CN109988117A - The preparation method of a kind of 3- methyl-quinoxaline -2 (1H) -one analog derivative - Google Patents
The preparation method of a kind of 3- methyl-quinoxaline -2 (1H) -one analog derivative Download PDFInfo
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Abstract
The invention discloses a kind of preparation methods of 3- methyl-quinoxaline -2 (1H) -one class compound, this method is that the research of quinoxalinone derivatives is carried out visible light catalytic under photochemical catalyst effect with iodobenzene diacetate to react to get 3- methyl-quinoxaline ketone compounds；Compared with the prior art, the advantage of the synthetic method has: 1) the derivative raw material of (1H) -one of quinoxaline -2 used is cheap and easy to get, advantageously reduce cost, 2) it can be reacted through illumination at room temperature, mild condition, and one step obtain product, reaction yield is high, and operation environmental protection is conducive to industrial production, 3) this method is good to functional group's applicability, can obtain various 3- methyl-quinoxaline ketone compounds derivatives.
Description
Technical field
The present invention relates to a kind of synthetic methods of Quinoxalinone derivative, in particular to quinoxaline -2 (1H) -one class
Compound and iodobenzene diacetate are starting material, under photochemical catalyst effect, prepare 3- methyl-quinoxaline -2 through one step of photocatalysis
The method of (1H) -one, belongs to technical field of organic synthesis.
Background technique
Methyl is the smallest alkyl moiety, there is this group in most drugs molecule, and introducing methyl in the molecule can
To improve the drug solubility of drug molecule, selectivity and metabolic activity.Methyl is introduced at the ortho position in metabolism site, generates space
Steric hindrance can extend drug half-life, such as Simvastatin, if drug half-life is too long, Pharmaceutical Chemist can also be by introducing first
Base generates new metabolism site, shortens drug half-life, such as Etoricoxib, and influence of the methyl in pharmaceutical chemistry is referred to as
“magic methyl effect”。
(1H) -one of quinoxaline -2 is as a kind of important azepine ring derivatives, in natural products, pharmacy and material
Application in science is very universal, and wherein (1H) the -one derivative of 3- methyl-quinoxaline -2 can regulate and control quinoline because it has
The characteristic of quinoline ketone bioactivity is even more to have attracted the interest of large quantities of organic chemistry researchers.For example, compound A is a kind of
The introducing of c-met kinase inhibitor (Bioorg.Med.Chem.2015,23,6560), methyl significantly improves the medicine of the molecule
Object activity.
(1H) -one of quinoxaline -2 C3 arylation, acylation, Phosphation, ammonification and trifluoromethylations etc. are ground at present
Studying carefully has relevant report, but but yet there are no relevant report about the C3 directly methylations of quinoxaline -2 (1H) -one class compound.
Summary of the invention
For technological gap existing for the position the C3 alkylated reaction in the prior art to quinoxaline -2 (1H) -one, the present invention
Purpose be to be to provide a kind of to realize (1H) -one of 3- methyl-quinoxaline -2 in a mild condition using light-catalyzed reaction and its spread out
The synthetic method of biology, this method are avoided using the metallic catalyst for having pollution to environment, together by using photochemical catalyst
When normal-temperature light according to etc. it is mild under the conditions of react, avoid high temperature and other complicated operations, and reaction cost and energy consumption can be reduced,
The efficiency for improving reaction achievees the purpose that greening chemistry simultaneously.
In order to achieve the above technical purposes, the present invention provides a kind of 3- methyl-quinoxaline -2 (1H) -one class compounds
Preparation method, 1 structure the research of quinoxalinone derivatives of formula and 2 iodobenzene diacetate of formula and the lower progress visible light catalytic of photochemical catalyst effect
Reaction is to get 3 structure 3- methyl-quinoxaline ketone compounds of formula；
Wherein,
R1For hydrogen, alkyl or aralkyl；
R2And R3Independent choice hydrogen, alkyl, alkoxy, nitro, amino, acyl group, halogenic substituent, hydroxyl, cyano or trifluoro
Methyl.
In 3 compound of formula 1, formula 2 and formula of the invention.R1It is the group replaced on nitrogen-atoms, can choose as hydrogen original
Son is also possible to other groups and replaces hydrogen atom, as alkyl or aralkyl replace hydrogen.Alkyl is C1~C8Alkyl, can be straight
Alkyl group or branched alkyl or cyclic alkyl, specific such as methyl, ethyl, butyl, isopropyl, cyclohexyl.
Aralkyl is mainly that the alkyl chain substitution of alkyl has aryl, and the length of alkyl chain is C1~C8, in any carbon atom of alkyl chain
Upper substituted aryl, aryl such as phenyl, naphthalene or substituted-phenyl, substituted-phenyl are containing some conventional substituent groups on phenyl ring, such as
C1~C5Alkyl, C1~C5Alkoxy, halogenic substituent etc., most common aralkyl such as benzyl, phenylethyl etc..R2With
R3It is the substituent group for including, R on the phenyl ring of the research of quinoxalinone derivatives2And R3The research of quinoxalinone derivatives C3 are alkylated
Reaction influence is relatively small, and the position of substitution can be any position that can replace on phenyl ring, and its range of choice is wider, such as
Hydrogen, alkyl, alkoxy, nitro, amino, acyl group, halogenic substituent, hydroxyl, cyano or trifluoromethyl etc., work as R2Or R3Select alkane
When base, alkyl C1~C8Alkyl, can be straight chained alkyl or be branched alkyl or cyclic alkyl, specifically such as
Methyl, ethyl, butyl, isopropyl, cyclohexyl etc.；R2Or R3When selecting alkoxy, alkoxy C1~C8Alkoxy, such as
Methoxyl group, ethyoxyl, isobutoxy etc.；R2Or R3When selecting acyl group, acyl group is formoxyl, acetyl group or propiono；R2Or R3
When selecting halogenic substituent, halogenic substituent is fluorine, chlorine, bromine or iodine.
Preferred scheme, the molar ratio of quinoxaline -2- ketones derivant and iodobenzene diacetate are as follows: 1:1~1:20.More preferably
For 1:1~1:10.
Preferred scheme, the molar ratio of quinoxaline -2- ketones derivant and photochemical catalyst are as follows: 1:0.01~1:0.05.
More preferably scheme, the photochemical catalyst include Ru (bpy)3Cl2, Eosin B (C20H6Br2N2Na2O9), Eosinum Natricum
(eosin Y, C20H6Br4Na3O5), the molten Yihong of alcohol, rhodamine B, edible pigment it is at least one of red.Most preferred photochemical catalyst is
Ru(bpy)3Cl2。
Preferred scheme, the condition of the visible light catalytic reaction are as follows: under visible light illumination, in room temperature reaction 6~12
Hour.
Preferred scheme, the visible light source are LED white light source, blue-light source or the green light source that power is 3W~24W.Compared with
Preferred visible light source is the LED white light source that power is 12W.
Preferred scheme, the light-catalyzed reaction is in DMSO, DMF, CHCl3、CH3In OH, PEG-200, PEG-400 at least
It is carried out in a kind of reaction medium.More preferably reaction medium is PEG-200.
The synthetic route of 3- methylquinoline -2 (1H) -one class compound of the invention is as follows:
The synthetic reaction mechanism of 3- methyl-quinoxaline -2 (1H) -one class compound of the invention is as follows: photochemical catalyst is by light
Activation release electronics, the electronics of release are captured by iodobenzene diacetate, and the iodobenzene diacetate for capturing electronics passes through cracking release methyl
Free radical, 3 carbon of methyl free radicals attack the research of quinoxalinone derivatives form intermediate A, and intermediate A is taken by force by photochemical catalyst
Son of wiring back is converted to unstable intermediate B, and intermediate B occurs intramolecular and recombinates and discharge Hydrogen Proton, obtains target compound.
Compared with the prior art, technical solution of the present invention bring advantageous effects:
It is of the invention by using environmentally protective photochemical catalyst to avoid using the metal catalytic for having pollution to environment
Agent.
The research of quinoxalinone derivatives C3 methylation reaction of the invention is high-efficient, can obtain highly selective yield.
Reaction condition of the invention is mild, can with normal-temperature light according to etc. it is mild under the conditions of react, avoid high temperature and other be complicated
Operation, and reduce reaction cost and energy consumption.
The present invention is good to functional group's applicability, can obtain various 3- methyl-quinoxaline ketone compounds derivatives, is quinoline
The synthesis of quinoline ketone compounds derivative provides a kind of completely new path.
Specific embodiment
Following embodiment is intended to further illustrate the content of present invention, rather than limits the claims in the present invention protection scope.
Condition optimizing experiment:
Specific reaction condition is carried out as follows: at 25 DEG C, in 10mL reaction tube, sequentially adding compound 1a
(0.2mmol), iodobenzene diacetate 2a (0.44mmol), photochemical catalyst, solvent (1mL) are uniformly mixed, then in 12w White LED
Under light irradiation, it is stirred to react 8h.It is detected with TLC to cyclopentyl methyl ether (2ml × 3) extraction after the reaction was completed, is added, upper layer is taken to extract
Take liquid, be concentrated in vacuo to solvent-free at 50 DEG C, obtain crude product, then with volume ratio be 2:1 petroleum ether and ethyl acetate it is mixed
It closes eluant, eluent to rinse, silicagel column rapid column chromatography obtains product 3aa.
In order to which high yield obtains 3- methyl -2 (1H)-the research of quinoxalinone derivatives, carried out according to above-mentioned reaction condition following
Control experiment group 1~13 investigates some condition elements for influencing reaction, the main type including photochemical catalyst, molten
Agent, specific optimization process see the table below:
As can be seen from the above table, the Ru (bpy) in the photochemical catalyst that all experiments use3Cl2, Eosin B, Eosinum Natricum
Equal photochemical catalysts can realize the synthesis of 3- methyl -2 (1H)-the research of quinoxalinone derivatives, but Ru (bpy)3Cl2With most
Good catalytic effect.And the dosage of catalyst can reach good catalytic effect 1% or so.Selection for solvent,
Optimal solvent is PEG-200；Secondly, DMF and DMSO are also to react preferable good solvent, and acetonitrile, tetrahydrofuran and two
Chloroethanes is hardly obtained target product as solvent.
Case study on implementation 1~12 is to react with optimal conditions in detail below, investigates different substituent group to the shadow of reaction
It rings.
Embodiment 1
At 25 DEG C, in 10mL reaction tube, (1H) the -one 1a of 1- methyl-quinoxaline -2 (0.2mmol), diethyl are sequentially added
Sour iodobenzene 2a (0.44mmol), Ru (bpy)3Cl2·6H2O (0.002mmol), PEG-200 (1mL) are uniformly mixed, then exist
Under the irradiation of 12w white led lamps, it is stirred to react 8h.It is detected with TLC to after the reaction was completed, addition cyclopentyl methyl ether (2ml × 3) extracts
Take, take upper layer of extraction liquid, be concentrated in vacuo to solvent-free at 50 DEG C, obtain crude product, then with volume ratio be 2:1 petroleum ether and
Ethyl acetate mixtures of eluents is rinsed, and silicagel column rapid column chromatography obtains 1, the 3- dimethylquinoxalin -2 (1H)-in this example
Ketone product 3aa is white solid 32.8mg, yield 91%.
Products therefrom nuclear magnetic spectrum data are as follows:1H NMR(400MHz,CDCl3): δ=7.80 (d, J=8.0Hz, 1H),
7.54–7.50(m,1H),7.35–7.29(m,2H),3.70(s,3H),2.60(s,3H)；13C NMR(100MHz,CDCl3):δ
=158.4,155.2,133.2,132.6,129.6,129.4,123.6,113.6,29.0,21. 6.
Embodiment 2
At 25 DEG C, in 10mL reaction tube, bromo- -2 (1H) the -one 1b of 1- methyl-quinoxaline of 6- is sequentially added
(0.2mmol), iodobenzene diacetate 2a (0.44mmol), Ru (bpy)3Cl2·6H2O (0.002mmol), PEG-200 (1mL) are mixed
It closes uniformly, then under the irradiation of 12W white led lamps, is stirred to react 8h.It is detected with TLC to after the reaction was completed, cyclopenta first is added
Ether (2ml × 3) extraction, takes upper layer of extraction liquid, is concentrated in vacuo to solvent-free at 50 DEG C, obtain crude product, be then with volume ratio
The petroleum ether and ethyl acetate mixtures of eluents of 2:1 rinses, and silicagel column rapid column chromatography obtains the 6- bromo- 1,3- in this example
Dimethylquinoxalin -2 (1H) -one product 3ba is white solid 42.8mg, yield 85%.
Products therefrom nuclear magnetic spectrum data are as follows:1H NMR(400MHz,CDCl3): δ=7.94 (d, J=2.0Hz, 1H),
7.60(dd,J1=8.8Hz, J2=2.0Hz, 1H), 7.16 (d, J=8.8Hz, 1H), 3.67 (s, 3H), 2.59 (s, 3H)；13C
NMR(100MHz,CDCl3): δ=159.8,154.8,133.5,132.4,132.3,131.9,116.1,115.0,29.2,
21.7。
Products therefrom high resolution mass spectrum data are as follows: HRMS calc.for r C10H10BrN2O[M+H]+:252.9971,
found 252.9968。
Embodiment 3
At 25 DEG C, in 10mL reaction tube, fluoro- -2 (1H) the -one 1c of 1- methyl-quinoxaline of 7- is sequentially added
(0.2mmol), iodobenzene diacetate 2a (0.44mmol), Ru (bpy)3Cl2·6H2O (0.002mmol), PEG-200 (1mL) are mixed
It closes uniformly, then under the irradiation of 12W white led lamps, is stirred to react 6h.It is detected with TLC to after the reaction was completed, cyclopenta first is added
Ether (2ml × 3) extraction, takes upper layer of extraction liquid, is concentrated in vacuo to solvent-free at 50 DEG C, obtain crude product, be then with volume ratio
The petroleum ether and ethyl acetate mixtures of eluents of 2:1 rinses, and silicagel column rapid column chromatography obtains the 7- fluoro- 1,3- in this example
Dimethylquinoxalin -2 (1H) -one product 3ca is white solid 35.3mg, yield 92%.
Products therefrom nuclear magnetic spectrum data are as follows:1H NMR(400MHz,CDCl3): δ=7.79-7.76 (m, 1H), 7.07-
7.02(m,1H),6.98(dd,J1=10.0Hz, J2=2.4Hz, 1H), 3.66 (s, 3H), 2.57 (s, 3H)；13C NMR
(100MHz,CDCl3): δ=164.1,161.6,157.2,155.1,134.7,134.6,131.3,131.2,129.4,
111.5,111.2,100.7,100.4,29.3,21.4；19F NMR(376MHz,CDCl3): δ=- 108.3.
Products therefrom high resolution mass spectrum data are as follows: HRMS (ESI) m/z calcd.for C10H10FN2O[M+H]+:
193.0772,found 193.0770。
Embodiment 4
At 25 DEG C, in 10mL reaction tube, -2 (1H) -one 1d of 6- nitro -1- methyl-quinoxaline is sequentially added
(0.2mmol), iodobenzene diacetate 2a (0.44mmol), Ru (bpy)3Cl2·6H2O (0.002mmol), PEG-200 (1mL) are mixed
It closes uniformly, then under the irradiation of 12W white LED lamp, is stirred to react 8h.It is detected with TLC to after the reaction was completed, cyclopenta first is added
Ether (2ml × 3) extraction, takes upper layer of extraction liquid, is concentrated in vacuo to solvent-free at 50 DEG C, obtain crude product, be then with volume ratio
The petroleum ether and ethyl acetate mixtures of eluents of 2:1 rinses, and silicagel column rapid column chromatography obtains nitro -1 6- in this example,
3- dimethylquinoxalin -2 (1H) -one product 3da is yellow solid 36.8mg, yield 84%.
Products therefrom nuclear magnetic spectrum data are as follows:1H NMR(400MHz,CDCl3): δ=8.69 (d, J=2.4Hz, 1H),
8.38(dd,J1=9.2Hz, J2=2.4Hz, 1H), 7.39 (d, J=9.2Hz, 1H), 3.75 (s, 3H), 2.63 (s, 3H)；13C
NMR(100MHz,CDCl3): δ=161.2,154.8,143.4,137.9,131.8,125.2,124.2,114.2,29.6,
21.7。
Products therefrom high resolution mass spectrum data are as follows: HRMS (ESI) m/z calcd.for C10H10N3O3[M+H]+:
220.0717,found 220.0713。
Embodiment 5
At 25 DEG C, in 10mL reaction tube, 7- Trifluoromethyl-1-(1H) -one of methyl-quinoxaline-2 1e is sequentially added
(0.2mmol), iodobenzene diacetate 2a (0.44mmol), Ru (bpy)3Cl2·6H2O (0.002mmol), PEG-200 (1mL) are mixed
It closes uniformly, then under the irradiation of 12W white led lamps, is stirred to react 7h.It is detected with TLC to after the reaction was completed, cyclopenta first is added
Ether (2ml × 3) extraction, takes upper layer of extraction liquid, is concentrated in vacuo to solvent-free at 50 DEG C, obtain crude product, be then with volume ratio
The petroleum ether and ethyl acetate mixtures of eluents of 2:1 rinses, and silicagel column rapid column chromatography obtains the 7- fluoroform in this example
Base -1,3- dimethylquinoxalin -2 (1H) -one product 3ea is white solid 43.6mg, yield 90%.
Products therefrom nuclear magnetic spectrum data are as follows:1H NMR(400MHz,CDCl3): δ=7.91 (d, J=8.8Hz, 1H),
7.57 (d, J=8.4Hz, 1H), 7.53 (s, 1H), 3.73 (s, 3H), 2.62 (s, 3H)；13C NMR(100MHz,CDCl3): δ=
161.2,154.9,134.3,133.3,132.0,131.3,131.0,130.2,125.0,122.3,120.2,120.1,
111.0,29.2,21.8；19F NMR(376MHz,CDCl3): δ=- 62.3.
Products therefrom high resolution mass spectrum data are as follows: HRMS (ESI) m/z calcd.for C11H10F3N2O[M+H]+:
243.0740,found 243.0744。
Embodiment 6
At 25 DEG C, in 10mL reaction tube, 7- Trifluoromethyl-1-(1H) -one of methyl-quinoxaline-2 1f is sequentially added
(0.2mmol), iodobenzene diacetate 2a (0.44mmol), Ru (bpy)3Cl2·6H2O (0.002mmol), PEG-200 (1mL) are mixed
It closes uniformly, then under the irradiation of 12W white led lamps, is stirred to react 8h.It is detected with TLC to after the reaction was completed, cyclopenta first is added
Ether (2ml × 3) extraction, takes upper layer of extraction liquid, is concentrated in vacuo to solvent-free at 50 DEG C, obtain crude product, be then with volume ratio
The petroleum ether and ethyl acetate mixtures of eluents of 2:1 rinses, and silicagel column rapid column chromatography obtains methyl esters -1 6- in this example,
3- dimethylquinoxalin -2 (1H) -one product 3fa is white solid 40.4mg, yield 87%.
Products therefrom nuclear magnetic spectrum data are as follows:1H NMR(400MHz,CDCl3): δ=8.48 (d, J=2.0Hz, 1H),
8.17(dd,J1=8.8Hz, J2=2.0Hz, 1H), 7.32 (d, J=8.4Hz, 1H), 3.95 (s, 3H), 3.72 (s, 3H), 2.60
(s,3H)；13C NMR(100MHz,CDCl3): δ=166.1,159.4,155.1,136.5,132.0,131.3,130.4,
125.5,113.6,52.3,29.3,21.6.
Products therefrom high resolution mass spectrum data are as follows: HRMS (ESI) m/z calcd.for C12H13N2O3[M+H]+:
233.0921,found 233.0919.
Embodiment 7
At 25 DEG C, in 10mL reaction tube, -2 (1H) -one 1g of 1,6,7- trimethyl quinoxaline is sequentially added
(0.2mmol), iodobenzene diacetate 2a (0.44mmol), Ru (bpy)3Cl2·6H2O (0.002mmol), PEG-200 (1mL) are mixed
It closes uniformly, then under the irradiation of 12W white led lamps, is stirred to react 8h.It is detected with TLC to after the reaction was completed, cyclopenta first is added
Ether (2ml × 3) extraction, takes upper layer of extraction liquid, is concentrated in vacuo to solvent-free at 50 DEG C, obtain crude product, be then with volume ratio
The petroleum ether and ethyl acetate mixtures of eluents of 2:1 rinse, silicagel column rapid column chromatography, obtain 1 in this example, and 3,6,7- tetra-
Methyl-quinoxaline -2 (1H) -one product 3ga is white solid 33.5mg, yield 83%.
Products therefrom nuclear magnetic spectrum data are as follows:1H NMR(400MHz,CDCl3): δ=7.54 (s, 1H), 7.04 (s, 1H),
3.67(s,3H),2.56(s,3H),2.40(s,3H),2.33(s,3H)；13C NMR(100MHz,CDCl3): δ=157.0,
155.3,139.2,132.4,131.2,131.0,129.5,114.2,28.9,21.5,20.5,19.2。
Products therefrom high resolution mass spectrum data are as follows: HRMS (ESI) m/z calcd.for C12H15N2O[M+H]+:
203.1179,found 203.1176。
Embodiment 8
At 25 DEG C, in 10mL reaction tube, -2 (1H) -one 1h (0.2mmol) of 1- benzyl quinoxaline, diethyl are sequentially added
Sour iodobenzene 2a (0.44mmol), Ru (bpy)3Cl2·6H2O (0.002mmol), PEG-200 (1mL) are uniformly mixed, then exist
Under the irradiation of 12W white led lamps, it is stirred to react 6h.It is detected with TLC to after the reaction was completed, addition cyclopentyl methyl ether (2ml × 3) extracts
Take, take upper layer of extraction liquid, be concentrated in vacuo to solvent-free at 50 DEG C, obtain crude product, then with volume ratio be 2:1 petroleum ether and
Ethyl acetate mixtures of eluents is rinsed, and silicagel column rapid column chromatography obtains 3- methyl-1-benzyl quinoxaline-2 in this example
(1H) -one product 3ha is white solid 43.5mg, yield 87%.
Products therefrom nuclear magnetic spectrum data are as follows:1H NMR(400MHz,CDCl3): δ=7.82 (dd, J1=7.6Hz, J2=
1.6Hz,1H),7.42–7.38(m,1H),7.34–7.27(m,4H),7.25–7.23(m,3H),5.50(s,2H),2.66(s,
3H)；13C NMR(100MHz,CDCl3): δ=158.5,155.3,135.2,132.9,132.6,129.6,129.6,128.9,
127.7,126.9,123.7,114.4,45.9,21.7.
Embodiment 9
At 25 DEG C, in 10mL reaction tube, -2 (1H) -one 1i (0.2mmol) of 1- propargyl quinoxaline is sequentially added, two
Acetic acid iodobenzene 2a (0.44mmol), Ru (bpy)3Cl2·6H2O (0.002mmol), PEG-200 (1mL) are uniformly mixed, then exist
Under the irradiation of 12W white led lamps, it is stirred to react 7h.It is detected with TLC to after the reaction was completed, addition cyclopentyl methyl ether (2ml × 3) extracts
Take, take upper layer of extraction liquid, be concentrated in vacuo to solvent-free at 50 DEG C, obtain crude product, then with volume ratio be 2:1 petroleum ether and
Ethyl acetate mixtures of eluents is rinsed, and silicagel column rapid column chromatography obtains 3- methyl-1-propargyl quinoxaline-2 in this example
(1H) -one product 3ia is white solid 43.5mg, yield 95%.
Products therefrom nuclear magnetic spectrum data are as follows:1H NMR(400MHz,CDCl3): δ=7.82 (dd, J1=8.0Hz, J2=
1.6Hz, 1H), 7.58-7.54 (m, 1H), 7.46-7.44 (m, 1H), 7.38-7.34 (m, 1H), 5.05 (d, J=2.8Hz,
2H), 2.60 (s, 3H), 2.29 (t, J=2.4Hz, 1H)；13C NMR(100MHz,CDCl3): δ=158.3,154.2,132.8,
131.7,129.7,129.6,124.0,114.1,76.8,73.2,31.5,21.5。
Products therefrom high resolution mass spectrum data are as follows: HRMS (ESI) m/z calcd.for C12H11N2O[M+H]+:
199.0866,found 199.0862。
Embodiment 10
At 25 DEG C, in 10mL reaction tube, 2- (- 1 (2H)-yl of 2- oxo quinoxaline) ethyl acetate 1j is sequentially added
(0.2mmol), iodobenzene diacetate 2a (0.44mmol), Ru (bpy)3Cl2·6H2O (0.002mmol), PEG-200 (1mL) are mixed
It closes uniformly, then under the irradiation of 12W white led lamps, is stirred to react 8h.It is detected with TLC to after the reaction was completed, cyclopenta first is added
Ether (2ml × 3) extraction, takes upper layer of extraction liquid, is concentrated in vacuo to solvent-free at 50 DEG C, obtain crude product, be then with volume ratio
The petroleum ether and ethyl acetate mixtures of eluents of 2:1 rinses, and silicagel column rapid column chromatography obtains the 3- methyl -2- in this example
(- 1 (2H)-yl of 2- oxo quinoxaline) ethyl acetate product 3ja is white solid 39.8mg, yield 81%.
Products therefrom nuclear magnetic spectrum data are as follows:1H NMR(400MHz,CDCl3): δ=7.83 (dd, J1=8.0Hz, J2=
1.6Hz,1H),7.51–7.47(m,1H),7.36–7.32(m,1H),7.06(dd,J1=8.4Hz, J2=0.8Hz, 1H), 5.02
(s, 2H), 4.28-4.22 (m, 2H), 2.61 (s, 3H), 1.27 (t, J=7.2Hz, 3H)；13C NMR(100MHz,CDCl3):δ
=167.1,158.2,154.8,132.7,132.4,129.8,129.7,123.9,113.0,62 .1,43.5,21.5,14.1
Products therefrom high resolution mass spectrum data are as follows: HRMS (ESI) m/z calcd.for C13H15N2O3[M+H]+:
247.1077,found 247.1068.
Embodiment 11
At 25 DEG C, in 10mL reaction tube, -2 (1H) -one 1k (0.2mmol) of 1- phenyl quinoxaline, diethyl are sequentially added
Sour iodobenzene 2a (0.44mmol), Ru (bpy)3Cl2·6H2O (0.002mmol), PEG-200 (1mL) are uniformly mixed, then exist
Under the irradiation of 12W white led lamps, it is stirred to react 6h.It is detected with TLC to after the reaction was completed, addition cyclopentyl methyl ether (2ml × 3) extracts
Take, take upper layer of extraction liquid, be concentrated in vacuo to solvent-free at 50 DEG C, obtain crude product, then with volume ratio be 2:1 petroleum ether and
Ethyl acetate mixtures of eluents is rinsed, and silicagel column rapid column chromatography obtains 3- methyl-1-phenyl quinoxaline-2 in this example
(1H) -one product 3ka is white solid 42.5mg, yield 90%.
Products therefrom nuclear magnetic spectrum data are as follows:1H NMR(400MHz,CDCl3): δ=7.86-7.83 (m, 1H), 7.63-
7.53(m,3H),7.33–7.28(m,4H),6.67–6.65(m,1H),2.64(s,3H)；13CNMR(100MHz,CDCl3): δ=
159.2,154.9,135.8,134.1,132.5,130.3,129.4,129.2,129.0,128.2,123.8,115.4,21.4.
Embodiment 12
At 25 DEG C, in 10mL reaction tube, -2 (1H) -one 1l (0.2mmol) of 1- allyl quinoxaline, diethyl are sequentially added
Sour iodobenzene 2a (0.44mmol), Ru (bpy)3Cl2·6H2O (0.002mmol), PEG-200 (1mL) are uniformly mixed, then exist
Under the irradiation of 12W white LED lamp, it is stirred to react 8h.It is detected with TLC to after the reaction was completed, addition cyclopentyl methyl ether (2ml × 3) extracts
Take, take upper layer of extraction liquid, be concentrated in vacuo to solvent-free at 50 DEG C, obtain crude product, then with volume ratio be 2:1 petroleum ether and
Ethyl acetate mixtures of eluents is rinsed, and silicagel column rapid column chromatography obtains 3- methyl-1-allyl quinoxaline-2 in this example
(1H) -one product 3la is white solid 36.4mg, yield 91%.
Products therefrom nuclear magnetic spectrum data are as follows:1H NMR(400MHz,CDCl3): δ=7.81 (d, J=8.0Hz, 1H),
7.48 (t, J=7.6Hz, 1H), 7.34-7.28 (m, 2H), 5.98-5.88 (m, 1H), 5.26 (d, J=12.0Hz, 1H), 5.16
(d, J=16.8Hz, 1H), 4.90 (d, J=4.8Hz, 2H), 2.61 (s, 3H)；13CNMR(100MHz,CDCl3): δ=158.4,
154.7,132.8,132.4,130.6,129.5,129.5,123.6,118.0,114.2,44.5,21.5。
Products therefrom high resolution mass spectrum data are as follows: HRMS (ESI) m/z calcd.for C12H13N2O[M+H]+:
201.1022,found 201.1019。
Claims (7)
1. a kind of preparation method of 3- methyl-quinoxaline -2 (1H) -one class compound, it is characterised in that: 1 structure quinokysalines of formula
Class compound carries out visible light catalytic under photochemical catalyst effect with 2 iodobenzene diacetate of formula and reacts to get 3 structure 3- methyl quinoline of formula
Quinoline ketone compounds；
Wherein,
R1For hydrogen, alkyl or aralkyl；
R2And R3Independent choice hydrogen, alkyl, alkoxy, nitro, amino, acyl group, halogenic substituent, hydroxyl, cyano or fluoroform
Base.
2. a kind of preparation method of 3- methyl-quinoxaline -2 (1H) -one class compound according to claim 1, feature exist
In:
R1When selected from alkyl, alkyl C1~C8Alkyl；R1When selected from aralkyl, aralkyl is benzyl or phenylethyl；
R2Or R3When selecting alkyl, alkyl C1~C8Alkyl；R2Or R3When selecting alkoxy, alkoxy C1~C8Alcoxyl
Base；R2Or R3When selecting acyl group, acyl group is formoxyl, acetyl group or propiono；R2Or R3When selecting halogenic substituent, halogen is taken
Dai Jiwei fluorine, chlorine, bromine or iodine.
3. a kind of preparation method of 3- methyl-quinoxaline -2 (1H) -one class compound according to claim 1, feature exist
In:
The molar ratio of quinoxaline -2 (1H) -one analog derivative and iodobenzene diacetate are as follows: 1:1~1:20；
The molar ratio of quinoxaline -2 (1H) -one analog derivative and photochemical catalyst are as follows: 1:0.01~1:0.05.
4. a kind of preparation method of 3- methyl-quinoxaline -2 (1H) -one class compound according to claim 3, feature exist
In: the photochemical catalyst includes Ru (bpy)3Cl2, Eosin B, Eosinum Natricum, the molten Yihong of alcohol, rhodamine B, edible pigment it is red in extremely
Few one kind.
5. a kind of preparation side of 3- methyl-quinoxaline -2 (1H) -one class compound according to any one of claims 1 to 4
Method, it is characterised in that: the condition of the visible light catalytic reaction are as follows: under visible light illumination, in room temperature reaction 6~12 hours.
6. a kind of preparation method of 3- methyl-quinoxaline -2 (1H) -one class compound according to claim 5, feature exist
In: the visible light source is LED white light source, blue-light source or the green light source that power is 3W~24W.
7. a kind of preparation method of 3- methyl-quinoxaline -2 (1H) -one class compound according to claim 1, feature exist
In: the light-catalyzed reaction is in DMSO, DMF, CHCl3、CH3In at least one of OH, PEG-200, PEG-400 reaction medium into
Row.
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