CN106279082A - Substituted furan chalcone derivant and preparation method thereof - Google Patents

Substituted furan chalcone derivant and preparation method thereof Download PDF

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CN106279082A
CN106279082A CN201610631120.0A CN201610631120A CN106279082A CN 106279082 A CN106279082 A CN 106279082A CN 201610631120 A CN201610631120 A CN 201610631120A CN 106279082 A CN106279082 A CN 106279082A
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methyl
hydroxy
ethyl
ketone
base
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CN106279082B (en
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吴军
何兴瑞
娄永根
商志才
顾海宁
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Zhejiang University ZJU
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Zhejiang University ZJU
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
    • C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
    • C07D407/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

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  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

The present invention relates to medicinal chemistry arts, it is desirable to provide a kind of substituted furan chalcone derivant and preparation method thereof.This substituted furan chalcone derivant has the structure as shown in formula I: wherein, and B ring is selected from phenyl, furyl or thienyl；R1、R2、R3It is each independently selected from hydrogen atom, halogen, hydroxyl, cyano group, nitro, the alkyl chain of C1～C7, the alkoxyl of C1～C7, dimethylamino or diethylin.This product is the natural furan chalcone derivative analog that a class has new skeleton, has potential pharmaceutically active, and the preparation of this compounds can be that the pharmaceutically active research of furan chalcone provides support.Its preparation methods steps is simple, and loss rate is low, is a kind of brand-new route from nonaro-maticity raw material synthesis furan chalcone derivant.Significant for industrialized production.

Description

Substituted furan chalcone derivant and preparation method thereof
Technical field
The present invention relates to field of medicaments, more particularly, to a kind of substituted furan chalcone derivant and preparation thereof Method.
Background technology
Chalcone Compounds belongs to flavone compound, is distributed widely in natural plants, and its chemical constitution is 1,3- Diphenyl-2-propylene-1-ketone, it receives significant attention because having multiple biological activity.Research finds, Chalcone Compounds And derivant has anticancer, antiinflammatory, antioxidation, parasiticide, antibacterial isoreactivity.
Methyl substituted furan ring structure is widely present in natural product, and has various biological activity, such as red Ginseng ketone can treat cardiovascular disease, and furan Buddhist art alkane has Allelopathic Effect in Plants, and sesquiterpenoids cacalol has anti- Hyperglycemia and antibacterial effect.
Therefore furan nucleus is had potential pharmaceutically active by methyl substituted furan Chalcone Compounds and derivant thereof, And this compounds is in the news the most not yet.Invention is a kind of simply, and the furan chalcone derivative prepared of high yield derives The brand-new synthetic route of thing.
Summary of the invention
The technical problem to be solved in the present invention is, overcomes deficiency of the prior art, it is provided that a kind of substituted furan looks into ear Ketones derivant and preparation method thereof.
For solving technical problem, the solution of the present invention is:
A kind of substituted furan chalcone derivant is provided, there is the structure as shown in formula I:
Wherein,
B ring is selected from phenyl, furyl or thienyl；
R1、R2、R3It is each independently selected from hydrogen atom, halogen, hydroxyl, cyano group, nitro, the alkyl chain of C1～C7, C1～C7 Alkoxyl, dimethylamino or diethylin.
In the present invention, this substituted furan chalcone derivant has any one structure following:
The present invention still further provides the preparation method of described substituted furan chalcone derivant, including following Step:
(1) by 1, hydroresorcinol and potassium hydroxide are dispersed in water, after stirring at normal temperature 5min, add chloracetyl second The methanol solution of acetoacetic ester；After reaction system is stirred at room temperature 5 days, it is acidified with the hydrochloric acid of 4N；Filter the reaction after acidifying Liquid, obtains solid product: 3-methyl-4-oxygen-4,5,6,7-tetrahydrochysene benzfuran-2-Ethyl formates；
Described 1, hydroresorcinol is 1:1:1 with potassium hydroxide, the mol ratio of chloroacetyl acetacetic ester, every milliliter of water correspondence 1, the inventory of hydroresorcinol is 0.1g, and the inventory of the chloroacetyl acetacetic ester that every ml methanol is corresponding is 0.2g；
(2) by 3-methyl-4-oxygen-4,5,6,7-tetrahydrochysene benzfuran-2-Ethyl formate, potassium hydroxide methanol and water Mixed solvent dissolves；After reaction system is stirred at room temperature reaction 5h, adjust pH to 1 with the hydrochloric acid of 6N；Filtering reacting liquid, obtains Solid product: 3-methyl-4-oxygen-4,5,6,7-tetrahydrochysene benzfuran-2-formic acid；
Described mixed solvent is that methanol is formulated by the volume ratio of 2.5:1 with water；The 3-that every milliliter of mixed solvent is corresponding Methyl-4-oxygen-4, the inventory of 5,6,7-tetrahydrochysene benzfuran-2-Ethyl formates is 0.2g, 3-methyl-4-oxygen-4,5,6,7- Tetrahydrochysene benzfuran-2-Ethyl formate is 1:6 with the mol ratio of potassium hydroxide；
(3) by 3-methyl-4-oxygen-4,5,6,7-tetrahydrochysene benzfuran-2-formic acid are dispersed in diethylene glycol, add copper Powder and pyridine；Reaction system is heated to 175 DEG C, is kept stirring for 10h；Reaction system is cooled to room temperature, adds frozen water, and use The hydrochloric acid acidifying of 4N；Reactant liquor after being acidified with petroleum ether extraction three times, washes with water once by the extract of merging, then will Extract anhydrous sodium sulfate is dried, is spin-dried for, and obtains solid product: 3-methyl-6,7-Dihydrobenzofuranes-4-(5H)-one；
Wherein, 3-methyl-4-oxygen-4 that every milliliter of diethylene glycol is corresponding, feeding intake of 5,6,7-tetrahydrochysene benzfuran-2-formic acid Amount is 0.1g；3-methyl-4-oxygen-4,5,6,7-tetrahydrochysene benzfuran-2-formic acid is 1:1:2 with the mol ratio of copper powder and pyridine；
(4) under nitrogen protection, sodium hydride is scattered in ethylene glycol dimethyl ether solution uniformly, reaction system is cooled down To 0 DEG C, it is subsequently adding 3-methyl-6, the ethylene glycol dimethyl ether solution of 7-Dihydrobenzofuranes-4 (5H)-one, keeps system 0 DEG C stirring 30min；In system, add the ethylene glycol dimethyl ether solution of ethyl acetate, then system is heated to 90 DEG C；Keep After 3h, system is cooled to room temperature, adds saturated ammonium chloride solution cancellation reaction；Being extracted with ethyl acetate 3 times, organic facies is used Anhydrous sodium sulfate is dried, concentrates, and obtains product: 5-acetyl-3-methyl-6, the thick product of 7-Dihydrobenzofuranes-4 (5H)-one；
Described 3-methyl-6,7-Dihydrobenzofuranes-4 (5H)-one is 1:5:3 with sodium hydride, the mol ratio of ethyl acetate, 3-methyl-6,7-Dihydrobenzofuranes-4 (5H) the-one inventory that every milliliter of glycol dimethyl ether is corresponding is 0.04g；
(5) by 5-acetyl-3-methyl-6,7-Dihydrobenzofuranes-4 (5H)-one is dispersed in toluene solution, Xiang Ti Addition 2,3-bis-chloro-5,6-dicyan 1,4-benzoquinone in system, be heated to 130 DEG C and keep 6h；System is cooled to room temperature, concentrates after filtration Filtrate；Filtrate is separated with silica gel chromatographic column, obtains the pure of 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone Product；
Described 5-acetyl-3-methyl-6,7-Dihydrobenzofuranes-4 (5H)-one and 2,3-bis-chloro-5,6-dicyan 1,4-benzoquinone Mol ratio be 1:1.2,5-acetyl-3-methyl-6 that every milliliter of toluene is corresponding, feeding intake of 7-Dihydrobenzofuranes-4 (5H)-one Amount is 0.1g；
(6) under nitrogen protection, by step (5) gained 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone It is scattered in uniformly in reaction dissolvent a, keeps system at room temperature；It is subsequently adding highly basic, stirs 10min～1h；Again to system The a solution of middle addition reactive group, reacts 1 hour to 24 hours；It is subsequently adding and doubles the shrend of solvent a volume and go out reaction, Again with hydrochloric acid by the most acid for system regulation；Filter and separate out thick product, i.e. obtain pure substituted furan with ethyl alcohol recrystallization and look into Ear ketones derivant；
In reaction system, 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone and reactive group, the rubbing of highly basic That ratio is 1:1～5:1～5；Every milliliter of 1-corresponding for reaction dissolvent a (4-hydroxy-3-methyl benzofuran-5-base) ethyl-1- The inventory of ketone is 0.02 to 0.06g；Described reaction dissolvent a is oxolane or dioxane；
The structural formula of described reactive group is:
Wherein, B ring is selected from phenyl, furyl or thienyl；R1、R2、R3It is each independently selected from hydrogen atom, halogen, hydroxyl Base, cyano group, nitro, the alkyl chain of C1～C7, the alkoxyl of C1～C7, dimethylamino or diethylin.
In the present invention, step (6) described highly basic is that (described highly basic is preferably sodium hydride, described molten for sodium hydride or hydrofining Agent is preferably oxolane).
Compared with prior art, the beneficial effect that the present invention can obtain:
(1) the furan chalcone derivant that the present invention provides is that a class has the natural furan chalcone of new skeleton seemingly Thing, has potential pharmaceutically active, and the preparation of this compounds can be the pharmaceutically active research offer of furan chalcone Support.
(2) preparation method of the furan chalcone derivant that the present invention provides, step is simple, and loss rate is low, is a kind of The brand-new route from nonaro-maticity raw material synthesis furan chalcone derivant.Important meaning is had for industrialized production Justice.
Accompanying drawing explanation
Fig. 1 is the synthesis schematic diagram of the substituted furan chalcone derivant that the present invention provides.
Detailed description of the invention
Below in conjunction with specific embodiment, the present invention is described in detail.Following example will assist in the technology of this area Personnel are further appreciated by the present invention, but limit the present invention the most in any form.It should be pointed out that, the ordinary skill to this area For personnel, without departing from the inventive concept of the premise, it is also possible to make some deformation and improvement.These broadly fall into the present invention Protection domain.
Embodiment 1
By 1, hydroresorcinol and potassium hydroxide are dispersed in water uniformly, after stirring at normal temperature 5min, add chloracetyl second The methanol solution of acetoacetic ester, is then stirred at room temperature system 5 days, is then acidified by the hydrochloric acid of system 4N, filter acidifying After reactant liquor, the solid obtained is product: 3-methyl-4-oxygen-4,5,6,7-tetrahydrochysene benzfuran-2-Ethyl formates.Should In step 1, hydroresorcinol is 1:1:1 with the mol ratio of potassium hydroxide and chloroacetyl acetacetic ester, every milliliter of water corresponding 1, The inventory of hydroresorcinol is 0.1g, and the inventory of the chloroacetyl acetacetic ester that every ml methanol is corresponding is 0.2g.This step Productivity is 65%.The structure of products therefrom is:
Molecular formula: C12H14O4
Chinese name: 3-methyl-4-oxygen-4,5,6,7-tetrahydrochysene benzfuran-2-Ethyl formate
English name: ethyl 3-methyl-4-oxo-4,5,6,7-tetrahydrobenzofuran-2- carboxylate
Molecular weight: 222.09
Outward appearance: white solid
Proton nmr spectra: (400MHz, Chloroform-d) δ 4.38 (q, J=7.1Hz, 2H), 2.94 (t, J= 6.3Hz, 2H), 2.60 2.46 (m, 5H), 2.20 (p, J=6.4Hz, 2H), 1.40 (t, J=7.1Hz, 3H) ppm.
Embodiment 2
The mixing with first alcohol and water by 3-methyl-4-oxygen-4,5,6,7-tetrahydrochysene benzfuran-2-Ethyl formate and potassium hydroxide Bonding solvent dissolves, and system is stirred at room temperature after dissolving reaction 5h.Then the hydrochloric acid of reactant liquor 6N is adjusted pH to 1, filter Reactant liquor, the solid filtering gained is product: 3-methyl-4-oxygen-4,5,6,7-tetrahydrochysene benzfuran-2-formic acid.This step Mixed solvent used by is that methanol is formulated with 2.5:1 with water.3-methyl-4-oxygen-4 that every milliliter of mixed solvent is corresponding, The inventory of 5,6,7-tetrahydrochysene benzfuran-2-Ethyl formate is 0.2g.3-methyl-4-oxygen-4,5,6,7-tetrahydrochysene in this step Coumarilic acid ethyl ester is 1:6 with the mol ratio of potassium hydroxide.The productivity of this step is 90%.The structure of products therefrom is:
Molecular formula: C10H10O4
Chinese name: 3-methyl-4-oxygen-4,5,6,7-tetrahydrochysene benzfuran-2-formic acid
English name: 3-methyl-4-oxo-4,5,6,7-tetrahydrobenzofuran-2-carboxylic acid
Molecular weight: 194.06
Outward appearance: white solid
Proton nmr spectra: (400MHz, DMSO-d6) δ 2.91 (t, J=6.2Hz, 2H), 2.44 (m, 5H), 2.08 (p, J =6.4Hz, 2H) ppm.
Embodiment 3
By 3-methyl-4-oxygen-4,5,6,7-tetrahydrochysene benzfuran-2-formic acid are scattered in diethylene glycol uniformly, add copper Powder and pyridine, be then heated to system 175 DEG C, be kept stirring for 10h.System is cooled to room temperature, adds frozen water, and with 4N's Hydrochloric acid is acidified, the reactant liquor after being acidified with petroleum ether extraction three times, washes with water once by the extract of merging, then will extraction Liquid anhydrous sodium sulfate is dried, and is spin-dried for.The solid of gained is product: 3-methyl-6,7-Dihydrobenzofuranes-4-(5H)-one. In this step, the inventory of the 3-methyl-4-oxygen-4,5,6,7-tetrahydrochysene benzfuran-2-formic acid that every milliliter of diethylene glycol is corresponding is 0.1g.In this step, 3-methyl-4-oxygen-4,5,6,7-tetrahydrochysene benzfuran-2-formic acid is 1 with the mol ratio of copper powder and pyridine: 1:2.The productivity of this step is 85%.The structure of products therefrom is:
Molecular formula: C9H10O2
Chinese name: 3-methyl-6,7-Dihydrobenzofuranes-4-(5H)-one
English name: 3-methyl-6,7-dihydrobenzofuran-4 (5H)-one
Molecular weight: 150.07
Outward appearance: yellow solid
Proton nmr spectra: (400MHz, Chloroform-d) δ 7.11 6.98 (m, 1H), 2.83 (t, J=6.3Hz, 2H), 2.47 (dd, J=7.2,5.8Hz, 2H), 2.26 2.06 (m, 5H) ppm.
Carbon-13 nmr spectra (101MHz, Chloroform-d) δ 195.70,167.40,138.90,120.41,119.07, 38.29,23.63,22.75,9.07ppm。
Embodiment 4
Under nitrogen protection, sodium hydride is scattered in ethylene glycol dimethyl ether solution uniformly, system is cooled to 0 DEG C, Then in system, add 3-methyl-6, the ethylene glycol dimethyl ether solution of 7-Dihydrobenzofuranes-4 (5H)-one, keep system to exist 0 DEG C of stirring 30min.Then in system, add the ethylene glycol dimethyl ether solution of ethyl acetate, then system is heated to 90 DEG C. After keeping 3h, system is cooled to room temperature, adds saturated ammonium chloride solution cancellation reaction, be extracted with ethyl acetate 3 times, organic It is dried with anhydrous sodium sulfate, concentrates, i.e. can obtain this step product 5-acetyl-3-methyl-6,7-Dihydrobenzofuranes-4 (5H)- The thick product of ketone.3-methyl-6,7-Dihydrobenzofuranes-4 (5H)-one and sodium hydride and the mol ratio of ethyl acetate in this step For 1:5:3,3-methyl-6 that every milliliter of glycol dimethyl ether is corresponding, 7-Dihydrobenzofuranes-4 (5H)-one inventory is 0.04g。
Product 5-acetyl-3-methyl-6,7-Dihydrobenzofuranes-4 (5H)-one of gained is dispersed in toluene solution In, addition 2,3-bis-chloro-5,6-dicyan 1,4-benzoquinone in system, it is heated to 130 DEG C and keeps 6h.System is cooled to room temperature, mistake Filter, concentrated filtrate, thick product silica gel chromatographic column is separated and i.e. can get pure product 1-(4-hydroxy-3-methyl benzo furan Mutter-5-base) ethyl-1-ketone.In this step, 5-acetyl-3-methyl-6,7-Dihydrobenzofuranes-4 (5H)-one is chloro-with 2,3-bis- The mol ratio of 5,6-dicyan 1,4-benzoquinone is 1:1.2,5-acetyl-3-methyl-6 that every milliliter of toluene is corresponding, 7-Dihydrobenzofuranes- The inventory of 4 (5H)-one is 0.1g.The productivity of this two step is 70%.The structure of products therefrom is:
Molecular formula: C11H10O3
Chinese name: 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone
English name: 1-(4-hydroxy-3-methylbenzofuran-5-yl) ethan-1-one
Molecular weight: 190.06
Outward appearance: yellow solid
Proton nmr spectra: (400MHz, Chloroform-d) δ 13.28 (s, 1H), 7.58 (d, J=8.8Hz, 1H), 7.28 (q, J=1.4Hz, 1H), 6.93 (d, J=8.9Hz, 1H), 2.63 (s, 3H), 2.41 (d, J=1.4Hz, 3H).
Carbon-13 nmr spectra (101MHz, Chloroform-d) δ 204.10,160.50,160.42,140.79,126.97, 117.87,117.26,114.05,103.71,26.93,9.57.
Embodiment 5-1:
Under nitrogen protection, intermediate 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone is divided uniformly Dissipate in oxolane, at room temperature, add sodium hydride, stir 15 minutes.Then in system, add p-tolyl aldehyde Tetrahydrofuran solution, adds complete holding system in room temperature, and then stirring reaction 2 hours adds in system and double solvent The shrend of volume is gone out reaction, with hydrochloric acid by system regulation to acid.Filter the thick product separated out, by thick product ethyl alcohol recrystallization I.e. can get clean product.In this step 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone with to methylbenzene first The mol ratio of aldehyde and sodium hydride is 1:1:2, and the inventory that every milliliter of reaction dissolvent is corresponding is 0.045g.Gained furan chalcone Derivant is: (E)-1-(4-hydroxy-3-methyl benzofuran-5-base)-3-(p-methylphenyl)-2-propylene-1-ketone, yield 85%, the structure of this derivant is:
Molecular formula: C19H16O3
Chinese name: (E)-1-(4-hydroxy-3-methyl benzofuran-5-base)-3-(p-methylphenyl)-2-propylene-1- Ketone
English name: (E)-1-(4-hydroxy-3-methylbenzofuran-5-yl)-3-(p-tolyl) prop-2- en-1-one
Molecular weight: 292.11
Outward appearance: red solid
Proton nmr spectra: (400MHz, Chloroform-d) δ 14.03 (s, 1H), 7.91 (d, J=15.4Hz, 1H), 7.80 (d, J=8.9Hz, 1H), 7.64 (d, J=15.5Hz, 1H), 7.60 7.54 (m, 2H), 7.30 (q, J=1.4Hz, 1H), 7.23 (s, 1H), 6.99 (d, J=8.9Hz, 1H), 2.44 (d, J=1.4Hz, 3H), 2.41 (s, 3H).
Carbon-13 nmr spectra: (101MHz, Chloroform-d) δ 193.44,161.97,160.46,144.70, 141.34,140.77,132.06,129.77,128.63,125.99,119.69,118.12,117.33,114.27,103.69, 21.59,9.65.
Embodiment 5-2:
Under nitrogen protection, intermediate 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone is divided uniformly Dissipate in oxolane, at room temperature, add sodium hydride, stir 10 minutes.Then in system, add cumaldehyde Tetrahydrofuran solution, add complete holding system in room temperature, stirring reaction 24 hours, then add in system double molten The shrend of agent volume is gone out reaction, with hydrochloric acid by system regulation to acid.Filter the thick product separated out, thick product ethanol is heavily tied Crystalline substance i.e. can get clean product.1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone and p-isopropyl in this step The mol ratio of benzaldehyde and sodium hydride is 1:1:2, and the inventory that every milliliter of reaction dissolvent is corresponding is 0.045g.Gained furan looks into ear Ketones derivant is: (E)-1-(4-hydroxy-3-methyl benzofuran-5-base)-3-(p-isopropyl phenyl)-2-propylene-1-ketone, Yield 87%, the structure of this derivant is:
Molecular formula: C21H20O3
Chinese name: (E)-1-(4-hydroxy-3-methyl benzofuran-5-base)-3-(p-isopropyl phenyl)-2-propylene- 1-ketone
English name: (E)-1-(4-hydroxy-3-methylbenzofuran-5-yl)-3-(4- isopropylphenyl)prop-2-en-1-one
Molecular weight: 320.14
Outward appearance: brown solid
Proton nmr spectra: (400MHz, Chloroform-d) δ 14.04 (s, 1H), 7.89 (d, J=15.4Hz, 1H), 7.77 (d, J=8.9Hz, 1H), 7.66 7.52 (m, 3H), 7.31 7.25 (m, 3H), 6.97 (d, J=8.9Hz, 1H), 2.94 (hept, J=6.9Hz, 1H), 2.42 (d, J=1.4Hz, 3H), 1.27 (d, J=6.9Hz, 6H).
Carbon-13 nmr spectra: (101MHz, Chloroform-d) δ 193.40,161.97,160.45,152.18, 144.69,140.75,132.44,128.76,127.14,125.98,119.73,118.10,117.32,114.28,103.68, 34.18,23.79,9.65.
Embodiment 5-3:
Under nitrogen protection, intermediate 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone is divided uniformly Dissipate in oxolane, at room temperature, add sodium hydride, stir 1h.Then in system, add the four of p-t-Butylbenzaldehyde Hydrogen tetrahydrofuran solution, adds complete holding system in room temperature, and then stirring reaction 1 hour adds in system and double solvent body Long-pending shrend is gone out reaction, with hydrochloric acid by system regulation to acidity.Filter the thick product separated out, by thick product ethyl alcohol recrystallization be Available clean product.In this step 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone with to tert-butyl benzene first The mol ratio of aldehyde and sodium hydride is 1:1:2, and the inventory that every milliliter of reaction dissolvent is corresponding is 0.02g.Gained furan chalcone Derivant is: (E)-3-(to tert-butyl-phenyl)-1-(4-hydroxy-3-methyl benzofuran-5-base)-2-propylene-1-ketone, yield 84%, the structure of this derivant is:
Molecular formula: C22H22O3
Chinese name: (E)-3-(to tert-butyl-phenyl)-1-(4-hydroxy-3-methyl benzofuran-5-base)-2-propylene- 1-ketone
English name:
(E)-3-(4-(tert-butyl)phenyl)-1-(4-hydroxy-3-methylbenzofuran-5-yl) prop-2-en-1-one
Molecular weight: 334.16
Outward appearance: bright yellow solid
Proton nmr spectra: (500MHz, Chloroform-d) δ 14.03 (s, 1H), 7.91 (d, J=15.4Hz, 1H), 7.79 (d, J=9.0Hz, 1H), 7.70 7.55 (m, 3H), 7.49 7.42 (m, 2H), 7.29 (t, J=1.6Hz, 1H), 6.99 (d, J=8.9Hz, 1H), 2.44 (d, J=1.5Hz, 3H), 1.35 (s, 9H).
Carbon-13 nmr spectra: (126MHz, Chloroform-d) δ 193.12,161.98,160.47,153.50, 144.75,140.81,140.60,130.25,125.94,119.89,118.14,117.33,114.21,105.80,103.70, 61.04,56.25,9.63.
Embodiment 5-4:
Under nitrogen protection, intermediate 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone is divided uniformly Dissipate in oxolane, at room temperature, add sodium hydride, stir 15 minutes.Then in system, add p-ethoxybenzaldehyde Tetrahydrofuran solution, add complete holding system in room temperature, stirring reaction 2 hours, then add in system double molten The shrend of agent volume is gone out reaction, with hydrochloric acid by system regulation to acid.Filter the thick product separated out, thick product ethanol is heavily tied Crystalline substance i.e. can get clean product.In this step 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone with to ethyoxyl The mol ratio of benzaldehyde and sodium hydride is 1:2:2, and the inventory that every milliliter of reaction dissolvent is corresponding is 0.06g.Gained furan looks into ear Ketones derivant is: (E)-3-(to ethoxyl phenenyl)-1-(4-hydroxy-3-methyl benzofuran-5-base)-2-propylene-1-ketone, Yield 85%, the structure of this derivant is:
Molecular formula: C20H18O4
Chinese name: (E)-3-(to ethoxyl phenenyl)-1-(4-hydroxy-3-methyl benzofuran-5-base)-2-propylene- 1-ketone
English name: (E)-3-(4-ethoxyphenyl)-1-(4-hydroxy-3-methylbenzofuran-5-yl) prop-2-en-1-one
Molecular weight: 322.12
Outward appearance: bright yellow solid
Proton nmr spectra: (400MHz, Chloroform-d) δ 14.11 (s, 1H), 7.93 7.74 (m, 2H), 7.66 7.50 (m, 3H), 7.29 (t, J=1.5Hz, 1H), 7.01 6.89 (m, 3H), 4.09 (q, J=7.0Hz, 2H), 2.44 (d, J= 1.4Hz, 3H), 1.44 (d, J=7.0Hz, 3H).
Carbon-13 nmr spectra: (101MHz, Chloroform-d) δ 193.35,161.91,161.27,160.38, 144.54,140.71,130.44,127.33,125.91,118.09,117.32,114.93,114.29,103.60,63.70, 14.74,9.65.
Embodiment 5-5:
Under nitrogen protection, intermediate 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone is divided uniformly Dissipate in oxolane, at room temperature, add sodium hydride, stir 15 minutes.Then add in system fluorine-based benzaldehyde Tetrahydrofuran solution, adds complete holding system in room temperature, and then stirring reaction 12 hours adds in system and double solvent The shrend of volume is gone out reaction, with hydrochloric acid by system regulation to acid.Filter the thick product separated out, by thick product ethyl alcohol recrystallization I.e. can get clean product.In this step 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone with to fluorine-based benzene first The mol ratio of aldehyde and sodium hydride is 1:3:3, and the inventory that every milliliter of reaction dissolvent is corresponding is 0.045g.Gained furan chalcone Derivant is: (E)-3-(to fluorophenyl)-1-(4-hydroxy-3-methyl benzofuran-5-base)-2-propylene-1-ketone, yield 74%, the structure of this derivant is:
Molecular formula: C18H13FO3
Chinese name: (E)-3-(to fluorophenyl)-1-(4-hydroxy-3-methyl benzofuran-5-base)-2-propylene-1-ketone
English name: (E)-3-(4-fluorophenyl)-1-(4-hydroxy-3-methylbenzofuran-5-yl) prop-2-en-1-one
Molecular weight: 296.08
Outward appearance: yellow solid
Proton nmr spectra: (400MHz, Chloroform-d) δ 13.97 (s, 1H), 7.90 (d, J=15.4Hz, 1H), 7.80 (d, J=8.9Hz, 1H), 7.74 7.57 (m, 3H), 7.33 (q, J=1.4Hz, 1H), 7.22 7.10 (m, 2H), 7.02 (d, J=8.9Hz, 1H), 2.47 (d, J=1.4Hz, 3H).
Carbon-13 nmr spectra: (101MHz, Chloroform-d) δ 193.12,162.01,160.53,143.24, 140.84,131.05 (d, J=3.3Hz), 130.48 (d, J=8.7Hz), 125.93,120.48 (d, J=2.5Hz), 118.15,117.33,116.31,116.09,114.17,103.81,9.63.
Embodiment 5-6:
Under nitrogen protection, intermediate 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone is divided uniformly Dissipate in oxolane, at room temperature, add sodium hydride, stir 15 minutes.Then in system, add the four of 4-chloro-benzaldehyde Hydrogen tetrahydrofuran solution, adds complete holding system in room temperature, and then stirring reaction 2 hours adds in system and double solvent body Long-pending shrend is gone out reaction, with hydrochloric acid by system regulation to acidity.Filter the thick product separated out, by thick product ethyl alcohol recrystallization be Available clean product.In this step 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone and 4-chloro-benzaldehyde and The mol ratio of sodium hydride is 1:1:2, and the inventory that every milliliter of reaction dissolvent is corresponding is 0.045g.Gained furan chalcone derives Thing is: (E)-3-(rubigan)-1-(4-hydroxy-3-methyl benzofuran-5-base)-2-propylene-1-ketone, yield 81%, should The structure of derivant is:
Molecular formula: C18H13ClO3
Chinese name: (E)-3-(rubigan)-1-(4-hydroxy-3-methyl benzofuran-5-base)-2-propylene-1-ketone
English name: (E)-3-(4-chlorophenyl)-1-(4-hydroxy-3-methylbenzofuran-5-yl) prop-2-en-1-one
Molecular weight: 312.06
Outward appearance: bright yellow solid
Proton nmr spectra: (400MHz, Chloroform-d) δ 13.93 (d, J=2.7Hz, 1H), 7.96 7.74 (m, 2H), 7.73 7.55 (m, 3H), 7.53 7.37 (m, 2H), 7.32 (s, 1H), 7.01 (dd, J=9.0,3.1Hz, 1H), 2.46 (d, J=3.5Hz, 3H).
Carbon-13 nmr spectra: (101MHz, Chloroform-d) δ 192.51,161.54,160.06,142.53, 140.37,136.10,132.75,129.18,128.79,125.42,120.71,117.64,116.83,113.66,103.35, 9.13.
Embodiment 5-7:
Under nitrogen protection, intermediate 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone is divided uniformly Dissipate in oxolane, at room temperature, add sodium hydride, stir 15 minutes.Then in system, add the four of p-bromobenzaldehyde Hydrogen tetrahydrofuran solution, adds complete holding system in room temperature, and then stirring reaction 2 hours adds in system and double solvent body Long-pending shrend is gone out reaction, with hydrochloric acid by system regulation to acidity.Filter the thick product separated out, by thick product ethyl alcohol recrystallization be Available clean product.In this step 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone and p-bromobenzaldehyde and The mol ratio of sodium hydride is 1:1:2, and the inventory that every milliliter of reaction dissolvent is corresponding is 0.045g.Gained furan chalcone derives Thing is: (E)-3-(p-bromophenyl)-1-(4-hydroxy-3-methyl benzofuran-5-base)-2-propylene-1-ketone, yield 76%, should The structure of derivant is:
Molecular formula: C18H13BrO3
Chinese name: (E)-3-(p-bromophenyl)-1-(4-hydroxy-3-methyl benzofuran-5-base)-2-propylene-1-ketone
English name: (E)-3-(4-bromophenyl)-1-(4-hydroxy-3-methylbenzofuran-5-yl) prop-2-en-1-one
Molecular weight: 356.00
Outward appearance: bright yellow solid
Proton nmr spectra: (400MHz, Chloroform-d) δ 13.90 (s, 1H), 7.86 7.69 (m, 2H), 7.67 7.45 (m, 5H), 7.29 (t, J=1.4Hz, 1H), 6.98 (d, J=8.9Hz, 1H), 2.43 (d, J=1.4Hz, 3H).
Carbon-13 nmr spectra: (101MHz, Chloroform-d) δ 192.99,162.05,160.56,143.10, 140.87,133.66,132.25,129.88,125.93,125.00,121.28,118.15,117.33,114.15,103.87, 9.64.
Embodiment 5-8:
Under nitrogen protection, intermediate 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone is divided uniformly Dissipate in oxolane, at room temperature, add sodium hydride, stir 15 minutes.Then add in system Dimethylaminobenzene first The tetrahydrofuran solution of aldehyde, adds complete holding system and reacts 2 hours in room temperature, stirring, then add in system and double The shrend of solvent volume is gone out reaction, with hydrochloric acid by system regulation to acid.Filter the thick product separated out, by thick product ethanol weight Crystallization i.e. can get clean product.In this step 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone with to diformazan The mol ratio of amido benzaldehyde and sodium hydride is 1:1:1, and the inventory that every milliliter of reaction dissolvent is corresponding is 0.045g.Gained furan Chalcone derivant is: (E)-3-(to dimethylaminophenyl)-1-(4-hydroxy-3-methyl benzofuran-5-base)-2-third Alkene-1-ketone, yield 86%, the structure of this derivant is:
Molecular formula: C20H19NO3
Chinese name: (E)-3-(to dimethylaminophenyl)-1-(4-hydroxy-3-methyl benzofuran-5-base)-2-third Alkene-1-ketone
English name: (E)-3-(4-(dimethylamino) phenyl)-1-(4-hydroxy-3- methylbenzofuran-5-yl)prop-2-en-1-one
Molecular weight: 321.14
Outward appearance: red solid
Proton nmr spectra: (400MHz, Chloroform-d) δ 14.35 (s, 1H), 7.90 (d, J=15.2Hz, 1H), 7.79 (d, J=8.9Hz, 1H), 7.64 7.52 (m, 2H), 7.46 (d, J=15.2Hz, 1H), 7.28 (q, J=1.4Hz, 1H), 6.97 (d, J=8.9Hz, 1H), 6.75 6.66 (m, 2H), 3.05 (s, 6H), 2.44 (d, J=1.4Hz, 3H).
Carbon-13 nmr spectra: (101MHz, Chloroform-d) δ 193.29,161.80,160.18,152.12, 145.61,140.56,130.68,125.82,122.56,118.05,117.30,114.99,114.44,111.84,103.33, 40.15,9.69.
Embodiment 5-9:
Under nitrogen protection, intermediate 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone is divided uniformly Dissipate in dioxane, at room temperature, add sodium hydride, stir 15 minutes.Then add cyanobenzaldehyde in system Dioxane solution, adds complete holding system in room temperature, and then stirring reaction 2 hours adds in system and double solvent The shrend of volume is gone out reaction, with hydrochloric acid by system regulation to acid.Filter the thick product separated out, by thick product ethyl alcohol recrystallization I.e. can get clean product.In this step 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone with to cyano group benzene first The mol ratio of aldehyde and sodium hydride is 1:1:2, and the inventory that every milliliter of reaction dissolvent is corresponding is 0.045g.Gained furan chalcone Derivant is: (E)-4-(3-(4-hydroxy-3-methyl benzofuran-5-base)-3-oxo-1-propylene-1-base) benzonitrile, yield 73%, the structure of this derivant is:
Molecular formula: C19H13NO3
Chinese name: (E)-4-(3-(4-hydroxy-3-methyl benzofuran-5-base)-3-oxo-1-propylene-1-base) benzene Formonitrile HCN
English name: (E)-4-(3-(4-hydroxy-3-methylbenzofuran-5-yl)-3-oxoprop-1-en- 1-yl)benzonitrile
Molecular weight: 303.09
Outward appearance: yellow solid
Proton nmr spectra: (400MHz, Chloroform-d) δ 13.77 (s, 1H), 7.87 (d, J=15.5Hz, 1H), 7.82 7.64 (m, 6H), 7.32 (s, 1H), 7.01 (d, J=8.9Hz, 1H), 2.44 (s, 3H).
Carbon-13 nmr spectra: (101MHz, DMSO-d6)δ192.07,161.07,160.26,141.32,140.55, 138.58,132.22,128.29,125.43,123.64,117.87,117.74,116.87,113.62,113.11,103.62, 9.10.
Embodiment 5-10:
Under nitrogen protection, intermediate 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone is divided uniformly Dissipate in oxolane, at room temperature, add sodium hydride, stir 15 minutes.Then add in system diethylin benzene first The tetrahydrofuran solution of aldehyde, adds complete holding system and reacts 2 hours in room temperature, stirring, then add in system and double The shrend of solvent volume is gone out reaction, with hydrochloric acid by system regulation to acid.Filter the thick product separated out, by thick product ethanol weight Crystallization i.e. can get clean product.In this step 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone with to diethyl The mol ratio of amido benzaldehyde and sodium hydride is 1:5:5, and the inventory that every milliliter of reaction dissolvent is corresponding is 0.045g.Gained furan Chalcone derivant is: (E)-3-(to diethylin phenyl)-1-(4-hydroxy-3-methyl benzofuran-5-base)-2-third Alkene-1-ketone, yield 88%, the structure of this derivant is:
Molecular formula: C22H23NO3
Chinese name: (E)-3-(to diethylin phenyl)-1-(4-hydroxy-3-methyl benzofuran-5-base)-2-third Alkene-1-ketone
English name: (E)-3-(4-(diethylamino) phenyl)-1-(4-hydroxy-3- methylbenzofuran-5-yl)prop-2-en-1-one
Molecular weight: 349.17
Outward appearance: yellow solid
Proton nmr spectra: (400MHz, Chloroform-d) δ 14.40 (s, 1H), 7.90 (d, J=15.1Hz, 1H), 7.80 (d, J=8.9Hz, 1H), 7.55 (d, J=8.5Hz, 2H), 7.44 (d, J=15.1Hz, 1H), 7.30 7.24 (m, 1H), 6.97 (d, J=8.9Hz, 1H), 6.66 (d, J=8.4Hz, 2H), 3.42 (q, J=7.1Hz, 4H), 2.44 (d, J=1.4Hz, 3H), 1.21 (t, J=7.1Hz, 6H).
Carbon-13 nmr spectra: (101MHz, Chloroform-d) δ 193.27,161.78,160.14,149.88, 145.71,140.53,131.05,125.78,121.75,118.05,117.31,114.49,114.32,111.29,103.28, 44.56,12.62,9.69.
Embodiment 5-11:
Under nitrogen protection, intermediate 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone is divided uniformly Dissipate in oxolane, at room temperature, add sodium hydride, stir 15 minutes.Then in system, add paranitrobenzaldehyde Tetrahydrofuran solution, adds complete holding system in room temperature, and then stirring reaction 2 hours adds in system and double solvent The shrend of volume is gone out reaction, with hydrochloric acid by system regulation to acid.Filter the thick product separated out, by thick product ethyl alcohol recrystallization I.e. can get clean product.1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone and p-nitrophenyl first in this step The mol ratio of aldehyde and sodium hydride is 1:1:2, and the inventory that every milliliter of reaction dissolvent is corresponding is 0.02g.Gained furan chalcone Derivant is: (E)-1-(4-hydroxy-3-methyl benzofuran-5-base)-3-(p-nitrophenyl)-2-propylene-1-ketone, yield 81%, the structure of this derivant is:
Molecular formula: C18H13NO5
Chinese name: (E)-1-(4-hydroxy-3-methyl benzofuran-5-base)-3-(p-nitrophenyl)-2-propylene-1- Ketone
English name: (E)-1-(4-hydroxy-3-methylbenzofuran-5-yl)-3-(4-nitrophenyl) prop-2-en-1-one
Molecular weight: 323.08
Outward appearance: dark red solid
Proton nmr spectra: (400MHz, Chloroform-d) δ 13.78 (s, 1H), 8.36 8.29 (m, 2H), 7.95 (d, J=15.6Hz, 1H), 7.87 7.78 (m, 4H), 7.35 (d, J=1.5Hz, 1H), 7.06 (d, J=8.9Hz, 1H), 2.48 (d, J=1.4Hz, 3H).
Carbon-13 nmr spectra: (101MHz, Chloroform-d) δ 192.93,162.06,160.57,142.77, 140.85,134.90,133.62,131.45,127.96,127.73,126.04,123.61,117.34,114.14,103.86, 9.63.
Embodiment 5-12:
Under nitrogen protection, intermediate 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone is divided uniformly Dissipate in oxolane, at room temperature, add sodium hydride, stir 15 minutes.Then in system, add the four of 2-fluorobenzaldehyde Hydrogen tetrahydrofuran solution, adds complete holding system in room temperature, and then stirring reaction 2 hours adds in system and double solvent body Long-pending shrend is gone out reaction, with hydrochloric acid by system regulation to acidity.Filter the thick product separated out, by thick product ethyl alcohol recrystallization be Available clean product.In this step 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone and 2-fluorobenzaldehyde and The mol ratio of sodium hydride is 1:1:2, and the inventory that every milliliter of reaction dissolvent is corresponding is 0.06g.Gained furan chalcone derives Thing is: (E)-3-(2-fluorophenyl)-1-(4-hydroxy-3-methyl benzofuran-5-base)-2-propylene-1-ketone, yield 73%, should The structure of derivant is:
Molecular formula: C18H13FO3
Chinese name: (E)-3-(2-fluorophenyl)-1-(4-hydroxy-3-methyl benzofuran-5-base)-2-propylene-1-ketone
English name: (E)-3-(2-fluorophenyl)-1-(4-hydroxy-3-methylbenzofuran-5-yl) prop-2-en-1-one
Molecular weight: 296.08
Outward appearance: bright yellow solid
Proton nmr spectra: (400MHz, Chloroform-d) δ 13.94 (d, J=2.5Hz, 1H), 7.99 (d, J= 15.7Hz, 1H), 7.90 7.72 (m, 2H), 7.66 (t, J=7.7Hz, 1H), 7.41 (q, J=7.0,6.5Hz, 1H), 7.30 (s, 1H), 7.19 (dt, J=27.0,8.8Hz, 2H), 7.00 (d, J=8.8Hz, 1H), 2.45 (s, 3H).
Carbon-13 nmr spectra: (101MHz, Chloroform-d) δ 192.76,161.53,160.04,140.31,136.80 (d, J=1.8Hz), 131.48 (d, J=8.7Hz), 129.52 (d, J=3.1Hz), 125.55,124.04 (d, J=3.7Hz), 122.89 (d, J=11.4Hz), 122.45,122.34,117.58,115.96,115.74,113.69,103.33,9.13.
Embodiment 5-13:
Under nitrogen protection, intermediate 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone is divided uniformly Dissipate in oxolane, at room temperature, add sodium hydride, stir 15 minutes.Then in system, add the four of 2-chlorobenzaldehyde Hydrogen tetrahydrofuran solution, adds complete holding system in room temperature, and then stirring reaction 2 hours adds in system and double solvent body Long-pending shrend is gone out reaction, with hydrochloric acid by system regulation to acidity.Filter the thick product separated out, by thick product ethyl alcohol recrystallization be Available clean product.In this step 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone and 2-chlorobenzaldehyde and The mol ratio of sodium hydride is 1:1:2, and the inventory that every milliliter of reaction dissolvent is corresponding is 0.045g.Gained furan chalcone derives Thing is: (E)-3-(2-chlorphenyl)-1-(4-hydroxy-3-methyl benzofuran-5-base)-2-propylene-1-ketone, yield 83%, should The structure of derivant is:
Molecular formula: C18H13ClO3
Chinese name: (E)-3-(2-chlorphenyl)-1-(4-hydroxy-3-methyl benzofuran-5-base)-2-propylene-1-ketone
English name: (E)-3-(2-chlorophenyl)-1-(4-hydroxy-3-methylbenzofuran-5-yl) prop-2-en-1-one
Molecular weight: 312.06
Outward appearance: bright yellow solid
Proton nmr spectra: (400MHz, Chloroform-d) δ 13.89 (s, 1H), 8.32 (d, J=15.5Hz, 1H), 7.85 7.75 (m, 2H), 7.68 (d, J=15.5Hz, 1H), 7.52 7.44 (m, 1H), 7.41 7.31 (m, 3H), 7.02 (d, J =8.9Hz, 1H), 2.47 (d, J=1.4Hz, 3H).
Carbon-13 nmr spectra: (101MHz, Chloroform-d) δ 192.56,161.58,160.09,140.38, 139.80,135.12,132.65,130.82,129.89,127.40,126.61,125.55,122.98,117.67,116.87, 113.68,103.38,9.15.
Embodiment 5-14:
Under nitrogen protection, intermediate 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone is divided uniformly Dissipate in oxolane, at room temperature, add hydrofining, stir 15 minutes.Then in system, add the four of 2-bromobenzaldehyde Hydrogen tetrahydrofuran solution, adds complete holding system in room temperature, and then stirring reaction 2 hours adds in system and double solvent body Long-pending shrend is gone out reaction, with hydrochloric acid by system regulation to acidity.Filter the thick product separated out, by thick product ethyl alcohol recrystallization be Available clean product.In this step 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone and 2-bromobenzaldehyde and The mol ratio of hydrofining is 1:1:1, and the inventory that every milliliter of reaction dissolvent is corresponding is 0.045g.Gained furan chalcone derives Thing is: (E)-3-(2-bromophenyl)-1-(4-hydroxy-3-methyl benzofuran-5-base)-2-propylene-1-ketone, yield 81%, should The structure of derivant is:
Molecular formula: C18H13BrO3
Chinese name: (E)-3-(2-bromophenyl)-1-(4-hydroxy-3-methyl benzofuran-5-base)-2-propylene-1-ketone
English name: (E)-3-(2-bromophenyl)-1-(4-hydroxy-3-methylbenzofuran-5-yl) prop-2-en-1-one
Molecular weight: 356.00
Outward appearance: bright yellow solid
Proton nmr spectra: (400MHz, Chloroform-d) δ 13.87 (s, 1H), 8.26 (d, J=15.4Hz, 1H), 7.78 (d, J=8.7Hz, 2H), 7.71 7.55 (m, 2H), 7.45 7.27 (m, 3H), 7.01 (d, J=8.9Hz, 1H), 2.46 (s,3H).
Carbon-13 nmr spectra: (101MHz, Chloroform-d) δ 192.93,162.06,160.57,142.77, 140.85,134.90,133.62,131.45,127.96,127.73,126.04,123.61,118.13,117.34,114.14, 103.86,9.63.
Embodiment 5-15:
Under nitrogen protection, intermediate 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone is divided uniformly Dissipate in oxolane, at room temperature, add hydrofining, stir 15 minutes.Then in system, add Benzaldehyde,2-methoxy Tetrahydrofuran solution, add complete holding system in room temperature, stirring reaction 2 hours, then add in system double molten The shrend of agent volume is gone out reaction, with hydrochloric acid by system regulation to acid.Filter the thick product separated out, thick product ethanol is heavily tied Crystalline substance i.e. can get clean product.1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone and 2-methoxyl group in this step The mol ratio of benzaldehyde and hydrofining is 1:2:2, and the inventory that every milliliter of reaction dissolvent is corresponding is 0.045g.Gained furan looks into ear Ketones derivant is: (E)-1-(4-hydroxy-3-methyl benzofuran-5-base)-3-(2-methoxyphenyl)-2-propylene-1-ketone, Yield 86%, the structure of this derivant is:
Molecular formula: C19H16O4
Chinese name: (E)-1-(4-hydroxy-3-methyl benzofuran-5-base)-3-(2-methoxyphenyl)-2-propylene- 1-ketone
English name: (E)-1-(4-hydroxy-3-methylbenzofuran-5-yl)-3-(2- methoxyphenyl)prop-2-en-1-one
Molecular weight: 308.10
Outward appearance: bright yellow solid
Proton nmr spectra: (400MHz, Chloroform-d) δ 14.10 (s, 1H), 8.20 (d, J=15.6Hz, 1H), 7.84 7.69 (m, 2H), 7.63 (dd, J=7.7,1.8Hz, 1H), 7.37 (ddd, J=8.6,7.5,1.7Hz, 1H), 7.27 (s, 1H), 6.96 (td, J=13.0,11.9,7.9Hz, 3H), 3.92 (s, 3H), 2.43 (d, J=1.4Hz, 3H).
Carbon-13 nmr spectra: (101MHz, Chloroform-d) δ 193.89,161.95,160.39,158.92, 140.69,140.19,131.97,129.52,126.09,123.77,121.37,120.77,118.05,117.32,114.38, 111.25,103.59,55.57,9.66.
Embodiment 5-16:
Under nitrogen protection, intermediate 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone is divided uniformly Dissipate in oxolane, at room temperature, add hydrofining, stir 15 minutes.Then in system, add 2,4-dimethyl benzene first The tetrahydrofuran solution of aldehyde, adds complete holding system and reacts 2 hours in room temperature, stirring, then add in system and double The shrend of solvent volume is gone out reaction, with hydrochloric acid by system regulation to acid.Filter the thick product separated out, by thick product ethanol weight Crystallization i.e. can get clean product.1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone and 2,4-bis-in this step The mol ratio of tolyl aldehyde and hydrofining is 1:5:5, and the inventory that every milliliter of reaction dissolvent is corresponding is 0.045g.Gained furan Chalcone derivant is: (E)-3-(2,4-3,5-dimethylphenyl)-1-(4-hydroxy-3-methyl benzofuran-5-base)-2-third Alkene-1-ketone, yield 85%, the structure of this derivant is:
Molecular formula: C20H18O3
Chinese name: (E)-3-(2,4-3,5-dimethylphenyl)-1-(4-hydroxy-3-methyl benzofuran-5-base)-2-third Alkene-1-ketone
English name: (E)-3-(2,4-dimethylphenyl)-1-(4-hydroxy-3-methylbenzofuran- 5-yl)prop-2-en-1-one
Molecular weight: 306.13
Outward appearance: dark yellow solid
Proton nmr spectra: (400MHz, Chloroform-d) δ 14.03 (s, 1H), 8.19 (d, J=15.2Hz, 1H), 7.78 (d, J=8.9Hz, 1H), 7.63 (d, J=8.0Hz, 1H), 7.55 (d, J=15.3Hz, 1H), 7.29 (q, J=1.4Hz, 1H), 7.07 (d, J=7.2Hz, 2H), 6.98 (d, J=8.9Hz, 1H), 2.47 (s, 3H), 2.44 (d, J=1.4Hz, 3H), 2.35(s,3H).
Carbon-13 nmr spectra: (101MHz, Chloroform-d) δ 193.43,161.96,160.42,142.13, 140.93,140.73,138.54,131.79,130.92,127.19,126.49,125.99,120.69,118.08,117.31, 114.27,103.66,21.40,19.81,9.63.
Embodiment 5-17:
Under nitrogen protection, intermediate 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone is divided uniformly Dissipate in oxolane, at room temperature, add sodium hydride, stir 15 minutes.Then in system, add 2,4,6-trimethylbenzene The tetrahydrofuran solution of formaldehyde, adds complete holding system in room temperature, stirring reaction 2 hours, then addition twice in system Shrend in solvent volume is gone out reaction, with hydrochloric acid by system regulation to acid.Filter the thick product separated out, by thick product ethanol Recrystallization i.e. can get clean product.1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone and 2,4 in this step, The mol ratio of 6-trimethylbenzaldehyde and sodium hydride is 1:1:2, and the inventory that every milliliter of reaction dissolvent is corresponding is 0.045g.Gained Furan chalcone derivant is: (E)-1-(4-hydroxy-3-methyl benzofuran-5-base)-3-(2,4,6-trimethylphenyl)- 2-propylene-1-ketone, yield 86%, the structure of this derivant is:
Molecular formula: C21H20O3
Chinese name: (E)-1-(4-hydroxy-3-methyl benzofuran-5-base)-3-(2,4,6-trimethylphenyl)-2-third Alkene-1-ketone
English name: (E)-1-(4-hydroxy-3-methylbenzofuran-5-yl)-3-mesitylprop-2- en-1-one
Molecular weight: 320.14
Outward appearance: bright yellow solid
Proton nmr spectra: (400MHz, Chloroform-d) δ 13.94 (s, 1H), 8.07 (d, J=15.8Hz, 1H), 7.67 (d, J=8.9Hz, 1H), 7.34 7.26 (m, 2H), 7.01 6.88 (m, 3H), 2.45 (d, J=1.4Hz, 3H), 2.42 (s,6H),2.31(s,3H).
Carbon-13 nmr spectra: (101MHz, Chloroform-d) δ 193.50,161.99,160.46,143.06, 140.79,138.78,137.26,131.46,129.37,126.06,125.99,118.11,117.33,114.23,103.77, 21.31,21.12,9.64.
Embodiment 5-18:
Under nitrogen protection, intermediate 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone is divided uniformly Dissipate in oxolane, at room temperature, add sodium hydride, stir 15 minutes.Then in system, add 3,4,5-trimethoxy The tetrahydrofuran solution of benzaldehyde, adds complete holding system in room temperature, stirring reaction 2 hours, then addition two in system The shrend of times solvent volume is gone out reaction, with hydrochloric acid by system regulation to acid.Filter the thick product separated out, by thick product second Alcohol recrystallization i.e. can get clean product.1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone and 3 in this step, The mol ratio of 4,5-TMB and sodium hydride is 1:1:2, and the inventory that every milliliter of reaction dissolvent is corresponding is 0.045g. Gained furan chalcone derivant is: (E)-1-(4-hydroxy-3-methyl benzofuran-5-base)-3-(3,4,5-trimethoxy Phenyl)-2-propylene-1-ketone, yield 87%, the structure of this derivant is:
Molecular formula: C21H20O6
Chinese name: (E)-1-(4-hydroxy-3-methyl benzofuran-5-base)-3-(3,4,5-trimethoxyphenyl)-2- Propylene-1-ketone
English name: (E)-1-(4-hydroxy-3-methylbenzofuran-5-yl)-3-(3,4,5- trimethoxyphenyl)prop-2-en-1-one
Molecular weight: 368.13
Outward appearance: bright yellow solid
Proton nmr spectra: (500MHz, Chloroform-d) δ 14.01 (s, 1H), 7.86 7.76 (m, 2H), 7.54 (d, J=15.3Hz, 1H), 7.30 (d, J=1.7Hz, 1H), 7.00 (d, J=8.8Hz, 1H), 6.88 (s, 2H), 3.94 (s, 6H), 3.92 (s, 3H), 2.44 (d, J=1.5Hz, 3H).
Carbon-13 nmr spectra: (126MHz, Chloroform-d) δ 193.42,161.95,160.44,154.41, 144.57,140.74,132.02,128.47,125.99,125.96,119.86,118.10,117.31,114.27,103.68, 34.98,31.15,9.63.
Embodiment 5-19:
Under nitrogen protection, intermediate 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone is divided uniformly Dissipate in oxolane, at room temperature, add sodium hydride, stir 15 minutes.Then in system, add 2,4 dichloro benzene formaldehyde Tetrahydrofuran solution, add complete holding system in room temperature, stirring reaction 2 hours, then add in system double molten The shrend of agent volume is gone out reaction, with hydrochloric acid by system regulation to acid.Filter the thick product separated out, thick product ethanol is heavily tied Crystalline substance i.e. can get clean product.1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone and 2,4-dichloro in this step The mol ratio of benzaldehyde and sodium hydride is 1:1:2, and the inventory that every milliliter of reaction dissolvent is corresponding is 0.045g.Gained furan looks into ear Ketones derivant is: (E)-3-(2,4-Dichlorobenzene base)-1-(4-hydroxy-3-methyl benzofuran-5-base)-2-propylene-1-ketone, Yield 80%, the structure of this derivant is:
Molecular formula: C18H12Cl2O3
Chinese name: (E)-3-(2,4 dichloro benzene base)-1-(4-hydroxy-3-methyl benzofuran-5-base)-2-propylene- 1-ketone
English name: (E)-3-(2,4-dichlorophenyl)-1-(4-hydroxy-3-methylbenzofuran- 5-yl)prop-2-en-1-one
Molecular weight: 346.02
Outward appearance: dark yellow solid
Proton nmr spectra: (400MHz, Chloroform-d) δ 13.84 (s, 1H), 8.24 (d, J=15.5Hz, 1H), 7.83 7.59 (m, 3H), 7.51 (d, J=2.1Hz, 1H), 7.37 7.31 (m, 2H), 7.02 (d, J=8.9Hz, 1H), 2.47 (d, J=1.4Hz, 3H).
Carbon-13 nmr spectra: (101MHz, Chloroform-d) δ 192.26,161.63,160.15,140.43, 138.52,136.14,135.69,131.22,129.73,128.10,127.09,125.47,123.27,117.69,116.86, 113.62,103.47,9.14.
Embodiment 5-20:
Under nitrogen protection, intermediate 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone is divided uniformly Dissipate in oxolane, at room temperature, add sodium hydride, stir 15 minutes.Then in system, add 2-bromo-4-fluorobenzaldehyde Tetrahydrofuran solution, add complete holding system in room temperature, stirring reaction 2 hours, then add in system double molten The shrend of agent volume is gone out reaction, with hydrochloric acid by system regulation to acid.Filter the thick product separated out, thick product ethanol is heavily tied Crystalline substance i.e. can get clean product.1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone and 2-bromo-4-fluorine in this step The mol ratio of benzaldehyde and sodium hydride is 1:1:2, and the inventory that every milliliter of reaction dissolvent is corresponding is 0.045g.Gained furan looks into ear Ketones derivant is: (E)-3-(2-bromo-4-fluorophenyl)-1-(4-hydroxy-3-methyl benzofuran-5-base)-2-propylene-1- Ketone, yield 82%, the structure of this derivant is:
Molecular formula: C18H12BrFO3
Chinese name: (E)-3-(2-bromo-4-fluorophenyl)-1-(4-hydroxy-3-methyl benzofuran-5-base)-2-propylene- 1-ketone
English name: (E)-3-(2-bromo-4-fluorophenyl)-1-(4-hydroxy-3- methylbenzofuran-5-yl)prop-2-en-1-one
Molecular weight: 374.00
Outward appearance: yellow solid
Proton nmr spectra: (400MHz, Chloroform-d) δ 13.82 (s, 1H), 8.17 (d, J=15.3Hz, 1H), 7.75 (t, J=8.4Hz, 2H), 7.53 (d, J=15.4Hz, 1H), 7.39 (dd, J=8.2,2.5Hz, 1H), 7.30 (s, 1H), 7.16 7.05 (m, 1H), 6.98 (d, J=8.9Hz, 1H), 2.43 (s, 3H).
Carbon-13 nmr spectra: (101MHz, Chloroform-d) δ 192.77,164.49,162.09,160.61, 141.60,140.91,131.30 (d, J=3.5Hz), 129.15 (d, J=8.9Hz), 126.40 (d, J=9.6Hz), 125.98,123.41 (d, J=2.07Hz), 120.88 (d, J=24.6Hz), 118.18,117.37,115.35 (d, J= 21.6Hz),114.10,103.92,9.63.
Embodiment 5-21:
Under nitrogen protection, intermediate 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone is divided uniformly Dissipate in oxolane, at room temperature, add sodium hydride, stir 15 minutes.Then in system, add the four of 3-chlorobenzaldehyde Hydrogen tetrahydrofuran solution, adds complete holding system in room temperature, and then stirring reaction 2 hours adds in system and double solvent body Long-pending shrend is gone out reaction, with hydrochloric acid by system regulation to acidity.Filter the thick product separated out, by thick product ethyl alcohol recrystallization be Available clean product.In this step 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone and 3-chlorobenzaldehyde and The mol ratio of sodium hydride is 1:1:2, and the inventory that every milliliter of reaction dissolvent is corresponding is 0.045g.Gained furan chalcone derives Thing is: (E)-3-(3-chlorphenyl)-1-(4-hydroxy-3-methyl benzofuran-5-base)-2-propylene-1-ketone, yield 81%, should The structure of derivant is:
Molecular formula: C18H13ClO3
Chinese name: (E)-3-(3-chlorphenyl)-1-(4-hydroxy-3-methyl benzofuran-5-base)-2-propylene-1-ketone
English name: (E)-3-(3-chlorophenyl)-1-(4-hydroxy-3-methylbenzofuran-5-yl) prop-2-en-1-one
Molecular weight: 312.06
Outward appearance: yellow solid
Proton nmr spectra: (400MHz, Chloroform-d) δ 13.86 (s, 1H), 7.85 7.72 (m, 2H), 7.63 (t, J=7.6Hz, 2H), 7.50 (d, J=7.0Hz, 1H), 7.42 7.27 (m, 3H), 6.99 (d, J=8.8Hz, 1H), 2.43 (s,3H).
Carbon-13 nmr spectra: (101MHz, Chloroform-d) δ 192.88,162.05,160.60,142.75, 140.87,136.59,135.01,130.45,130.22,127.92,126.92,125.97,122.07,118.13,117.32, 114.13,103.90,9.60.
Embodiment 5-22:
Under nitrogen protection, intermediate 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone is divided uniformly Dissipate in oxolane, at room temperature, add sodium hydride, stir 15 minutes.Then in system, add the four of 3-bromobenzaldehyde Hydrogen tetrahydrofuran solution, adds complete holding system in room temperature, and then stirring reaction 2 hours adds in system and double solvent body Long-pending shrend is gone out reaction, with hydrochloric acid by system regulation to acidity.Filter the thick product separated out, by thick product ethyl alcohol recrystallization be Available clean product.In this step 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone and 3-bromobenzaldehyde and The mol ratio of sodium hydride is 1:1:2, and the inventory that every milliliter of reaction dissolvent is corresponding is 0.045g.Gained furan chalcone derives Thing is: (E)-3-(3-bromophenyl)-1-(4-hydroxy-3-methyl benzofuran-5-base)-2-propylene-1-ketone, yield 80%, should The structure of derivant is:
Molecular formula: C18H13BrO3
Chinese name: (E)-3-(3-bromophenyl)-1-(4-hydroxy-3-methyl benzofuran-5-base)-2-propylene-1-ketone
English name: (E)-3-(3-bromophenyl)-1-(4-hydroxy-3-methylbenzofuran-5-yl) prop-2-en-1-one
Molecular weight: 356.00
Outward appearance: yellow solid
Proton nmr spectra: (400MHz, Chloroform-d) δ 13.79 (s, 1H), 7.80 7.62 (m, 3H), 7.55 (d, J=15.4Hz, 1H), 7.51 7.41 (m, 2H), 7.21 (d, J=7.4Hz, 2H), 6.92 (d, J=8.8Hz, 1H), 2.35 (s,3H).
Carbon-13 nmr spectra: (101MHz, Chloroform-d) δ 191.81,161.01,159.56,141.60, 139.83,135.83,132.32,129.80,129.44,126.35,124.94,122.09,121.03,117.09,116.28, 113.09,102.87,8.57.
Embodiment 5-23:
Under nitrogen protection, intermediate 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone is divided uniformly Dissipate in oxolane, at room temperature, add sodium hydride, stir 15 minutes.Then tolyl aldehyde between adding in system Tetrahydrofuran solution, adds complete holding system in room temperature, and then stirring reaction 2 hours adds in system and double solvent The shrend of volume is gone out reaction, with hydrochloric acid by system regulation to acid.Filter the thick product separated out, by thick product ethyl alcohol recrystallization I.e. can get clean product.1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone and a methylbenzene first in this step The mol ratio of aldehyde and sodium hydride is 1:1:2, and the inventory that every milliliter of reaction dissolvent is corresponding is 0.045g.Gained furan chalcone Derivant is: (E)-1-(4-hydroxy-3-methyl benzofuran-5-base)-3-(aminomethyl phenyl)-2-propylene-1-ketone, yield 84%, the structure of this derivant is:
Molecular formula: C19H16O3
Chinese name: (E)-1-(4-hydroxy-3-methyl benzofuran-5-base)-3-(aminomethyl phenyl)-2-propylene-1- Ketone
English name: (E)-1-(4-hydroxy-3-methylbenzofuran-5-yl)-3-(m-tolyl) prop-2- en-1-one
Molecular weight: 292.11
Outward appearance: yellow solid
Proton nmr spectra: (400MHz, Chloroform-d) δ 14.00 (s, 1H), 7.88 (d, J=15.5Hz, 1H), 7.79 (d, J=8.9Hz, 1H), 7.65 (d, J=15.5Hz, 1H), 7.46 (d, J=7.7Hz, 2H), 7.34 7.28 (m, 2H), 7.24 (d, J=7.5Hz, 1H), 6.99 (d, J=8.9Hz, 1H), 2.44 (d, J=1.4Hz, 3H), 2.41 (s, 3H).
Carbon-13 nmr spectra: (101MHz, Chloroform-d) δ 193.38,161.99,160.49,144.80, 140.78,138.68,134.73,131.60,129.11,128.90,126.03,125.91,120.52,118.11,117.33, 114.26,103.73,21.38,9.65.
Embodiment 5-24:
Under nitrogen protection, intermediate 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone is divided uniformly Dissipate in oxolane, at room temperature, add sodium hydride, stir 15 minutes.Then in system, add m-methoxybenzaldehyde Tetrahydrofuran solution, add complete holding system in room temperature, stirring reaction 2 hours, then add in system double molten The shrend of agent volume is gone out reaction, with hydrochloric acid by system regulation to acid.Filter the thick product separated out, thick product ethanol is heavily tied Crystalline substance i.e. can get clean product.1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone and 3-methoxyl group in this step The mol ratio of benzaldehyde and sodium hydride is 1:1:2, and the inventory that every milliliter of reaction dissolvent is corresponding is 0.045g.Gained furan looks into ear Ketones derivant is: (E)-1-(4-hydroxy-3-methyl benzofuran-5-base)-3-(3-methoxyphenyl)-2-propylene-1-ketone, Yield 86%, the structure of this derivant is:
Molecular formula: C19H16O4
Chinese name: (E)-1-(4-hydroxy-3-methyl benzofuran-5-base)-3-(3-methoxyphenyl)-2-propylene- 1-ketone
English name: (E)-1-(4-hydroxy-3-methylbenzofuran-5-yl)-3-(3- methoxyphenyl)prop-2-en-1-one
Molecular weight: 308.10
Outward appearance: khaki solid
Proton nmr spectra: (400MHz, Chloroform-d) δ 13.96 (s, 1H), 7.86 (d, J=15.4Hz, 1H), 7.77 (d, J=9.0Hz, 1H), 7.62 (d, J=15.4Hz, 1H), 7.34 (t, J=7.9Hz, 1H), 7.29 (q, J=1.4Hz, 1H), 7.27 7.23 (m, 1H), 7.16 (t, J=2.0Hz, 1H), 7.01 6.92 (m, 2H), 3.86 (s, 3H), 2.43 (d, J= 1.3Hz,3H).
Carbon-13 nmr spectra: (101MHz, Chloroform-d) δ 193.27,162.00,160.51,159.95, 144.48,140.81,136.14,129.99,126.00,121.19,121.02,118.11,117.32,116.40,114.22, 113.61,103.77,55.38,9.63.
Embodiment 5-25:
Under nitrogen protection, intermediate 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone is divided uniformly Dissipate in oxolane, at room temperature, add sodium hydride, stir 15 minutes.Then in system, add the four of 2 furan carboxyaldehyde Hydrogen tetrahydrofuran solution, adds complete holding system in room temperature, and then stirring reaction 2 hours adds in system and double solvent body Long-pending shrend is gone out reaction, with hydrochloric acid by system regulation to acidity.Filter the thick product separated out, by thick product ethyl alcohol recrystallization be Available clean product.In this step 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone and 2 furan carboxyaldehyde and The mol ratio of sodium hydride is 1:1:2, and the inventory that every milliliter of reaction dissolvent is corresponding is 0.045g.Gained furan chalcone derives Thing is: (E)-3-(furan-2-base)-1-(4-hydroxy-3-methyl benzofuran-5-base)-2-propylene-1-ketone, yield 77%, should The structure of derivant is:
Molecular formula: C16H12O4
Chinese name: (E)-3-(furan-2-base)-1-(4-hydroxy-3-methyl benzofuran-5-base)-2-propylene-1-ketone
English name: (E)-3-(furan-2-yl)-1-(4-hydroxy-3-methylbenzofuran-5-yl) prop-2-en-1-one
Molecular weight: 268.07
Outward appearance: yellow solid
Proton nmr spectra: (400MHz, Chloroform-d) δ 14.05 (s, 1H), 7.79 (d, J=9.0Hz, 1H), 7.68 (d, J=15.1Hz, 1H), 7.63 7.52 (m, 2H), 7.29 (q, J=1.4Hz, 1H), 6.98 (d, J=8.9Hz, 1H), 6.75 (d, J=3.4Hz, 1H), 6.53 (dd, J=3.4,1.8Hz, 1H), 2.44 (d, J=1.4Hz, 3H).
Carbon-13 nmr spectra: (101MHz, Chloroform-d) δ 192.94,161.93,160.50,151.66, 145.21,140.75,130.41,126.02,118.31,118.06,117.31,116.67,114.26,112.81,103.75, 9.66.
Embodiment 5-26:
Under nitrogen protection, intermediate 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone is divided uniformly Dissipate in oxolane, at room temperature, add sodium hydride, stir 15 minutes.Then in system, add the four of 2 thiophene carboxaldehyde Hydrogen tetrahydrofuran solution, adds complete holding system in room temperature, and then stirring reaction 2 hours adds in system and double solvent body Long-pending shrend is gone out reaction, with hydrochloric acid by system regulation to acidity.Filter the thick product separated out, by thick product ethyl alcohol recrystallization be Available clean product.In this step 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone and 2 thiophene carboxaldehyde and The mol ratio of sodium hydride is 1:1:2, and the inventory that every milliliter of reaction dissolvent is corresponding is 0.045g.Gained furan chalcone derives Thing is: (E)-1-(4-hydroxy-3-methyl benzofuran-5-base)-3-(thiophene-2-base)-2-propylene-1-ketone, yield 79%, should The structure of derivant is:
Molecular formula: C16H12O3S
Chinese name: (E)-1-(4-hydroxy-3-methyl benzofuran-5-base)-3-(thiophene-2-base)-2-propylene-1-ketone
English name: (E)-1-(4-hydroxy-3-methylbenzofuran-5-yl)-3-(thiophen-2-yl) prop-2-en-1-one
Molecular weight: 284.05
Outward appearance: dark red solid
Proton nmr spectra: (400MHz, Chloroform-d) δ 14.04 (s, 1H), 8.07 (dt, J=15.1,0.7Hz, 1H), 7.78 (d, J=8.9Hz, 1H), 7.51 7.44 (m, 2H), 7.41 (dt, J=3.4,0.9Hz, 1H), 7.32 (q, J= 1.4Hz, 1H), 7.14 (dd, J=5.0,3.6Hz, 1H), 7.02 (d, J=8.9Hz, 1H), 2.46 (d, J=1.4Hz, 3H).
Carbon-13 nmr spectra: (101MHz, Chloroform-d) δ 192.25,161.45,160.00,140.29, 139.84,136.55,131.89,128.72,127.96,125.39,119.01,117.61,116.82,113.63,103.27, 9.15.

Claims (4)

1. a substituted furan chalcone derivant, it is characterised in that there is the structure as shown in formula I:
Wherein,
B ring is selected from phenyl, furyl or thienyl；
R1、R2、R3It is each independently selected from hydrogen atom, halogen, hydroxyl, cyano group, nitro, the alkyl chain of C1～C7, the alkane of C1～C7 Epoxide, dimethylamino or diethylin.
Substituted furan chalcone derivant the most according to claim 1, it is characterised in that this substituted furan looks into ear Ketones derivant has any one structure following:
3. the preparation method of the substituted furan chalcone derivant described in claim 1 or 2, it is characterised in that include with Lower step:
(1) by 1, hydroresorcinol and potassium hydroxide are dispersed in water, after stirring at normal temperature 5min, add chloracetyl acetic acid second The methanol solution of ester；After reaction system is stirred at room temperature 5 days, it is acidified with the hydrochloric acid of 4N；Filter the reactant liquor after acidifying, To solid product: 3-methyl-4-oxygen-4,5,6,7-tetrahydrochysene benzfuran-2-Ethyl formate；
Described 1, hydroresorcinol and potassium hydroxide, the mol ratio of chloroacetyl acetacetic ester are 1:1:1, every milliliter of water corresponding 1, The inventory of hydroresorcinol is 0.1g, and the inventory of the chloroacetyl acetacetic ester that every ml methanol is corresponding is 0.2g；
(2) by the mixing of 3-methyl-4-oxygen-4,5,6,7-tetrahydrochysene benzfuran-2-Ethyl formate, potassium hydroxide methanol and water Solvent dissolves；After reaction system is stirred at room temperature reaction 5h, adjust pH to 1 with the hydrochloric acid of 6N；Filtering reacting liquid, obtains solid Product: 3-methyl-4-oxygen-4,5,6,7-tetrahydrochysene benzfuran-2-formic acid；
Described mixed solvent is that methanol is formulated by the volume ratio of 2.5:1 with water；The 3-methyl that every milliliter of mixed solvent is corresponding- 4-oxygen-4, the inventory of 5,6,7-tetrahydrochysene benzfuran-2-Ethyl formates is 0.2g, 3-methyl-4-oxygen-4,5,6,7-tetrahydrochysene benzene And the mol ratio of furan-2-Ethyl formate and potassium hydroxide is 1:6；
(3) by 3-methyl-4-oxygen-4,5,6,7-tetrahydrochysene benzfuran-2-formic acid are dispersed in diethylene glycol, add copper powder and Pyridine；Reaction system is heated to 175 DEG C, is kept stirring for 10h；Reaction system is cooled to room temperature, adds frozen water, and with 4N's Hydrochloric acid is acidified；Reactant liquor after being acidified with petroleum ether extraction three times, washes with water once by the extract of merging, then will extraction Liquid anhydrous sodium sulfate is dried, is spin-dried for, and obtains solid product: 3-methyl-6,7-Dihydrobenzofuranes-4-(5H)-one；
Wherein, 3-methyl-4-oxygen-4 that every milliliter of diethylene glycol is corresponding, the inventory of 5,6,7-tetrahydrochysene benzfuran-2-formic acid is 0.1g；3-methyl-4-oxygen-4,5,6,7-tetrahydrochysene benzfuran-2-formic acid is 1:1:2 with the mol ratio of copper powder and pyridine；
(4) under nitrogen protection, sodium hydride is scattered in ethylene glycol dimethyl ether solution uniformly, reaction system is cooled to 0 DEG C, it being subsequently adding 3-methyl-6, the ethylene glycol dimethyl ether solution of 7-Dihydrobenzofuranes-4 (5H)-one, holding system is stirred at 0 DEG C Mix 30min；In system, add the ethylene glycol dimethyl ether solution of ethyl acetate, then system is heated to 90 DEG C；After keeping 3h, System is cooled to room temperature, adds saturated ammonium chloride solution cancellation reaction；Being extracted with ethyl acetate 3 times, organic facies is with anhydrous Sodium sulfate is dried, concentrates, and obtains product: 5-acetyl-3-methyl-6, the thick product of 7-Dihydrobenzofuranes-4 (5H)-one；
Described 3-methyl-6,7-Dihydrobenzofuranes-4 (5H)-one is 1:5:3 with sodium hydride, the mol ratio of ethyl acetate, every milli 3-methyl-6,7-Dihydrobenzofuranes-4 (5H) the-one inventory rising glycol dimethyl ether corresponding is 0.04g；
(5) by 5-acetyl-3-methyl-6,7-Dihydrobenzofuranes-4 (5H)-one is dispersed in toluene solution, in system Addition 2,3-bis-chloro-5,6-dicyan 1,4-benzoquinone, it is heated to 130 DEG C and keeps 6h；System is cooled to room temperature, after filtration, concentrates filter Liquid；Filtrate is separated with silica gel chromatographic column, obtains the pure product of 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone Thing；
Rubbing of described 5-acetyl-3-methyl-6,7-Dihydrobenzofuranes-4 (5H)-one 5,6-dicyan 1,4-benzoquinone chloro-with 2,3-bis- That ratio is 1:1.2,5-acetyl-3-methyl-6 that every milliliter of toluene is corresponding, and the inventory of 7-Dihydrobenzofuranes-4 (5H)-one is 0.1g；
(6) under nitrogen protection, by uniform for step (5) gained 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone Be scattered in reaction dissolvent a, keep system at room temperature；It is subsequently adding highly basic, stirs 10min～1h；Add in system again Enter a solution of reactive group, react 1 hour～24 hours；It is subsequently adding and doubles the shrend of solvent a volume and go out reaction, then use Hydrochloric acid is by the most acid for system regulation；Filter and separate out thick product, i.e. obtain pure substituted furan chalcone derivative with ethyl alcohol recrystallization Analog derivative；
In reaction system, 1-(4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone and reactive group, the mol ratio of highly basic For 1:1～5:1～5；Every milliliter of 1-corresponding for reaction dissolvent a (4-hydroxy-3-methyl benzofuran-5-base) ethyl-1-ketone Inventory is 0.02 to 0.06g；Described reaction dissolvent a is oxolane or dioxane；
The structural formula of described reactive group is:
Wherein, B ring is selected from phenyl, furyl or thienyl；R1、R2、R3It is each independently selected from hydrogen atom, halogen, hydroxyl, cyanogen Base, nitro, the alkyl chain of C1～C7, the alkoxyl of C1～C7, dimethylamino or diethylin.
Method the most according to claim 3, it is characterised in that step (6) described highly basic is sodium hydride or hydrofining.
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