CN106565735A - Method for preparing 2-amino-4-aryl-4H-pyrano-[3, 2-c]coumarin derivate - Google Patents
Method for preparing 2-amino-4-aryl-4H-pyrano-[3, 2-c]coumarin derivate Download PDFInfo
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Abstract
The invention provides a method for preparing a 2-amino-4-aryl-4H-pyrano-[3, 2-c]coumarin derivate, and belongs to the technical field of the catalysis of ionic liquid. In a preparation reaction, the mole ratio of aromatic aldehyde, an active methylene compound and 4-hydroxycoumarin is 1 to 1 to 1; the molar weight of a basic ionic liquid catalyst is 5 to 8 percent of that of the used aromatic aldehyde; the volume dose, which is metered by a milliliter, of a reaction solvent ethanol is 3 to 5 times of the molar weight, which is metered by a millimole, of the aromatic aldehyde; and the refluxing reaction time is 7min to 35min. After the reaction is terminated, the cooling to a room temperature is carried out; the suction filtration is carried out; a filter residue is subjected to vacuum drying; and afterwards, the 2-amino-4-aryl-4H-pyrano-[3, 2-c]coumarin derivate is obtained. Compared with a preparation method in which other basic ionic liquid is used as a catalyst, the method for preparing the 2-amino-4-aryl-4H-pyrano-[3, 2-c]coumarin derivate has the characteristics that the use level of the catalyst is few, further, the loss amount in recycling is few, recyclable times are many, the purification process of a product is simple, a whole reaction condition is mild, the method is convenient for industrialized large-scale production, and the like.
Description
Technical field
The invention belongs to ionic liquid-catalyzed technical field, and in particular to one kind prepares 2- amino -4- aryl -4H- pyrans
And the method for [3,2-c] coumarin derivative.
Background technology
Coumarin is the important material with biological activity and pharmacologically active of a class, with good sterilizing, parasite killing, is resisted
Blood coagulation etc. is acted on, it is also possible to make estrogen.In addition, coumarin derivative also has excellent optical characteristics, it is good fluorescence
Brightening agent, laser dye, fluorescent probe and nonlinear optical material.And 4H- pyran compounds are the structure lists of natural product
Unit, is also the important synthon for building other heterocyclic compounds, with multiple biological activities and pharmacologically active, can be used in anti-mistake
The aspects such as quick, anticancer.
2- amino -4- aryl -4H- pyrans simultaneously [3,2-c] coumarin derivative knot containing 4H- pyrans and coumarin simultaneously
Structure, can serve as potentially suppressing Measles viruss to replicate reagent, suppress uterotonic pharmacophore, potential multiple drug effect opposing
Reversal agents and same human leukaemia cell (HL-60) binding reagents of prevention [3H] thymidine.The traditional synthesis side of this kind of compound
Method is, by the use of the organic base such as piperidines or pyridine as catalyst, to flow back to be prepared in organic solvent.But this method is deposited
The shortcomings of response time length, low yield, environmental pollution, catalyst can not be recycled.In recent years, some new synthetic technologys
2- amino -4- aryl -4H- pyrans is applied to new catalyst simultaneously in the preparation process of [3,2-c] coumarin derivative, such as
Using microwave technology, using KF/Al2O3、MgO、H6P2W18O62·18H2O, ammonium dihydrogen phosphate etc. make catalyst.But these are new
Preparation method yet suffers from that response time length, reaction temperature be high, catalyst is difficult to recycle, industrial applications are restricted etc. lacks
Point.Therefore, a kind of efficient, the green preparation side of 2- amino -4- aryl -4H- pyrans simultaneously [3,2-c] coumarin derivative is developed
Method becomes many organic synthesiss worker questions of common concern.
Functionalized ion liquid, particularly more stable to water and air bronsted alkali ionic liquid, due to it
With being applied to 2- amino -4- the features such as species is more, active site density height, uniform intensity distribution, active sites are not easily runed off
Aryl -4H- pyrans is simultaneously in the preparation reaction of [3,2-c] coumarin derivative.Such as external Ahmad Shaabani etc. are with alkali
Property ionic liquid trifluoroacetic acidization 1,1,3,3-N, N, N ', N '-tetramethyl guanidinesalt as catalysts, in condition of no solvent
Under can effectively be catalyzed aromatic aldehyde, Cyanoacetyl-Cyacetazid and 4 hydroxy coumarin " one kettle way " to prepare a series of 2- amino -4- fragrant
Base -4H- pyrans simultaneously [3,2-c] coumarin derivative (Ionic liquid promoted efficient and rapid
One-pot synthesis of pyran annulated heterocyclic systems [J], Catalysis
Letters, 2005,104：39～43).In order to reduce preparing trifluoroacetic acidization 1,1,3,3-N, N, N ', N '-tetramethyl guanidinesalt
The expense of ionic liquid, and then the preparation cost of 2- amino -4- aryl -4H- pyrans simultaneously [3,2-c] coumarin derivative is reduced,
Guo Hongyun of Zhejiang Polytechnical University etc. employs less expensive alkali ionic liquid ethanol amine acetate as catalyst, in second
Alcohol is under conditions of reaction dissolvent, can to prepare 2- amino -4- with catalysis aromatic aldehyde, 4 hydroxy coumarin and Cyanoacetyl-Cyacetazid under room temperature fragrant
Base -4H- pyrans simultaneously [3,2-c] coumarin derivative, the method has the features such as simple to operate, reaction condition is gentle, yield is high
(Yang Zhangyan. applied research [D] of the ionic liquid in Multicomponent reactions, Zhejiang Polytechnical University, 2010).Additionally, this
Applicant using the higher methoxylation choline of basicity as catalyst, ethanol water as reaction dissolvent, at a temperature of backflow
Simultaneously [3,2-c] coumarin derivative (one kind catalysis preparation 4,5- of preparation 2- amino -4- aryl -4H- pyrans can be effectively catalyzed
The method [P] of dihydropyran [c] 1-benzopyran derivatives, application number：201610330995.7).
Above-mentioned to make catalyst in alkali ionic liquid, ethanol water is made to prepare 2- under solvent or solvent-free reaction condition
Amino -4- aryl -4H- pyrans causes it to make simultaneously during [3,2-c] coumarin derivative because the basicity of catalyst is relatively low
Large usage quantity and relatively low to some reaction raw materials catalysis yields.Additionally, because whole operation process is more complicated, in catalytic efficiency
In the case of change less, the loss amount of catalyst is larger, and it is relatively low to can be recycled number of times, and in ionic-liquid catalyst valency is prepared
In the case that lattice are more expensive, it is unfavorable in industrialized production by large-scale use.Finally, if containing water in reaction dissolvent,
For the aromatic aldehyde that some easily volatilize with vapor at a temperature of backflow, such as paranitrobenzaldehyde, 4-chloro-benzaldehyde etc.
Utilization rate will be reduced.
The content of the invention
It is an object of the invention to overcome utilize in prior art ionic liquid-catalyzed preparation 2- amino -4- aryl -4H- pyrroles
Ionic-liquid catalyst usage amount present in simultaneously [3,2-c] coumarin derivative process of muttering is big, recycle in number of dropouts compared with
Greatly, can be recycled that number of times is less and purification of products process complicated, reaction raw materials utilization rate is low and selectable range is narrow etc. lacks
Point, and a kind of alkali ionic liquid higher with catalysis activity is provided and makees catalyst, with ethanol as solvent condition under catalysis prepare
The method of 2- amino -4- aryl -4H- pyrans simultaneously [3,2-c] coumarin derivative.
The structural formula of alkaline ionic liquid catalyst used in the present invention is：
One kind provided by the present invention prepares the side of 2- amino -4- aryl -4H- pyrans simultaneously [3,2-c] coumarin derivative
Method, its chemical equation is：
Wherein：Aromatic aldehyde (I) in above-mentioned reaction, active methylene compound (II) and 4 hydroxy coumarin (III) rub
You are than being 1：1：1, the mole of alkaline ionic liquid catalyst is the 5～8% of aromatic aldehyde used, the reaction dissolvent in terms of milliliter
The volume of ethanol be by mM in terms of 3～5 times of aromatic aldehyde mole, reaction pressure is an atmospheric pressure, back flow reaction
Time is 7～35min.Reaction is cooled to room temperature after terminating, and pulverizes the solid of precipitation, stands, sucking filtration, after filtering residue vacuum drying
To 2- amino -4- aryl -4H- pyrans simultaneously [3,2-c] coumarin derivative (IV).The alkali ionic liquid that contains in filtrate and few
The complete raw material of amount unreacted, can reuse without processing.
Aromatic aldehyde used by the present invention is benzaldehyde, 4-chloro-benzaldehyde, o-chlorobenzaldehyde, m chlorobenzaldehyde, 2,4- dichloros
Benzaldehyde, 2,3- dichlorobenzaldehydes, 3,4- dichlorobenzaldehydes, 3,4- dimethylbenzaldehydes, p-tolyl aldehyde, o-methyl-benzene first
Aldehyde, paranitrobenzaldehyde, p-bromobenzaldehyde, hydroxy benzaldehyde, P-methoxybenzal-dehyde, o-bromobenzaldehye, m-nitro first
Any one in aldehyde, 1-Formyl-2-nitrobenzene.
Active methylene compound used by the present invention is Cyanoacetyl-Cyacetazid or cyan-acetic ester.
The preparation method of alkaline ionic liquid catalyst used in the present invention, is shown in pertinent literature (Biodiesel
production by transesterification catalyzed by an efficient choline ionic
Liquid catalyst, Applied Energy, 108 (2013), 333-339).
The present invention compared with the preparation method that other alkali ionic liquids make catalyst, with advantages below：
1st, catalyst loss amount in recycling is less, number of times can be recycled more；
2nd, the catalysis activity of catalyst is stronger, and usage amount is less, and the species of catalytic reaction thing is more；
3rd, reaction raw materials utilization rate is high, and loss of product amount is few；
4th, purification of products process is simple, energy-saving and emission-reduction；
5th, reaction condition is gentle, workable, applied widely；
6th, whole course of reaction green economy, is easy to industrialization large-scale production.
Description of the drawings
Fig. 1 is that simultaneously [3,2-c] coumarin spreads out alkali ionic liquid of the present invention catalysis preparation 2- amino -4- aryl -4H- pyrans
Biological process chart.
Fig. 2 is that alkaline ionic liquid catalyst of the present invention is preparing 2- amino-5-oxo -4- phenyl -4,5- dihydropyran
Product yield figure when recycling in [c] .alpha.-5:6-benzopyran -3- nitriles.
Fig. 3 is that alkaline ionic liquid catalyst of the present invention is preparing 2- amino-5-oxo -4- (4- chlorphenyls) -4,5- bis-
Product yield figure when recycling in hydrogen pyrans [c] .alpha.-5:6-benzopyran -3- nitriles.
Fig. 4 is alkaline ionic liquid catalyst of the present invention in preparation 2- amino-5-oxo -4- (3,4- Dichlorobenzene base) -4,
Product yield figure when recycling in 5- dihydropyran [c] .alpha.-5:6-benzopyran -3- carboxylates.
Fig. 5 is that alkaline ionic liquid catalyst of the present invention is preparing 2- amino-5-oxo -4- (4- hydroxy phenyls) -4,5-
Product yield figure when recycling in dihydropyran [c] .alpha.-5:6-benzopyran -3- carboxylates.
Specific embodiment
The substantive features and remarkable result of the present invention 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 nuclear-magnetism of model AVANCE-II 500MHz and 400MHz
Resonance instrument；The model Bruker tensor 37FT-IR that examination of infrared spectrum sign uses German Bruker companies are red
External spectrum instrument (KBr tablettings)；The fusing point of product is determined using capillary tube method.
Embodiment 1
1mmol benzaldehydes, 1mmol Cyanoacetyl-Cyacetazid, 1mmol 4 hydroxy coumarins and 0.05mmol alkali ionic liquids are added
Enter in the 25ml single port bottles with stirrer and condensing tube for filling 3ml ethanol.It is stirred vigorously lower back flow reaction 7min, TLC
(thin plate chromatography) is detected, raw material point disappears, and is cooled to room temperature, pulverizes the solid of precipitation, is stood, and sucking filtration, filtering residue is vacuum dried
After obtain 2- amino-5-oxo -4- phenyl -4,5- dihydropyran [c] .alpha.-5:6-benzopyran -3- nitriles, yield is 91%.In filtrate directly
Benzaldehyde, Cyanoacetyl-Cyacetazid and 4 hydroxy coumarin is added to be reused.
2- amino-5-oxo -4- phenyl -4,5- dihydropyran [c] .alpha.-5:6-benzopyran -3- nitriles：M.p.257～259 DEG C；1H
NMR (500MHz, DMSO-d6):δ=4.29 (s, 1H), 7.20 (d, J=7.8Hz, 2H), 7.32 (br s, 1H), 7.33 (br
S, 2H), 7.37 (t, J=7.5Hz, 2H), 7.46 (d, J=8.4Hz, 1H), 7.49 (t, J=7.6Hz, 1H), 7.68 (t, J=
7.5Hz, 1H), 7.91 (d, J=7.8Hz, 1H)；IR(KBr)：3369,3284,3170,2193,1706,1667,1608cm-1
Embodiment 2
By 1mmol 4-chloro-benzaldehydes, 1mmol Cyanoacetyl-Cyacetazid, 1mmol 4 hydroxy coumarins and 0.06mmol alkali ion liquid
Body is added in the 25ml single port bottles with stirrer and condensing tube for filling 5ml ethanol.It is stirred vigorously lower back flow reaction
14min, TLC (thin plate chromatography) detect that raw material point disappears, and is cooled to room temperature, pulverizes the solid of precipitation, stand, sucking filtration, filtering residue Jing
2- amino-5-oxo -4- (4- chlorphenyls) -4,5- dihydropyran [c] .alpha.-5:6-benzopyran -3- nitriles are obtained after vacuum drying, yield is
89%.It is directly added into 4-chloro-benzaldehyde, Cyanoacetyl-Cyacetazid and 4 hydroxy coumarin in filtrate to be reused.
2- amino-5-oxo -4- (4- chlorphenyls) -4,5- dihydropyran [c] .alpha.-5:6-benzopyran -3- nitriles：M.p.255～257
℃；1H NMR (500MHz, DMSO-d6)：δ=4.38 (s, 1H), 7.24 (d, J=7.8Hz, 2H), 7.33 (br s, 2H), 7.35
(br s, 2H), 7.39 (t, J=8.0Hz, 1H), 7.62 (t, J=7.6Hz, 1H), 7.71 (t, J=7.8Hz, 1H), 7.92 (d,
J=7.8Hz, 1H)；IR(KBr)：3371,3304,3169,2180,1712,1674,1601cm-1
Embodiment 3
By 1mmol o-chlorobenzaldehydes, 1mmol Cyanoacetyl-Cyacetazid, 1mmol 4 hydroxy coumarins and 0.06mmol alkali ion liquid
Body is added in the 25ml single port bottles with stirrer and condensing tube for filling 4ml ethanol.It is stirred vigorously lower back flow reaction
17min, TLC (thin plate chromatography) detect that raw material point disappears, and is cooled to room temperature, pulverizes the solid of precipitation, stand, sucking filtration, filtering residue Jing
2- amino-5-oxo -4- (2- chlorphenyls) -4,5- dihydropyran [c] .alpha.-5:6-benzopyran -3- nitriles are obtained after vacuum drying, yield is
88%.It is directly added into o-chlorobenzaldehyde, Cyanoacetyl-Cyacetazid and 4 hydroxy coumarin in filtrate to be reused.
2- amino-5-oxo -4- (2- chlorphenyls) -4,5- dihydropyran [c] .alpha.-5:6-benzopyran -3- nitriles：M.p.265～267
℃；1H NMR (500MHz, DMSO-d6)：δ=4.47 (s, 1H), 7.17 (d, J=7.8Hz, 1H), 7.22 (t, J=7.5Hz,
2H), 7.26 (br s, 2H), 7.45 (d, J=8.4Hz, 1H), 7.49 (d, J=7.8Hz, 1H), 7.55 (t, J=7.6Hz,
1H), 7.61 (t, J=7.5Hz, 1H), 7.88 (d, J=7.8Hz, 1H)；IR(KBr)：3379,3291,3174,2185,1700,
1675,1603cm-1
Embodiment 4
By 1mmol 2,3- dichlorobenzaldehydes, 1mmol Cyanoacetyl-Cyacetazid, 1mmol 4 hydroxy coumarins and 0.07mmol alkalescence from
Sub- liquid is added in the 25ml single port bottles with stirrer and condensing tube for filling 5ml ethanol.It is stirred vigorously lower back flow reaction
20min, TLC (thin plate chromatography) detect that raw material point disappears, and is cooled to room temperature, pulverizes the solid of precipitation, stand, sucking filtration, filtering residue Jing
2- amino-5-oxo -4- (2,3- Dichlorobenzene base) -4,5- dihydropyran [c] .alpha.-5:6-benzopyran -3- nitriles are obtained after vacuum drying, is received
Rate is 85%.It is directly added into 2,3- dichlorobenzaldehydes, Cyanoacetyl-Cyacetazid and 4 hydroxy coumarin in filtrate to be reused.
2- amino-5-oxo -4- (2,3- Dichlorobenzene base) -4,5- dihydropyran [c] .alpha.-5:6-benzopyran -3- nitriles：M.p.280～
282℃；1H NMR (500MHz, DMSO-d6)：δ=4.81 (s, 1H), 7.30 (dd, J=8.2Hz, 1.8Hz, 1H), 7.37 (d, J
=8.2Hz, 1H), 7.41 (br s, 2H), 7.46 (d, J=8.2Hz, 1H), 7.52 (t, J=7.7Hz, 1H), 7.57 (d, J=
2.1Hz, 1H), 7.73 (t, J=8.2Hz, 1H), 7.95 (d, J=8.9Hz, 1H)；IR(KBr)：3454,3292,3151,
3070,2194,1715,1673,1589cm-1
Embodiment 5
By 1mmol P-methoxybenzal-dehyde, 1mmol Cyanoacetyl-Cyacetazid, 1mmol 4 hydroxy coumarins and 0.07mmol alkalescence from
Sub- liquid is added in the 25ml single port bottles with stirrer and condensing tube for filling 4ml ethanol.It is stirred vigorously lower back flow reaction
24min, TLC (thin plate chromatography) detect that raw material point disappears, and is cooled to room temperature, pulverizes the solid of precipitation, stand, sucking filtration, filtering residue Jing
2- amino-5-oxo -4- (4- methoxyphenyls) -4,5- dihydropyran [c] .alpha.-5:6-benzopyran -3- nitriles are obtained after vacuum drying, is received
Rate is 87%.It is directly added into P-methoxybenzal-dehyde, Cyanoacetyl-Cyacetazid and 4 hydroxy coumarin in filtrate to be reused.
2- amino-5-oxo -4- (4- methoxyphenyls) -4,5- dihydropyran [c] .alpha.-5:6-benzopyran -3- nitriles：M.p.239～
242℃；1H NMR (500MHz, DMSO-d6)：δ=3.77 (s, 3H), 4.48 (s, 1H), 6.92 (d, J=8.2Hz, 2H), 7.25
(d, J=8.2Hz, 2H), 7.44 (br s, 2H), 7.49 (d, J=8.2Hz, 1H), 7.58 (t, J=7.8Hz, 1H), 7.73 (t,
J=7.8Hz, 1H), 7.88 (t, J=7.8Hz, 1H)；IR(KBr)：3377,3310,3195,2197,1706,1676,
1603cm-1
Embodiment 6
By 1mmol m-nitrobenzaldehydes, 1mmol Cyanoacetyl-Cyacetazid, 1mmol 4 hydroxy coumarins and 0.06mmol alkali ions
Liquid is added in the 25ml single port bottles with stirrer and condensing tube for filling 5ml ethanol.It is stirred vigorously lower back flow reaction
16min, TLC (thin plate chromatography) detect that raw material point disappears, and is cooled to room temperature, pulverizes the solid of precipitation, stand, sucking filtration, filtering residue Jing
2- amino-5-oxo -4- (3- nitrobenzophenones) -4,5- dihydropyran [c] .alpha.-5:6-benzopyran -3- nitriles, yield are obtained after vacuum drying
For 86%.It is directly added into m-nitrobenzaldehyde, Cyanoacetyl-Cyacetazid and 4 hydroxy coumarin in filtrate to be reused.
2- amino-5-oxo -4- (3- nitrobenzophenones) -4,5- dihydropyran [c] .alpha.-5:6-benzopyran -3- nitriles：M.p.260～
262℃；1H NMR (500MHz, DMSO-d6)：δ=4.63 (s, 1H), 7.35 (d, J=6.8Hz, 1H), 7.37 (t, J=
7.6Hz, 1H), 7.43 (dd, J=7.5Hz, 1.3Hz, 1H), 7.62 (br s, 2H), 7.73 (t, J=7.6Hz, 1H), 7.81
(d, J=6.8Hz, 1H), 7.86 (dd, J=6.8Hz, 1.2Hz, 1H), 8.04 (dd, J=8.4Hz, 1.4Hz, 1H), 8.22 (s,
1H)；IR(KBr)：3398,3320,3182,2194,1701,1669,1532,1337cm-1
Embodiment 7
By 1mmol 3,4- dimethylbenzaldehydes, 1mmol Cyanoacetyl-Cyacetazid, 1mmol 4 hydroxy coumarins and 0.07mmol are alkaline
Ionic liquid is added in the 25ml single port bottles with stirrer and condensing tube for filling 5ml ethanol.It is stirred vigorously lower backflow anti-
Answer 27min, TLC (thin plate chromatography) detections, raw material point to disappear, be cooled to room temperature, pulverize the solid of precipitation, stand, sucking filtration, filtering residue
2- amino-5-oxo -4- (3,4- 3,5-dimethylphenyl) -4,5- dihydropyran [c] .alpha.-5:6-benzopyran -3- is obtained after vacuum dried
Nitrile, yield is 83%.3,4- dimethylbenzaldehydes, Cyanoacetyl-Cyacetazid and 4 hydroxy coumarin are directly added in filtrate to carry out repeating to make
With.
2- amino-5-oxo -4- (3,4- 3,5-dimethylphenyl) -4,5- dihydropyran [c] .alpha.-5:6-benzopyran -3- nitriles：m.p.256
～258 DEG C；1H NMR (400MHz, CDCl3)：δ=2.16 (s, 3H), 2.20 (s, 3H), 4.39 (s, 1H), 6.93 (dd, J=
8.1Hz, 1.6Hz, 1H), 6.97 (s, 1H), 7.05 (d, J=8.1Hz, 1H), 7.32 (s, 2H), 7.41～7.53 (m, 2H),
7.68～7.76 (m, 1H), 7.89 (dd, J=7.5Hz, 1.6Hz, 1H)；IR(KBr)：3387,3352,2231,1706,1604,
1492,1450,1378,1255,1173,1118,1050,949,905,771cm-1
Embodiment 8
1mmol o-chlorobenzaldehydes, 1mmol cyan-acetic esters, 1mmol 4 hydroxy coumarins and 0.06mmol is alkaline
Ionic liquid is added in the 25ml single port bottles with stirrer and condensing tube for filling 5ml ethanol.It is stirred vigorously lower backflow anti-
Answer 26min, TLC (thin plate chromatography) detections, raw material point to disappear, be cooled to room temperature, pulverize the solid of precipitation, stand, sucking filtration, filtering residue
2- amino-5-oxo -4- (2- chlorphenyls) -4,5- dihydropyran [c] .alpha.-5:6-benzopyran -3- carboxylates are obtained after vacuum dried,
Yield is 84%.It is directly added into o-chlorobenzaldehyde, cyan-acetic ester and 4 hydroxy coumarin in filtrate to be reused.
2- amino-5-oxo -4- (2- chlorphenyls) -4,5- dihydropyran [c] .alpha.-5:6-benzopyran -3- carboxylates：M.p.214～
216℃；1H NMR (400MHz, CDCl3)：δ=1.14 (t, J=7.2Hz, 3H), 4.05 (q, J=7.2Hz, 2H), 5.21 (s,
1H), 6.43 (br s, 2H), 7.06～7.15 (m, 2H), 7.27 (dd, J=8.0Hz, 2.0Hz, 1H), 7.32～7.39 (m,
2H), 7.41 (dd, J=8.0Hz, 2.0Hz, 1H), 7.55～7.61 (m, 2H), 7.83 (dd, J=8.0Hz, 1.5Hz, 1H)；IR
(KBr)：3403,3285,2991,1724,1697,1618,1534,1492,1383,1289,1205,1098,1054,952,
911,754cm-1
Embodiment 9
By 1mmol 2,4- dichlorobenzaldehydes, 1mmol cyan-acetic esters, 1mmol 4 hydroxy coumarins and 0.07mmol
Alkali ionic liquid is added in the 25ml single port bottles with stirrer and condensing tube for filling 5ml ethanol.It is stirred vigorously next time
Stream reaction 31min, TLC (thin plate chromatography) detections, raw material point disappears, and is cooled to room temperature, pulverizes the solid of precipitation, stands, sucking filtration,
2- amino-5-oxo -4- (2,4- Dichlorobenzene base) -4,5- dihydropyran [c] .alpha.-5:6-benzopyran -3- is obtained after filtering residue is vacuum dried
Carboxylate, yield is 82%.2,4- dichlorobenzaldehydes, cyan-acetic ester and 4 hydroxy coumarin are directly added in filtrate to be carried out
Reuse.
2- amino-5-oxo -4- (2,4- Dichlorobenzene base) -4,5- dihydropyran [c] .alpha.-5:6-benzopyran -3- carboxylates：
M.p.202～205 DEG C；1H NMR (400MHz, CDCl3)：δ=1.17 (t, J=7.2Hz, 3H), 4.06 (q, J=7.2Hz,
2H), 5.23 (s, 1H), 6.46 (br s, 2H), 7.15 (dd, J=7.2Hz, 2.3Hz, 1H), 7.31 (d, J=2.3Hz, 1H),
7.34～7.39 (m, 3H), 7.52～7.60 (m, 1H), 7.86 (dd, J=8.4Hz, 1.5Hz, 1H)；IR(KBr)：3368,
3236,1723,1695,1615,1524,1371,1273,1191,1082,1044,955,747cm-1
Embodiment 10
By 1mmol 3,4- dichlorobenzaldehydes, 1mmol cyan-acetic esters, 1mmol 4 hydroxy coumarins and 0.08mmol
Alkali ionic liquid is added in the 25ml single port bottles with stirrer and condensing tube for filling 5ml ethanol.It is stirred vigorously next time
Stream reaction 34min, TLC (thin plate chromatography) detections, raw material point disappears, and is cooled to room temperature, pulverizes the solid of precipitation, stands, sucking filtration,
2- amino-5-oxo -4- (3,4- Dichlorobenzene base) -4,5- dihydropyran [c] .alpha.-5:6-benzopyran -3- is obtained after filtering residue is vacuum dried
Carboxylate, yield is 81%.3,4- dichlorobenzaldehydes, cyan-acetic ester and 4 hydroxy coumarin are directly added in filtrate to be carried out
Reuse.
2- amino-5-oxo -4- (3,4- Dichlorobenzene base) -4,5- dihydropyran [c] .alpha.-5:6-benzopyran -3- carboxylates：
M.p.177～180 DEG C；1H NMR (400MHz, CDCl3)：δ=1.18 (t, J=7.2Hz, 3H), 4.08 (q, J=7.2Hz,
2H), 4.88 (s, 1H), 6.47 (br s, 2H), 7.20 (dd, J=8.5Hz, 2.0Hz, 1H), 7.33 (d, J=8.5Hz, 1H),
7.30～7.37 (m, 2H), 7.40 (d, J=2.4Hz, 1H), 7.55～7.63 (m, 1H), 7.81～7.87 (m, 1H)；IR
(KBr)：3446,3268,1737,1699,1612,1520,1492,1378,1284,1251,1196,1091,1049,728cm-1
Embodiment 11
By 1mmol hydroxy benzaldehydes, 1mmol cyan-acetic esters, 1mmol 4 hydroxy coumarins and 0.08mmol alkali
Property ionic liquid is added in the 25ml single port bottles with stirrer and condensing tube for filling 5ml ethanol.It is stirred vigorously lower backflow
Reaction 35min, TLC (thin plate chromatography) detection, raw material point disappears, and is cooled to room temperature, pulverizes the solid of precipitation, stands, sucking filtration, filter
2- amino-5-oxo -4- (4- hydroxy phenyls) -4,5- dihydropyran [c] .alpha.-5:6-benzopyran -3- carboxylic acids are obtained after slag is vacuum dried
Ester, yield is 80%.Hydroxy benzaldehyde, cyan-acetic ester and 4 hydroxy coumarin are directly added in filtrate to carry out repeating to make
With.
2- amino-5-oxo -4- (4- hydroxy phenyls) -4,5- dihydropyran [c] .alpha.-5:6-benzopyran -3- carboxylates：m.p.208
～210 DEG C；1H NMR (400MHz, CDCl3)：δ=1.15 (t, J=7.2Hz, 3H), 4.06 (q, J=7.2Hz, 2H), 4.89
(s, 1H), 6.39 (br s, 2H), 6.69 (d, J=8.5Hz, 2H), 7.26 (d, J=8.5Hz, 2H), 7.29～7.34 (m,
2H), 7.53 (m, 1H), 7.85 (dd, J=8.5Hz, 1.6Hz, 1H), 9.42 (s, 2H), 7.41 (dd, J=8.0Hz, 2.0Hz,
1H), 7.55～7.61 (m, 2H), 7.83 (dd, J=8.0Hz, 1.5Hz, 1H), 9.42 (s, 1H)；IR(KBr)：3294,3268,
1729,1691,1615,1532,1373,1283,1200,1184,1094,1047,950,845,752cm-1
Embodiment 12
With embodiment 1 as probe reaction, make the active replica test of catalysts alkali ionic liquid, ionic liquid
Reuse 10 times, product 2- amino-5-oxo -4- phenyl -4, the yield change of 5- dihydropyran [c] .alpha.-5:6-benzopyran -3- nitriles
See Fig. 2.
Embodiment 13
With embodiment 2 as probe reaction, make the active replica test of catalysts alkali ionic liquid, ionic liquid
Reuse 10 times, the product of product 2- amino-5-oxo -4- (4- chlorphenyls) -4,5- dihydropyran [c] .alpha.-5:6-benzopyran -3- nitriles
Fig. 3 is shown in rate change.
Embodiment 14
With embodiment 10 as probe reaction, make the active replica test of catalysts alkali ionic liquid, ionic liquid
Body is reused 10 times, product 2- amino-5-oxo -4- (3,4- Dichlorobenzene base) -4,5- dihydropyran [c] .alpha.-5:6-benzopyran -3-
Fig. 4 is shown in the yield change of carboxylate.
Embodiment 15
With embodiment 11 as probe reaction, make the active replica test of catalysts alkali ionic liquid, ionic liquid
Body is reused 10 times, product 2- amino-5-oxo -4- (4- hydroxy phenyls) -4,5- dihydropyran [c] .alpha.-5:6-benzopyran -3- carboxylics
Fig. 5 is shown in the yield change of acid esters.
Can be seen that by Fig. 2,3,4 and 5：Catalyst alkali ionic liquid is recycling catalysis preparation 2- amino -5- oxygen
Generation -4- phenyl -4,5- dihydropyran [c] .alpha.-5:6-benzopyran -3- nitriles, 2- amino-5-oxo -4- (4- chlorphenyls) -4,5- dihydro pyrroles
Mutter [c] .alpha.-5:6-benzopyran -3- nitriles, 2- amino-5-oxo -4- (3,4- Dichlorobenzene base) -4,5- dihydropyran [c] .alpha.-5:6-benzopyran -3-
During carboxylate and 2- amino-5-oxo -4- (4- hydroxy phenyls) -4,5- dihydropyran [c] .alpha.-5:6-benzopyran -3- carboxylates
Yield is in a slight decrease, but it is smaller to reduce amplitude.It could therefore be concluded that go out the catalyst alkali ionic liquid preparing in catalysis
2- amino -4- aryl -4H- pyrans simultaneously can be recycled during [3,2-c] coumarin derivative, and its catalysis activity is not
There is substantially reduction.
Claims (4)
1. the method that one kind prepares 2- amino -4- aryl -4H- pyrans simultaneously [3,2-c] coumarin derivative, it is characterised in that institute
The mol ratio for stating aromatic aldehyde, active methylene compound and 4 hydroxy coumarin in preparation reaction is 1：1：1, alkali ionic liquid
The mole of catalyst is the 5～8% of aromatic aldehyde used, the volume of the reaction dissolvent ethanol in terms of milliliter be by mM in terms of
3～5 times of aromatic aldehyde mole, reaction pressure is an atmospheric pressure, and reflux time is 7～35min, after reaction terminates
Room temperature is cooled to, the solid of precipitation is pulverized, is stood, sucking filtration, 2- amino -4- aryl -4H- pyrans is obtained simultaneously after filtering residue vacuum drying
[3,2-c] coumarin derivative；
The structural formula of the alkaline ionic liquid catalyst is：
2. one kind as claimed in claim 1 prepares the side of 2- amino -4- aryl -4H- pyrans simultaneously [3,2-c] coumarin derivative
Method, it is characterised in that described aromatic aldehyde is benzaldehyde, 4-chloro-benzaldehyde, o-chlorobenzaldehyde, m chlorobenzaldehyde, 2,4- dichloros
Benzaldehyde, 2,3- dichlorobenzaldehydes, 3,4- dichlorobenzaldehydes, 3,4- dimethylbenzaldehydes, p-tolyl aldehyde, o-methyl-benzene first
Aldehyde, paranitrobenzaldehyde, p-bromobenzaldehyde, hydroxy benzaldehyde, P-methoxybenzal-dehyde, o-bromobenzaldehye, m-nitro first
Any one in aldehyde, 1-Formyl-2-nitrobenzene.
3. one kind as claimed in claim 1 prepares the side of 2- amino -4- aryl -4H- pyrans simultaneously [3,2-c] coumarin derivative
Method, it is characterised in that described active methylene compound is Cyanoacetyl-Cyacetazid or cyan-acetic ester.
4. one kind as claimed in claim 1 prepares the side of 2- amino -4- aryl -4H- pyrans simultaneously [3,2-c] coumarin derivative
Method, it is characterised in that the filtrate after sucking filtration can reuse at least 10 times without the need for any process.
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