The method that one kind catalysis prepares substitution benzo [g] 1-benzopyran derivatives
Technical field
The invention belongs to field of chemical technology, and in particular to one kind catalysis preparation 2- Amino 3 cyano -4- aryl -
5,10- dioxo -5, the method for 10- dihydro -4H- benzo [g] 1-benzopyran derivatives.
Background technology
2- Amino 3 cyano -4- aryl -5,10- dioxo -5,10- dihydro -4H- benzo [g] 1-benzopyran derivatives are
A kind of heterocyclic compound with important biomolecule activity containing benzopyran structure, lives with extensive physiologically active and pharmacology
Property, such as anti-depauperation, anti-allergic effects, hypoglycemic effect, antibacterial, active anticancer and for treating anaphylaxis tracheitis, sugar
Urine disease etc..Three component one kettle ways of such compound generally by aldehyde, active methylene compound and HNQ are anti-
Should be prepared, but using the traditional catalyst generally existing reaction time it is long, yield is not high enough, poisonous and harmful, it is expensive, after
The shortcomings of processing cumbersome.Therefore, exploitation one kind is green, efficient, conveniently and efficiently prepare 2- Amino 3 cyano -4- aryl -5,
10- dioxo -5, the method for 10- dihydro -4H- benzo [g] 1-benzopyran derivatives is universal as many organic synthesis workers
The problem of concern.
Functionalized acidic ionic liquid, bronsted acid ionic liquid particularly more stable to water and air, by
There are the features such as species is more, active site density is high, uniform intensity distribution, active sites are not easily runed off in it and 2- ammonia is applied to
Base -3- cyano group -4- aryl -5,10- dioxo -5, in the preparation reaction of 10- dihydro -4H- benzo [g] 1-benzopyran derivatives.
Such as Hamid Reza Shaterian etc. can be urged efficiently using formic acid 3- methylimidazole ionic liquids as catalyst
Change aromatic aldehyde, malononitrile and HNQ and the prepared 2- Amino 3 cyanos -4- virtues of three components " one kettle way " reaction occur
Base -5,10- dioxo -5,10- dihydro -4H- benzo [g] 1-benzopyran derivatives, the mole dosage of wherein catalyst is used
The 15% of aromatic aldehyde.Additionally, the acidic ionic liquid catalysts can be recycled at least 4 times, during recycling
Structure keeps not obviously lowered (the Effective preparation of 2-amino-3-cyano- of constant and catalysis activity
4-aryl-5,10-dioxo-5,10-dihydro-4H-benzo [g] chromene and hydroxyl naphthalene-
Isosorbide-5-Nitrae-dione derivatives under ambient and solvent-free conditions [J], Journal of
Molecular Liquids, 2013,177:353~360).But the structural matrix of the acidic ion liquid that the above method is used is
The glyoxaline structure of difficult for biological degradation, preparation price is higher, and this is opposite with the policy of green chemical industry.Additionally, above-mentioned acidity
The acidity of ionic liquid causes its usage amount when in use larger than relatively low.
In order to solve the above problems, the sulfuric acid hydrogenation triethylammonium salts that the seminar uses cheap, non-imidazole base instead are acid
Acidic ion liquid as heterogeneous catalysis, can be effectively catalyzed under conditions of solvent-free and room temperature preparation 2- amino-
3- cyano group -4- aryl -5,10- dioxo -5,10- dihydro -4H- benzo [g] 1-benzopyran derivatives, its catalyst mole with
Amount be reduced to aromatic aldehyde used 10% (Preparation of2-amino-3-cyano-4-aryl-5,10-dioxo-5,
10-dihydro-4H-benzo [g] chromene and hydroxyl naphthalene-1,4-dione derivatives
[J], Research on Chemical Intermediates, 2015,41:3171~3191).
The content of the invention
It is an object of the invention to overcome in the prior art using presence of acidic ionic liquid catalyst prepare 2- Amino 3 cyanos-
4- aryl -5,10- dioxo -5, due to ionic liquid present in 10- dihydro -4H- benzo [g] 1-benzopyran derivatives process
Acidity is low and cause its usage amount big and the shortcomings of loss amount is also larger, post processing is complicated in recycling, and provide it is a kind of easily
It is biodegradable, acidity is higher, prepare the low acidic ion liquid of simple, usage amount makees green catalyst, ethanol as solvent condition
Lower catalysis prepares 2- Amino 3 cyano -4- aryl -5,10- dioxo -5,10- dihydro -4H- benzo [g] 1-benzopyran derivatives
Method.
The structural formula of acidic ionic liquid catalysts used in the present invention is:
A kind of catalysis preparation 2- Amino 3 cyano -4- aryl -5 provided by the present invention, 10- dioxo -5,10- dihydros -
The method of 4H- benzos [g] 1-benzopyran derivatives, its chemical equation is:
Wherein:The mol ratio of aromatic aldehyde (I), malononitrile (II) and HNQ (III) is 1 in reaction:1:1,
The mole of acidic ionic liquid catalysts is the 3~6% of aromatic aldehyde used, and the reaction dissolvent water and ethanol in terms of milliliter are mixed
Liquid (V (water):V (ethanol)=1:1) volume be by mM in terms of 5~7 times of malononitrile mole, reaction pressure is one
Individual atmospheric pressure, reacts 10~20min under room temperature condition, reaction has a large amount of solids to separate out, pulverizes solid, stands, suction filtration after terminating,
Pure 2- Amino 3 cyanos -4- aryl -5,10- dioxo -5,10- bis- are obtained after gained filter residue ethyl alcohol recrystallization, vacuum drying
Hydrogen -4H- benzo [g] 1-benzopyran derivatives (IV).Filtrate is directly used in next secondary response without any treatment, can repeat to make
With at least 7 times, its product yield is not obviously lowered.
Aromatic aldehyde used by the present invention is benzaldehyde, o-chlorobenzaldehyde, 4-chloro-benzaldehyde, p-tolyl aldehyde, adjacent nitro
Benzaldehyde, paranitrobenzaldehyde, m-nitrobenzaldehyde, P-methoxybenzal-dehyde, parahydroxyben-zaldehyde, 3-bromobenzaldehyde, 2,4-
Any one in dichlorobenzaldehyde.
The preparation method of acidic ionic liquid catalysts used in the present invention, referring to pertinent literature (Novel
multiple-acidic ionic liquids:catalysts for environmentally friendly benign
synthesis of trans-β-nitrostyrenes under solvent-free conditions,Industrial&
Engineering Chemistry Research, 2014,53:547~552).
The present invention compared with the preparation method of other acid as catalyst, with advantages below:
1st, two-SO are contained3The acidity of the acidic ion liquid of H is high, and catalysis activity is good;
2nd, catalyst usage amount it is few and recycle in loss amount it is also less, recycle number of times it is more;
3rd, raw material availability is high, and Atom economy is preferable;
4th, the raw material for preparing catalyst is cheap and easy to get;
5th, whole preparation process is simple and convenient, and reaction condition is gentleer, is easy to industrialization to mass produce.
Brief description of the drawings
Fig. 1 is that presence of acidic ionic liquid catalyst of the present invention prepares 2- Amino 3 cyano -4- aryl -5,10- dioxo -5,10-
The process chart of dihydro -4H- benzo [g] 1-benzopyran derivatives.
Fig. 2 is that acidic ionic liquid catalysts of the present invention prepare 2- Amino 3 cyano -4- phenyl -5,10- dioxies in catalysis
Product yield variation diagram when being recycled in generation -5,10- dihydro -4H- benzo [g] chromene reaction.
Fig. 3 is that acidic ionic liquid catalysts of the present invention prepare 2- Amino 3 cyanos -4- (2- chlorphenyls) -5 in catalysis,
10- dioxo -5, product yield variation diagram when being recycled in the reaction of 10- dihydro -4H- benzo [g] chromene.
Fig. 4 is that acidic ionic liquid catalysts of the present invention prepare 2- Amino 3 cyanos -4- (4- methoxybenzenes in catalysis
Base) -5,10- dioxo -5, product yield variation diagram when being recycled in the reaction of 10- dihydro -4H- benzo [g] chromene.
Specific embodiment
Substantive features of the invention and remarkable result can be emerged from from following embodiments, but they are not to this
Invention is imposed any restrictions, and those skilled in the art's content of the invention makes some nonessential modifications and adaptations,
Belong to protection scope of the present invention.Below by specific embodiment, the present invention is further illustrated, wherein in embodiment
The test of product is characterized and uses German Bruker companies, the NMR of model AVANCE-II 300MHz;
The fusing point of product is determined using capillary tube method.
Embodiment 1
By 2mmol benzaldehydes, 2mmol malononitrile, 2mmol HNQs and 0.06mmol acidic ion liquids
It is added separately to fill 10ml water and ethanol mixed liquor (V (water):V (ethanol)=1:1) with stirrer and condenser pipe
In 50ml single port bottles.Stirring reaction 12min, TLC (thin plate chromatography) detections, raw material point disappearance at room temperature, reaction has big after terminating
Amount solid is separated out, and pulverizes solid, is stood, suction filtration, and pure 2- amino -3- cyanogen is obtained after gained filter residue ethyl alcohol recrystallization, vacuum drying
Base -4- phenyl -5,10- dioxo -5,10- dihydro -4H- benzo [g] chromene, yield is 94%.Benzene first is added in filtrate
Reused after aldehyde, malononitrile and HNQ.
2- Amino 3 cyano -4- phenyl -5,10- dioxo -5,10- dihydro -4H- benzo [g] chromene:m.p.260
~262 DEG C;1H NMR (300MHz, DMSO-d6):δ=4.63 (s, 1H, CH), 7.24~8.08 (m, 11H, ArH, NH2)
Embodiment 2
By 2mmol p-tolyl aldehydes, 2mmol malononitrile, 2mmol HNQs and 0.08mmol it is acid from
Sub- liquid is added separately to fill 12ml water and ethanol mixed liquor (V (water):V (ethanol)=1:1) with stirrer and condensation
In the 50ml single port bottles of pipe.Stirring reaction 16min, TLC (thin plate chromatography) detections, raw material point disappearance, react after terminating at room temperature
There are a large amount of solids to separate out, pulverize solid, stand, suction filtration, obtained after gained filter residue ethyl alcohol recrystallization, vacuum drying pure 2- amino-
3- cyano group -4- (4- aminomethyl phenyls) -5,10- dioxo -5,10- dihydro -4H- benzo [g] chromene, yield is 90%.Filter
Reused after adding p-tolyl aldehyde, malononitrile and HNQ in liquid.
2- Amino 3 cyanos -4- (4- aminomethyl phenyls) -5,10- dioxo -5,10- dihydro -4H- benzo [g] benzo pyrrole
Mutter:M.p.246~248 DEG C;1H NMR (300MHz, DMSO-d6):δ=2.22 (s, 3H, CH3), 4.58 (s, 1H, CH), 7.07
~8.03 (m, 10H, ArH, NH2)
Embodiment 3
2mmol P-methoxybenzal-dehyde, 2mmol malononitrile, 2mmol HNQs and 0.08mmol is acid
Ionic liquid is added separately to fill 12ml water and ethanol mixed liquor (V (water):V (ethanol)=1:1) with stirrer and cold
In the 50ml single port bottles of solidifying pipe.Stirring reaction 14min at room temperature, TLC (thin plate chromatography) detection, raw material point disappear, and reaction terminates
After there are a large amount of solids to separate out, pulverize solid, stand, suction filtration, obtain pure 2- ammonia after gained filter residue ethyl alcohol recrystallization, vacuum drying
Base -3- cyano group -4- (4- methoxyphenyls) -5,10- dioxo -5,10- dihydro -4H- benzo [g] chromene, yield is
88%.Reused after adding P-methoxybenzal-dehyde, malononitrile and HNQ in filtrate.
2- Amino 3 cyanos -4- (4- methoxyphenyls) -5,10- dioxo -5,10- dihydro -4H- benzo [g] benzo pyrrole
Mutter:M.p.247~248 DEG C;1H NMR (300MHz, DMSO-d6):δ=3.69 (s, 3H, CH3), 4.56 (s, 1H, CH), 6.82
~8.02 (m, 10H, ArH, NH2)
Embodiment 4
By 2mmol parahydroxyben-zaldehydes, 2mmol malononitrile, 2mmol HNQs and 0.12mmol it is acid from
Sub- liquid is added separately to fill 12ml water and ethanol mixed liquor (V (water):V (ethanol)=1:1) with stirrer and condensation
In the 50ml single port bottles of pipe.Stirring reaction 15min, TLC (thin plate chromatography) detections, raw material point disappearance, react after terminating at room temperature
There are a large amount of solids to separate out, pulverize solid, stand, suction filtration, obtained after gained filter residue ethyl alcohol recrystallization, vacuum drying pure 2- amino-
3- cyano group -4- (4- hydroxy phenyls) -5,10- dioxo -5,10- dihydro -4H- benzo [g] chromene, yield is 90%.Filter
Reused after adding parahydroxyben-zaldehyde, malononitrile and HNQ in liquid.
2- Amino 3 cyanos -4- (4- hydroxy phenyls) -5,10- dioxo -5,10- dihydro -4H- benzo [g] benzo pyrrole
Mutter:M.p.255~257 DEG C;1H NMR (300MHz, DMSO-d6):δ=4.48 (s, 1H, CH), 6.63~8.01 (m, 10H,
ArH, NH2), 9.33 (s, 1H, OH)
Embodiment 5
By 2mmol paranitrobenzaldehydes, 2mmol malononitrile, 2mmol HNQs and 0.10mmol it is acid from
Sub- liquid is added separately to fill 14ml water and ethanol mixed liquor (V (water):V (ethanol)=1:1) with stirrer and condensation
In the 50ml single port bottles of pipe.Stirring reaction 13min, TLC (thin plate chromatography) detections, raw material point disappearance, react after terminating at room temperature
There are a large amount of solids to separate out, pulverize solid, stand, suction filtration, obtained after gained filter residue ethyl alcohol recrystallization, vacuum drying pure 2- amino-
3- cyano group -4- (4- nitrobenzophenones) -5,10- dioxo -5,10- dihydro -4H- benzo [g] chromene, yield is 91%.Filter
Reused after adding paranitrobenzaldehyde, malononitrile and HNQ in liquid.
2- Amino 3 cyanos -4- (4- nitrobenzophenones) -5,10- dioxo -5,10- dihydro -4H- benzo [g] benzo pyrrole
Mutter:M.p.236~238 DEG C;1H NMR (300MHz, DMSO-d6):δ=4.79 (s, 1H, CH), 7.46~8.15 (m, 10H,
ArH, NH2)
Embodiment 6
By 2mmol 3-bromobenzaldehydes, 2mmol malononitrile, 2mmol HNQs and 0.08mmol acid ions
Liquid is added separately to fill 12ml water and ethanol mixed liquor (V (water):V (ethanol)=1:1) with stirrer and condenser pipe
50ml single port bottles in.Stirring reaction 12min, TLC (thin plate chromatography) detections, raw material point disappearance at room temperature, react has after terminating
A large amount of solids are separated out, and pulverize solid, are stood, suction filtration, and pure 2- amino -3- is obtained after gained filter residue ethyl alcohol recrystallization, vacuum drying
Cyano group -4- (3- bromophenyls) -5,10- dioxo -5,10- dihydro -4H- benzo [g] chromene, yield is 92%.In filtrate
Reused after adding 3-bromobenzaldehyde, malononitrile and HNQ.
2- Amino 3 cyanos -4- (3- bromophenyls) -5,10- dioxo -5,10- dihydro -4H- benzo [g] chromene:
M.p.257~259 DEG C;1H NMR (300MHz, DMSO-d6):δ=4.63 (s, 1H, CH), 7.23~8.05 (m, 10H, ArH,
NH2)
Embodiment 7
By 2mmol o-chlorobenzaldehydes, 2mmol malononitrile, 2mmol HNQs and 0.10mmol acid ions
Liquid is added separately to fill 10ml water and ethanol mixed liquor (V (water):V (ethanol)=1:1) with stirrer and condenser pipe
50ml single port bottles in.Stirring reaction 14min, TLC (thin plate chromatography) detections, raw material point disappearance at room temperature, react has after terminating
A large amount of solids are separated out, and pulverize solid, are stood, suction filtration, and pure 2- amino -3- is obtained after gained filter residue ethyl alcohol recrystallization, vacuum drying
Cyano group -4- (2- chlorphenyls) -5,10- dioxo -5,10- dihydro -4H- benzo [g] chromene, yield is 89%.In filtrate
Reused after adding o-chlorobenzaldehyde, malononitrile and HNQ.
2- Amino 3 cyanos -4- (2- chlorphenyls) -5,10- dioxo -5,10- dihydro -4H- benzo [g] chromene:
M.p.240~242 DEG C;1H NMR (300MHz, DMSO-d6):δ=5.13 (s, 1H, CH), 7.21~8.04 (m, 10H, ArH,
NH2)
Embodiment 8
By 2mmol 2,4- dichlorobenzaldehydes, 2mmol malononitrile, 2mmol HNQs and 0.10mmol acid
Property ionic liquid is added separately to fill 10ml water and ethanol mixed liquor (V (water):V (ethanol)=1:1) with stirrer and
In the 50ml single port bottles of condenser pipe.Stirring reaction 13min, TLC (thin plate chromatography) detections, raw material point disappearance, react knot at room temperature
The a large amount of solids of Shu Houyou are separated out, and pulverize solid, are stood, suction filtration, and pure 2- ammonia is obtained after gained filter residue ethyl alcohol recrystallization, vacuum drying
Base -3- cyano group -4- (2,4- dichlorophenyl) -5,10- dioxo -5,10- dihydro -4H- benzo [g] chromene, yield is
90%.Reused after 2,4- dichlorobenzaldehydes, malononitrile and HNQ are added in filtrate.
2- Amino 3 cyanos -4- (2,4- dichlorophenyl) -5,10- dioxo -5,10- dihydro -4H- benzo [g] benzo pyrrole
Mutter:M.p.240~242 DEG C;1H NMR (300MHz, DMSO-d6):δ=5.13 (s, 1H, CH), 7.21~8.04 (m, 10H,
ArH, NH2)
Embodiment 9
With embodiment 1 as probe reaction, make the active replica test of catalysts acidic ion liquid, ionic liquid
Reuse 7 times, product 2- Amino 3 cyano -4- phenyl -5,10- dioxo -5,10- dihydro -4H- benzo [g] chromene
Yield change see Fig. 2.
Embodiment 10
With embodiment 2 as probe reaction, make the active replica test of catalysts acidic ion liquid, ionic liquid
Reuse 7 times, product 2- Amino 3 cyanos -4- (4- aminomethyl phenyls) -5,10- dioxo -5,10- dihydro -4H- benzos [g]
Fig. 3 is shown in the yield change of chromene.
Embodiment 11
With embodiment 3 as probe reaction, make the active replica test of catalysts acidic ion liquid, ionic liquid
Reuse 7 times, product 2- Amino 3 cyanos -4- (4- methoxyphenyls) -5,10- dioxo -5,10- dihydro -4H- benzos
Fig. 4 is shown in the yield change of [g] chromene.
Be can be seen that by Fig. 2,3 and 4:Acidity of catalyst ionic liquid is recycling preparation 2- Amino 3 cyano -4- benzene
Base -5,10- dioxo -5,10- dihydro -4H- benzo [g] chromene, 2- Amino 3 cyanos -4- (4- aminomethyl phenyls) -5,
10- dioxo -5,10- dihydro -4H- benzos [g] chromenes and 2- Amino 3 cyanos -4- (4- methoxyphenyls) -5,10-
Yield during dioxo -5,10- dihydro -4H- benzo [g] chromene is in a slight decrease, but it is smaller to reduce amplitude.
Therefore, the acidity of catalyst ionic liquid prepares 2- Amino 3 cyano -4- aryl -5,10- dioxo -5,10- bis- in catalysis
Can be recycled during hydrogen -4H- benzo [g] 1-benzopyran derivatives, its catalysis activity is not obviously lowered.