react under part 12 hours.TLC (thin-layered chromatography) detection reaction, does not detect 8,10- dimethyl -6-
The generation of Phenylindole simultaneously [1,2-a] quinoxaline.
Embodiment 13:
0.2 mM of 2- (4,6- dimethyl -1H- indoles -1- base) aniline, 0.01 mM is sequentially added in reaction tube
Palladium acetate, 0.4 mM of ammonium persulfate and 0.4 mM of benzoyl formic acid.It is solvent that 2 milliliters of toluene, which are then added, at 78 DEG C
Under the conditions of be stirred to react 12 hours after stop reaction.TLC (thin-layered chromatography) detection reaction, does not detect 8,10- dimethyl-
The generation of 6- Phenylindole simultaneously [1,2-a] quinoxaline.
Embodiment 14:
0.2 mM of 2- (4,6- dimethyl -1H- indoles -1- base) aniline, 0.01 mM is sequentially added in reaction tube
Palladium acetate, 0.4 mM of ammonium persulfate and 0.4 mM of benzoyl formic acid.It is molten that 2 milliliters of diethylene glycol dimethyl ethers, 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 0.5 gram of 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 50:1: ethyl acetate mixed solvent.Obtain pure 8,10- bis-
Simultaneously [1,2-a] quinoxaline, yield are up to 76% to methyl -6- Phenylindole.
Gained 8,10- dimethyl -6- Phenylindole simultaneously compose respectively such as Fig. 2 and Fig. 3 institute by the hydrogen spectrum of [1,2-a] quinoxaline and carbon
Show, structure indicator data are as follows:
Yellow solid;mp 176-177℃;IR: ν=3063,2920,2852,1623,1534,1446,1387,
1330,1216,859,812,740,689cm-1;1H NMR(400MHz,CDCl3) δ 8.54 (d, J=8.6Hz, 1H), 8.23 (s,
1H), 8.16-8.10 (m, 2H), 7.96 (d, J=8.0Hz, 1H), 7.63-7.54 (m, 4H), 7.46 (t, J=7.5Hz, 1H),
7.29(s,1H),7.19(s,1H),2.83(s,3H),2.62(s,3H);13C NMR(100MHz,CDCl3)δ153.0,138.8,
138.5,138.0,133.0,132.7,130.0,129.8,129.4,129.1,128.9,128.5,126.7,123.7,
122.5,122.5,114.9,112.8,101.3,22.2,18.4;HRMS(ESI)m/z:calcd for C23H19N2[M+H]+,
323.1543;found 323.1546.
The structure of 8,10- dimethyl -6- Phenylindole simultaneously [1,2-a] quinoxaline is as follows:
Embodiment 15:
0.2 mM of 2- (4,6- dimethyl -1H- indoles -1- base) aniline, 0.01 mM is sequentially added in reaction tube
Palladium acetate, 0.4 mM of ammonium persulfate and 0.4 mM of benzoyl formic acid.It is molten that 2 milliliters of diethylene glycol dimethyl ethers, 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 70 DEG C 12 hours
It is secondary, merge organic phase and dried, filtered using 0.5 gram of 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 50:1: ethyl acetate mixed solvent.Obtain pure 8,10- bis-
Methyl -6- Phenylindole simultaneously [1,2-a] quinoxaline, yield 55%.
Embodiment 16:
0.2 mM of 2- (4,6- dimethyl -1H- indoles -1- base) aniline, 0.01 mM is sequentially added in reaction tube
Palladium acetate, 0.4 mM of ammonium persulfate and 0.4 mM of benzoyl formic acid.It is molten that 2 milliliters of diethylene glycol dimethyl ethers, 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 85 DEG C 12 hours
It is secondary, merge organic phase and dried, filtered using 0.5 gram of 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 50:1: ethyl acetate mixed solvent.Obtain pure 8,10- bis-
Methyl -6- Phenylindole simultaneously [1,2-a] quinoxaline, yield 67%.
Embodiment 17:
0.2 mM of 2- (4,6- dimethyl -1H- indoles -1- base) aniline, 0.01 mM is sequentially added in reaction tube
Palladium acetate, 0.4 mM of ammonium persulfate and 0.4 mM of benzoyl formic acid.It is molten that 2 milliliters of diethylene glycol dimethyl ethers, which are then added,
Agent, nitrogen protection stop reaction, are cooled to room temperature and filter after being stirred to react under the conditions of 78 DEG C 12 hours, filtrate acetic acid
Ethyl ester extracts 3 times, merges organic phase and is dried, filtered using 0.5 gram of anhydrous magnesium sulfate, vacuum rotary steam obtains crude product, most passes through afterwards
Column chromatographic isolation and purification, column chromatographic eluate used are the petroleum ether of volume ratio 50:1: ethyl acetate mixed solvent.It obtains pure
8,10- dimethyl -6- Phenylindole simultaneously [1,2-a] quinoxaline, yield 75%.
Embodiment 18:
0.2 mM of 2- (4,6- dimethyl -1H- indoles -1- base) aniline, 0.01 mM is sequentially added in reaction tube
Palladium acetate, 0.4 mM of ammonium persulfate and 0.2 mM of benzoyl formic acid.It is molten that 2 milliliters of diethylene glycol dimethyl ethers, 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 0.5 gram of 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 50:1: ethyl acetate mixed solvent.Obtain pure 8,10- bis-
Methyl -6- Phenylindole simultaneously [1,2-a] quinoxaline, yield 47%.
Embodiment 19:
0.2 mM of 2- (4,6- dimethyl -1H- indoles -1- base) aniline, 0.01 mM is sequentially added in reaction tube
Palladium acetate, 0.2 mM of ammonium persulfate and 0.4 mM of benzoyl formic acid.It is molten that 2 milliliters of diethylene glycol dimethyl ethers, 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 0.5 gram of 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 50:1: ethyl acetate mixed solvent.Obtain pure 8,10- bis-
Methyl -6- Phenylindole simultaneously [1,2-a] quinoxaline, yield 40%.
Embodiment 20:
0.2 mM of 2- (4,6- dimethyl -1H- indoles -1- base) aniline, 0.01 mM is sequentially added in reaction tube
Palladium acetate, 0.4 mM of ammonium persulfate and 0.4 mM of benzoyl formic acid.It is molten that 2 milliliters of diethylene glycol dimethyl ethers, 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 6 hours
It is secondary, merge organic phase and dried, filtered using 0.5 gram of 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 50:1: ethyl acetate mixed solvent.Obtain pure 8,10- bis-
Methyl -6- Phenylindole simultaneously [1,2-a] quinoxaline, yield 49%.
Embodiment 21:
0.2 mM of 2- (4,6- dimethyl -1H- indoles -1- base) aniline, 0.01 mM is sequentially added in reaction tube
Palladium acetate, 0.4 mM of ammonium persulfate and 0.4 mM of benzoyl formic acid.It is molten that 2 milliliters of diethylene glycol dimethyl ethers, 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 24 hours
It is secondary, merge organic phase and dried, filtered using 0.5 gram of 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 50:1: ethyl acetate mixed solvent.Obtain pure 8,10- bis-
Methyl -6- Phenylindole simultaneously [1,2-a] quinoxaline, yield 66%.
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- (4,6- dimethyl -1H- indoles -1- base), 0.4 mmoles of benzoyl formic acid
You, 0.01 mM of catalyst, 0.4 mM and 2.0 milliliters of solvent of oxidant sequentially adds in test tube, small in 78 DEG C of reactions 12
When (be not necessarily to inert gas shielding);bSeparation yield, n.d. representative do not detect product;cReaction temperature is 70 DEG C;dReaction temperature
It is 85 DEG C;eNitrogen protection;fBenzoyl formic acid dosage is 0.2 mM;gThe dosage of ammonium persulfate is 0.2 mM;hWhen reaction
Between be 6 hours;iReaction time is 24 hours.
The present invention realizes 8,10- dimethyl -6- Phenylindole, and simultaneously [1,2-a] quinoxaline efficiently synthesizes.The reaction item
Part can simply be completed in air;It is raw materials used nontoxic and cheap and easy to get;The reaction has stronger choosing to oxidant and solvent
Selecting property (persulfate is best oxidant, and diethylene glycol dimethyl ether is best reaction dissolvent);Step economy is high, selects
Property safety single, easy to operate, mild condition, high income be reaction major advantage, which is 8,10- dimethyl -6- benzene
The synthesis of base indoles simultaneously [1,2-a] quinoxaline provides new approaches.
Claims (1)
1. a kind of level-one amine guiding constructs 8,10- dimethyl -6- Phenylindole simultaneously [1,2-a] quinoxaline method, feature exists
In specific steps are as follows: in reaction tube, 2- (4,6- dimethyl -1 are addedHIndoles -1- base) aniline and benzoyl formic acid be original
Material, using persulfate as oxidant, using organic solvent as solvent, 70 ~ 90oIt is stirred 10 ~ 24 hours under C, it is cold after reaction
But to room temperature, filtering reacting liquid, after vacuum rotary steam crude product, obtain 8,10- dimethyl -6- Phenylindole through column chromatographic purifying
And [1,2-a] quinoxaline;
2- (the 4,6- dimethyl -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- (4,6- dimethyl -1HIndoles -1-
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- (4,
6- dimethyl -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 |
---|---|---|---|
CN201811576552.1A CN109485650A (en) | 2018-12-22 | 2018-12-22 | The method of level-one amine guiding building 8,10- dimethyl -6- Phenylindole simultaneously [1,2-a] quinoxaline |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201811576552.1A CN109485650A (en) | 2018-12-22 | 2018-12-22 | The method of level-one amine guiding building 8,10- dimethyl -6- Phenylindole simultaneously [1,2-a] quinoxaline |
Publications (1)
Publication Number | Publication Date |
---|---|
CN109485650A true CN109485650A (en) | 2019-03-19 |
Family
ID=65711433
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201811576552.1A Withdrawn CN109485650A (en) | 2018-12-22 | 2018-12-22 | The method of level-one amine guiding building 8,10- dimethyl -6- Phenylindole simultaneously [1,2-a] quinoxaline |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN109485650A (en) |
-
2018
- 2018-12-22 CN CN201811576552.1A patent/CN109485650A/en not_active Withdrawn
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Li et al. | Regioselective and stereoselective sulfonylation of alkynylcarbonyl compounds in water | |
CN108299423B (en) | Synthesis method of dihydropyrrolo-2-aminoquinoline compound | |
Liu et al. | Modular synthesis of dihydro-isoquinolines: palladium-catalyzed sequential C (sp 2)–H and C (sp 3)–H bond activation | |
Pan et al. | One-pot synthesis of 3-trifluoromethylbenzo [b][1, 4] oxazines from CF 3-imidoyl sulfoxonium ylides with 2-bromophenols | |
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 | |
CN109485650A (en) | The method of level-one amine guiding building 8,10- dimethyl -6- Phenylindole simultaneously [1,2-a] quinoxaline | |
CN109485649A (en) | The method of the level-one amine guiding building fluoro- 6- Phenylindole of the chloro- 4- of 2- simultaneously [1,2-a] quinoxaline | |
CN109627247A (en) | The method of level-one amine guiding building 8- benzyloxy -6- Phenylindole simultaneously [1,2-a] quinoxaline | |
CN109503595A (en) | The method of level-one amine guiding building 10- methoxyl group -6- Phenylindole simultaneously [1,2-a] quinoxaline | |
CN109503597A (en) | The method of level-one amine guiding building 6- (4- methoxyphenyl) 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 | |
CN109503599A (en) | The method of level-one amine guiding building 6- (3- methoxyphenyl) 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 | |
CN109627245A (en) | The method of level-one amine guiding building 8- methoxyl group -6- Phenylindole simultaneously [1,2-a] quinoxaline | |
CN109438450A (en) | The method of level-one amine guiding building 9- methoxyl group -6- Phenylindole simultaneously [1,2-a] quinoxaline | |
CN109575034A (en) | The method of level-one amine guiding building 6- Phenylindole simultaneously [1,2-a] quinoxaline | |
CN109503600A (en) | The method of the level-one amine guiding building fluoro- 6- Phenylindole of 2- 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 | |
CN109627248A (en) | The method of level-one amine guiding building 6- (the bromo- 2- fluorophenyl of 4-) 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 | |
CN109438453A (en) | The method of level-one amine guiding building 6- (furans -2- base) 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 | |
CN109575033A (en) | The method of level-one amine guiding building 6- (2- aminomethyl phenyl) 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 |
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: 20190319 |
|
WW01 | Invention patent application withdrawn after publication |