CN105541773B - A kind of preparation method of 3,4- dihydros -4- aryl-coumarin class compounds - Google Patents
A kind of preparation method of 3,4- dihydros -4- aryl-coumarin class compounds Download PDFInfo
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Abstract
The present invention relates to the preparation method of the field of chemical synthesis, specifically a kind of 4 aryl-coumarin class compound of 3,4 dihydro, its main feature is that using substituted benzaldehyde as starting material, under the catalysis of piperidines, malonic acid generation substituted phenyl acrylic acid derivative is added in；The montmorillonite K 10 being acidified with sulfuric acid is catalyst, and substituted phenyl acrylic acid derivative reacts generation 3,4 dihydro, 4 aryl-coumarin class compound with phenolic compound heating.Compared with prior art, the 3 of the present invention, the preparation method of 4 dihydro, 4 aryl-coumarin class compound has the characteristics that raw material cheap and easy to get, easy to operate, catalyst recoverable, environmentally protective, post processing is simple, production cost is relatively low, has good application value.
Description
Technical field
The present invention relates to pharmaceutical synthesis field, specifically 3,4- of one kind dihydros -4- aryl-coumarin class compounds
Preparation method.
Background technology
Hydrogenated derivatives of 3, the 4- dihydro -4- aryl-coumarin class compounds as 4- aryl-coumarins have and its phase
As bioactivity (Bioorg.Med.Chem.2005,13:4300).2001, Lee et al. showed 4- (3', 4'- dihydroxy
Phenyl) -5,7- dihydroxy -3,4- dihydrocoumarin have stronger antioxidation (Synthesis, 2001,15:2247-
2254).2014, Zhang et al. had found that the antioxidant activity of such compound is mainly related with its parallel dihydroxy based structures
(Biochimie, 2014,107：203-210).In addition, Roelems et al. is research shows that 4- (4'- hydroxy phenyls) -5,7- dihydroxies
Base -8- alkyl -3,4- dihydrocoumarin have estrogen-like action (Eur.J.Med.Chem, 2005,40:1042).About it
The research report of activity is less, this just needs us to synthesize a variety of such compounds, and carries out deep activity research.
It is cinnamic acid or derivatives thereof and phenols to synthesize the most common method of 3,4- dihydro -4- aryl-coumarin class compounds
Split.Research about conditions such as its catalyst and reaction temperatures is numerous, such as reacts more violent polyphosphoric acids method
(PPA) and p-methyl benzenesulfonic acid method, it is chiefly used in split cinnamic acid and polyphenol；Relatively mild but longer the time trifluoro of reaction condition
Acetic and reaction time medium boron trifluoride ether method, be chiefly used in cinnamic acid derivative of the split with electron donating group with
Polyphenol；Solid acid montmorillonite K10 is that the reaction of catalyst can be used for cinnamoyl chloride and polyphenol of the split containing o-dihydroxy.More than but
The method of existing synthesis 3,4- dihydro -4- aryl-coumarin class compounds is in the presence of reaction is violent, the reaction time is long, catalyst is toxic
And the shortcomings of cannot recycling, and the method that catalyst is made in existing montmorillonite need to carry out substitution compounds derived from phenyl acrylic acid
Chloride is cumbersome again with phenolic compound split, and chloride need to strictly control anhydrous, condition harshness.
Invention content
The technical assignment of the present invention is in view of the above shortcomings of the prior art, to provide that a kind of synthesis technology is simple, reaction is easy
The preparation method of the 3,4- dihydro -4- aryl-coumarin class compounds of control.
The present invention provides the preparation method of one kind 3,4- dihydro -4- aryl-coumarin class compounds, its main feature is that take
It is starting material for benzaldehyde, under the catalysis of piperidines, adds in malonic acid generation substituted phenyl acrylic acid derivative；With sulfuric acid acid
The montmorillonite K-10 of change is catalyst, and substituted phenyl acrylic acid derivative reacts generating structure formula (I) with phenolic compound heating
3, the 4- dihydro -4- aryl-coumarin class compounds represented,
Wherein, R1、R2、R3、R4For H or OH；
R5、R6、R7For H, OH or OCH3。
Synthetic route can be represented with following reaction equations：
Preferably, the above method may comprise steps of：
A, using substituted benzaldehyde as starting material, in pyridine solution, malonic acid is added in, using piperidines as catalyst, heating
Perkin condensation reactions occur, substitution compounds derived from phenyl acrylic acid is obtained through isolating and purifying；
B, using nitrobenzene as solvent, montmorillonite K- that compounds derived from phenyl acrylic acid and phenolic compound is replaced to be acidified in sulfuric acid
Under 10 catalysis, esterification cyclization occurs, then through isolating and purifying to obtain 3,4- dihydro -4- aryl-coumarin class compounds.
Preferably, the recycling of catalyst montmorillonite K-10 is further included in this method.Recoverying and utilizing method is：It will step
Filter residue in rapid b after the filtering of esterification cyclization liquid is placed in drying in 30~50 DEG C of vacuum drying chambers, can directly be answered after dry
For catalyzing and synthesizing same 3,4- dihydros -4- aryl-coumarin class compounds.
The molar ratio of substituted benzaldehyde and malonic acid is preferably 1 in step a：(1~1.5), most preferably 1：1.2；
The molar ratio of substituted benzaldehyde and pyridine is preferably 1：(1~5), most preferably 1：2.5；
The molar ratio of piperidines and pyridine is preferably 1：(10~50), most preferably 1：24；
Reaction temperature is 75 DEG C~95 DEG C, and the reaction time is 4~12 hours.
It is isolated and purified described in step a and refers to reaction product cooling down 10~20min, 1~5M cryosel acid solutions is added to be adjusted to
Acidity is placed no less than 2 hours, is filtered, water washing and precipitating must replace compounds derived from phenyl acrylic acid crude product, then be tied again with absolute ethyl alcohol
It is brilliant to replace compounds derived from phenyl acrylic acid sterling.
The sulfuric acid acidization tool of montmorillonite K-10 is preferably in step b：Montmorillonite K-10 is added in sulfuric acid solution and is made
Suspension is heated to reflux 3-6 hours, is filtered, and distillation is washed to neutrality, and acidification is completed after vacuum drying.
Sulfuric acid concentration is preferably 10%~35% (mass percent), and most preferably 30%；
It is preferably 5~12ml that every gram of montmorillonite, which needs sulfuric acid volume, most preferably 10ml；
90~100 DEG C of souring temperature, most preferably 95 DEG C；30~50 DEG C of vacuum drying temperature.
Replace compounds derived from phenyl acrylic acid in step b：Phenolic compound：The molar ratio of nitrobenzene is preferably 1：(1~
1.2)：(10~20), most preferably 1：1.1：19；Per 5mmol, substitution compounds derived from phenyl acrylic acid needs the amount of catalyst K-10 excellent
It is selected as 1~6g, most preferably 2g；Reaction temperature is 80~120 DEG C, 2~10 hours reaction time.
It is isolated and purified described in step b and refers to while hot filter esterification cyclization suspension, filtrate adds petroleum ether, natural
Cooling crystallization or low temperature stirring, filter, petroleum ether precipitates to obtain 3,4- dihydro -4- aryl-coumarin class crude compounds.Its
In, added petroleum ether amount is 1~5 times of nitrobenzene volume in filtrate.
Crude product petroleum ether-ethyl acetate of the purity less than 90% or acetone-water recrystallize to obtain sterling.
The preparation method of the 3,4- dihydro -4- aryl-coumarin class compounds of the present invention has following compared with prior art
Prominent advantageous effect：
(1) present invention reacts by Perkin using substituted benzaldehyde and polyphenol compound as starting material, is esterified ring
Change etc. reactions prepare 3,4- dihydro -4- aryl-coumarin class compounds, have it is easy to operate, the reaction time is short, isolates and purifies letter
The features such as single, green non-pollution, thus feasible process, conducive to popularization and application；
(2) low in raw material price, it is simple and easy to get, it is easy to industrial production.
Specific embodiment
The preparation method of the 3,4- dihydro -4- aryl-coumarin class compounds of the present invention is made with specific embodiment following detailed
Carefully illustrate.
Unless otherwise instructed, the content of following each ingredients used is mass percentage content.
Embodiment one：The preparation of acid montmorillonite K-10
13g montmorillonites K-10 is added in 130ml sulfuric acid solutions (mass concentration 30%), suspension is made, 90~100
It is heated to reflux 4 hours, filters at DEG C, distillation is washed to neutrality, is dried in vacuo at 40 DEG C, obtains 12.95g acid montmorillonites K-
10。
Embodiment two：The preparation of 4- (4'- methoxyphenyls) -7- hydroxyl -3,4- dihydrocoumarin
1st, 6.24g (60mmol) malonic acid is added in three mouthfuls of reaction bulbs of 100ml, 6ml (49.4mmol) is to methoxyl group
Benzaldehyde, 10ml (124mmol) pyridine, 0.5ml (5.1mmol) hexahydropyridine, flow back 7h after being heated to 80 DEG C, and reaction finishes,
10min is cooled down, adds in 60ml3mol/ml cryosel acid solutions, places a night, is filtered, is precipitated with 400ml water washings, obtains white
Crude product.Crude product is recrystallized with absolute ethyl alcohol, obtains white sterling 4- methoxyphenylpropenes acid 7.8g, yield 97.5%.
2nd, in three mouthfuls of reaction bulbs of 100ml, 0.89g (5mmol) 4- methoxyphenylpropenes acid, 0.6g are added in
(5.5mmol) resorcinol, 10ml (98mmol) nitrobenzene, stirs evenly, is heated to 100 DEG C, adds the acidification of 2g sulfuric acid
Montmorillonite K-10, TLC detection reaction process (solvent：Dichloromethane：Methanol=10：1) it, reacts and finishes after 3 hours, while hot mistake
It filters, in filtrate plus 20ml petroleum ethers, one night nature crystallization of placement filter, 20ml petroleum ethers precipitation, dry in vacuum drying chamber
It is dry to obtain white sterling 0.8g, yield 59.2%.
IR:3332(OH)；1736 (C=O)；3040,1614,1583,1507,1450,1105,1028,984,832 (benzene
Ring)；1236,1146(C-O)；2800(-OCH3).
1HNMR(600MHZ,DMSO-d6)δ：3.03(2H,m,C-3H),3.73(3H,s,OCH3), 4.32 (1H, t, J=
6.0Hz, C-4H), 6.53 (1H, dd, J=2.4and 8.4Hz, C-6H), 6.55 (1H, d, J=2.4Hz, C-8H), 6.84
(1H, d, J=8.4Hz, C-8H), (4H, 2 × d, J=1.8Hz, C-2'H, C-6'H, C-3'H the and C-5' of 6.90and 7.06
H),9.74(1H,s,OH)
Ms:m/Z:207.7[M+1]+,162.6.
Embodiment three：The preparation of 4- (3', 4'- Dimethoxyphenyl) -7- hydroxyl -3,4- dihydrocoumarin
1st, 6.24g (60mmol) malonic acid, 8.3g (50mmol) 3,4- dimethoxies are added in three mouthfuls of reaction bulbs of 100ml
Benzaldehyde, 10ml (124mmol) pyridine, 0.5ml (5.1mmol) hexahydropyridine, flow back 4h after being heated to 85 DEG C, has reacted
Finish, cool down 10min, add in 60ml3mol/ml cryosel acid solutions, place a night, filter, precipitated, obtained white with 400ml water washings
Color crude product.Crude product is recrystallized with absolute ethyl alcohol, obtains white sterling 3,4- dimethoxy phenylpropene acid 9.0g, yield 86.5%.
2nd, in three mouthfuls of reaction bulbs of 100ml, 1.04g (5mmol) 3,4- dimethoxy phenylpropenes acid, 0.6g are added in
(5.5mmol) resorcinol, 5ml (49mmol) nitrobenzene, stirs evenly, is heated to 100 DEG C, adds the illiteracy of 2g sulfuric acid acidification
De- soil K-10, TLC detection reaction process (solvent：Dichloromethane：Methanol=10：1) it, reacts and finishes after 5.5 hours, while hot mistake
It filters, in filtrate plus 20ml petroleum ethers, 3 days natural crystallizations of placement filter, 20ml petroleum ethers precipitate, ethyl acetate-light petrol
Recrystallize to obtain light yellow sterling 0.5g, yield 33.3%.
IR:3433(OH)；1767 (C=O)；3030,1628,1597,1514,1447,1101,1025,848,810 (benzene
Ring)；1267,1142(C-O)；2790(-OCH3).
1HNMR(600MHZ,DMSO-d6)δ：3.05(2H,m,C-3H),3.70and 3.71(6H,2×s,3H and 3H
each,2×OCH3), 4.29 (1H, t, J=6.0Hz, C-4H), 6.52 (1H, s, C-8H), 6.53-6.56 (2H, m, C-6'H,
C-5'H),6.83-6.89(3H,m,C-6H,C-2'H,C-5H),9.74(1H,s,OH).
Ms:m/Z:300.8[M+1]+,258.7,190.6,162.7.
Example IV：The preparation of 4- (3'- methoxyl group -4'- hydroxy phenyls) -7- hydroxyl -3,4- dihydrocoumarin
1st, addition 6.24g (60mmol) malonic acid in three mouthfuls of reaction bulbs of 100ml, 7.6g (50mmol) 3- methoxyl groups-
4- hydroxy benzaldehydes, 10ml (124mmol) pyridine, 0.5ml (5.1mmol) hexahydropyridine, flow back 12h after being heated to 75 DEG C, instead
It should finish, cool down 10min, add in 60ml3mol/ml cryosel acid solutions, place a night, filter, be precipitated, obtained with 400ml water washings
To white crude.Crude product is recrystallized with absolute ethyl alcohol, obtains white sterling 3- methoxyl groups -4- hydroxy phenyl acrylic acid 8.4g, yield
86.6%.
2nd, in three mouthfuls of reaction bulbs of 100ml, 0.97g (5mmol) 3- methoxyl group -4- hydroxy phenyl acrylic acid is added in,
0.6g (5.5mmol) resorcinol, 10ml (98mmol) nitrobenzene, stirs evenly, is heated to 100 DEG C, adds 2g sulfuric acid acid
Montmorillonite K-10, TLC the detection reaction process (solvent of change：Dichloromethane：Methanol=10：1) it, reacts and finishes after 3 hours, take advantage of
Heat filtering in filtrate plus 20ml petroleum ethers, is placed a night nature crystallization, is filtered, 20ml petroleum ethers precipitation, and ethyl acetate-
Petroleum ether recrystallizes, and filters, dry white sterling 0.5g, yield 34.9% in vacuum drying chamber.
IR:3415(OH)；1724 (C=O)；2994,1625,1602,1518,1454,1112,1028,841,809 (benzene
Ring)；1259,1152(C-O)；2929(-OCH3).
1HNMR(600MHz,DMSO-d6)δ:3.03(2H,m,C-3H),3.71(3H,s,OCH3), 4.24 (1H, t, J=
6.0Hz, C-4H), 6.44 (1H, d, J=7.8Hz, C-6H), 6.51 (1H, s, C-8H), 6.54 (1H, d, J=8.4, C-6'H),
6.70 (1H, d, J=7.8, C-5'H), 6.78 (1H, s, C-2'H), 6.84 (1H, d, J=7.8, C-5H), 8.93and 9.72
(2H,2×s,2×-OH).
Ms:m/Z:287.1[M+1]+,162.8.
Embodiment five：The preparation of 4- (4'- methoxyphenyls) -7,8- dihydroxy -3,4- dihydrocoumarin
4- methoxyphenylpropene acid preparation methods are identical with embodiment two.
In three mouthfuls of reaction bulbs of 100ml, 0.89g (5mmol) 4- methoxyphenylpropenes acid, 0.69g are added in
(5.5mmol) pyrogallol, 10ml (98mmol) nitrobenzene, stirs evenly, is heated to 100 DEG C, adds the acidification of 2g sulfuric acid
Montmorillonite K-10, TLC detection reaction process (solvent：Dichloromethane：Methanol=10：1) it, reacts and finishes after 10 hours, while hot
Filtering in filtrate plus 20ml petroleum ethers, is placed a night nature crystallization, is filtered, dry faint yellow sterling in vacuum drying chamber
0.85g, yield 59.4%.
IR:3330(OH)；1738 (C=O)；3050,1634,1612,1512,1458,1109,1030,1002,830,
802 (phenyl ring)；1236,1154(C-O)；2805(-OCH3).
1HNMR(400MHz,DMSO-d6)δ:3.01(2H,m,C-3H),3.72(6H,s,2×-OCH3),4.28(1H,t,J
=6.8Hz, C-4H), 6.28 (1H, d, J=8.0Hz, C-6H), 6.53 (1H, d, J=8.0Hz, C-5H), 6.88and 7.06
(4H, 2 × d, J=8.0Hz, C-2'H, C-6'H, C-3'H and C-5'H), 8.91and9.29 (2H, 2 × s, 2 ×-OH)
Ms:m/Z:286.8[M+1]+,244.6,178.6,160.6.
Embodiment six：The preparation of 4- (3', 4'- Dimethoxyphenyl) -7,8- dihydroxy -3,4- dihydrocoumarin
3,4- dimethoxy phenylpropene acid preparation methods are identical with embodiment three.
In three mouthfuls of reaction bulbs of 100ml, 0.52g (2.5mmol) 3,4- dimethoxy phenylpropenes acid, 0.35g are added in
(2.78mmol) pyrogallol, 5ml (49mmol) nitrobenzene, stirs evenly, is heated to 100 DEG C, adds the acidification of 1g sulfuric acid
Montmorillonite K-10, TLC detection reaction process (solvent：Dichloromethane：Methanol=10：1) it, reacts and finishes after 5 hours, while hot mistake
It filters, in filtrate plus 20ml petroleum ethers, one night nature crystallization of placement filter, 20ml petroleum ethers precipitation, ethyl acetate-pet
Ether recrystallizes, and filters, dry white sterling 0.5g, yield 63.3% in vacuum drying chamber.
IR:3423(OH)；1754 (C=O)；2935,1610,1515,1470,1413,1025,807 (phenyl ring)；1240,
1137(C-O)；2829(-OCH3).
1HNMR(600MHz,DMSO-d6)δ:3.03(2H,m,C-3H),3.70and 3.72(6H,2×s,3H and 3H
each,2×OCH3), 4.24 (1H, dd, J=7.6Hz and 6.4Hz, C-4H), 6.41,6.64,6.66and 6.80 (4H, 4
× d, J=8.4Hz, C-6'H, C-5'H, C-6H, C-5H), 6.94 (1H, s, C-2'H), 8.92and9.29 (2H, 2 × s, 2 ×-
OH)
Ms:m/Z:316.8[M+1]+,178.5.
Embodiment seven：The preparation of 4- (3'- hydroxyl -4'- methoxyphenyls) -7,8- dihydroxy -3,4- dihydrocoumarin
1st, 6.24g (60mmol) malonic acid, 7.6g (50mmol) 3- hydroxyls -4- are added in three mouthfuls of reaction bulbs of 100ml
Methoxybenzaldehyde, 10ml (124mmol) pyridine, 0.5ml (5.1mmol) hexahydropyridine, flow back 5h after being heated to 80 DEG C, reaction
It finishes, cools down 10min, add in 60ml3mol/ml cryosel acid solutions, place a night, filter, precipitated, obtained with 400ml water washings
White crude.Crude product is recrystallized with absolute ethyl alcohol, obtains white sterling 3- hydroxyls -4- methoxyphenylpropene acid 8.6g, yield
88.6%.
2nd, in three mouthfuls of reaction bulbs of 100ml, 0.97g (5mmol) 3- hydroxyl -4- methoxyphenylpropenes acid is added in,
0.69g (5.5mmol) pyrogallol, 10ml (98mmol) nitrobenzene, stirs evenly, is heated to 100 DEG C, adds 2g sulfuric acid acid
Montmorillonite K-10, TLC the detection reaction process (solvent of change：Dichloromethane：Methanol=10：1) it, reacts and finishes after 10 hours,
It filters while hot, in filtrate plus 20ml petroleum ethers, one night nature crystallization of placement filter, 20ml petroleum ethers precipitation, acetic acid second
Ester-petroleum ether recrystallization, dry white sterling 0.70g, yield 46.4% in vacuum drying chamber.
IR:3499,3420(OH)；1752 (C=O)；3010,1610,1591,1518,1469,1030,786,698 (benzene
Ring)；1277,1068(C-O)；2810(-OCH3).
1HNMR(600MHz,DMSO-d6)δ:2.97(2H,m,C-3H),3.72(3H,s,OCH3), 4.19 (1H, t, J=
5.4Hz, C-4H), 6.32 (1H, d, 7.8Hz, C-6H), 6.51,6.53and 6.54 (3H, 3 × d, J=6.0Hz, C-5H, C-
6'H and C-2'H), 6.84 (1H, d, J=7.8Hz, C-5'H), 8.90,8.95and 9.29 (3H, 3 × s, 3 ×-OH)
Ms:m/Z:302.9[M+1]+,283.7,260.7,178.6,150.6.
Embodiment eight：The preparation of 4- (3', 4'- Dimethoxyphenyl) -5,7- dihydroxy -3,4- dihydrocoumarin
3,4- dimethoxy phenylpropene acid preparation methods are identical with embodiment three.
In three mouthfuls of reaction bulbs of 100ml, 0.52g (2.5mmol) 3,4- dimethoxy phenylpropenes acid, 0.35g are added in
(2.78mmol) phloroglucin, 10ml (98mmol) nitrobenzene, stirs evenly, is heated to 100 DEG C, adds the acidification of 1g sulfuric acid
Montmorillonite K-10, TLC detection reaction process (solvent：Dichloromethane：Methanol=10：1) it, reacts and finishes after 7 hours, while hot mistake
It filters, 20ml petroleum ethers is added in filtrate, stand overnight nature crystallization, filter, 20ml petroleum ethers precipitation, ethyl acetate-pet
Ether recrystallizes, dry white sterling 0.33g, yield 41.8% in vacuum drying chamber.
IR:3402,(OH)；1778 (C=O)；1632,1610,1500,1460,1012,825 (phenyl ring)；1237,1148
(C-O).
1HNMR(600MHz,DMSO-d6)δ:3.02(2H,m,C-3H),3.68and 3.70(6H,2×s,3H and 3H
each,2×OCH3), 4.37 (1H, d, J=6.6Hz, C-4H), 6.01 (1H, s, C-6H), 6.17 (1H, s, C-8H), 6.40
(1H, d, J=8.4Hz, C-6'H), 6.81 (2H, d, J=9.6Hz, C-2'H and C-5'H), 9.56and 9.74 (2H, 2 ×
s,2×-OH).
Ms:m/Z:316.9[M+1]+,178.7,164.7,110.8.
Embodiment nine：The preparation of 4- (3'- methoxyl group -4'- hydroxy phenyls) -5,7- dihydroxy -3,4- dihydrocoumarin
3- methoxyl group -4- hydroxy phenyl method for producing acrylic acid is identical with example IV.
In three mouthfuls of reaction bulbs of 100ml, 0.97g (5mmol) 3- methoxyl group -4- hydroxy phenyl acrylic acid, 0.69g are added in
(5.5mmol) phloroglucin, 10ml (98mmol) nitrobenzene, stirs evenly, is heated to 100 DEG C, adds the acidification of 2g sulfuric acid
Montmorillonite K-10, TLC detection reaction process (solvent：Dichloromethane：Methanol=10：1) it, reacts and finishes after 5 hours, while hot mistake
It filters, 20ml petroleum ethers is added in filtrate, stand overnight nature crystallization, filter, 20ml petroleum ethers precipitation, ethyl acetate-pet
Ether recrystallizes, dry white sterling 0.5g, yield 33.1% in vacuum drying chamber.
IR:3404,(OH)；1767 (C=O)；3030,1628,1597,1514,1447,1101,1025,848,810 (benzene
Ring)；1267,1142(C-O),2790(-OCH3).
1HNMR(600MHz,DMSO-d6)δ:3.01(2H,m,C-3H),3.70(3H,s,3H,OCH3),4.33(1H,d,J
=6.6Hz, C-4H), 6.00 (1H, s, C-6H), 6.16 (1H, s, C-8H), 6.30 (1H, d, J=7.8Hz, C-6'H), 6.62
(1H, d, J=8.4Hz, C-5'H), 6.75 (1H, s, C-2'H), 8.91,9.54and9.72,3H, 3 × s, 3 ×-OH)
Ms:m/Z:303.1[M+1]+,261.1,179.1,151.1,111.2.
Embodiment ten：Catalyst montmorillonite K-10 is recycled
1st, the method for recycling montmorillonite K-10 in one the method for embodiment：After being esterified cyclization, suspension is taken advantage of
Heat filtering, filter residue are placed in drying in 40 DEG C of vacuum drying chambers, and recycling obtains the acid montmorillonite K-10 that can be reused；
2nd, 4- (4'- methoxyphenyls) -7- hydroxyl -3,4- dihydrocoumarin is catalyzed and synthesized with above-mentioned recycling montmorillonite
In three mouthfuls of reaction bulbs of 100ml, 0.89g (5mmol) 4- methoxyphenylpropenes acid, 0.6g are added in
(5.5mmol) resorcinol, 10ml (98mmol) nitrobenzene, stirs evenly, is heated to 100 DEG C, adds 2g recycling montmorillonites
K-10, TLC detect reaction process (solvent：Dichloromethane：Methanol=10：1), reaction terminates to filter while hot, adds in filtrate
20ml petroleum ethers place a night nature crystallization, filter, 20ml petroleum ethers precipitation, dry 4- (4'- in vacuum drying chamber
Methoxyphenyl) -7- hydroxyl -3,4- dihydrocoumarin；
3rd, it repeats above-mentioned recycling, utilize process.
Claims (5)
1. one kind 3, the preparation method of 4- dihydro -4- aryl-coumarin class compounds, it is characterised in that：This method is with substituted benzoyl
Aldehyde is starting material, under the catalysis of piperidines, adds in malonic acid generation substituted phenyl acrylic acid derivative；The illiteracy being acidified with sulfuric acid
De- soil K-10 is catalyst, and substituted phenyl acrylic acid derivative reacts generating structure formula (I) expression with phenolic compound heating
3,4- dihydro -4- aryl-coumarin class compounds,
Wherein, R1、R2、R3、R4For H or OH；
R5、R6、R7For H, OH or OCH3,
Above-mentioned preparation method includes the following steps：
A, using substituted benzaldehyde as starting material, in pyridine solution, malonic acid is added in, using piperidines as catalyst, heating occurs
Perkin condensation reactions obtain substitution compounds derived from phenyl acrylic acid through isolating and purifying；
B, using nitrobenzene as solvent, compounds derived from phenyl acrylic acid and phenolic compound is replaced to be urged in the montmorillonite K-10 that sulfuric acid is acidified
Under change, esterification cyclization occurs, then through isolating and purifying to obtain 3,4- dihydro -4- aryl-coumarin class compounds；
The sulfuric acid acidization tool of montmorillonite K-10 is：
Montmorillonite K-10 being added in sulfuric acid solution, suspension is made, be heated to reflux 3-6 hours, filtered, distillation is washed to neutrality,
Acidification is completed after vacuum drying,
Sulfuric acid concentration is 10%~35%；It is 5~12ml that every gram of montmorillonite, which needs sulfuric acid volume,；
90~100 DEG C of souring temperature；
30~50 DEG C of vacuum drying temperature.
2. the preparation method of 3,4- dihydros -4- aryl-coumarin class compounds according to claim 1, it is characterised in that：
This method includes the recycling of catalyst montmorillonite K-10.
3. the preparation method of 3,4- dihydros -4- aryl-coumarin class compounds according to claim 2, which is characterized in that
The recoverying and utilizing method of catalyst montmorillonite K-10 is：To be esterified in step b the filter residue after the filtering of cyclization liquid be placed in 30~
It is dry in 50 DEG C of vacuum drying chambers, it may be directly applied to catalyze and synthesize same 3,4- dihydros -4- aryl-coumarins after dry
Class compound.
4. the preparation method of 3,4- dihydros -4- aryl-coumarin class compounds according to claim 1 or 2, feature exist
The molar ratio of substituted benzaldehyde and malonic acid is 1 in step a：(1~1.5)；
The molar ratio of substituted benzaldehyde and pyridine is 1：(1~5)；
The molar ratio of piperidines and pyridine is 1：(10~50)；
Reaction temperature is 75 DEG C~95 DEG C, and the reaction time is 4~12 hours.
5. the preparation method of 3,4- dihydros -4- aryl-coumarin class compounds according to claim 1 or 2, feature exist
Replace compounds derived from phenyl acrylic acid in step b：Phenolic compound：The molar ratio of nitrobenzene is 1：(1~1.2)：(10~20)；
It is 1~6g that per 5mmol, substitution compounds derived from phenyl acrylic acid, which needs the amount of catalyst K-10,；Reaction temperature is 80~120 DEG C, reaction
2~10 hours time.
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