CN109400611A - A kind of synthetic method of 1- vinyl -4,5- pyrrolin [1,2-a] quinoxaline compounds - Google Patents
A kind of synthetic method of 1- vinyl -4,5- pyrrolin [1,2-a] quinoxaline compounds Download PDFInfo
- Publication number
- CN109400611A CN109400611A CN201811130849.5A CN201811130849A CN109400611A CN 109400611 A CN109400611 A CN 109400611A CN 201811130849 A CN201811130849 A CN 201811130849A CN 109400611 A CN109400611 A CN 109400611A
- Authority
- CN
- China
- Prior art keywords
- pyrrolin
- vinyl
- reaction
- formula
- synthetic method
- 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
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)
- Pyrrole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
The invention discloses a kind of synthesis 1- vinyl -4,5- pyrrolin [1,2-a] quinoxaline derivant new method, include the following steps: that the amino benzenes compounds, end group aryne, (acetonitrile) [(2- biphenyl) di-t-butyl phosphine] hexafluoro-antimonic acid gold (I) for facing a pyrroles and replacing are added in dry toluene, reaction 24 hours is carried out under the conditions of 100 DEG C of heating, post-process isolated 1- vinyl -4,5- pyrrolin [1,2-a] quinoxaline derivant.A kind of new method synthesizing 1- vinyl -4,5- pyrrolin [1,2-a] quinoxaline derivant by facing amino benzenes compounds that pyrroles replaces with aryl terminal alkyne compound provided by the present invention.The present invention entirely has many advantages, such as that easy to operate, mild condition, substrate functional group good compatibility, product yield high, catalyst and product are easily separated, has potential bioactivity, can pass through its pharmaceutical activity of follow-up test, carry out the screening of drug.
Description
Technical field
The invention belongs to chemosynthesis technical fields, and in particular to a kind of 1- vinyl -4,5- pyrrolin [1,2-a] quinoline
The synthetic method of quinoline compound.
Background technique
Quinoxaline compound is very important heterocyclic compound in one, wherein 4,5- pyrrolin [1,2-a] quinoline
Quinoline class compound and the like is the important feature for constituting many natural products molecules and biologically active drug molecule
Unit is with a wide range of applications in field of pharmaceutical chemistry research, and e.g., 6FQXP structure shown in formula (10) has anti HIV-1 virus
Drug effect, CB1 receptor antagonist shown in formula (11) can be used for treating obesity.
4,5- pyrrolin [1,2-a] quinoxaline compound has important pharmacological action, therefore has attracted chemist
Extensive concern, developed the methods of the such compounds of various synthesis.Existing 4,5- pyrrolin [1,2-a] quinoxaline chemical combination
The synthetic method of object mainly has the Pictet-Spengler of Bronsted acid and Louis acid catalysis reaction, is replaced with facing a pyrroles
Aniline and aldehyde be raw material (Eur.J.Org.Chem.2011,6998-7010.；Adv.Syn.Cat.2018,360,1334-
And transition metal-catalyzed method, 1339.) using face aniline that a pyrroles replaces and alkynes as raw material (J.Am.Chem.Soc.,
2005,127 17000-17006).Although this method is current synthesis 4,5- pyrrolin [1,2-a] quinoxaline compound
Universal method, but this method has condition harsh, reaction needs additional additive, it is often more important that such method cannot lead to
It crosses single step reaction and carries out functional groupization reaction on pyrrole ring.The present invention is former using aniline and the alkynes that a pyrroles replaces is faced
Material, uses gold complex as catalyst, has obtained the product different from other methods, realizes and occurs instead with two molecule alkynes
It answers, efficiently constructs 1- vinyl -4,5- pyrrolin [1,2-a] quinoxaline compound of multifunctional dough.
Summary of the invention
In order to solve problems in the prior art, 1- vinyl -4, the 5- pyrrolin good the present invention provides a kind of yield
The synthetic method of [1,2-a] quinoxaline compounds.
In order to solve the above technical problems, the present invention provides the following technical scheme that a kind of 1- vinyl -4,5- of the invention
The synthetic method of pyrrolin [1,2-a] quinoxaline compounds, under Au catalyst effect, to face a pyrroles shown in formula (2)
Substituted amino benzenes compounds with and formula (3) shown in aryl Terminal Acetylenes be that raw material carries out in a solvent in the case where Au catalyst acts on
Reaction, thin plate chromatography tracking reaction until the reaction is complete, obtain reaction mixture, the reaction mixture is post-treated to be obtained
The quinoxaline compounds of 1- vinyl -4,5- pyrrolin [1,2-a] shown in formula (1)；Its chemical equation is as follows:
In formula (2) or formula (1), the R is hydrogen, methyl, aryl or halogen；In formula (3) or formula (1), Ar is phenyl, naphthalene
Base, heterocycle (including but not limited to furan nucleus, thiphene ring, pyridine ring etc.), substituted heterocycle are replaced by methyl, methoxyl group, halogen
Phenyl.
Further, the solvent is appointing in dichloroethanes, nitromethane, toluene, tetrahydrofuran, acetonitrile or chlorobenzene
It anticipates one kind.
Further, the solvent is toluene.
Further, the Au catalyst is one of following shown Au catalyst；
Further, the ratio between the amount of substance of amino benzenes compounds and aryl Terminal Acetylenes that a pyrroles replaces of facing is 1:
2-1:5。
Further, the Au catalyst is with the ratio between the amount for facing the amino benzenes compounds substance that a pyrroles replaces
0.01-0.2。
Further, the reaction temperature is 25-100 DEG C, and the reaction time is 1-24 hours.
Further, the reaction postprocessing method are as follows: after reaction, reaction mixture is subjected to concentrated by rotary evaporation,
And separated by silica gel column chromatography, using petroleum ether: the mixed solution of ethyl acetate volume ratio 20:1-5:1 carries out ladder as eluant, eluent
Degree elution, obtains 1- vinyl -4,5- pyrrolin [1,2-a] quinoxaline compounds shown in formula (1).
The utility model has the advantages that synthetic method of the present invention, regioselectivity is good, and reaction substrate range is wide, and post-processing is simple,
And achieve preferable yield (68-88%).
(1) synthetic method of the present invention is using gold complex as catalyst, using toluene as solvent, heats 100 DEG C of conditions
Under reacted, post-process a kind of isolated 1- vinyl -4,5- pyrrolin [1,2-a] quinoxaline compounds, product tool
There is potential bioactivity, its pharmaceutical activity of follow-up test can be passed through, carry out the screening of drug.It can also be used as a kind of important
Organic intermediate is applied to the fields such as medicine, pesticide.
(2) present invention researches and develops a kind of 1- vinyl -4,5- pyrrolin [1,2-a] quinoxaline derivant obtained with latent
Bioactivity, can pass through its pharmaceutical activity of follow-up test, carry out the screening of drug.It can also be used as a kind of important organic
Intermediate is applied to the fields such as medicine, pesticide.
(3) provided by the present invention a kind of by facing an amino benzenes compounds for pyrroles's substitution and end group aryne in Au catalyst
Under effect, the new method of 1- vinyl -4,5- pyrrolin [1,2-a] quinoxaline compounds is efficiently synthesized.Entire reaction has
The advantages that easy to operate, mild condition, substrate functional group good compatibility, product yield high, easily separated catalyst and product.
Detailed description of the invention
In order to illustrate the technical solution of the embodiments of the present invention more clearly, required use in being described below to embodiment
Attached drawing be briefly described, it should be apparent that, drawings in the following description are only some embodiments of the invention, for this
For the those of ordinary skill of field, without any creative labor, it can also be obtained according to these attached drawings other
Attached drawing；Wherein:
Fig. 1 is compound 4- (4- bromophenyl) -1- (1- (4- bromophenyl) vinyl) -4- methyl) -4,5- pyrrolin
The single crystal diffraction figure of [1,2-a] quinoxaline (1ae).
Specific embodiment
In order to make the foregoing objectives, features and advantages of the present invention clearer and more comprehensible, right combined with specific embodiments below
A specific embodiment of the invention is described in detail.
In the following description, numerous specific details are set forth in order to facilitate a full understanding of the present invention, but the present invention can be with
Implemented using other than the one described here other way, those skilled in the art can be without prejudice to intension of the present invention
In the case of do similar popularization, therefore the present invention is not limited by the specific embodiments disclosed below.
Secondly, " one embodiment " or " embodiment " referred to herein, which refers to, may be included at least one realization side of the invention
A particular feature, structure, or characteristic in formula." in one embodiment " that different places occur in the present specification not refers both to
The same embodiment, nor the individual or selective embodiment mutually exclusive with other embodiments.
Embodiment 1
Reaction equation are as follows:
Into 25mL round-bottomed flask, 2- (1H-1- pyrrole radicals) aniline 2a (0.2mmol), phenylacetylene 3a is sequentially added
(0.5mmol), toluene 2mL, Au catalyst (4) (acetonitrile) [(2- biphenyl) di-t-butyl phosphine] hexafluoro-antimonic acid gold (I)
(0.01mmol) is stirred 24 hours under the conditions of 100 DEG C.TLC monitoring reaction, after reaction, rotary evaporation removes solvent, crude product
By 280 mesh silica gel column chromatographies, ladder is carried out by eluant, eluent of the mixed solvent of petroleum ether and ethyl acetate (volume ratio 10:1)
Degree elution collects eluent revolving and removes solvent, obtains target product 1aa, be white solid (yield 78%).
1H NMR(400MHz,CDCl3): δ 7.32-7.13 (m, 10H), 6.71 (t, J=7.24Hz, 1H), 6.62 (d, J=
6.92Hz, 1H), 6.39 (t, J=7.26Hz, 1H), 6.32 (s, 1H), 6.08 (s, 1H), 5.69 (s, 1H), 5.51 (s, 1H),
4.29(s,1H),1.88(s,1H).
13C NMR(100MHz,CDCl3):δ145.9,142.6,139.9,136.2,136.1,130.2,128.3,
128.2,127.8,126.9,126.7,126.0,125.9,124.3,118.9,118.7,115.8,113.6,103.7,57.8,
29.2.
Embodiment 2
Reaction equation are as follows:
Into 25mL round-bottomed flask, 2- (1H-1- pyrrole radicals) aniline 2a (0.2mmol), 4- methyl phenylacetylene are sequentially added
3b (0.5mmol), toluene 2mL, Au catalyst (4) (acetonitrile) [(2- biphenyl) di-t-butyl phosphine] hexafluoro-antimonic acid gold (I)
(0.01mmol) is stirred 24 hours under the conditions of 100 DEG C.TLC monitoring reaction, after reaction, rotary evaporation removes solvent, crude product
By 300 mesh silica gel column chromatographies, ladder is carried out by eluant, eluent of the mixed solvent of petroleum ether and ethyl acetate (volume ratio 20:1)
Degree elution collects eluent revolving and removes solvent, obtains target product 1ab, be white solid (yield 85%).
1H NMR(400MHz,CDCl3): δ 7.26-7.13 (m, 5H), 7.01 (q, J=8.00Hz, 4H), 6.71 (t, J=
7.56Hz, 1H), 6.60 (d, J=7.72Hz, 1H), 6.40 (t, J=7.70Hz), 6.28 (d, J=3.44Hz, 1H), 6.05
(d, J=3.4Hz, 1H), 5.65 (s, 1H), 5.42 (s, 1H), 4.24 (br, s, 1H), 2.24 (s, 6H), 1.85 (s, 3H)
13C NMR(100MHz,CDCl3):δ143.1,142.5,137.6,137.3,136.2,136.1,130.3,
129.0,128.9,126.5,126.1,125.9,124.2,118.9,118.7,115.9,115.1,113.4,103.6,57.5,
29.2,21.2,21.0.
Embodiment 3
Reaction equation are as follows:
Into 25mL round-bottomed flask, 2- (1H-1- pyrrole radicals) aniline 2a (0.2mmol), 4- amyl phenylacetylene are sequentially added
3c (0.5mmol), toluene 2mL, Au catalyst (4) (acetonitrile) [(2- biphenyl) di-t-butyl phosphine] hexafluoro-antimonic acid gold (I)
(0.01mmol) is stirred 24 hours under the conditions of 100 DEG C.TLC monitoring reaction, after reaction, rotary evaporation removes solvent, crude product
By 200 mesh silica gel column chromatographies, ladder is carried out by eluant, eluent of the mixed solvent of petroleum ether and ethyl acetate (volume ratio 15:1)
Degree elution collects eluent revolving and removes solvent, obtains target product 1ac, be white solid (yield 88%).
1H NMR(400MHz,CDCl3): δ 7.25-7.15 (m, 5H), 7.05-6.98 (m, 4H), 6.71 (t, J=
7.51Hz, 1H), 6.61 (d, J=7.64Hz, 1H), 6.40 (t, J=7.66Hz, 1H), 6.28 (d, J=3.44Hz, 1H),
6.02 (d, J=3.40Hz, 1H), 5.66 (s, 1H), 5.43 (s, 1H), 4.24 (s, 1H), 2.52-2.48 (m, 4H), 1.85 (s,
3H),1.58-1.50(m,5H),1.33-1.19(m,9H),0.90-0.83(m,7H).
13C NMR(100MHz,CDCl3):δ143.2,142.6,142.5,141.5,137.3,136.3,136.1,
130.3,128.4,128.2,126.6,126.0,125.9,124.2,118.8,115.8,115.0,113.4,103.6,57.5,
35.6,35.5,31.6,31.4,31.03,30.98,29.2,22.6,14.1.
Embodiment 4
Reaction equation are as follows:
Into 25mL round-bottomed flask, 2- (1H-1- pyrrole radicals) aniline 2a (0.2mmol), 4- chlorobenzene acetylene 3c are sequentially added
(0.5mmol), toluene 2mL, Au catalyst (4) (acetonitrile) [(2- biphenyl) di-t-butyl phosphine] hexafluoro-antimonic acid gold (I)
(0.01mmol) is stirred 24 hours under the conditions of 100 DEG C.TLC monitoring reaction, after reaction, rotary evaporation removes solvent, crude product
It is to wash with the mixed solvent of petroleum ether and ethyl acetate (volume ratio 20:1-10:1) by 200~300 mesh silica gel column chromatographies
De- agent carries out gradient elution, collects eluent revolving and removes solvent, obtain target product 1ad, is faint yellow solid (yield
68%).
1H NMR(400MHz,CDCl3): δ 7.24-7.13 (m, 9H), 6.74 (t, J=7.54Hz, 1H), 6.63 (d, J=
7.64Hz, 1H), 6.42 (t, J=7.60Hz, 1H), 6.32 (d, J=3.48Hz, 1H), 6.07 (d, J=3.40Hz, 1H),
5.66(s,1H),5.53(s,1H),4.25(s,1H),1.85(s,3H).
13C NMR(100MHz,CDCl3):δ144.4,141.5,138.4,135.9,135.8,133.6,132.8,
129.7,128.5,128.3,127.9,127.4,125.8,124.6,119.2,118.6,116.4,116.0,113.8,
103.8,57.5,29.0.
Embodiment 5
Reaction equation are as follows:
Into 25mL round-bottomed flask, 2- (1H-1- pyrrole radicals) aniline 2a (0.2mmol), 4- bromobenzene acetylene 3c are sequentially added
(0.5mmol), toluene 2mL, Au catalyst (4) (acetonitrile) [(2- biphenyl) di-t-butyl phosphine] hexafluoro-antimonic acid gold (I)
(0.01mmol) is stirred 24 hours under the conditions of 100 DEG C.TLC monitoring reaction, after reaction, rotary evaporation removes solvent, crude product
It is to wash with the mixed solvent of petroleum ether and ethyl acetate (volume ratio 20:1-10:1) by 200~300 mesh silica gel column chromatographies
De- agent carries out gradient elution, collects eluent revolving and removes solvent, obtain target product 1ae, is faint yellow solid (yield
71%).
1H NMR(400MHz,CDCl3): δ 7.35-7.25 (m, 5H), 7.17-7.15 (m, 3H), 7.07 (d, J=
8.16Hz, 2H), 6.75 (t, J=7.50Hz, 1H), 6.64 (d, J=7.72Hz, 1H), 6.43 (t, J=7.64Hz, 1H),
6.32 (d, J=3.12Hz, 1H), 6.08 (s, 1H), 5.68 (s, 1H), 5.54 (s, 1H), 4.26 (s, 1H), 1.85 (s, 3H)
13C NMR(100MHz,CDCl3):δ144.9,141.6,138.8,135.8,135.7,131.4,131.3,
129.7,128.2,127.8,125.8,124.7,121.9,121.0,119.3,118.5,116.5,116.1,113.9,
103.8,57.5,29.0.
Embodiment 6
Reaction equation are as follows:
Under protection of argon gas, 25mL round-bottomed flask is taken, is sequentially added 2a (0.2mmol), 6- methoxyl group -2- naphthalyne 3f
(0.5mmol), toluene 2mL, (acetonitrile) [(2- biphenyl) di-t-butyl phosphine] hexafluoro-antimonic acid are golden (I) (0.01mmol), 100 DEG C of conditions
Under, with 400rpm stirring 24 hours.TLC monitoring reaction, after reaction, is rotated using Heidolph Rotary Evaporators, turn
Speed is 200rpm, and temperature is 40 DEG C, vacuum degree 0.06Mpa, and the processing time is 10min.Pass through 200~300 mesh silicagel columns again
Chromatography, eluant, eluent is ethyl acetate: petroleum ether=7:100, isolated target product 1af (yield 80%).
1H NMR(400MHz,CDCl3): δ 7.65-7.53 (m, 7H), 7.46 (d, J=8.60Hz, 1H), 7.31 (d, J=
8.16Hz,1H),7.23(s,1H),7.10-7.02(m,4H),6.67-6.60(m,2H),6.37-6.32(m,2H),6.10(d,
J=3.16Hz, 1H), 5.80 (s, 1H), 5.54 (s, 1H), 4.33 (s, 1H), 3.86 (s, 3H), 3.84 (s, 3H), 1.96 (s,
3H).
13C NMR(100MHz,CDCl3):δ157.8,157.7,142.5,141.1,136.3,136.1,135.3,
134.2,133.5,130.4,129.9,129.7,128.8,128.4,126.9,126.8,126.0,125.9,125.2,
125.1,124.5,124.4,118.9,118.8,118.7,118.6,115.9,115.8,113.6,105.6,105.5,
104.0,57.8,55.34,55.28,28.9.
Embodiment 7
Reaction equation are as follows:
Under protection of argon gas, 25mL round-bottomed flask is taken, is sequentially added 2a (0.2mmol), 3g (0.5mmol), toluene 2mL,
(acetonitrile) [(2- biphenyl) di-t-butyl phosphine] hexafluoro-antimonic acid is golden (I) (0.01mmol), under the conditions of 100 DEG C, with 400rpm stirring 24
Hour.TLC monitoring reaction, after reaction, is rotated, revolving speed 200rpm, temperature is using Heidolph Rotary Evaporators
40 DEG C, vacuum degree 0.06Mpa, the processing time is 10min.Again by 200~300 mesh silica gel column chromatographies, eluant, eluent is acetic acid
Ethyl ester: petroleum ether=6:100, isolated target product 1ag (yield 76%).
1H NMR(400MHz,CDCl3): δ 7.28 (t, J=7.80Hz, 2H), 7.21-7.05 (m, 3H), 6.97 (s, 1H),
6.89 (s, 1H), 6.80 (t, J=6.50Hz, 1H), 6.67 (d, J=7.72Hz, 1H), 6.50 (t, J=7.74Hz, 1H),
6.29 (d, J=3.44Hz, 1H), 6.00 (d, J=3.4Hz, 1H), 5.68 (s, 1H), 5.42 (s, 1H), 4.15 (s, 1H),
1.90(s,3H).
13C NMR(100MHz,CDCl3):δ147.9,141.9,137.3,136.2,135.9,130.3,126.3,
125.9,125.80,125.77,125,6,124.4,123.0,120.8,119.1,118.5,115.7,114.7,112.9,
102.9,55.7,28.7.
Embodiment 8
Reaction equation are as follows:
Under protection of argon gas, 25mL round-bottomed flask is taken, 4- methyl -2- (1H-1- pyrrole radicals) aniline 2b is sequentially added
(0.2mmol), phenylacetylene 3a (0.5mmol), toluene 2mL, (acetonitrile) [(2- biphenyl) di-t-butyl phosphine] hexafluoro-antimonic acid gold (I)
(0.01mmol), under the conditions of 100 DEG C, with 400rpm stirring 24 hours.TLC monitoring reaction, after reaction, uses Heidolph
Rotary Evaporators revolving, revolving speed 200rpm, temperature are 40 DEG C, vacuum degree 0.06Mpa, and the processing time is 10min.Lead to again
Cross 200~300 mesh silica gel column chromatographies, eluant, eluent is ethyl acetate: petroleum ether=5:100, isolated target product 1ba (are received
Rate 77%).
1H NMR(300MHz,CDCl3): δ 7.37-7.10 (m, 10H), δ 6.97 (s, 1H), δ 6.47 (t, J=8.73Hz,
2H), δ 6.33 (d, J=3.45Hz, 1H), δ 6.06 (d, J=3.39Hz, 1H), δ 5.61 (d, J=1.53Hz, 1H), δ 5.52
(d, J=1.44Hz, 1H), δ 1.90 (s, 3H), δ 1.83 (s, 3H)
13C NMR(75MHz,CDCl3):δ146.0,143.0,140.2,136.2,133.5,130.2,128.2,127.7,
126.8,126.7,125.9,125.8,124.6,119.6,115.7,115.6,113.6,103.6,57.7,29.2,20.6.
Embodiment 9
Reaction equation are as follows:
Under protection of argon gas, 25mL round-bottomed flask is taken, the chloro- 2- of 4- (1H-1- pyrrole radicals) aniline 2c is sequentially added
(0.2mmol), phenylacetylene 3a (0.5mmol), toluene 2mL, (acetonitrile) [(2- biphenyl) di-t-butyl phosphine] hexafluoro-antimonic acid gold (I)
(0.01mmol), under the conditions of 100 DEG C, with 400rpm stirring 24 hours.TLC monitoring reaction, after reaction, uses Heidolph
Rotary Evaporators revolving, revolving speed 200rpm, temperature are 40 DEG C, vacuum degree 0.06Mpa, and the processing time is 10min.Lead to again
Cross 200~300 mesh silica gel column chromatographies, eluant, eluent is ethyl acetate: petroleum ether=7:100, isolated target product 1ca (are received
Rate 76%).
1H NMR(500MHz,CDCl3): δ 7.23-7.15 (m, 12H), 6.62 (d, J=6.65Hz, 1H), 6.49 (d, J=
8.35Hz, 1H), 6.38 (d, J=3.25Hz, 1H), 6.10 (s, 1H), 5.67 (s, 1H), 5.55 (s, 1H), 4.40 (br, s,
1H),1.86(s,3H).
13C NMR(125MHz,CDCl3):δ145.5,142.5,139.8,135.9,134.6,130.4,128.4,
128.3,128.0,127.1,126.8,126.5,125.8,123.9,123.5,119.0,116.5,116.4,114.0,
104.1,57.8,29.1.
Embodiment 10
Reaction equation are as follows:
Under protection of argon gas, 25mL round-bottomed flask is taken, the chloro- 2- of 4- (1H-1- pyrrole radicals) aniline 2c is sequentially added
(0.2mmol), 3b (0.5mmol), toluene 2mL, (acetonitrile) [(2- biphenyl) di-t-butyl phosphine] hexafluoro-antimonic acid gold (I)
(0.01mmol), under the conditions of 100 DEG C, with 400rpm stirring 24 hours.TLC monitoring reaction, after reaction, uses Heidolph
Rotary Evaporators revolving, revolving speed 200rpm, temperature are 40 DEG C, vacuum degree 0.06Mpa, and the processing time is 10min.Lead to again
Cross 200~300 mesh silica gel column chromatographies, eluant, eluent is ethyl acetate: petroleum ether=7:100, isolated target product 1cb (are received
Rate 68%).
1H NMR(500MHz,CDCl3): δ 7.29 (d, J=1.85Hz, 1H), 7.16 (t, J=8.50Hz, 4H), 7.08-
7.04 (m, 4H), 6.68 (dd, J=1.90,8.25Hz, 1H), 6.53 (d, J=8.30Hz, 1H), 6.89 (d, J=3.35Hz,
1H), 6.12 (s, 1H), 5.68 (d, J=1.40Hz, 1H), 5.52 (s, 1H), 2.29 (s, 3H), 2.28 (s, 3H), 1.89 (s,
3H).
13C NMR(125MHz,CDCl3):δ142.6,142.4,137.8,137.0,136.7,136.0,134.7,
130.6,129.1,129.0,126.6,125.7,123.9,123.5,118.9,116.5,115.7,113.9,104.0,57.6,
29.2,21.2,21.0.
Embodiment 11
A kind of synthetic method of 1- vinyl -4,5- pyrrolin [1,2-a] quinoxaline compounds of the invention, is urged in gold
Under agent effect, with face shown in formula (2) amino benzenes compounds that pyrroles replaces with and formula (3) shown in aryl Terminal Acetylenes be former
Material is reacted in a solvent under Au catalyst effect, and thin plate chromatography tracking reaction until the reaction is complete, it is mixed to obtain reaction
Object is closed, the reaction mixture is post-treated to obtain 1- vinyl -4,5- pyrrolin [1,2-a] quinoxaline shown in formula (1)
Compound；Its chemical equation is as follows:
In formula (2) or formula (1), the R is hydrogen, methyl, aryl or halogen；In formula (3) or formula (1), Ar is phenyl, naphthalene
Base, heterocycle (including but not limited to furan nucleus, thiphene ring, pyridine ring etc.), substituted heterocycle are replaced by methyl, methoxyl group, halogen
Phenyl.
The solvent is dichloroethanes.
The Au catalyst is one of following shown Au catalyst；
The ratio between the amount of substance of amino benzenes compounds and aryl Terminal Acetylenes that a pyrroles replaces of facing is 1:2.
The Au catalyst and the ratio between the amount of amino benzenes compounds substance for facing pyrroles's substitution are 0.01.
The reaction temperature is 25 DEG C, and the reaction time is 20 hours.
Embodiment 12
A kind of synthetic method of 1- vinyl -4,5- pyrrolin [1,2-a] quinoxaline compounds of the invention, is urged in gold
Under agent effect, with face shown in formula (2) amino benzenes compounds that pyrroles replaces with and formula (3) shown in aryl Terminal Acetylenes be former
Material is reacted in a solvent under Au catalyst effect, and thin plate chromatography tracking reaction until the reaction is complete, it is mixed to obtain reaction
Object is closed, the reaction mixture is post-treated to obtain 1- vinyl -4,5- pyrrolin [1,2-a] quinoxaline shown in formula (1)
Compound；Its chemical equation is as follows:
In formula (2) or formula (1), the R is hydrogen, methyl, aryl or halogen；In formula (3) or formula (1), Ar is phenyl, naphthalene
Base, heterocycle (including but not limited to furan nucleus, thiphene ring, pyridine ring etc.), substituted heterocycle are replaced by methyl, methoxyl group, halogen
Phenyl.
The solvent is nitromethane.
The Au catalyst is one of following shown Au catalyst；
The ratio between the amount of substance of amino benzenes compounds and aryl Terminal Acetylenes that a pyrroles replaces of facing is 1:5.
The Au catalyst and the ratio between the amount of amino benzenes compounds substance for facing pyrroles's substitution are 0.2.
The reaction temperature is 80 DEG C, and the reaction time is 1 hour.
Embodiment 13
A kind of synthetic method of 1- vinyl -4,5- pyrrolin [1,2-a] quinoxaline compounds of the invention, is urged in gold
Under agent effect, with face shown in formula (2) amino benzenes compounds that pyrroles replaces with and formula (3) shown in aryl Terminal Acetylenes be former
Material is reacted in a solvent under Au catalyst effect, and thin plate chromatography tracking reaction until the reaction is complete, it is mixed to obtain reaction
Object is closed, the reaction mixture is post-treated to obtain 1- vinyl -4,5- pyrrolin [1,2-a] quinoxaline shown in formula (1)
Compound；Its chemical equation is as follows:
In formula (2) or formula (1), the R is hydrogen, methyl, aryl or halogen；In formula (3) or formula (1), Ar is phenyl, naphthalene
Base, heterocycle (including but not limited to furan nucleus, thiphene ring, pyridine ring etc.), substituted heterocycle are replaced by methyl, methoxyl group, halogen
Phenyl.
The solvent is any one in tetrahydrofuran, acetonitrile or chlorobenzene.
The Au catalyst is one of following shown Au catalyst；
The ratio between the amount of substance of amino benzenes compounds and aryl Terminal Acetylenes that a pyrroles replaces of facing is 1:3.
The Au catalyst and the ratio between the amount of amino benzenes compounds substance for facing pyrroles's substitution are 0.1.
The reaction temperature is 25-100 DEG C, and the reaction time is 24 hours.
It should be noted that the above examples are only used to illustrate the technical scheme of the present invention and are not limiting, although referring to preferable
Embodiment describes the invention in detail, those skilled in the art should understand that, it can be to technology of the invention
Scheme is modified or replaced equivalently, and without departing from the spirit and scope of the technical solution of the present invention, should all be covered in this hair
In bright scope of the claims.
Claims (8)
1. a kind of synthetic method of 1- vinyl -4,5- pyrrolin [1,2-a] quinoxaline compounds, it is characterised in that including such as
Lower step: under Au catalyst effect, with face shown in formula (2) amino benzenes compounds that pyrroles replaces with and formula (3) it is shown
Aryl Terminal Acetylenes be raw material, under Au catalyst effect, reacted in a solvent, thin plate chromatography tracking reaction is until reacted
Entirely, reaction mixture is obtained, the reaction mixture is post-treated to obtain 1- vinyl -4,5- pyrrolin shown in formula (1)
[1,2-a] quinoxaline compounds；Its chemical equation is as follows:
In formula (2) or formula (1), the R is hydrogen, methyl, aryl or halogen；In formula (3) or formula (1), Ar be phenyl, naphthalene,
Heterocycle (including but not limited to furan nucleus, thiphene ring, pyridine ring etc.), substituted heterocycle are replaced by methyl, methoxyl group, halogen
Phenyl.
2. the synthetic method of 1- vinyl -4,5- pyrrolin [1,2-a] quinoxaline compounds as described in claim 1,
Be characterized in that: the solvent is any one in dichloroethanes, nitromethane, toluene, tetrahydrofuran, acetonitrile or chlorobenzene.
3. the synthetic method of 1- vinyl -4,5- pyrrolin [1,2-a] quinoxaline compounds as claimed in claim 2,
Be characterized in that: the solvent is toluene.
4. the synthetic method of 1- vinyl -4,5- pyrrolin [1,2-a] quinoxaline compounds as described in claim 1,
Be characterized in that: the Au catalyst is one of following shown Au catalyst；
5. the synthetic method of 1- vinyl -4,5- pyrrolin [1,2-a] quinoxaline compounds as described in claim 1,
Be characterized in that: the ratio between the amount of substance of amino benzenes compounds and aryl Terminal Acetylenes that a pyrroles replaces of facing is 1:2-1:5.
6. the synthetic method of 1- vinyl -4,5- pyrrolin [1,2-a] quinoxaline compounds as described in claim 1,
Be characterized in that: the Au catalyst and the ratio between the amount of amino benzenes compounds substance for facing pyrroles's substitution are 0.01-0.2.
7. the synthetic method of 1- vinyl -4,5- pyrrolin [1,2-a] quinoxaline compounds as described in claim 1,
Be characterized in that: the reaction temperature is 25-100 DEG C, and the reaction time is 1-24 hours.
8. the synthetic method of 1- vinyl -4,5- pyrrolin [1,2-a] quinoxaline compounds as described in claim 1,
It is characterized in that: the reaction postprocessing method are as follows: after reaction, reaction mixture is subjected to concentrated by rotary evaporation, and pass through silicon
Plastic column chromatography separation, using petroleum ether: the mixed solution of ethyl acetate volume ratio 20:1-5:1 carries out gradient elution as eluant, eluent, obtains
To the quinoxaline compounds of 1- vinyl -4,5- pyrrolin [1,2-a] shown in formula (1).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811130849.5A CN109400611B (en) | 2018-09-27 | 2018-09-27 | Synthesis method of 1-vinyl-4, 5-dihydropyrrole [1,2-a ] quinoxaline compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811130849.5A CN109400611B (en) | 2018-09-27 | 2018-09-27 | Synthesis method of 1-vinyl-4, 5-dihydropyrrole [1,2-a ] quinoxaline compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109400611A true CN109400611A (en) | 2019-03-01 |
| CN109400611B CN109400611B (en) | 2021-08-24 |
Family
ID=65466450
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811130849.5A Active CN109400611B (en) | 2018-09-27 | 2018-09-27 | Synthesis method of 1-vinyl-4, 5-dihydropyrrole [1,2-a ] quinoxaline compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109400611B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110592157A (en) * | 2019-10-09 | 2019-12-20 | 吉林大学 | Method for synthesizing quinoxaline compound by double-protein catalytic cascade reaction |
| CN114957085A (en) * | 2022-05-19 | 2022-08-30 | 华南师范大学 | Synthetic method and application of polycyano-substituted indole heterocyclic compound |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3939159A (en) * | 1974-05-29 | 1976-02-17 | American Hoechst Corporation | Spiro(pyrrolo (1,2-A)quinoxalines) |
| CN101003462A (en) * | 2007-01-25 | 2007-07-25 | 中国林业科学研究院林产化学工业研究所 | Method for preparing 1,3 propylene glycol by using glycerol method |
| CN103333171A (en) * | 2013-06-17 | 2013-10-02 | 南京工业大学 | Synthesis method of pyrrole[1,2-a]quinoxaline derivative |
| CN108409743A (en) * | 2018-03-07 | 2018-08-17 | 兰州大学 | A kind of preparation method of pyrrolo- [1,2-a] quinoxaline compounds of alkyl nitrile substitution |
-
2018
- 2018-09-27 CN CN201811130849.5A patent/CN109400611B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3939159A (en) * | 1974-05-29 | 1976-02-17 | American Hoechst Corporation | Spiro(pyrrolo (1,2-A)quinoxalines) |
| CN101003462A (en) * | 2007-01-25 | 2007-07-25 | 中国林业科学研究院林产化学工业研究所 | Method for preparing 1,3 propylene glycol by using glycerol method |
| CN103333171A (en) * | 2013-06-17 | 2013-10-02 | 南京工业大学 | Synthesis method of pyrrole[1,2-a]quinoxaline derivative |
| CN108409743A (en) * | 2018-03-07 | 2018-08-17 | 兰州大学 | A kind of preparation method of pyrrolo- [1,2-a] quinoxaline compounds of alkyl nitrile substitution |
Non-Patent Citations (3)
| Title |
|---|
| CATALINA FERRER LLABRÉS，: ""Cyclization of Indoles and Enol Ethers with Alkynes Catalyzed by Platinum and Gold"", 《CATALAN INSITUTE OF CHEMICAL RESEARCH》 * |
| GUANNAN LIU等，: ""Synthesis of Pyrrolo[1,2-a]quinoxalines via Gold(I)-Mediated Cascade Reactions"", 《ACS COMB. SCI.》 * |
| XIANGDONG LI等，: ""Synthesis of Multiple-Substituted Pyrroles via Gold(I)-Catalyzed Hydroamination/Cyclization Cascade" 及其Supporting Information", 《ORG. LETT.》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110592157A (en) * | 2019-10-09 | 2019-12-20 | 吉林大学 | Method for synthesizing quinoxaline compound by double-protein catalytic cascade reaction |
| CN110592157B (en) * | 2019-10-09 | 2021-01-01 | 吉林大学 | Method for synthesizing quinoxaline compound by double-protein catalytic cascade reaction |
| CN114957085A (en) * | 2022-05-19 | 2022-08-30 | 华南师范大学 | Synthetic method and application of polycyano-substituted indole heterocyclic compound |
| CN114957085B (en) * | 2022-05-19 | 2023-11-14 | 华南师范大学 | Synthetic method and application of polycyano substituted indole heterocyclic compound |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109400611B (en) | 2021-08-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Ryu et al. | Rhodium‐Catalyzed Direct C H Amination of Benzamides with Aryl Azides: A Synthetic Route to Diarylamines | |
| Waldo et al. | Room temperature icl-induced dehydration/iodination of 1-acyl-5-hydroxy-4, 5-dihydro-1 h-pyrazoles. A selective route to substituted 1-acyl-4-iodo-1 h-pyrazoles | |
| Long et al. | Synthesis of 1-aminoisoquinolines by gold (III)-mediated domino reactions from 2-alkynylbenzamides and ammonium acetate | |
| Hirata et al. | Catalytic enantioselective synthesis of NC axially chiral phenanthridin-6-one derivatives | |
| Le Duc et al. | Effect of Electronic Enrichment of NHCs on the Catalytic Activity of [Pd (NHC)(acac) Cl] in Buchwald–Hartwig Coupling | |
| WO2019095678A1 (en) | Method for preparing green quinoline compound | |
| Chen et al. | Palladium-catalyzed synthesis of α-iminonitriles from aryl halides via isocyanide double insertion reaction | |
| Li et al. | The P-chiral phosphane ligand (MeO-BIBOP) for efficient and practical large-scale Rh-catalyzed asymmetric hydrogenation of N-acetyl enamides with high TONs | |
| Christophersen et al. | Synthesis of 2, 3-substituted thienylboronic acids and esters | |
| Liu et al. | Palladium-catalyzed aminocarbonylation of alkynes to succinimides | |
| Aziz et al. | Direct Alkynylation of 3 H-Imidazo [4, 5-b] pyridines Using gem-Dibromoalkenes as Alkynes Source | |
| Pan et al. | Multicomponent reaction of imidazo [1, 5-a] pyridine carbenes with aldehydes and dimethyl acetylenedicarboxylate or allenoates: A straightforward approach to fully substituted furans | |
| CN105130872B (en) | A kind of preparation method of 3 position trifluoromethyl substituted indole | |
| CN105001028A (en) | Synthesis method for asymmetric conjugate diyne compound | |
| Xiao et al. | RuHCl (CO)(PPh3) 3-Catalyzed Direct Amidation of Arene C–H Bond with Azides | |
| CN109400611A (en) | A kind of synthetic method of 1- vinyl -4,5- pyrrolin [1,2-a] quinoxaline compounds | |
| Nguyen et al. | Trisulfur-Radical-anion-triggered C (sp2)–H amination of electron-deficient alkenes | |
| CN106957207A (en) | 2 aryl（Alkenyl）The preparation method of vinvlsulfonamido fluorine compounds | |
| Reeves et al. | Development of an Enantioselective Hydrogenation Route to (S)-1-(2-(Methylsulfonyl) pyridin-4-yl) propan-1-amine | |
| Tracey et al. | Rhodium (I)-catalyzed [2+ 2+ 2] cycloadditions of ynamides in the synthesis of amide-substituted chiral Biaryls | |
| Ma et al. | Development of β, β-Dibrominated Secondary Enamides and Their Application to the Synthesis of 5-Br Oxazoles | |
| Kawamura et al. | 2-Phenylimidazole− PdCl2 and 2-Phenylimidazoline− PdCl2 Complexes: Single-Crystal and Powder X-ray Diffractometry, 1H NMR Spectra, and Comparison of Catalytic Activities in Coupling Reactions | |
| CN109942616A (en) | A kind of aryl amide analog derivative and its preparation method and application containing alkynyl | |
| Khandaka et al. | Aerobic Cu and amine free Sonogashira and Stille couplings of aryl bromides/chlorides with a magnetically recoverable Fe3O4@ SiO2 immobilized Pd (II)-thioether containing NHC | |
| Wang et al. | N1-Allylation of Arylhydrazines via a Palladium-Catalyzed Allylic Substitution |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |