CN105001068A - One-step green synthesis method for hydroxychalcone and flavanone - Google Patents
One-step green synthesis method for hydroxychalcone and flavanone Download PDFInfo
- Publication number
- CN105001068A CN105001068A CN201510349875.7A CN201510349875A CN105001068A CN 105001068 A CN105001068 A CN 105001068A CN 201510349875 A CN201510349875 A CN 201510349875A CN 105001068 A CN105001068 A CN 105001068A
- Authority
- CN
- China
- Prior art keywords
- flavanone
- dry sample
- cinnamophenone
- methylene dichloride
- trihydroxy
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
- C07C45/72—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups
- C07C45/74—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups combined with dehydration
-
- 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
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
- C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
- C07D311/28—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only
- C07D311/32—2,3-Dihydro derivatives, e.g. flavanones
Abstract
The invention discloses a one-step green synthesis method for both hydroxychalcone and flavanone, which belongs to the field of organic chemistry. According to the invention, one-step green synthesis of hydroxychalcone and flavanone is realized by reacting 2,4-dihydroxy benzaldehyde with a hydroxyacetophenone derivative at 120 DEG C for 6 h under the catalysis of boric acid, with polyethylene glycol 400 used as a solvent; and gel column chromatography and preparative high performance liquid chromatography are employed for separation, so high-purity hydroxychalcone and high-purity flavanone are obtained. The synthesis method provided by the invention has the advantages of easy availability of raw materials, high product purity, simple operation, simple post-treatment, environment friendliness, low toxicity and good industrial application prospects.
Description
Technical field
The present invention relates to the method for a step green syt hydroxylated chalcone and flavanone, belong to organic chemistry filed.
Background technology
Chalcones is a class of flavonoid compound, has tyrosinase inhibitory activity, in addition antibacterial, anticancer, anti-inflammatory and anti-oxidant isoreactivity.Natural cinnamophenone is extensively present in fruit, vegetables, spices, tea, soybean food and some herbal medicine.The main method of current cinnamophenone synthesis is that aromatic aldehyde and methyl phenyl ketone are in the basic conditions by Clasein-Schmidt condensation reaction.In the past few decades, the method for many synthesizing chalcones is developed from researchist all over the world.But these methods have a lot of defect, as the reaction conditions of harshness, toxic reagent and metal catalyst, strong acid and strong base, oil product, long reaction times, low-yield, low selectivity and loaded down with trivial details finishing sequence.In addition, in most cases, synthesis of hydroxy chalcone derivative needs protection and goes to protect hydroxyl, not only increases reaction step number and time, also increases the chance using poisonous or harmful reagent simultaneously.Although also have some green synthesis methods at present, as used calcium hydroxide to make catalyzer, spent glycol is as reaction solvent etc., and these green synthesis methods also exist the problems such as low-yield, oil product and loaded down with trivial details aftertreatment equally.Flavanone is obtained by cinnamophenone cyclization usually, when synthesizing dihydro flavonoid, exists and synthesizes same problem with cinnamophenone, and need many single step reactions on the basis of cinnamophenone again.
Green synthesis method because of its environmental friendliness, subtract the characteristics such as dirty reduction of discharging, in scientific research and industrial application, there is far-reaching Research Significance and important using value.Along with the raising day by day of environmental protection, economy and social desirability, with the focus adopting green synthetic chemistry that nontoxic raw material, solid acid/alkaline catalysts and green solvent are representative to become research both at home and abroad.The present invention, by using gentle method, selects innoxious solvent as reaction solvent, and selects non-toxic catalyst, single stage method green syt hydroxylated chalcone and hydroxyl dihydro anthoxanthin.
Summary of the invention
The object of the invention is to solve current synthesis of hydroxy class cinnamophenone and flavanone compound exist and use the problem such as toxic reagent and metal catalyst, strong acid and strong base, oil product, long reaction times, low-yield, low selectivity and loaded down with trivial details finishing sequence, a kind of simple to operate, novel method that can obtain the high hydroxylated chalcone of purity and hydroxyl dihydro anthoxanthin is provided.The general formula of described hydroxylated chalcone is such as formula shown in I, and the general formula of hydroxyl dihydro anthoxanthin is such as formula shown in II:
R in formula
1=R
2=R
3=R
4=R
5=hydrogen atom (H), hydroxyl (OH).
Described method, under the catalysis of boric acid, hydroxyacetophenone derivative and 2,4-Dihydroxy benzaldehyde passes through aldol reaction in poly(oxyethylene glycol) 400, first generate hydroxylated chalcone (I), the further cyclisation of hydroxylated chalcone of generation obtains hydroxyl dihydro anthoxanthin (II).The product synthesized by the method obtains hydroxylated chalcone and hydroxyl dihydro anthoxanthin after being separated further by extraction, silica gel column chromatography, gel filtration chromatography or extraction, gel filtration chromatography, preparative liquid chromatography.
In one embodiment of the invention, the structural formula of described hydroxylated chalcone is as shown in formula III, V, VII or IX.
In one embodiment of the invention, shown in the structural formula as I V of described hydroxyl dihydro anthoxanthin, VI, VIII or X.
In one embodiment of the invention, the method preparing compound (III) or (IV) comprises the following steps:
(1) take mol ratio as 2, the 4-Dihydroxy benzaldehydes of 2:1 and 2-hydroxy acetophenone being raw material, under the catalysis of boric acid, take poly(oxyethylene glycol) 400 as solvent, in 120 DEG C of reactions 6 hours;
(2) reaction solution ethyl acetate or methylene dichloride or chloroform extraction 3 times, organic phase is concentrated to obtain dry sample;
(3) silicagel column on dry sample, for 2', 2,4-trihydroxy-cinnamophenone, with methylene dichloride: methyl alcohol (50:1, v/v) wash-out; For 2', 4'-dihydroxyl flavanone, with dichloromethane eluent;
(4) the object eluate sample that step (3) is collected concentrates to obtain dry sample, be separated through silica gel column chromatography, Sephadex LH-20 gel filtration chromatography again, obtain 2', 2,4-trihydroxy-cinnamophenone (III) or 2', 4'-dihydroxyl flavanone (IV).
In one embodiment of the invention, the method preparing compound (V) and (VI) comprises the following steps:
(1) take mol ratio as 2, the 4-Dihydroxy benzaldehydes of 2:1 and 2,6-resacetophenone being raw material, under the catalysis of boric acid, take poly(oxyethylene glycol) 400 as solvent, in 120 DEG C of reactions 6 hours;
(2) reaction solution ethyl acetate or methylene dichloride or trichloromethane etc. extract 3 times, and organic phase is concentrated to obtain dry sample;
(3) silicagel column on dry sample, respectively with methylene dichloride, methylene chloride-methanol (25:1), methylene chloride-methanol (10:1) wash-out;
(4) for 2', 6', 2,4-tetrahydroxy cinnamophenone, collect step (3) methylene chloride-methanol (10:1) wash-out position, for 5,2', 4'-trihydroxy-flavanone, collect step (3) methylene chloride-methanol (25:1) wash-out position, the eluate sample of collection concentrates to obtain dry sample, then is separated through silica gel column chromatography, Sephadex LH-20 gel filtration chromatography, obtain 2' respectively, 6', 2,4-tetrahydroxy cinnamophenone (V) or 5,2', 4'-trihydroxy-flavanone (VI).
In one embodiment of the invention, the method preparing compound (VII) and (VIII) comprises the following steps:
(1) take mol ratio as 2, the 4-Dihydroxy benzaldehydes of 2:1 and 2,4-dihydroxyacetophenone being raw material, under the catalysis of boric acid, take poly(oxyethylene glycol) 400 as solvent, in 120 DEG C of reactions 6 hours;
(2) reaction solution ethyl acetate or methylene dichloride or chloroform extraction 3 times, organic phase is concentrated to obtain dry sample;
(3) silicagel column on dry sample, with methylene dichloride: methyl alcohol (20:1, v/v) wash-out;
(4) eluate sample that step (3) is collected concentrates to obtain dry sample, be separated obtain 2' through Sephadex LH-20 gel filtration chromatography, preparative high performance liquid chromatography again, 4', 2,4-tetrahydroxy cinnamophenone (VII) and 7,2', 4'-trihydroxy-flavanone (VIII).
In one embodiment of the invention, the method preparing compound (IX) and (X) comprises the following steps:
(1) take mol ratio as 2, the 4-Dihydroxy benzaldehydes of 2:1 and 2,4,6-trihydroxy-acetophenone being raw material, under the catalysis of boric acid, take poly(oxyethylene glycol) 400 as solvent, in 120 DEG C of reactions 6 hours;
(2) reaction solution ethyl acetate or methylene dichloride or chloroform extraction 3 times, organic phase is concentrated to obtain dry sample;
(3) silicagel column on dry sample, with methylene dichloride: methyl alcohol (15:1, v/v) wash-out;
(4) eluate sample that step (3) is collected concentrates to obtain dry sample, be separated obtain 2' through Sephadex LH-20 gel filtration chromatography, preparative high performance liquid chromatography again, 4', 6', 2,4-penta hydroxy group cinnamophenone (IX) and 5,7,2', 4'-tetrahydroxy flavanone (X).
Usefulness of the present invention is: a kind of method providing single stage method green syt hydroxylated chalcone and hydroxyl dihydro anthoxanthin, has simple to operate, gentle environmental protection, product purity advantages of higher.
Embodiment
Embodiment 1 2', the preparation method of 2,4-trihydroxy-cinnamophenone
Take 0.036mol 2,4-Dihydroxy benzaldehyde, 0.018mol 2-hydroxy acetophenone, 2.1g boric acid in 50mL round-bottomed flask, add PEG 400 stirring and dissolving of 25mL, be placed in 120 DEG C of oil bath stirring and refluxing 6h, TLC follows the tracks of reaction process.Reaction solution is extracted with ethyl acetate three times, and organic phase is evaporated to drying; Dry sample silica gel (200-300 order) column chromatography, methylene dichloride: methyl alcohol (50:1, v/v) wash-out, TLC detects, and same stream divides and merges rear recycling design, containing the solid part dissolve with methanol of object, then gel filtration chromatography (Sephadex LH-20) is separated further, methanol-water (v/v, 7:3) wash-out, receives flow point with automatic receptor, TLC detects, obtain 2', 2,4-trihydroxy-cinnamophenone.Column chromatography yield is 25.6%, product purity >95%.
2', 2,4-trihydroxy-cinnamophenone spectroscopic data of the nuclear magnetic resonance is as follows:
Molecular formula is C
15h
12o
4.
1H-NMR(Acetone-d
6,400MHz)δ:13.26(1H,s,OH-2'),9.15(2H,br s,OH-2,4),8.31(1H,d,J=15.6Hz,H-β),8.15(1H,dd,J=8.4,1.2Hz,H-6'),7.91(1H,d,J=15.6Hz,H-α),7.74(1H,d,J=8.4Hz,H-6),7.52(1H,ddd,J=8.4,6.8,1.6Hz,H-4'),6.97(1H,m,H-5'),6.95(1H,d,J=8.4Hz,H-3'),6.54(1H,d,J=2.4Hz,H-3),6.48(1H,dd,J=8.4,2.4Hz,H-5)。
13C-NMR(Acetone-d
6,100MHz)δ:195.2(C=O),164.5(C-4),162.8(C-2'),160.4(C-2),142.6(C-β),136.8(C-4'),132.2(C-6),130.9(C-6'),121.2(C-1'),119.6(C-5'),118.9(C-α),117.1(C-3'),115.2(C-1),109.5(C-5),103.7(C-3)。
Embodiment 2 2', the preparation method of 4'-dihydroxyl flavanone
Take 0.036mol 2,4-Dihydroxy benzaldehyde, 0.018mol 2-hydroxy acetophenone, 2.1g boric acid in 50mL round-bottomed flask, add the PEG400 stirring and dissolving of 25mL, be placed in 120 DEG C of oil bath stirring and refluxing 6h, TLC follows the tracks of reaction process.Reaction solution is extracted with ethyl acetate three times, and organic phase is evaporated to drying; Dry sample silica gel (200-300 order) column chromatography, dichloromethane eluent, TLC detects, same stream divides and merges rear recycling design, solid part dissolve with methanol, then gel filtration chromatography (Sephadex LH-20) is separated further, methanol-water (v/v, 7:3) wash-out, receive flow point with automatic receptor, TLC detects, and same stream divides and merges rear recycling design, obtain 2', 4'-dihydroxyl flavanone.Column chromatography yield is 18.4%, product purity >98%.
2', 4'-dihydroxyl flavanone spectroscopic data of the nuclear magnetic resonance is as follows:
Molecular formula is C
15h
12o
4.
1H-NMR(Acetone-d
6,400MHz)δ:7.84(1H,dd,J=8.0,1.6Hz,H-5),7.54(1H,m,H-6),7.35(1H,d,J=8.4Hz,H-6'),7.05(2H,overlapped,H-7,8),6.45(1H,dd,J=8.4,2.4Hz,H-5'),6.49(1H,d,J=2.0Hz,H-3'),5.77(1H,dd,J=13.2,2.4Hz,H-2),3.15(1H,dd,J=16.8,13.2Hz,H-3),2.79(1H,dd,J=16.8,2.4Hz,H-3)。
13C-NMR(Acetone-d
6,100MHz)δ:193.0(C-4,C=O),163.1(C-9),159.5(C-2'),156.3(C-4'),136.7(C-7),129.0(C-6'),127.4(C-5),122.0(C-6),121.9(C-10),118.9(C-8),117.8(C-1'),107.9(C-5'),103.6(C-3'),75.8(C-2),44.0(C-3)。
Embodiment 3 2', the preparation method of 6', 2,4-tetrahydroxy cinnamophenone
Take 0.036mol 2,4-Dihydroxy benzaldehyde, 0.018mol 2,6-resacetophenone, 2.1g boric acid in 50mL round-bottomed flask, add the PEG400 stirring and dissolving of 25mL, be placed in 120 DEG C of oil bath stirring and refluxing 6h, TLC follows the tracks of reaction process.Reaction solution is extracted with ethyl acetate three times, and organic phase is evaporated to drying; Dry sample silica gel column chromatography, use isopyknic methylene dichloride respectively, methylene chloride-methanol (25:1), methylene chloride-methanol (10:1) wash-out, collect methylene chloride-methanol (10:1) wash-out position, recycling design, solid part dissolve with methanol, then gel filtration chromatography (Sephadex LH-20) is separated further, methanol-water (v/v, 7:3) wash-out, TLC detects, and obtains 2', 6', 2,4-tetrahydroxy cinnamophenone [yield (column chromatography gained) is 20.2%, purity >95%].
2,6,2', 4'-tetrahydroxy cinnamophenone spectroscopic data of the nuclear magnetic resonance is as follows:
Molecular formula is C
15h
12o
5.
1H-NMR(Acetone-d
6,400MHz)δ:6.53(1H,d,J=8.4Hz,H-3'),6.56(1H,d,J=8.4Hz,H-5'),6.59(1H,dd,J=8.4,2.4Hz,H-5),6.61(1H,d,J=2.4Hz,H-3),7.12(1H,d,J=16.4Hz,H
α),7.24(1H,dd,J=8.4,8.4Hz,H-4'),7.58(1H,d,J=16.4Hz,H
β),7.64(1H,d,J=8.4Hz,H-6),9.33,9.03(2H,s,OH-2,4),12.68(1H,s,OH-2')。
13C-NMR(Acetone-d
6,100MHz)δ:98.4(C-3),102.2(C-5'),106.4(C-5),109.1(C-3')115.6(C-1'),115.7(C-1),126.0(C-α),130.2(C-6),131.8(C-4'),139.0(C-β),157.4(C-2'),158.2(C-6'),159.6(C-2),163.0(C-4),194.5(C=O)。
The preparation method of embodiment 45,2', 4'-trihydroxy-flavanone
Take 0.036mol 2,4-Dihydroxy benzaldehyde, 0.018mol 2,6-resacetophenone, 2.1g boric acid in 50mL round-bottomed flask, add the PEG400 stirring and dissolving of 25mL, be placed in 120 DEG C of oil bath stirring and refluxing 6h, TLC follows the tracks of reaction process.Reaction solution is extracted with ethyl acetate three times, and organic phase is evaporated to drying; Dry sample silica gel column chromatography, use isopyknic methylene dichloride respectively, methylene chloride-methanol (25:1) wash-out, collect methylene chloride-methanol (25:1) wash-out position, recycling design, solid part dissolve with methanol, filters the insoluble part that obtains that is 5,2', 4'-trihydroxy-flavanone.The further gel filtration chromatography of filtrate (Sephadex LH-20) is separated, methanol-water (v/v, 7:3) wash-out, TLC detects, reclaim and obtain 5 inside solution, 2', 4'-trihydroxy-flavanone [yield (column chromatography gained) is 24.8%, purity >98%].
5,2', 4'-trihydroxy-flavanone spectroscopic data of the nuclear magnetic resonance is as follows:
Molecular formula is C
15h
12o
5.
1H-NMR(Acetone-d
6,400MHz)δ:11.84(1H,s,OH-5),8.64(1H,s,OH-4'),8.39(1H,s,OH-2'),7.44(1H,t,J=8.4Hz,H-7),7.34(1H,d,J=8.4Hz,H-6'),6.49(1H,d,J=6.8Hz,H-6),6.47(1H,d,J=7.6Hz,H-8),6.45(1H,dd,J=8.4,2.4Hz,H-5'),6.48(1H,d,J=2.0Hz,H-3'),5.78(1H,dd,J=13.6,2.8Hz,H-2),3.31(1H,dd,J=17.2,13.2Hz,H-3eq.),2.83(1H,dd,J=17.2,2.8Hz,H-3ax.)。
13C-NMR(Acetone-d
6,100MHz)δ:200.5(C-4,C=O),163.4(C-5),163.2(C-9),159.7(C-2'),156.5(C-4'),139.0(C-7),129.2(C-6'),117.4(C-1'),109.5(C-6),108.9(C-10),108.0(C-5'),103.6(C-3'),75.6(C-2),43.2(C-3)。
Embodiment 5 2', the preparation method of 4', 2,4-tetrahydroxy cinnamophenone sample
Take 0.036mol 2,4-Dihydroxy benzaldehyde, 0.018mol 2,4-dihydroxyacetophenone, 2.1g boric acid in 50mL round-bottomed flask, add the PEG400 stirring and dissolving of 25mL, be placed in 120 DEG C of oil bath stirring and refluxing 6h, TLC follows the tracks of reaction process.Reaction solution is extracted with ethyl acetate three times, and organic phase is evaporated to drying; Silicagel column on dry sample, with methylene dichloride: methyl alcohol (20:1, v/v) wash-out, TLC detects, and after same stream divides merging, recycling design collects to obtain dry thing; Dry sample gel filtration chromatography (Sephadex LH-20) is separated, methanol-water (v/v, 1:1) wash-out, and TLC detects, and same stream divides and merges rear recycling design; Solid methanol dissolves rear preparative high-performance liquid chromatographic (Waters preparative high performance liquid chromatography instrument, dual wavelength detector, preparative column is YMC, 250mm × 20mm, granularity 5 μ) be separated, determined wavelength 369nm, 50% ~ 80% methanol-water gradient elution gets final product [yield (preparation liquid phase gained) is 35.4%, purity 98.4%].
2', 4', the spectroscopic data of the nuclear magnetic resonance of 2,4-tetrahydroxy cinnamophenone is as follows:
Molecular formula is C
15h
12o
5.
1H-NMR(Acetone-d
6,400MHz)δ:13.788(1H,s,OH-2'),9.533(1H,s,OH-4),9.317(1H,s,OH-2),9.004(1H,s,OH-4'),8.22(1H,d,J=15.2Hz,H-β),8.02(1H,d,J=9.2Hz,H-6),7.79(1H,d,J=15.2Hz,H-α),7.69(1H,d,J=8.4Hz,H-6'),6.52(1H,d,J=2.0Hz,H-3),6.462(1H,d,J=7.2,2.4Hz,H-5'),6.457(1H,dd,J=10.0,2.0Hz,H-5),6.36(1H,d,J=2.4Hz,H-3')。
13C-NMR(Acetone-d
6,100MHz)δ:194.5(C=O),167.7(C-4),166.4(C-2),163.1(C-4'),161.1(C-2'),142.4(C-β),133.4(C-6),132.7(C-6'),118.0(C-α),115.9(C-1),115.2(C-1'),109.4(C-5),109.3(C-5'),104.1(C-3),103.9(C-3')。
The preparation method of embodiment 67,2', 4'-trihydroxy-flavanone sample
Take 0.036mol 2,4-Dihydroxy benzaldehyde, 0.018mol 2,4-dihydroxyacetophenone, 2.1g boric acid in 50mL round-bottomed flask, add the PEG400 stirring and dissolving of 25mL, be placed in 120 DEG C of oil bath stirring and refluxing 6h, TLC follows the tracks of reaction process.Reaction solution is extracted with ethyl acetate three times, and organic phase is evaporated to silicagel column on dry dry sample, with methylene dichloride: methyl alcohol (20:1, v/v) wash-out, and TLC detects, and after same stream divides merging, recycling design collects to obtain dry thing; Dry sample gel filtration chromatography (Sephadex LH-20) is separated, methanol-water (v/v, 1:1) wash-out; Preparative high-performance liquid chromatographic (Waters preparative high performance liquid chromatography instrument is used after collecting elutriant, dual wavelength detector, preparative column is YMC, 250mm × 20mm, granularity 5 μ) be separated, determined wavelength 254nm, namely 50% ~ 80% methanol-water gradient elution obtains [yield (preparation liquid phase gained) is 8.0%, purity 99.0%].
7,2', 4'-trihydroxy-flavanone spectroscopic data of the nuclear magnetic resonance is as follows:
Molecular formula is C
15h
12o
5.
1H-NMR(Acetone-d
6,400MHz)δ:2.68(1H,dd,J=2.8,16.8Hz,H-3),3.04(1H,dd,J=13.2,16.8Hz,H-3),5.72(1H,dd,J=2.8,13.2Hz,H-2),6.43(1H,dd,J=8.0,2.4Hz,H-6),6.43(1H,d,J=2.4Hz,H-8),6.47(1H,d,J=2.0Hz,H-3'),6.57(1H,dd,J=8.4,2.0Hz,H-5'),7.33(1H,d,J=8.4Hz,H-6'),7.74(1H,d,J=8.8Hz,H-5),9.47(1H,br s,OH-7),8.65(1H,s,OH-4'),8.41(1H,br s,OH-2')。
13C-NMR(Acetone-d
6,100MHz)δ:43.9(C-3),76.0(C-2),103.6(C-8),103.7(C-3'),107.9(C-6),111.2(C-5'),115.3(C-10),118.0(C-1'),129.0(C-6'),129.6(C-5),156.3(C-9),159.5(C-7),165.1(C-2'),165.3(C-4'),191.3(C=O)。
Embodiment 72', 4', 6', the preparation method of 2,4-penta hydroxy group cinnamophenone sample
Take 0.036mol 2,4-Dihydroxy benzaldehyde, 0.018mol 2,4,6-trihydroxy-acetophenone, 2.1g boric acid in 50mL round-bottomed flask, add the PEG400 stirring and dissolving of 25mL, be placed in 120 DEG C of oil bath stirring and refluxing 6h, TLC follows the tracks of reaction process.Reaction solution is extracted with ethyl acetate three times, and organic phase is evaporated to drying; Silicagel column on dry sample, with methylene chloride-methanol (15:1) for eluent, TLC detects, and after same stream divides merging, recycling design obtains dry thing; Dry sample gel filtration chromatography (Sephadex LH-20) containing object is separated, methanol-water (v/v, 1:1) wash-out; TLC detects, and same stream divides and merges rear recycling design; Solid is to use preparative high-performance liquid chromatographic (Waters preparative high performance liquid chromatography instrument after dissolve with methanol, dual wavelength detector, preparative column is YMC, 250mm × 20mm, granularity 5 μ) be separated, determined wavelength 254nm, namely 40% ~ 70% methanol-water gradient elution obtains [yield (preparation liquid phase gained) is 28.0%, purity 98.3%].
2', 4', 6', the spectroscopic data of the nuclear magnetic resonance of 2,4-penta hydroxy group cinnamophenone is as follows:
Molecular formula is C
15h
12o
6.
1H-NMR(Acetone-d
6,400MHz)δ:6.48(2H,s,H-3',5'),6.56(1H,dd,J=8.4,2.0Hz,H-5),6.50(1H,d,J=2.0Hz,H-3),7.69(1H,d,J=8.4Hz,H-6),7.79(1H,d,J=15.6Hz,H-α),8.10(1H,d,J=15.6Hz,H-β),9.75,9.56,9.38,(3H,s,OH-4',2,4),12.56(2H,s,OH-2',6')。
13C-NMR(Acetone-d
6,100MHz)δ:92.6(C-3',5'),104.6(C-3),107.2(C-5),118.5(C-1),108.6(C-1'),118.2(C-α),132.3(C-6),137.6(C-β),160.5(C-4),161.6(C-2',6'),163.2(C-2),165.3(C-4),194.5(C=O)。
The preparation method of embodiment 85,7,2', 4'-tetrahydroxy flavanone sample
Take 0.036mol 2,4-Dihydroxy benzaldehyde, 0.018mol 2,4,6-trihydroxy-acetophenone, 2.1g boric acid in 50mL round-bottomed flask, add the PEG400 stirring and dissolving of 25mL, be placed in 120 DEG C of oil bath stirring and refluxing 6h, TLC follows the tracks of reaction process.Reaction solution is extracted with ethyl acetate three times, and organic phase is evaporated to drying; Silicagel column on dry sample, with methylene chloride-methanol (15:1) for eluent, TLC detects, and after same stream divides merging, recycling design obtains dry thing; Dry sample gel filtration chromatography (Sephadex LH-20) containing object is separated, methanol-water (v/v, 1:1) wash-out; TLC detects, and same stream divides and merges rear recycling design; Solid is to use preparative high-performance liquid chromatographic (Waters preparative high performance liquid chromatography instrument after dissolve with methanol, dual wavelength detector, preparative column is YMC, 250mm × 20mm, granularity 5 μ) be separated, determined wavelength 254nm, namely 30% ~ 65% methanol-water gradient elution obtains [yield (preparation liquid phase gained) is 7.0%, purity 99.2%].
5,7,2', 4'-tetrahydroxy flavanone spectroscopic data of the nuclear magnetic resonance is as follows:
Molecular formula is C
15h
12o
6.
1H-NMR(CD
3OD,400MHz)δ:7.22(1H,d,J=8.2Hz,H-6'),6.33(1H,dd,J=8.2,2.4Hz,H-5'),6.31(1H,d,J=2.1Hz,H-3'),5.90(1H,d,J=1.7Hz,H-8),5.86(1H,d,J=2.2Hz,H-6),5.59(1H,dd,J=13.2,2.9Hz,H-2),3.06(1H,dd,J=17.2,13.1Hz,H-3),2.69(1H,dd,J=17.2,2.9Hz,H-3)。
13C-NMR(CD
3OD,100MHz)δ:196.9(C-4,C=O),166.6(C-7),163.6(C-5),163.5(C-9),158.7(C-4'),155.8(C-2'),128.4(C-6'),115.4(C-1'),106.5(C-5'),102.4(C-3'),101.7(C-10),95.7(C-6),94.9(C-8),73.9(C-2),41.1(C-3)。
Although the present invention with preferred embodiment openly as above; but it is also not used to limit the present invention, any person skilled in the art, without departing from the spirit and scope of the present invention; all can do various changes and modification, what therefore protection scope of the present invention should define with claims is as the criterion.
Claims (6)
1. the method for one-step synthesis hydroxylated chalcone and flavanone, it is characterized in that, under the catalysis of boric acid, hydroxyacetophenone derivative and 2,4-Dihydroxy benzaldehyde passes through aldol reaction in poly(oxyethylene glycol) 400, first hydroxylated chalcone is generated, the further cyclisation of hydroxylated chalcone generated obtains hydroxyl dihydro anthoxanthin, after being separated further by extraction, silica gel column chromatography, gel filtration chromatography or extraction, gel filtration chromatography, preparative liquid chromatography, obtain hydroxylated chalcone and hydroxyl dihydro anthoxanthin; The general formula of described hydroxylated chalcone is such as formula shown in I, and the general formula of described hydroxyl dihydro anthoxanthin is such as formula shown in II:
R in formula
1=R
2=R
3=R
4=R
5=H or OH.
2. method according to claim 1, is characterized in that, the structural formula of described hydroxylated chalcone is as shown in formula III, V, VII or IX, and the structural formula of described hydroxyl dihydro anthoxanthin is such as formula shown in IV, VI, VIII or X:
3. method according to claim 1, is characterized in that, comprises the following steps:
(1) take mol ratio as 2, the 4-Dihydroxy benzaldehydes of 2:1 and 2-hydroxy acetophenone being raw material, under the catalysis of boric acid, take poly(oxyethylene glycol) 400 as solvent, in 120 DEG C of reactions 6 hours;
(2) reaction solution ethyl acetate or methylene dichloride or chloroform extraction 3 times, organic phase is concentrated to obtain dry sample;
(3) silicagel column on dry sample, for 2', 2,4-trihydroxy-cinnamophenone, the methylene dichloride to mix by volume: methyl alcohol is eluent; For 2', 4'-dihydroxyl flavanone, with dichloromethane eluent;
(4) the object eluate sample that step (3) is collected concentrates to obtain dry sample, then is separated through silica gel column chromatography, Sephadex LH-20 gel filtration chromatography, obtains 2', 2,4-trihydroxy-cinnamophenone or 2', 4'-dihydroxyl flavanone.
4. method according to claim 1, is characterized in that, comprises the following steps:
(1) take mol ratio as 2, the 4-Dihydroxy benzaldehydes of 2:1 and 2,6-resacetophenone being raw material, under the catalysis of boric acid, take poly(oxyethylene glycol) 400 as solvent, in 120 DEG C of reactions 6 hours;
(2) reaction solution ethyl acetate or methylene dichloride or chloroform extraction 3 times, organic phase is concentrated to obtain dry sample;
(3) silicagel column on dry sample, respectively with methylene dichloride, with volume ratio 25:1 mixing methylene chloride-methanol, with volume ratio 10:1 mixing methylene chloride-methanol wash-out;
(4) for 2', 6', 2,4-tetrahydroxy cinnamophenone, collect the wash-out position of the methylene chloride-methanol that step (3) mixes with volume ratio 10:1, for 5,2', 4'-trihydroxy-flavanone, collect the wash-out position of the methylene chloride-methanol that step (3) mixes with volume ratio 25:1, the eluate sample of collection concentrates to obtain dry sample, then is separated through silica gel column chromatography, SephadexLH-20 gel filtration chromatography, obtain 2' respectively, 6', 2,4-tetrahydroxy cinnamophenone or 5,2', 4'-trihydroxy-flavanone.
5. method according to claim 1, is characterized in that, comprises the following steps:
(1) take mol ratio as 2, the 4-Dihydroxy benzaldehydes of 2:1 and 2,4-dihydroxyacetophenone being raw material, under the catalysis of boric acid, take poly(oxyethylene glycol) 400 as solvent, in 120 DEG C of reactions 6 hours;
(2) reaction solution ethyl acetate or methylene dichloride or chloroform extraction 3 times, organic phase is concentrated to obtain dry sample;
(3) silicagel column on dry sample, the methylene dichloride with 20:1 mixing by volume: methyl alcohol is for eluent;
(4) eluate sample that step (3) is collected concentrates to obtain dry sample, then is separated obtains 2', 4' through Sephadex LH-20 gel filtration chromatography, preparative high performance liquid chromatography, 2,4-tetrahydroxy cinnamophenone and 7,2', 4'-trihydroxy-flavanone.
6. method according to claim 1, is characterized in that, comprises the following steps:
(1) take mol ratio as 2, the 4-Dihydroxy benzaldehydes of 2:1 and 2,4,6-trihydroxy-acetophenone being raw material, under the catalysis of boric acid, take poly(oxyethylene glycol) 400 as solvent, in 120 DEG C of reactions 6 hours;
(2) reaction solution ethyl acetate or methylene dichloride or chloroform extraction 3 times, organic phase is concentrated to obtain dry sample;
(3) silicagel column on dry sample, the methylene dichloride with 15:1 mixing by volume: methyl alcohol is for eluent;
(4) eluate sample that step (3) is collected concentrates to obtain dry sample, then is separated obtains 2', 4' through Sephadex LH-20 gel filtration chromatography, preparative high performance liquid chromatography, 6', 2,4-penta hydroxy group cinnamophenone and 5,7,2', 4'-tetrahydroxy flavanone.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201510349875.7A CN105001068A (en) | 2015-06-23 | 2015-06-23 | One-step green synthesis method for hydroxychalcone and flavanone |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201510349875.7A CN105001068A (en) | 2015-06-23 | 2015-06-23 | One-step green synthesis method for hydroxychalcone and flavanone |
Publications (1)
Publication Number | Publication Date |
---|---|
CN105001068A true CN105001068A (en) | 2015-10-28 |
Family
ID=54373984
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201510349875.7A Pending CN105001068A (en) | 2015-06-23 | 2015-06-23 | One-step green synthesis method for hydroxychalcone and flavanone |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN105001068A (en) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2020087688A1 (en) * | 2018-11-01 | 2020-05-07 | 中国科学院华南植物园 | Dihydrofuran chalcone compound and preparation method therefor |
WO2020087687A1 (en) * | 2018-10-29 | 2020-05-07 | 中国科学院华南植物园 | Isopentenyl chalcone compound and preparation method therefor |
CN115160280A (en) * | 2022-06-07 | 2022-10-11 | 贵州农业职业学院 | Method for synthesizing flavanone compound |
CN115894939A (en) * | 2022-11-02 | 2023-04-04 | 江南大学 | Preparation method and application of chalcone modified organosilicon UVA ultraviolet filter |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101602754A (en) * | 2009-07-16 | 2009-12-16 | 李青山 | A kind of flavanone derivatives and its production and use |
-
2015
- 2015-06-23 CN CN201510349875.7A patent/CN105001068A/en active Pending
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101602754A (en) * | 2009-07-16 | 2009-12-16 | 李青山 | A kind of flavanone derivatives and its production and use |
Non-Patent Citations (2)
Title |
---|
关丽萍等: "羟基查尔酮类衍生物的合成", 《有机化学》 * |
石磊等: "二氢黄酮类衍生物的合成及抗肿瘤活性研究", 《中国药物化学杂志》 * |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2020087687A1 (en) * | 2018-10-29 | 2020-05-07 | 中国科学院华南植物园 | Isopentenyl chalcone compound and preparation method therefor |
US11104631B1 (en) | 2018-10-29 | 2021-08-31 | South China Botanical Garden, Chinese Academy Of Sciences | Isopentenyl chalcone compound and preparation method thereof |
WO2020087688A1 (en) * | 2018-11-01 | 2020-05-07 | 中国科学院华南植物园 | Dihydrofuran chalcone compound and preparation method therefor |
US11161829B1 (en) | 2018-11-01 | 2021-11-02 | South China Botanical Garden, Chinese Academy Of Sciences | Dihydrofuran chalcone compound and preparation method thereof |
CN115160280A (en) * | 2022-06-07 | 2022-10-11 | 贵州农业职业学院 | Method for synthesizing flavanone compound |
CN115160280B (en) * | 2022-06-07 | 2023-08-04 | 贵州农业职业学院 | Synthesis method of flavonoid compound |
CN115894939A (en) * | 2022-11-02 | 2023-04-04 | 江南大学 | Preparation method and application of chalcone modified organosilicon UVA ultraviolet filter |
CN115894939B (en) * | 2022-11-02 | 2023-12-01 | 江南大学 | Preparation method and application of chalcone modified organic silicon UVA ultraviolet filter |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Wähälä et al. | Expedient synthesis of polyhydroxyisoflavones | |
Mihigo et al. | Total synthesis, antiprotozoal and cytotoxicity activities of rhuschalcone VI and analogs | |
CN105001068A (en) | One-step green synthesis method for hydroxychalcone and flavanone | |
Morimoto et al. | Tannins and Related Compounds. LXI.: Isolation and Structures of Novel Bi-and Triflavanoids from the Leaves of Cassia fistula L. | |
Rahman et al. | Synthesis of biologically relevant biflavanoids–a review | |
Asakawa et al. | Prenyl bibenzyls from the liverwort Radula kojana | |
Sagrera et al. | Total Synthesis of 3′, 3′′′-Binaringenin and Related Biflavonoids | |
CN104860912A (en) | Dimer ketone compound and preparation method and application thereof | |
Yilmaz | Synthesis of an oligomer-supported calix [4] arene and selective extraction of Li+ | |
CN102600897A (en) | Design of novel chiral catalyst system and application of novel chiral catalyst system in synthesis of anticancer drug spisulosine (ES-285) | |
Nedialkov et al. | Two benzophenone O-arabinosides and a chromone from Hypericum annulatum | |
Muhaisen | Chemical constituents from the bark of Lannea acida Rich (Anacardiaceae) | |
CN110483541B (en) | Isopentenyl flavonoid compound and preparation method and application thereof | |
Ahmed et al. | Antioxidant activity with flavonoidal constituents from Aerva persica | |
CN104926776B (en) | The green synthesis method of 4- phenacylidene flavane analog derivatives | |
Vitor et al. | Straightforward synthesis of cytosporone analogs AMS35AA and AMS35BB | |
CN108558778B (en) | Dihydro quinazolinone compound and preparation method thereof | |
Jordán et al. | Synthesis of 6, 7-Dibromoflavone and Its Regioselective Diversification via Suzuki–Miyaura Reactions | |
Tahara et al. | New 5-O-methylisoflavones in the roots of yellow lupin (Lupinus luteus L. cv. Barpine) | |
Brahmachari et al. | 5, 8-Dihydroxy-6, 7, 4'-trimethoxyflavone, a novel flavonoid constituent of Linmophila indica | |
Nawghare et al. | Efficient Synthesis of 3‐Methyl‐Flavanones and Evaluation of Their Anti‐Bacterial Activity | |
CN109535120A (en) | The preparation method of 7- substitution -3,4,4,7- tetrahydro cyclobutane and cumarin -5- ketone | |
CA2726277C (en) | Method for the preparation of c-4 coupled flavonoids, proanthocyanidins and analogues thereof | |
Clement et al. | Benzoate esters and flavonoids from Desmos pedunculosus | |
Subburaj et al. | Microwave-Assisted Rate-Enhanced Method for the Synthesis of 2, 2-Dimethyl-2H-chromenes. |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20151028 |
|
RJ01 | Rejection of invention patent application after publication |