CN106554254A - A kind of synthetic method of 2,3 ', 4,5 ' tetrahydroxy bibenzyl of natural product - Google Patents
A kind of synthetic method of 2,3 ', 4,5 ' tetrahydroxy bibenzyl of natural product Download PDFInfo
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- CN106554254A CN106554254A CN201610860101.5A CN201610860101A CN106554254A CN 106554254 A CN106554254 A CN 106554254A CN 201610860101 A CN201610860101 A CN 201610860101A CN 106554254 A CN106554254 A CN 106554254A
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- tetrahydroxy
- bibenzyl
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- 229930014626 natural product Natural products 0.000 title claims abstract description 47
- 238000010189 synthetic method Methods 0.000 title claims abstract description 15
- IEOZKGCYMAJAHS-UHFFFAOYSA-N 2,3',4,5'-Tetrahydroxystilbene Natural products OC1=CC(O)=CC=C1CCC1=CC(O)=CC(O)=C1 IEOZKGCYMAJAHS-UHFFFAOYSA-N 0.000 title claims description 20
- 238000006243 chemical reaction Methods 0.000 claims abstract description 57
- 150000003935 benzaldehydes Chemical class 0.000 claims abstract description 16
- 238000006482 condensation reaction Methods 0.000 claims abstract description 8
- 239000002994 raw material Substances 0.000 claims abstract description 4
- 239000012065 filter cake Substances 0.000 claims description 54
- -1 3,5-dihydroxy phenyl Chemical group 0.000 claims description 49
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 45
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 44
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 44
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 42
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 42
- 239000002904 solvent Substances 0.000 claims description 40
- 239000007787 solid Substances 0.000 claims description 38
- 238000003756 stirring Methods 0.000 claims description 38
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 35
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 33
- 238000001914 filtration Methods 0.000 claims description 31
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 claims description 24
- 238000001953 recrystallisation Methods 0.000 claims description 24
- IOVOJJDSFSXJQN-UHFFFAOYSA-N (3,5-dihydroxyphenyl)acetic acid Chemical class OC(=O)CC1=CC(O)=CC(O)=C1 IOVOJJDSFSXJQN-UHFFFAOYSA-N 0.000 claims description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 16
- 239000003513 alkali Substances 0.000 claims description 15
- PGXWDLGWMQIXDT-UHFFFAOYSA-N methylsulfinylmethane;hydrate Chemical compound O.CS(C)=O PGXWDLGWMQIXDT-UHFFFAOYSA-N 0.000 claims description 13
- 238000005406 washing Methods 0.000 claims description 13
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- 239000003054 catalyst Substances 0.000 claims description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 8
- 238000005984 hydrogenation reaction Methods 0.000 claims description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 6
- HUCVOHYBFXVBRW-UHFFFAOYSA-M caesium hydroxide Chemical compound [OH-].[Cs+] HUCVOHYBFXVBRW-UHFFFAOYSA-M 0.000 claims description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 6
- 239000000376 reactant Substances 0.000 claims description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 6
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 5
- 229910000564 Raney nickel Inorganic materials 0.000 claims description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 230000000694 effects Effects 0.000 claims description 4
- PDHAOJSHSJQANO-OWOJBTEDSA-N Oxyresveratrol Chemical compound OC1=CC(O)=CC=C1\C=C\C1=CC(O)=CC(O)=C1 PDHAOJSHSJQANO-OWOJBTEDSA-N 0.000 claims description 3
- 229920001030 Polyethylene Glycol 4000 Polymers 0.000 claims description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 3
- BQFCCCIRTOLPEF-UHFFFAOYSA-N chembl1976978 Chemical compound CC1=CC=CC=C1N=NC1=C(O)C=CC2=CC=CC=C12 BQFCCCIRTOLPEF-UHFFFAOYSA-N 0.000 claims description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 3
- 239000001632 sodium acetate Substances 0.000 claims description 3
- 235000017281 sodium acetate Nutrition 0.000 claims description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
- 208000035126 Facies Diseases 0.000 claims description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical group [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- YHASWHZGWUONAO-UHFFFAOYSA-N butanoyl butanoate Chemical compound CCCC(=O)OC(=O)CCC YHASWHZGWUONAO-UHFFFAOYSA-N 0.000 claims description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 239000000706 filtrate Substances 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 238000012805 post-processing Methods 0.000 claims description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 claims 2
- YSMRWXYRXBRSND-UHFFFAOYSA-N TOTP Chemical compound CC1=CC=CC=C1OP(=O)(OC=1C(=CC=CC=1)C)OC1=CC=CC=C1C YSMRWXYRXBRSND-UHFFFAOYSA-N 0.000 claims 1
- 239000012153 distilled water Substances 0.000 claims 1
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 claims 1
- 239000003208 petroleum Substances 0.000 claims 1
- 239000011591 potassium Substances 0.000 claims 1
- 229910052700 potassium Inorganic materials 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 6
- VKVOJYUPJRVDPP-UHFFFAOYSA-N 2,2-dihydroxy-2-phenylacetic acid Chemical class OC(=O)C(O)(O)C1=CC=CC=C1 VKVOJYUPJRVDPP-UHFFFAOYSA-N 0.000 abstract 1
- RSNNHDKEOIZSOG-UHFFFAOYSA-N 3-(3,5-dihydroxyphenyl)-7-hydroxychromen-2-one Chemical compound O=C1OC2=CC(O)=CC=C2C=C1C1=CC(O)=CC(O)=C1 RSNNHDKEOIZSOG-UHFFFAOYSA-N 0.000 abstract 1
- NSRKPHLHEMCETL-UHFFFAOYSA-N 5-(2-phenylethenyl)benzene-1,2,3,4-tetrol Chemical class OC1=C(O)C(O)=CC(C=CC=2C=CC=CC=2)=C1O NSRKPHLHEMCETL-UHFFFAOYSA-N 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 description 36
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 24
- 238000001035 drying Methods 0.000 description 24
- 239000001257 hydrogen Substances 0.000 description 14
- 229910052739 hydrogen Inorganic materials 0.000 description 14
- 235000011121 sodium hydroxide Nutrition 0.000 description 14
- QWUWMCYKGHVNAV-UHFFFAOYSA-N 1,2-dihydrostilbene Chemical group C=1C=CC=CC=1CCC1=CC=CC=C1 QWUWMCYKGHVNAV-UHFFFAOYSA-N 0.000 description 13
- 239000007864 aqueous solution Substances 0.000 description 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 13
- 238000010790 dilution Methods 0.000 description 12
- 239000012895 dilution Substances 0.000 description 12
- 238000010438 heat treatment Methods 0.000 description 12
- 239000012044 organic layer Substances 0.000 description 12
- 239000012298 atmosphere Substances 0.000 description 11
- 238000003810 ethyl acetate extraction Methods 0.000 description 10
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 150000003839 salts Chemical class 0.000 description 6
- 239000000126 substance Substances 0.000 description 5
- 150000002431 hydrogen Chemical class 0.000 description 4
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 3
- 239000002024 ethyl acetate extract Substances 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- 241000219321 Caryophyllaceae Species 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 241000283966 Pholidota <mammal> Species 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 1
- 208000005577 Gastroenteritis Diseases 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 238000006546 Horner-Wadsworth-Emmons reaction Methods 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 238000006069 Suzuki reaction reaction Methods 0.000 description 1
- 102000003425 Tyrosinase Human genes 0.000 description 1
- 108060008724 Tyrosinase Proteins 0.000 description 1
- 230000003064 anti-oxidating effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 229910001950 potassium oxide Inorganic materials 0.000 description 1
- 239000010970 precious metal Substances 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 108091006073 receptor regulators Proteins 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 1
- 235000019798 tripotassium phosphate Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/001—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by modification in a side chain
- C07C37/003—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by modification in a side chain by hydrogenation of an unsaturated part
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/01—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis
- C07C37/055—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis the substituted group being bound to oxygen, e.g. ether group
- C07C37/0555—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis the substituted group being bound to oxygen, e.g. ether group being esterified hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/06—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2
- C07D311/08—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring
- C07D311/16—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring substituted in position 7
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a kind of natural product 2,3 ', 4, the synthetic method of 5 ' tetrahydroxy bibenzyls, is 5 dihydroxyphenyl acetic acids and 2 with 3,4 4-dihydroxy benzaldehydes are raw material, condensation reaction occurs in the presence of a base and obtains 3 (3,5-dihydroxy phenyl) 7 Hydroxycoumarin, again Jing after the open loop decarboxylic reaction under alkalescence condition, E 2,3 ' is obtained, 4,5 ' tetrahydroxystilbenes, last hydrogenated reaction obtain natural product 2,3 ', 4,5 ' tetrahydroxy bibenzyls.This method raw material is simple and easy to get, and reaction scheme is simple and direct, and Atom economy is high, and simple in after-treatment, yield are higher.
Description
Technical field
The present invention relates to organic synthesis field, more particularly to a kind of natural product 2,3 ', 4, the synthesis of 5 '-tetrahydroxy bibenzyl
Method.
Background technology
2,3 ', 4,5 '-tetrahydroxy bibenzyl is isolated a kind of natural product from Pholidota plant
(Pholidota), while in Caryophyllaceae (Caryophyllaceae) plant speciess it has also been found that its presence, is natural product E-2,3 ',
The hydrogenated derivatives of 4,5 '-tetrahydroxystilbene.2,3 ', 4,5 '-tetrahydroxy bibenzyl has extremely strong tryrosinase
(Tyrosinase) inhibitory activity and antioxidation (Antioxidant) activity, research also find which can be used as γ-aminobutyric acid A
Receptor regulator (Nat.Prod.Rep.2009,26,916；Nat.Prod.Rep.2012,29；J.Nat.Prod.2012,75
2261；J.Phytochemistry 2008,69,1084；Bioorg.Med.Chem.2014,22,1276–1284；
Bioorg.Med.Chem.Lett.2006,16,5650-5653), therefore, 2,3 ', 4,5 '-tetrahydroxy bibenzyl is expected to anti-frightened
Faint, resisting hypertension and treatment headache, gastroenteritis, bronchitis are obtained and extensively applied.Relevant 2,3 ', 4,5 '-tetrahydroxy bibenzyl
The synthesis of compound, document report is reacted generally by Wittig, Wittig-Horner reacts, Suzuki cross-coupling reactions
And the method such as Perkin condensation reactions prepares E-2 first, 3 ', 4,5 '-tetrahydroxystilbene, then by hydrogenation system
Standby 2,3 ', 4,5 '-tetrahydroxy bibenzyl, but these methods exist reactions steps length, high cost, catalyst can not recycle,
Intermediate need protection with deprotection, Atom economy is poor, be difficult to prepare with scale the shortcomings of.
The content of the invention
It is an object of the invention to overcome shortcoming present in prior art, there is provided a kind of environmental friendliness, low cost, technique
The synthetic method of simple natural product 2,3 ', 4,5 '-tetrahydroxy bibenzyl.
The purpose of the present invention is achieved through the following technical solutions：
A kind of natural product 2,3 ', 4, the synthetic method of 5 '-tetrahydroxy bibenzyl comprises the steps：
(1) with 3,5- dihydroxyphenyl acetic acids (structural formula 1) and 2,4- 4-dihydroxy benzaldehyde (structural formula 2) for raw material, molten
In agent A, in the presence of alkali A, there is condensation reaction and obtain 3- (3,5-dihydroxy phenyl)-umbelliferone (structural formula 3)；
(2) in solvent B, under the conditions of alkali B, there is open loop decarboxylation in 3- (3,5-dihydroxy phenyl)-umbelliferone
Reaction, it is post-treated to obtain E-2,3 ', 4,5 '-tetrahydroxystilbene (structural formula 4)；
(3) in solvent C, under catalyst C effects, E-2,3 ', 4, there is hydrogenation in 5 '-tetrahydroxystilbene,
Obtain natural product 2,3 ', 4,5 '-tetrahydroxy bibenzyl (structural formula 5).
In step (1), the reactant liquor obtained after condensation reaction is poured in frozen water, stirring, sucking filtration, washes filter cake, and filter cake is used
Sodium hydrate aqueous solution dissolves, and is washed with ethyl acetate, is acidified to pH=3～4 with hydrochloric acid, separates out solid, and sucking filtration, washing are received
Collection filter cake, obtains 3- (3,5-dihydroxy phenyl)-umbelliferone after being dried.
In step (2), the post processing is that the reactant liquor that decarboxylic reaction is obtained is cooled to room temperature, is acidified to pH with hydrochloric acid
=3～4, ethyl acetate extraction is collected organic faciess, is dried, removes solvent, use alcohol-water recrystallization, obtain E-2,3 ', 4,5 '-
Tetrahydroxystilbene.
In step (3), the reactant mixture that hydrogenation is obtained carries out sucking filtration, reclaims catalyst, collects filtrate, is dried,
Solvent is removed, ethyl acetate-light petrol recrystallization obtains natural product 2,3 ', 4,5 '-tetrahydroxy bibenzyl.
In step (1), solvent orange 2 A is including but not limited to acetic anhydride, propionic andydride, butyryl oxide., and preferred solvent A is acetic anhydride；
Alkali A is including but not limited to sodium acetate, Sodium ethylate, triethylamine, 1,8- diazabicylos, 11 carbon -7- alkene (DBU), preferred alkali A
For triethylamine.
In step (1), the temperature of condensation reaction is 100～140 DEG C, and preferable reaction temperature is 110 DEG C；Response time is 5
～9 hours, preferred reaction time was 7 hours.
In step (1), 3,5- dihydroxyphenyl acetic acids, 2,4- 4-dihydroxy benzaldehydes, the mol ratio of alkali A are 1：(1.0～
1.2)：(2～4), preferably 3,5- dihydroxyphenyl acetic acids, 2,4- 4-dihydroxy benzaldehydes, the mol ratio of alkali A are 1：1：3.
In step (2), alkali B is including but not limited to sodium bicarbonate, sodium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide, hydrogen
Potassium oxide, Cesium hydrate., tripotassium phosphate, triethylamine, preferred alkali B are potassium hydroxide；Solvent B includes but are not limited to be distillation
Water, dimethyl sulfoxide (DMSO), PEG-4000 (PEG-400), ethylene glycol, (volume ratio is 3 to dimethyl sulfoxide-water：1)、N,N-
Dimethylformamide, preferred solvent B are that (volume ratio is 3 to dimethyl sulfoxide-water：1).
In step (2), the temperature of decarboxylic reaction is 100～180 DEG C, and preferable reaction temperature is 160 DEG C；Response time is 1
～3 hours, preferred reaction time was 2 hours.
In step (2), 3- (3,5-dihydroxy phenyl)-umbelliferone, the mol ratio of alkali B are 1：(5～15), preferably
3- (3,5-dihydroxy phenyl)-umbelliferone, the mol ratio of alkali B are 1：10.
In step (3), the time of hydrogenation is 1～8 hour, and preferred reaction time is 3 hours.
In step (3), solvent C is including but not limited to methanol, ethanol, isopropanol, acetone, tetrahydrofuran, preferred solvent
For methanol；Catalyst C is including but not limited to Raney's nickel, palladium carbon, and preferred catalyst is palladium carbon.
Chemical equation according to the present invention is as follows：
The present invention is had the advantage that and effect compared with prior art：
(1) course of reaction of the invention is without using precious metal catalyst, without the need for protective group, easy to operate, yield is high,
Atom economy is good, overall process environmental protection.
(2) initiation material of the invention, reagent, solvent are cheap and easy to get, and intermediate complicated need not be isolated and purified just
Next step reaction can be put into, is conducive to prepare with scale.
Description of the drawings
Fig. 1 is proton nmr spectra (400MHz, the DMSO-d of 2,3 ', 4,5 '-tetrahydroxy bibenzyl6)；
Fig. 2 is carbon-13 nmr spectra (100MHz, the DMSO-d of 2,3 ', 4,5 '-tetrahydroxy bibenzyl6)。
Specific embodiment
Further detailed description, but embodiments of the present invention not limited to this are done to the present invention with reference to embodiment.
Embodiment 1
(1) preparation of 3- (3,5-dihydroxy phenyl)-umbelliferone
3,5- dihydroxyphenyl acetic acids (2.52g, 15mmol), 2,4- 4-dihydroxy benzaldehydes are added in round-bottomed flask
(2.07g, 15mmol), triethylamine (4.55g, 45mmol), acetic anhydride (10mL), stirring, to 110 DEG C, reaction 7 is little for oil bath heating
When.After completion of the reaction, reacting liquor while hot is poured in 50mL frozen water, stirs, have solid to separate out, sucking filtration washes filter cake, collects filter
Cake, filter cake sodium hydrate aqueous solution dissolve, and are washed with ethyl acetate, are acidified to pH=3～4 with hydrochloric acid, separate out solid, take out
Filter cake is collected in filter, washing, obtains faint yellow solid, be 3- (3,5-dihydroxy phenyl)-umbelliferone after being dried, weight
3.24g, yield 80%.
(2) E-2,3 ', the preparation of 4,5 '-tetrahydroxystilbene
3- (3,5-dihydroxy phenyl)-umbelliferone (1.35g, 5mmol), potassium hydroxide are put into in round-bottomed flask
(2.80g, 50mmol), dimethyl sulfoxide-water (15ml-5ml), 160 DEG C of backflow 2h of oil bath, reaction is finished, plus the dilution of 50ml water, salt
Acid is acidified to pH=3～4, ethyl acetate extraction (10ml × 3), collected organic layer, anhydrous sodium sulfate drying, solvent evaporated, second
Alcohol-water recrystallization, obtains E-2, and 3 ', 4,5 '-tetrahydroxystilbene, weight 0.93g, yield 76%.1H NMR(400MHz,
DMSO-d6) δ 9.58 (s, 1H), 9.40 (s, 1H), 9.15 (s, 2H), 7.34 (d, J=8.4Hz, 1H), 7.14 (d, J=
16.4Hz, 1H), 6.76 (d, J=16.5Hz, 1H), 6.33 (d, J=5.6Hz, 3H), 6.24 (d, J=8.1Hz, 1H), 6.07
(s,1H)；13C NMR(100MHz,DMSO-d6)δ158.96,158.58,156.49,140.49,127.61,125.08,
123.64,115.72,107.68,104.45,103.03,101.82.
(3) preparation of 2,3 ', 4,5 '-tetrahydroxy of natural product bibenzyl
Add E-2 in round-bottomed flask, 3 ', 4,5 '-tetrahydroxystilbene (1.22g, 5mmol) adds 10ml first
Alcohol stirs dissolving, and 10% palladium carbon (61mg), atmosphere of hydrogen room temperature reaction 3 at one atm are added under condition of ice bath
Hour, sucking filtration reclaims palladium carbon, and anhydrous sodium sulfate drying, solvent evaporated, ethyl acetate-light petrol recrystallization obtain natural product
2,3 ', 4,5 '-tetrahydroxy bibenzyl, weight 1.11g, yield 90%.1H NMR(400MHz,DMSO-d6)δ9.13(s,1H),9.05
(s, 2H), 8.97 (s, 1H), 6.79 (d, J=8.2Hz, 1H), 6.27 (d, J=2.3Hz, 1H), 6.11 (dd, J=8.1,
2.3Hz, 1H), 6.07 (d, J=2.0Hz, 2H), 6.01 (t, J=2.0Hz, 1H), 2.56 (dt, J=9.1,5.3Hz, 4H) are (such as
Shown in Fig. 1).13C NMR(100MHz,DMSO-d6)δ158.61,156.74,156.15,144.79,130.40,118.83,
(106.78,106.28,102.80,100.43,36.59,31.61 as shown in Figure 2).
Embodiment 2
(1) preparation of 3- (3,5-dihydroxy phenyl)-umbelliferone
3,5- dihydroxyphenyl acetic acids (2.52g, 15mmol), 2,4- 4-dihydroxy benzaldehydes are added in round-bottomed flask
(2.07g, 15mmol), triethylamine (4.55g, 45mmol), propionic andydride (10mL), stirring, to 110 DEG C, reaction 7 is little for oil bath heating
When.After completion of the reaction, reacting liquor while hot is poured in 50mL frozen water, stirs, have solid to separate out, sucking filtration washes filter cake, collects filter
Cake, filter cake sodium hydrate aqueous solution dissolve, and are washed with ethyl acetate, are acidified to pH=3～4 with hydrochloric acid, separate out solid, take out
Filter cake is collected in filter, washing, obtains faint yellow solid, be 3- (3,5-dihydroxy phenyl)-umbelliferone after being dried, weight
2.75g, yield 68%.
(2) E-2,3 ', the preparation of 4,5 '-tetrahydroxystilbene
3- (3,5-dihydroxy phenyl)-umbelliferone (1.35g, 5mmol), potassium hydroxide are put into in round-bottomed flask
(2.80g, 50mmol), dimethyl sulfoxide-water (20ml, 3:1), 120 DEG C of backflow 2h of oil bath, reaction is finished, plus the dilution of 50ml water, salt
Acid is acidified to PH=3～4, ethyl acetate extraction (10ml × 3), collected organic layer, anhydrous sodium sulfate drying, solvent evaporated, second
Alcohol-water recrystallization, obtains E-2, and 3 ', 4,5 '-tetrahydroxystilbene, weight 0.60g, yield 49%.
(3) preparation of 2,3 ', 4,5 '-tetrahydroxy of natural product bibenzyl
Add E-2 in round-bottomed flask, 3 ', 4,5 '-tetrahydroxystilbene (1.22g, 5mmol) adds 10ml second
Alcohol stirs dissolving, and 10% palladium carbon (61mg) is added under condition of ice bath, and in atmosphere of hydrogen at one atm, room temperature is anti-
Answer 3 hours, sucking filtration, reclaim palladium carbon, anhydrous sodium sulfate drying, solvent evaporated, ethyl acetate-light petrol recrystallization obtain natural
Product 2,3 ', 4,5 '-tetrahydroxy bibenzyl, weight 1.08g, yield 88%.
Embodiment 3
(1) preparation of 3- (3,5-dihydroxy phenyl)-umbelliferone
3,5- dihydroxyphenyl acetic acids (2.52g, 15mmol), 2,4- 4-dihydroxy benzaldehydes are added in round-bottomed flask
(2.07g, 15mmol), triethylamine (4.55g, 45mmol), acetic anhydride (10mL), stirring, to 110 DEG C, reaction 9 is little for oil bath heating
When.After completion of the reaction, reacting liquor while hot is poured in 50mL frozen water, stirs, have solid to separate out, sucking filtration washes filter cake, collects filter
Cake, filter cake sodium hydrate aqueous solution dissolve, and are washed with ethyl acetate, are acidified to pH=3～4 with hydrochloric acid, separate out solid, take out
Filter cake is collected in filter, washing, obtains faint yellow solid, be 3- (3,5-dihydroxy phenyl)-umbelliferone after being dried, weight
2.87g, yield 71%.
(2) E-2,3 ', the preparation of 4,5 '-tetrahydroxystilbene
3- (3,5-dihydroxy phenyl)-umbelliferone (1.35g, 5mmol), potassium hydroxide are put into in round-bottomed flask
(2.80g, 50mmol), dimethyl sulfoxide-water (20ml, 3:1), 2h is reacted at 180 DEG C, reaction is finished, plus the dilution of 50ml water, hydrochloric acid
PH=3～4 are acidified to, ethyl acetate extracts (10ml × 3), collected organic layer, anhydrous sodium sulfate drying, solvent evaporated, ethanol-
Water recrystallization, obtains E-2, and 3 ', 4,5 '-tetrahydroxystilbene, weight 1.04g, yield 70%.
(3) preparation of 2,3 ', 4,5 '-tetrahydroxy of natural product bibenzyl
Add E-2 in round-bottomed flask, 3 ', 4,5 '-tetrahydroxystilbene (1.22g, 5mmol) adds 10ml second
Alcohol stirs dissolving, and 10% palladium carbon (61mg) is added under condition of ice bath, and in atmosphere of hydrogen at one atm, room temperature is anti-
Answer 1 hour, sucking filtration, reclaim palladium carbon, anhydrous sodium sulfate drying, solvent evaporated, ethyl acetate-light petrol recrystallization obtain natural
Product 2,3 ', 4,5 '-tetrahydroxy bibenzyl, weight 0.86g, yield 70%.
Embodiment 4
(1) preparation of 3- (3,5-dihydroxy phenyl)-umbelliferone
To in round-bottomed flask, 3,5- dihydroxyphenyl acetic acids (2.52g, 15mmol), 2,4- 4-dihydroxy benzaldehydes are added
(2.07g, 15mmol), triethylamine (4.55g, 45mmol), acetic anhydride (10mL), stirring, to 110 DEG C, reaction 5 is little for oil bath heating
When.After completion of the reaction, reacting liquor while hot is poured in 50mL frozen water, stirs, have solid to separate out, sucking filtration washes filter cake, collects filter
Cake, filter cake sodium hydrate aqueous solution dissolve, and are washed with ethyl acetate, are acidified to pH=3～4 with hydrochloric acid, separate out solid, take out
Filter cake is collected in filter, washing, obtains faint yellow solid, be 3- (3,5-dihydroxy phenyl)-umbelliferone after being dried, weight
2.03g, yield 50%.
(2) E-2,3 ', the preparation of 4,5 '-tetrahydroxystilbene
3- (3,5-dihydroxy phenyl)-umbelliferone (1.35g, 5mmol), potassium hydroxide are put into in round-bottomed flask
(2.80g, 50mmol), dimethyl sulfoxide-water (20ml, 3:1), 160 DEG C of backflow 1h of oil bath, reaction is finished, plus the dilution of 50ml water, salt
Acid is acidified to PH=3～4, ethyl acetate extraction (10ml × 3), collected organic layer, anhydrous sodium sulfate drying, solvent evaporated, second
Alcohol-water recrystallization, obtains E-2, and 3 ', 4,5 '-tetrahydroxystilbene, weight 0.52g, yield 43%.
(3) preparation of 2,3 ', 4,5 '-tetrahydroxy of natural product bibenzyl
Add E-2 in round-bottomed flask, 3 ', 4,5 '-tetrahydroxystilbene (1.22g, 5mmol) adds 10ml second
Alcohol stirs dissolving, and 10% palladium carbon (61mg) is added under condition of ice bath, and in atmosphere of hydrogen at one atm, room temperature is anti-
Answer 3 hours, sucking filtration, reclaim palladium carbon, anhydrous sodium sulfate drying, solvent evaporated, ethyl acetate-light petrol recrystallization obtain natural
Product 2,3 ', 4,5 '-tetrahydroxy bibenzyl, weight 1.11g, yield 90%.
Embodiment 5
(1) preparation of 3- (3,5-dihydroxy phenyl)-umbelliferone
3,5- dihydroxyphenyl acetic acids (2.52g, 15mmol), 2,4- 4-dihydroxy benzaldehydes are added in round-bottomed flask
(2.07g, 15mmol), triethylamine (3.03g, 30mmol), acetic anhydride (10mL), stirring, to 110 DEG C, reaction 7 is little for oil bath heating
When.After completion of the reaction, reacting liquor while hot is poured in 50mL frozen water, stirs, have solid to separate out, sucking filtration washes filter cake, collects filter
Cake, filter cake sodium hydrate aqueous solution dissolve, and are washed with ethyl acetate, are acidified to pH=3～4 with hydrochloric acid, separate out solid, take out
Filter cake is collected in filter, washing, obtains faint yellow solid, be 3- (3,5-dihydroxy phenyl)-umbelliferone after being dried, weight
2.97g, yield 73%.
(2) E-2,3 ', the preparation of 4,5 '-tetrahydroxystilbene
3- (3,5-dihydroxy phenyl)-umbelliferone (1.35g, 5mmol), potassium hydroxide are put into in round-bottomed flask
(2.80g, 50mmol), dimethyl sulfoxide-water (20ml, 3:1), 160 DEG C of backflow 3h of oil bath, reaction is finished, plus the dilution of 50ml water, salt
Acid is acidified to PH=3～4, ethyl acetate extraction (10ml × 3), collected organic layer, anhydrous sodium sulfate drying, solvent evaporated, second
Alcohol-water recrystallization, obtains E-2, and 3 ', 4,5 '-tetrahydroxystilbene, weight 0.72g, yield 59%.
(3) preparation of 2,3 ', 4,5 '-tetrahydroxy of natural product bibenzyl
Add E-2 in round-bottomed flask, 3 ', 4,5 '-tetrahydroxystilbene (1.22g, 5mmol) adds 10ml second
Alcohol stirs dissolving, and 10% palladium carbon (61mg) is added under condition of ice bath, and in atmosphere of hydrogen at one atm, room temperature is anti-
Answer 3 hours, sucking filtration, reclaim palladium carbon, anhydrous sodium sulfate drying, solvent evaporated, ethyl acetate-light petrol recrystallization obtain natural
Product 2,3 ', 4,5 '-tetrahydroxy bibenzyl, weight 1.11g, yield 90%.
Embodiment 6
(1) preparation of 3- (3,5-dihydroxy phenyl)-umbelliferone
3,5- dihydroxyphenyl acetic acids (2.52g, 15mmol), 2,4- 4-dihydroxy benzaldehydes are added in round-bottomed flask
(2.07g, 15mmol), triethylamine (6.06g, 60mmol), acetic anhydride (10mL), stirring, to 110 DEG C, reaction 7 is little for oil bath heating
When.After completion of the reaction, reacting liquor while hot is poured in 50mL frozen water, stirs, have solid to separate out, sucking filtration washes filter cake, collects filter
Cake, filter cake sodium hydrate aqueous solution dissolve, and are washed with ethyl acetate, are acidified to pH=3～4 with hydrochloric acid, separate out solid, take out
Filter cake is collected in filter, washing, obtains faint yellow solid, be 3- (3,5-dihydroxy phenyl)-umbelliferone after being dried, weight
2.75g, yield 68%.
(2) E-2,3 ', the preparation of 4,5 '-tetrahydroxystilbene
3- (3,5-dihydroxy phenyl)-umbelliferone (1.35g, 5mmol), Cesium hydrate. are put into in round-bottomed flask
(2.80g, 50mmol), DMSO-H2O (20ml, 3:1), 160 DEG C of backflow 2h of oil bath, reaction is finished, plus the dilution of 50ml water, hydrochloric acid
PH=3～4 are acidified to, ethyl acetate extracts (10ml × 3), collected organic layer, anhydrous sodium sulfate drying, solvent evaporated, ethanol-
Water recrystallization, obtains E-2, and 3 ', 4,5 '-tetrahydroxystilbene, weight 0.79g, yield 65%.
(3) preparation of 2,3 ', 4,5 '-tetrahydroxy of natural product bibenzyl (5)
Add E-2 in round-bottomed flask, 3 ', 4,5 '-tetrahydroxystilbene (1.22g, 5mmol) adds 10ml second
Alcohol stirs dissolving, and 10% palladium carbon (61mg) is added under condition of ice bath, and in atmosphere of hydrogen at one atm, room temperature is anti-
Answer 3 hours, sucking filtration, reclaim palladium carbon, anhydrous sodium sulfate drying, solvent evaporated, ethyl acetate-light petrol recrystallization obtain natural
Product 2,3 ', 4,5 '-tetrahydroxy bibenzyl, weight 1.11g, yield 90%.
Embodiment 7
(1) preparation of 3- (3,5-dihydroxy phenyl)-umbelliferone
To in round-bottomed flask, 3,5- dihydroxyphenyl acetic acids (2.52g, 15mmol), 2,4- 4-dihydroxy benzaldehydes are added
(2.50g, 18mmol), triethylamine (4.55g, 45mmol), acetic anhydride (10mL), stirring, to 110 DEG C, reaction 7 is little for oil bath heating
When.After completion of the reaction, reacting liquor while hot is poured in 50mL frozen water, stirs, have solid to separate out, sucking filtration washes filter cake, collects filter
Cake, filter cake sodium hydrate aqueous solution dissolve, and are washed with ethyl acetate, are acidified to pH=3～4 with hydrochloric acid, separate out solid, take out
Filter cake is collected in filter, washing, obtains faint yellow solid, be 3- (3,5-dihydroxy phenyl)-umbelliferone after being dried, weight
3.16g, yield 78%.
(2) E-2,3 ', the preparation of 4,5 '-tetrahydroxystilbene
To round-bottomed flask input 3- (3,5-dihydroxy phenyl)-umbelliferone (1.35g, 5mmol), sodium carbonate
(5.30g, 50mmol), dimethyl sulfoxide-water (20ml, 3:1), 160 DEG C of backflow 2h of oil bath, reaction is finished, plus the dilution of 50ml water, salt
Acid is acidified to PH=3～4, ethyl acetate extraction (10ml × 3), collected organic layer, anhydrous sodium sulfate drying, solvent evaporated, second
Alcohol-water recrystallization, obtains E-2, and 3 ', 4,5 '-tetrahydroxystilbene (4), weight 0.44g, yield 36%.
(3) preparation of 2,3 ', 4,5 '-tetrahydroxy of natural product bibenzyl
Add E-2 in round-bottomed flask, 3 ', 4,5 '-tetrahydroxystilbene (1.22g, 5mmol) adds 10ml first
Alcohol stirs dissolving, adds 150 μm and be dispersed in water Raney's nickel (61mg) under condition of ice bath, nitrogen atmosphere at one atm
Enclose room temperature reaction 3 hours, sucking filtration, recovery palladium carbon, anhydrous sodium sulfate drying, solvent evaporated, ethyl acetate-light petrol recrystallization,
Obtain natural product 2,3 ', 4,5 '-tetrahydroxy bibenzyl, weight 1.06g, yield 86%.
Embodiment 8
(1) preparation of 3- (3,5-dihydroxy phenyl)-umbelliferone (3)
To in round-bottomed flask, 3,5- dihydroxyphenyl acetic acids (2.52g, 15mmol), 2,4- 4-dihydroxy benzaldehydes are added
(2.07g, 15mmol), sodium acetate (3.69g, 45mmol), acetic anhydride (10mL), stirring, to 110 DEG C, reaction 7 is little for oil bath heating
When.After completion of the reaction, reacting liquor while hot is poured in 50mL frozen water, stirs, have solid to separate out, sucking filtration washes filter cake, collects filter
Cake, filter cake sodium hydrate aqueous solution dissolve, and are washed with ethyl acetate, are acidified to pH=3～4 with hydrochloric acid, separate out solid, take out
Filter cake is collected in filter, washing, obtains faint yellow solid, be 3- (3,5-dihydroxy phenyl)-umbelliferone after being dried, weight
0.93g, yield 23%.
(2) E-2,3 ', the preparation of 4,5 '-tetrahydroxystilbene
To round-bottomed flask input 3- (3,5-dihydroxy phenyl)-umbelliferone (1.35g, 5mmol), potassium carbonate
(6.90g, 50mmol), dimethyl sulfoxide-water (20ml, 3:1), 160 DEG C of backflow 2h of oil bath, reaction is finished, plus the dilution of 50ml water, salt
Acid is acidified to pH=3～4, ethyl acetate extraction (10ml × 3), collected organic layer, anhydrous sodium sulfate drying, solvent evaporated, second
Alcohol-water recrystallization, obtains E-2, and 3 ', 4,5 '-tetrahydroxystilbene, weight 0.56, yield 46%.
(3) preparation of 2,3 ', 4,5 '-tetrahydroxy of natural product bibenzyl
Add E-2 in round-bottomed flask, 3 ', 4,5 '-tetrahydroxystilbene (1.22g, 5mmol) adds 10ml tetra-
Hydrogen furan stirs dissolving, adds 150 μm and be dispersed in water Raney's nickel (61mg) under condition of ice bath, hydrogen at one atm
Atmosphere encloses room temperature reaction 3 hours, sucking filtration, reclaims palladium carbon, and anhydrous sodium sulfate drying, solvent evaporated, ethyl acetate-light petrol are tied again
Crystalline substance, obtains natural product 2, and 3 ', 4,5 '-tetrahydroxy bibenzyl, weight 0.97g, yield 79%.
Embodiment 9
(1) preparation of 3- (3,5-dihydroxy phenyl)-umbelliferone
3,5- dihydroxyphenyl acetic acids (2.52g, 15mmol), 2,4- 4-dihydroxy benzaldehydes are added in round-bottomed flask
(2.07g, 15mmol), DBU (6.84g, 45mmol), acetic anhydride (10mL), stirring, oil bath heating are reacted 7 hours to 110 DEG C.
After completion of the reaction, reacting liquor while hot is poured in 50mL frozen water, stirs, have solid to separate out, sucking filtration washes filter cake, collects filter cake,
Filter cake sodium hydrate aqueous solution dissolves, and is washed with ethyl acetate, is acidified to pH=3～4 with hydrochloric acid, separates out solid, sucking filtration, water
Wash, collect filter cake, faint yellow solid is obtained after being dried, be 3- (3,5-dihydroxy phenyl)-umbelliferone, weight 1.42g,
Yield 35%.
(2) E-2,3 ', the preparation of 4,5 '-tetrahydroxystilbene
To round-bottomed flask input 3- (3,5-dihydroxy phenyl)-umbelliferone (1.35g, 5mmol), potassium hydroxide
(2.80g, 50mmol), ethylene glycol (20ml), 160 DEG C of backflow 2h of oil bath, reaction is finished, plus the dilution of 50ml water, and hydrochloric acid is acidified to
PH=3～4, ethyl acetate extraction (10ml × 3), collected organic layer, anhydrous sodium sulfate drying, solvent evaporated, alcohol-water are tied again
Crystalline substance, obtains E-2, and 3 ', 4,5 '-tetrahydroxystilbene, weight 0.81g, yield 66%.
(3) preparation of 2,3 ', 4,5 '-tetrahydroxy of natural product bibenzyl
Add E-2 in round-bottomed flask, 3 ', 4,5 '-tetrahydroxystilbene (1.22g, 5mmol) adds 10ml tetra-
Hydrogen furan stirs dissolving, adds 150 μm and be dispersed in water Raney's nickel (61mg) under condition of ice bath, hydrogen at one atm
Atmosphere encloses room temperature reaction 3 hours, sucking filtration, reclaims palladium carbon, and anhydrous sodium sulfate drying, solvent evaporated, ethyl acetate-light petrol are tied again
Crystalline substance, obtains natural product 2, and 3 ', 4,5 '-tetrahydroxy bibenzyl, weight 0.97g, yield 79%.
Embodiment 10
(1) preparation of 3- (3,5-dihydroxy phenyl)-umbelliferone
3,5- dihydroxyphenyl acetic acids (2.52g, 15mmol), 2,4- 4-dihydroxy benzaldehydes are added in round-bottomed flask
(2.07g, 15mmol), triethylamine (4.55g, 45mmol), acetic anhydride (10mL), stirring, to 110 DEG C, reaction 7 is little for oil bath heating
When.After completion of the reaction, reacting liquor while hot is poured in 50mL frozen water, stirs, have solid to separate out, sucking filtration washes filter cake, collects filter
Cake, filter cake sodium hydrate aqueous solution dissolve, and are washed with ethyl acetate, are acidified to pH=3～4 with hydrochloric acid, separate out solid, take out
Filter cake is collected in filter, washing, obtains faint yellow solid, be 3- (3,5-dihydroxy phenyl)-umbelliferone after being dried, weight
3.24g, yield 80%.
(2) E-2,3 ', the preparation of 4,5 '-tetrahydroxystilbene
To round-bottomed flask input 3- (3,5-dihydroxy phenyl)-umbelliferone (1.35g, 5mmol), potassium hydroxide
(2.80g, 50mmol), DMSO (20ml), 160 DEG C of backflow 2h of oil bath, reaction is finished, plus the dilution of 50ml water, and hydrochloric acid is acidified to pH
=3～4, ethyl acetate extraction (10ml × 3), collected organic layer, anhydrous sodium sulfate drying, solvent evaporated, alcohol-water are tied again
Crystalline substance, obtains E-2, and 3 ', 4,5 '-tetrahydroxystilbene, weight 0.77g, yield 63%
(3) preparation of 2,3 ', 4,5 '-tetrahydroxy of natural product bibenzyl
Add E-2 in round-bottomed flask, 3 ', 4,5 '-tetrahydroxystilbene (1.22g, 5mmol) adds 10ml first
Alcohol stirs dissolving, and 10% palladium carbon (61mg), atmosphere of hydrogen room temperature reaction 3 at one atm are added under condition of ice bath
Hour, sucking filtration reclaims palladium carbon, and anhydrous sodium sulfate drying, solvent evaporated, ethyl acetate-light petrol recrystallization obtain natural product
2,3 ', 4,5 '-tetrahydroxy bibenzyl, weight 1.11g, yield 90%.
Embodiment 11
(1) preparation of 3- (3,5-dihydroxy phenyl)-umbelliferone
3,5- dihydroxyphenyl acetic acids (2.52g, 15mmol), 2,4- 4-dihydroxy benzaldehydes are added in round-bottomed flask
(2.07g, 15mmol), triethylamine (4.55g, 45mmol), acetic anhydride (10mL), stirring, to 110 DEG C, reaction 7 is little for oil bath heating
When.After completion of the reaction, reacting liquor while hot is poured in 50mL frozen water, stirs, have solid to separate out, sucking filtration washes filter cake, collects filter
Cake, filter cake sodium hydrate aqueous solution dissolve, and are washed with ethyl acetate, are acidified to pH=3～4 with hydrochloric acid, separate out solid, take out
Filter cake is collected in filter, washing, obtains faint yellow solid, be 3- (3,5-dihydroxy phenyl)-umbelliferone after being dried, weight
3.24g, yield 80%.
(2) E-2,3 ', the preparation of 4,5 '-tetrahydroxystilbene
To round-bottomed flask input 3- (3,5-dihydroxy phenyl)-umbelliferone (1.35g, 5mmol), potassium hydroxide
(1.40g, 25mmol), DMSO-H2O (20ml, 3:1), 160 DEG C of backflow 2h of oil bath, reaction is finished, plus the dilution of 50ml water, hydrochloric acid
PH=3～4 are acidified to, ethyl acetate extracts (10ml × 3), collected organic layer, anhydrous sodium sulfate drying, solvent evaporated, ethanol-
Water recrystallization, obtains E-2, and 3 ', 4,5 '-tetrahydroxystilbene, weight 0.46g, yield 38%
(3) preparation of 2,3 ', 4,5 '-tetrahydroxy of natural product bibenzyl
Add E-2 in round-bottomed flask, 3 ', 4,5 '-tetrahydroxystilbene (1.22g, 5mmol) adds 10ml first
Alcohol stirs dissolving, and 10% palladium carbon (61mg), atmosphere of hydrogen room temperature reaction 3 at one atm are added under condition of ice bath
Hour, sucking filtration reclaims palladium carbon, and anhydrous sodium sulfate drying, solvent evaporated, ethyl acetate-light petrol recrystallization obtain natural product
2,3 ', 4,5 '-tetrahydroxy bibenzyl, weight 1.11g, yield 90%.
Embodiment 12
(1) preparation of 3- (3,5-dihydroxy phenyl)-umbelliferone
3,5- dihydroxyphenyl acetic acids (2.52g, 15mmol), 2,4- 4-dihydroxy benzaldehydes are added in round-bottomed flask
(2.07g, 15mmol), triethylamine (4.55g, 45mmol), acetic anhydride (10mL), stirring, to 110 DEG C, reaction 7 is little for oil bath heating
When.After completion of the reaction, reacting liquor while hot is poured in 50mL frozen water, stirs, have solid to separate out, sucking filtration washes filter cake, collects filter
Cake, filter cake sodium hydrate aqueous solution dissolve, and are washed with ethyl acetate, are acidified to pH=3～4 with hydrochloric acid, separate out solid, take out
Filter cake is collected in filter, washing, obtains faint yellow solid, be 3- (3,5-dihydroxy phenyl)-umbelliferone after being dried, weight
3.24g, yield 80%.
(2) E-2,3 ', the preparation of 4,5 '-tetrahydroxystilbene
To round-bottomed flask input 3- (3,5-dihydroxy phenyl)-umbelliferone (1.35g, 5mmol), potassium hydroxide
(4.2g, 75mmol), DMSO-H2O (20ml, 3:1), 160 DEG C of backflow 2h of oil bath, reaction is finished, plus the dilution of 50ml water, hydrochloric acid acid
Change to pH=3～4, ethyl acetate extraction (10ml × 3), collected organic layer, anhydrous sodium sulfate drying, solvent evaporated, alcohol-water
Recrystallization, obtains E-2, and 3 ', 4,5 '-tetrahydroxystilbene, weight 0.51g, yield 42%.
(3) preparation of 2,3 ', 4,5 '-tetrahydroxy of natural product bibenzyl
Add E-2 in round-bottomed flask, 3 ', 4,5 '-tetrahydroxystilbene (1.22g, 5mmol) adds 10ml first
Alcohol stirs dissolving, and 10% palladium carbon (61mg), atmosphere of hydrogen room temperature reaction 3 at one atm are added under condition of ice bath
Hour, sucking filtration reclaims palladium carbon, and anhydrous sodium sulfate drying, solvent evaporated, ethyl acetate-light petrol recrystallization obtain natural product
2,3 ', 4,5 '-tetrahydroxy bibenzyl, weight 1.11g, yield 90%.
Claims (10)
1. a kind of natural product 2,3 ', 4, the synthetic method of 5 '-tetrahydroxy bibenzyl, it is characterised in that comprise the steps：
(1) with 3,5- dihydroxyphenyl acetic acids and 2,4- 4-dihydroxy benzaldehyde for raw material, in solvent orange 2 A, in the presence of alkali A, occur
Condensation reaction obtains 3- (3,5-dihydroxy phenyl)-umbelliferone；
(2) in solvent B, under the conditions of alkali B, there is open loop decarboxylic reaction in 3- (3,5-dihydroxy phenyl)-umbelliferone,
It is post-treated to obtain E-2,3 ', 4,5 '-tetrahydroxystilbene；
(3) in solvent C, under catalyst C effects, E-2,3 ', 4, there is hydrogenation in 5 '-tetrahydroxystilbene, obtain
Natural product 2,3 ', 4,5 '-tetrahydroxy bibenzyl.
2. natural product according to claim 12,3 ', 4, the synthetic method of 5 '-tetrahydroxy bibenzyl, it is characterised in that：Step
Suddenly in (1), the reactant liquor obtained after condensation reaction is poured in frozen water, stirring, and sucking filtration washes filter cake, filter cake sodium hydroxide water
Solution dissolves, and is washed with ethyl acetate, is acidified to pH=3～4 with hydrochloric acid, separates out solid, and sucking filtration, washing are collected filter cake, be dried
After obtain 3- (3,5-dihydroxy phenyl)-umbelliferone.
3. natural product according to claim 12,3 ', 4, the synthetic method of 5 '-tetrahydroxy bibenzyl, it is characterised in that：Step
Suddenly, in (2), the post processing is that the reactant liquor that decarboxylic reaction is obtained is cooled to room temperature, is acidified to pH=3～4, second with hydrochloric acid
Acetoacetic ester is extracted, and collects organic faciess, is dried, and is removed solvent, is used alcohol-water recrystallization, obtains E-2, and 3 ', 4,5 '-tetrahydroxy two
Styrene.
4. natural product according to claim 12,3 ', 4, the synthetic method of 5 '-tetrahydroxy bibenzyl, it is characterised in that：Step
Suddenly in (3), the reactant mixture that hydrogenation is obtained carries out sucking filtration, reclaims catalyst, collects filtrate, is dried, and removes solvent, second
Acetoacetic ester-petroleum ether recrystallization, obtains natural product 2, and 3 ', 4,5 '-tetrahydroxy bibenzyl.
5. natural product according to claim 12,3 ', 4, the synthetic method of 5 '-tetrahydroxy bibenzyl, it is characterised in that：Step
Suddenly, in (1), solvent orange 2 A is acetic anhydride, propionic andydride or butyryl oxide., and alkali A is sodium acetate, Sodium ethylate, triethylamine or 1,8- diaza two
11 carbon -7- alkene of ring；The temperature of condensation reaction is 100～140 DEG C, and the response time is 5～9 hours.
6. natural product according to claim 12,3 ', 4, the synthetic method of 5 '-tetrahydroxy bibenzyl, it is characterised in that：Step
Suddenly, in (1), 3,5- dihydroxyphenyl acetic acids, 2,4- 4-dihydroxy benzaldehydes, the mol ratio of alkali A are 1：(1.0～1.2)：(2～4).
7. natural product according to claim 12,3 ', 4, the synthetic method of 5 '-tetrahydroxy bibenzyl, it is characterised in that：Step
Suddenly, in (2), alkali B is sodium bicarbonate, sodium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide, potassium hydroxide, Cesium hydrate., tricresyl phosphate
Potassium or triethylamine, solvent B are distilled water, dimethyl sulfoxide, PEG-4000, ethylene glycol, dimethyl sulfoxide-water or N, N- dimethyl
Methanamide；The temperature of decarboxylic reaction is 100～180 DEG C, and the response time is 1～3 hour.
8. natural product according to claim 12,3 ', 4, the synthetic method of 5 '-tetrahydroxy bibenzyl, it is characterised in that：Step
Suddenly, in (2), 3- (3,5-dihydroxy phenyl)-umbelliferone, the mol ratio of alkali B are 1：(5～15).
9. natural product according to claim 12,3 ', 4, the synthetic method of 5 '-tetrahydroxy bibenzyl, it is characterised in that：Step
Suddenly, in (3), the time of hydrogenation is 1～8 hour.
10. natural product according to claim 12,3 ', 4, the synthetic method of 5 '-tetrahydroxy bibenzyl, it is characterised in that：
In step (3), solvent C is methanol, ethanol, isopropanol, acetone or tetrahydrofuran, and catalyst C is Raney's nickel or palladium carbon.
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| CN111620856A (en) * | 2020-07-06 | 2020-09-04 | 上海皓元医药股份有限公司 | Synthetic method of 7-cyclic amino substituted coumarin derivative |
| CN112358460A (en) * | 2020-11-20 | 2021-02-12 | 广东电网有限责任公司电力科学研究院 | Long-afterglow light-storing organic luminescent material and preparation method thereof |
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| KBROLY FELFIJLDI等: "Synthesis of E- and Z-o-Methoxy-Substituted 2,3-Diphenyl Propenoic Acids and Its Methyl Esters", 《SYNTHETIC COMMUNICATIONS》 * |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111620856A (en) * | 2020-07-06 | 2020-09-04 | 上海皓元医药股份有限公司 | Synthetic method of 7-cyclic amino substituted coumarin derivative |
| CN111620856B (en) * | 2020-07-06 | 2021-10-01 | 上海皓元医药股份有限公司 | Synthetic method of 7-cyclic amino substituted coumarin derivative |
| CN112358460A (en) * | 2020-11-20 | 2021-02-12 | 广东电网有限责任公司电力科学研究院 | Long-afterglow light-storing organic luminescent material and preparation method thereof |
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