CN101440080B - Mechanochemical preparation of flavonoid - Google Patents
Mechanochemical preparation of flavonoid Download PDFInfo
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- CN101440080B CN101440080B CN2008101632520A CN200810163252A CN101440080B CN 101440080 B CN101440080 B CN 101440080B CN 2008101632520 A CN2008101632520 A CN 2008101632520A CN 200810163252 A CN200810163252 A CN 200810163252A CN 101440080 B CN101440080 B CN 101440080B
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- 238000002360 preparation method Methods 0.000 title claims abstract description 40
- 229930003935 flavonoid Natural products 0.000 title claims description 30
- 235000017173 flavonoids Nutrition 0.000 title claims description 30
- 150000002215 flavonoids Chemical class 0.000 title 1
- 238000006243 chemical reaction Methods 0.000 claims abstract description 66
- -1 flavone compounds Chemical class 0.000 claims abstract description 38
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 29
- 239000000741 silica gel Substances 0.000 claims abstract description 29
- 229910002027 silica gel Inorganic materials 0.000 claims abstract description 29
- 238000000034 method Methods 0.000 claims abstract description 16
- 230000035484 reaction time Effects 0.000 claims abstract description 8
- 238000000227 grinding Methods 0.000 claims abstract description 5
- 239000011541 reaction mixture Substances 0.000 claims abstract description 5
- 239000002994 raw material Substances 0.000 claims abstract description 4
- 238000000746 purification Methods 0.000 claims description 27
- 239000000203 mixture Substances 0.000 claims description 25
- 239000007787 solid Substances 0.000 claims description 23
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 claims description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 17
- 239000002904 solvent Substances 0.000 claims description 13
- 239000000460 chlorine Substances 0.000 claims description 10
- 229910052801 chlorine Inorganic materials 0.000 claims description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- 238000000498 ball milling Methods 0.000 claims description 6
- FXBYOMANNHFNQV-UHFFFAOYSA-L magnesium;hydrogen sulfate Chemical compound [Mg+2].OS([O-])(=O)=O.OS([O-])(=O)=O FXBYOMANNHFNQV-UHFFFAOYSA-L 0.000 claims description 6
- 238000000926 separation method Methods 0.000 claims description 5
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 4
- 238000009835 boiling Methods 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 4
- 239000000706 filtrate Substances 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 4
- FWFGVMYFCODZRD-UHFFFAOYSA-N oxidanium;hydrogen sulfate Chemical compound O.OS(O)(=O)=O FWFGVMYFCODZRD-UHFFFAOYSA-N 0.000 claims description 4
- 229920006395 saturated elastomer Polymers 0.000 claims description 4
- 239000011734 sodium Substances 0.000 claims description 4
- 229910052708 sodium Inorganic materials 0.000 claims description 4
- JXAZAUKOWVKTLO-UHFFFAOYSA-L sodium pyrosulfate Chemical compound [Na+].[Na+].[O-]S(=O)(=O)OS([O-])(=O)=O JXAZAUKOWVKTLO-UHFFFAOYSA-L 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- JXRVKYBCWUJJBP-UHFFFAOYSA-L calcium;hydrogen sulfate Chemical compound [Ca+2].OS([O-])(=O)=O.OS([O-])(=O)=O JXRVKYBCWUJJBP-UHFFFAOYSA-L 0.000 claims description 3
- APGUSRKQFBWUPZ-UHFFFAOYSA-K disulfooxyalumanyl hydrogen sulfate Chemical compound [Al+3].OS([O-])(=O)=O.OS([O-])(=O)=O.OS([O-])(=O)=O APGUSRKQFBWUPZ-UHFFFAOYSA-K 0.000 claims description 3
- PIGJJOFBKFPZQG-UHFFFAOYSA-L hydrogen sulfate;iron(2+) Chemical compound [Fe+2].OS([O-])(=O)=O.OS([O-])(=O)=O PIGJJOFBKFPZQG-UHFFFAOYSA-L 0.000 claims description 3
- ISWJOCMVDARDLS-UHFFFAOYSA-L zinc;hydrogen sulfate Chemical compound [Zn+2].OS([O-])(=O)=O.OS([O-])(=O)=O ISWJOCMVDARDLS-UHFFFAOYSA-L 0.000 claims description 3
- 239000013078 crystal Substances 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 2
- 229930003944 flavone Natural products 0.000 abstract description 30
- 235000011949 flavones Nutrition 0.000 abstract description 30
- 238000004519 manufacturing process Methods 0.000 abstract description 7
- GAMYVSCDDLXAQW-AOIWZFSPSA-N Thermopsosid Natural products O(C)c1c(O)ccc(C=2Oc3c(c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O4)c3)C(=O)C=2)c1 GAMYVSCDDLXAQW-AOIWZFSPSA-N 0.000 abstract 3
- VHBFFQKBGNRLFZ-UHFFFAOYSA-N vitamin p Natural products O1C2=CC=CC=C2C(=O)C=C1C1=CC=CC=C1 VHBFFQKBGNRLFZ-UHFFFAOYSA-N 0.000 abstract 3
- 239000003054 catalyst Substances 0.000 abstract 1
- 238000005070 sampling Methods 0.000 description 23
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 19
- 238000005160 1H NMR spectroscopy Methods 0.000 description 19
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 19
- 150000002213 flavones Chemical class 0.000 description 13
- 229960004756 ethanol Drugs 0.000 description 5
- BNNLMTDHLVCZDZ-UHFFFAOYSA-N O1C(=CC(=O)C2=CC=CC=C12)C1=CC=CC=C1.[Cl] Chemical class O1C(=CC(=O)C2=CC=CC=C12)C1=CC=CC=C1.[Cl] BNNLMTDHLVCZDZ-UHFFFAOYSA-N 0.000 description 4
- 238000007363 ring formation reaction Methods 0.000 description 4
- OMICQBVLCVRFGN-UHFFFAOYSA-N 2-(4-methoxyphenyl)-1-benzopyran-4-one Chemical compound C1=CC(OC)=CC=C1C1=CC(=O)C2=CC=CC=C2O1 OMICQBVLCVRFGN-UHFFFAOYSA-N 0.000 description 2
- OPHKKQQCOYMLPW-UHFFFAOYSA-N 2-(4-methylphenyl)chromen-4-one Chemical class C1=CC(C)=CC=C1C1=CC(=O)C2=CC=CC=C2O1 OPHKKQQCOYMLPW-UHFFFAOYSA-N 0.000 description 2
- JECYUBVRTQDVAT-UHFFFAOYSA-N 2-acetylphenol Chemical group CC(=O)C1=CC=CC=C1O JECYUBVRTQDVAT-UHFFFAOYSA-N 0.000 description 2
- YTMFRMLVZQOBDR-UHFFFAOYSA-N 2-phenyl-3,4-dihydro-2h-chromen-4-ol Chemical compound O1C2=CC=CC=C2C(O)CC1C1=CC=CC=C1 YTMFRMLVZQOBDR-UHFFFAOYSA-N 0.000 description 2
- WTHXDBOJBGYKTM-UHFFFAOYSA-N 3,5-dichloro-2-phenylchromen-4-one Chemical class ClC=1C(=O)C=2C(Cl)=CC=CC=2OC=1C1=CC=CC=C1 WTHXDBOJBGYKTM-UHFFFAOYSA-N 0.000 description 2
- JSKLFWYOKPWRSQ-UHFFFAOYSA-N 6-chloro-2-(4-chlorophenyl)chromen-4-one Chemical class C1=CC(Cl)=CC=C1C1=CC(=O)C2=CC(Cl)=CC=C2O1 JSKLFWYOKPWRSQ-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 239000012445 acidic reagent Substances 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 238000000875 high-speed ball milling Methods 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 0 *c(c(*)c1*)c(*)c(*)c1/C1=C\COCc(c(*)c(*)c(*)c2*)c2O1 Chemical compound *c(c(*)c1*)c(*)c(*)c1/C1=C\COCc(c(*)c(*)c(*)c2*)c2O1 0.000 description 1
- CKSVYVHLZNMXLX-UHFFFAOYSA-N 2-(4-nitrophenyl)chromen-4-one Chemical class C1=CC([N+](=O)[O-])=CC=C1C1=CC(=O)C2=CC=CC=C2O1 CKSVYVHLZNMXLX-UHFFFAOYSA-N 0.000 description 1
- MLYYOHQNXPDGGV-UHFFFAOYSA-N 3,5-dimethoxy-2-phenylchromen-4-one Chemical compound COC=1C(=O)C=2C(OC)=CC=CC=2OC=1C1=CC=CC=C1 MLYYOHQNXPDGGV-UHFFFAOYSA-N 0.000 description 1
- KHSJXDWFRGYVSF-UHFFFAOYSA-N 3,5-dimethyl-2-phenylchromen-4-one Chemical class CC=1C(=O)C=2C(C)=CC=CC=2OC=1C1=CC=CC=C1 KHSJXDWFRGYVSF-UHFFFAOYSA-N 0.000 description 1
- GUNMIGXOVQWXEQ-UHFFFAOYSA-N 3-nitro-2-phenylchromen-4-one Chemical class O1C2=CC=CC=C2C(=O)C([N+](=O)[O-])=C1C1=CC=CC=C1 GUNMIGXOVQWXEQ-UHFFFAOYSA-N 0.000 description 1
- ANVFDWBCVDQNEZ-UHFFFAOYSA-N 6-methoxy-2-(4-methoxyphenyl)-1-benzopyran-4-one Chemical compound C1=CC(OC)=CC=C1C1=CC(=O)C2=CC(OC)=CC=C2O1 ANVFDWBCVDQNEZ-UHFFFAOYSA-N 0.000 description 1
- RDMTVGAVRNFIEE-UHFFFAOYSA-N 6-methyl-2-(4-methylphenyl)chromen-4-one Chemical class C1=CC(C)=CC=C1C1=CC(=O)C2=CC(C)=CC=C2O1 RDMTVGAVRNFIEE-UHFFFAOYSA-N 0.000 description 1
- NOQJBXPAMJLUSS-UHFFFAOYSA-N 6-methyl-2-phenylchromen-4-one Chemical class C=1C(=O)C2=CC(C)=CC=C2OC=1C1=CC=CC=C1 NOQJBXPAMJLUSS-UHFFFAOYSA-N 0.000 description 1
- ZDFHPVOEUNRYMP-UHFFFAOYSA-N 6-nitro-2-phenylchromen-4-one Chemical class C=1C(=O)C2=CC([N+](=O)[O-])=CC=C2OC=1C1=CC=CC=C1 ZDFHPVOEUNRYMP-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- 229960000935 dehydrated alcohol Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 235000021050 feed intake Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- DQFBYFPFKXHELB-VAWYXSNFSA-N trans-chalcone Chemical compound C=1C=CC=CC=1C(=O)\C=C\C1=CC=CC=C1 DQFBYFPFKXHELB-VAWYXSNFSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
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- Pyrane Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a mechanochemical preparation method for flavone compounds with a structure shown in a formula (II), which comprises the following steps: 1-(2'-hydroxy phenyl)-3-aryl-1, 3-propanedione with a structure shown in a formula (I) is taken as a raw material, hydrosulfate is taken as a catalyst, and silica gel is taken as a grinding aid to perform a ball grinding reaction in a closed ball grinding tank; and after the reaction is finished, a reaction mixture is separated and purified to obtain the flavone compounds with the structure shown in the formula (II). The method has the advantages of short reaction time, generally higher reaction yield, safe and reliable production, low production cost, simple post-treatment, small pollution and so on, and is the preparation method for the flavone compounds with better popularization and application prospects.
Description
(1) technical field
The present invention relates to a kind of Mechanochemical preparation of flavonoid compound.
(2) background technology
Flavonoid compound is the important natural product of a class, has anti-cardiovascular disease, anti-inflammatory, anti-liver virus, various active such as antibiotic.Flavonoid compound can directly obtain from food, also can extract from the plant of being rich in flavonoid compound, makes various protective foodss as foodstuff additive.The synthetic generally attention that is subjected to the chemist of flavonoid compound.
The existing quite long history of the chemosynthesis research of flavonoid compound, classical synthetic method mainly contains two kinds of routes, i.e. phenyl styryl ketone route and β-propanedione route.β-propanedione route is o-hydroxyacetophenone and aryl formyl chloride (or aryl formic acid or aryl formic anhydride) XianCheng's ester, and intramolecularly Claisen resets and generates β-propanedione intermediate again, and last cyclization generates flavonoid compound.Wherein ring-closure reaction is most important.
Acidization is often adopted in the cyclization of β-propanedione, promptly raw material in solvent with the acid reagent generation flavones that reacts.This method generally needs to carry out at reflux temperature, and the reaction times is longer.In recent years, the someone adopted I
2-DMSO, Co
III(salpr) (OH) or trifluoromethanesulfonic acid wait to synthesize flavones, also the someone adopts CuCl
2Or [EtNH
3] NO
3The synthetic flavones of auxiliary microwave method, but these methods still are in the research exploratory stage at present.
Mechanochemistry (mechnochemisty) also is called mechanical force and chemical, is to specialize in object in the effect of high energy mechanical power with bring out a subject that issues living physicochemical change, and be one of front subject of Green Chemistry.Solid-state chemical reaction under the mechanical force, the reaction system microenvironment is different from the solution, can form high local concentrations at reactive site, both improved speed of reaction, improve productive rate and selectivity again, also can make the separation purification of product become simple, reduced production cost simultaneously again.What is more important owing to there is not the intervention of solvent, can avoid in the reaction process solvent to the pollution of environment.Yet there are no the report that adopts the mechanochemistry method to prepare flavonoid compound.
Therefore, the ring-closure reaction of finishing β-propanedione with the mechanochemistry method prepares flavonoid compound, is the important breakthrough to traditional flavonoid compound synthetic method.
(3) summary of the invention
The technical problem to be solved in the present invention provide a kind of easy and simple to handle, production safety is reliable, the reaction times is short, reaction yield is high, production cost is low, do not have the preparation method of the flavonoid compound that the three wastes produce substantially.
The technical solution adopted in the present invention is:
A kind of structure is suc as formula the Mechanochemical preparation of the flavonoid compound shown in (II), described method comprises: with structure suc as formula the 1-shown in (I) (2 '-hydroxy phenyl)-3-aryl-1, the 3-propanedione is a raw material, with the hydrosulfate is catalyzer, with silica gel is grinding aid, ball-milling reaction in the closed ball milling jar; Reaction finishes the afterreaction mixture and obtains structure suc as formula the flavonoid compound shown in (II) after separation and purification.Reaction formula is as follows:
In formula (I), the formula (II), R
1～R
9Independent separately is H, CH
3, Cl, Br, OH, OCH
3Or NO
2
The present invention's suggestion usually reacts under the state of high speed ball milling, and the high speed ball milling of indication is often referred to rotating speed between 1290～2220rpm.
Hydrosulfate of the present invention can be selected from the combination of following one or more arbitrary proportions: sal enixum, sodium pyrosulfate, magnesium hydrogen sulfate, calcium bisulfate, aluminium hydrogen sulfate, hydrogen sulfate zinc, hydrogen sulfate iron; Contain or do not contain crystal water in the structural formula of described hydrosulfate.Further, described hydrosulfate is preferably the mixing of following one or more arbitrary proportions: sulfuric acid monohydrate hydrogen sodium, sal enixum, magnesium hydrogen sulfate.
Hydrosulfate of the present invention, 1-(2 '-hydroxy phenyl)-3-aryl-1, the ratio of the amount of substance that feeds intake of 3-propanedione compounds be recommended as 1: 3～and 1: 20, be preferably 1: 4～1: 10.
Described silica gel quality is 1-(2 '-hydroxy phenyl)-3-aryl-1, and 5～20 times of 3-propanedione compounds quality are preferably 5～8 times.
The described reaction times was generally 2～20 minutes, was preferably 5～10 minutes.
Described separation purification method carries out according to following steps: the solvent with heat washes complete reaction mixture, filters, and filtrate is steamed under boiling state and fallen partial solvent to saturated, is cooled to room temperature, separates out solid, and drying obtains flavonoid compound.
Described solvent is the combination of following one or more arbitrary proportions: ethanol, methyl alcohol, ethyl acetate, methylene dichloride, further, described solvent is for being ethanol.
Comparatively concrete, recommend described method to carry out: in ball grinder, to press hydrosulfate: 1-(2 '-hydroxy phenyl)-3-aryl-1 according to following steps, 3-propanedione compounds is 1: 4～10 to feed intake, and described hydrosulfate is the combination of one or more arbitrary proportions in sulfuric acid monohydrate hydrogen sodium, sal enixum, the magnesium hydrogen sulfate; Adding 1-(2 '-hydroxy phenyl)-3-aryl-1, the silica gel that 3-propanedione compounds quality is 5～8 times.To place ball mill in the ball grinder with the rotating speed ball-milling reaction of 1290～1920rpm 5～10 minutes.After reaction finishes, with hot ethanol complete reaction mixture is washed, filter, filtrate is steamed under boiling state and is fallen part ethanol to saturated, is cooled to room temperature, separates out solid, and drying obtains flavonoid compound.
Beneficial effect of the present invention is embodied in: (1) original method reaction generally all is to carry out in solvent, and the inventive method has been got rid of and easily environment produced the solvent that pollutes; (2) the inventive method need not to use strongly-acid reagent; (3) the inventive method has shortened the reaction times greatly; (4) the inventive method yield height not only, but also make reaction substrate select face to widen greatly, before having solved for the 1-of different substituents (2 '-hydroxy phenyl)-3-phenyl-1,3-propanedione derivative, yield changes problem greatly;
To sum up, the present invention has the reaction times weak point, reaction yield is generally higher, production safety is reliable, production cost is low, aftertreatment is simple and pollute advantages such as few, is a kind of preparation method with flavonoid compound of better popularizing application prospect.
(4) embodiment
The present invention is described further below in conjunction with specific embodiment, but protection scope of the present invention is not limited in this:
Embodiment 1: the preparation of flavones
In the 75mL ball grinder, add 1-(2 '-hydroxy phenyl)-3-phenyl-1, and the 3-propanedione (2.40g, 10mmol), (0.07g 0.5mmol) and silica gel (12g), adds abrading-ball to sal enixum again, tightens cover.Ball grinder is put into ball mill make mixture reaction 5min with the operation of the rotating speed of 1290rpm, TLC (sampling is dissolved in DMF) follows the tracks of extent of reaction.After reaction finishes, with hot dehydrated alcohol reaction mixture is washed, filter, filtrate is steamed under boiling state and is fallen part ethanol to saturated, is cooled to room temperature, separates out solid, and drying obtains flavones 2.02g, yield 90%.
White solid, mp:96-97 ℃.
1H NMR (400MHz, CDCl3): δ=8.24 (d, J=8.0Hz, 1H, ArH), 7.94 (d, J=8.0Hz, 2H, ArH), 7.71 (t, J=8.0Hz, 1H, ArH), 7.53-7.60 (m, 4H, ArH), 7.43 (t, J=8.0Hz, 1H, ArH), 6.86 (s, 1H, CH).
13C NMR (100MHz, CDCl
3): δ=163.33,156.29,133.77,131.75,131.59,129.03,126.27,125.68,125.21,120.11,118.17,107.64.IR (KBr): 1646,1605,1568,1128,768cm
-1.MS (EI): m/z (%)=222 (100) [M
+], 194 (60), 165 (9), 120 (55), 92 (43)
Embodiment 2: the preparation of flavones
In the 75mL ball grinder, add 1-(2 '-hydroxy phenyl)-3-phenyl-1, and the 3-propanedione (2.40g, 10mmol), (0.14g 1mmol) and silica gel (12g), adds abrading-ball to sal enixum again, tightens cover.Ball grinder is put into ball mill make mixture reaction 5min with the operation of the rotating speed of 1290rpm, TLC (sampling is dissolved in DMF) follows the tracks of extent of reaction.Purification procedures obtains flavones 2.04g with embodiment 1, yield 91%, and physical data is with embodiment 1.
Embodiment 3: the preparation of flavones
In the 75mL ball grinder, add 1-(2 '-hydroxy phenyl)-3-phenyl-1, and the 3-propanedione (2.40g, 10mmol), (0.27g 2mmol) and silica gel (24g), adds abrading-ball to sal enixum again, tightens cover.Ball grinder is put into ball mill make mixture reaction 5min with the operation of the rotating speed of 1290rpm, TLC (sampling is dissolved in DMF) follows the tracks of extent of reaction.Purification procedures obtains flavones 2.09g with embodiment 1, yield 93%, and physical data is with embodiment 1.
Embodiment 4: the preparation of flavones
In the 75mL ball grinder, add 1-(2 '-hydroxy phenyl)-3-phenyl-1, and the 3-propanedione (2.40g, 10mmol), (0.45g 3.3mmol) and silica gel (24g), adds abrading-ball to sal enixum again, tightens cover.Ball grinder is put into ball mill make mixture reaction 5min with the operation of the rotating speed of 1290rpm, TLC (sampling is dissolved in DMF) follows the tracks of extent of reaction.Purification procedures obtains flavones 2.11g with embodiment 1, yield 94%, and physical data is with embodiment 1.
Embodiment 5: the preparation of flavones
In the 75mL ball grinder, add 1-(2 '-hydroxy phenyl)-3-phenyl-1, and the 3-propanedione (2.40g, 10mmol), (0.27g 2mmol) and silica gel (48g), adds abrading-ball to sal enixum again, tightens cover.Ball grinder is put into ball mill make mixture reaction 5min with the operation of the rotating speed of 1290rpm, TLC (sampling is dissolved in DMF) follows the tracks of extent of reaction.Purification procedures obtains flavones 2.00g with embodiment 1, yield 89%, and physical data is with embodiment 1.
The preparation of embodiment 6:4 '-chlorine flavones
In the 75mL ball grinder, add 1-(2 '-hydroxy phenyl)-3-(4 " chloro-phenyl-)-1, and the 3-propanedione (2.75g, 10mmol), (0.12g 1mmol) and silica gel (14g), adds abrading-ball to sodium pyrosulfate again, tightens cover.Ball grinder is put into ball mill make mixture reaction 5min with the operation of the rotating speed of 1290rpm, TLC (sampling is dissolved in DMF) follows the tracks of extent of reaction.Purification procedures is with embodiment 1, obtain 4 '-chlorine flavones 2.31g, yield 90%.
White solid, mp:185-187 ℃.
1H NMR (400MHz, CDCl
3): δ=8.21 (d, J=8.0Hz, 1H, ArH), 7.84 (d, J=8.0Hz, 2H, ArH), 7.70 (t, J=8.0Hz, 1H, ArH), 7.54 (d, J=8.0Hz, 1H, ArH), 7.48 (d, J=8.0Hz, 2H, ArH), 7.42 (t, J=8.0Hz, 1H, ArH), 6.78 (s, 1H, CH).
13C NMR (100MHz, CDCl
3): δ=178.08,162.09,156.06,137.79,133.81,130.15,129.29,127.47,125.65,125.27,123.84,117.95,107.60.IR (KBr): 1641,1466,1090,828,772cm
-1.MS (EI): m/z (%)=256 (100) [M
+], 258 (M
++ 2,36), 230 (14), 228 (46), 221 (15), 120 (67), 92 (32)
Embodiment 7:6,4 '-the dichloro flavones
In the 75mL ball grinder, add 1-(2 '-hydroxyl-4 '-chloro-phenyl-)-3-(4 " chloro-phenyl-)-1, the 3-propanedione (3.09g, 10mmol), (0.14g 1mmol) and silica gel (16g), adds abrading-ball to sulfuric acid monohydrate hydrogen sodium again, tightens cover.Ball grinder is put into ball mill make mixture reaction 5min with the operation of the rotating speed of 1290rpm, TLC (sampling is dissolved in DMF) follows the tracks of extent of reaction.Purification procedures is with embodiment 1, obtain 6,4 '-dichloro flavones 2.62g, yield 90%.
White solid, mp:226-227 ℃.
1H NMR (400MHz, CDCl
3): δ=8.19 (s, 1H, ArH), 7.85 (d, J=8.0Hz, 2H, ArH), 7.64-7.67 (m, 1H, ArH), 7.51-7.54 (m, 3H, ArH), 6.79 (s, 1H, CH).
13C NMR (100MHz, CDCl
3): δ=176.98,162.51,154.49,138.21,134.09,131.40,129.90,129.47,127.57,125.25,124.94,119.75,107.63.IR (KBr): 1658,1492,1438,1092,906,831,664cm
-1.MS (EI): m/z (%)=290 (10) [M
+], 293 (M
++ 2,2), 262 (100), 199 (60), 163 (87)
The preparation of embodiment 8:4 '-methoxy flavone
In the 75mL ball grinder, add 1-(2 '-hydroxy phenyl)-3-(4 " p-methoxy-phenyl)-1, and the 3-propanedione (2.70g, 10mmol), (0.22g 1mmol) and silica gel (14g), adds abrading-ball to magnesium hydrogen sulfate again, tightens cover.Ball grinder is put into ball mill make mixture reaction 5min with the operation of the rotating speed of 1290rpm, TLC (sampling is dissolved in DMF) follows the tracks of extent of reaction.Purification procedures is with embodiment 1, obtain 4 '-methoxy flavone 2.37g, yield 94%.
Faint yellow solid, mp:157-159 ℃.
1H NMR (400MHz, CDCl
3): δ=8.21 (d, J=8.0Hz, 1H, ArH), 7.85 (d, J=8.4Hz, 2H, ArH), 7.65-7.69 (m, 1H, ArH), 7.53 (d, J=8.0Hz, 1H, ArH), 7.40 (t, J=7.2Hz, 1H, ArH), 6.98-7.01 (m, 2H, ArH), 6.72 (s, 1H, CH), 3.87 (s, 1H, CH
3).
13C NMR (100MHz, CDCl
3): δ=178.22,163.25,162.28,156.03,133.45,127.86,125.50,124.95,123.80,120.08,117.86,114.33,106.01,55.39.IR (KBr): 1649,1608,1465,1380,1133,827,767cm
-1.MS (EI): m/z (%)=252 (100) [M
+], 237 (7), 221 (15), 209 (13), 132 (63)
The preparation of embodiment 9:4 '-methyl flavones
In the 75mL ball grinder, add 1-(2 '-hydroxy phenyl)-3-(4 " aminomethyl phenyl)-1, and the 3-propanedione (2.54g, 10mmol), (0.23g 1mmol) and silica gel (13g), adds abrading-ball to calcium bisulfate again, tightens cover.Ball grinder is put into ball mill make mixture reaction 5min with the operation of the rotating speed of 1290rpm, TLC (sampling is dissolved in DMF) follows the tracks of extent of reaction.Purification procedures is with embodiment 1, obtain 4 '-methyl flavones 2.10g, yield 89%.
Yellow solid, mp:108-111 ℃.
1H NMR (400MHz, CDCl
3): δ=8.21 (d, J=8.0Hz, 1H, ArH), 7.78 (s, 2H, ArH), 7.65 (t, J=4.0Hz, 1H, ArH), 7.52 (s, 1H, ArH), 7.27 (s, 1H, ArH), 7.38 (t, J=8Hz, 2H, ArH), 6.76 (s, 1H, CH), 2.40 (s, 3H, CH
3).
13C NMR (100MHz, CDCl
3): δ=178.26,163.37,156.05,142.10,133.49,129.61,128.73,126.04,125.49,124.96,123.83,117.92,106.76,21.38.IR (KBr): 1637,1465,1371,1227,817,752,634cm
-1.MS (EI): m/z (%)=236 (100) [M
+], 221 (44), 120 (36), 115 (37), 104 (10), 92 (23)
Embodiment 10:6,8-two bromo-4 '-preparation of chlorine flavones
In the 75mL ball grinder, add 1-(2 '-hydroxyl-3 ', 5 '-dibromo phenyl)-3-(4 " aminomethyl phenyl)-1, the 3-propanedione (4.32g, 10mmol), (0.32g 1mmol) and silica gel (22g), adds abrading-ball to aluminium hydrogen sulfate again, tightens cover.Ball grinder is put into ball mill make mixture reaction 5min with the operation of the rotating speed of 1290rpm, TLC (sampling is dissolved in DMF) follows the tracks of extent of reaction.Purification procedures obtains 6 with embodiment 1,8-two bromo-4 '-chlorine flavones 3.73g, yield 90%.
Yellow solid, mp:248-251 ℃.
1H NMR (400MHz, CDCl
3): δ=8.29 (s, 1H, ArH), 8.04 (s, 1H, ArH), 7.93 (d, J=8.0Hz, 2H, ArH), 7.53 (d, J=8.0Hz, 2H, ArH), 6.84 (s, 1H, CH).
13C NMR (100MHz, CDCl
3): δ=176.21,162.51,151.74,139.47,138.63,129.63,129.41,127.89,127.74,126.00,118.73,118.11,113.03,107.29.IR (KBr): 1649,1612,1492,1092,839,699cm
-1.MS (EI): m/z (%)=414 (100) [M
+], 416 (M
++ 2,74), 278 (98), 250 (11), 197 (16), 163 (10), 136 (15)
Embodiment 11:7-methyl-4 '-preparation of chlorine flavones
In the 75mL ball grinder, add 1-(2 '-hydroxyl-4 '-aminomethyl phenyl)-3-(4 " chloro-phenyl-)-1, the 3-propanedione (2.89g, 10mmol), (0.26g 1mmol) and silica gel (15g), adds abrading-ball to hydrogen sulfate zinc again, tightens cover.Ball grinder is put into ball mill make mixture reaction 5min with the operation of the rotating speed of 1290rpm, TLC (sampling is dissolved in DMF) follows the tracks of extent of reaction.Purification procedures is with embodiment 1, obtain 7-methyl-4 '-chlorine flavones 2.49g, yield 92%.
Yellow solid, mp:177.9-180 ℃.
1H NMR (400MHz, CDCl
3): δ=8.05 (d, J=8.0Hz, 1H, ArH), 7.77-7.80 (m, 2H, ArH), 7.43-7.46 (m, 2H, ArH), 7.29 (s, 1H, ArH), 7.19 (d, J=8.0Hz, 1H, ArH), 6.70 (s, 1H, ArH), 2.47 (s, 3H, ArH).
13C NMR (100MHz, CDCl
3): δ=177.89,161.60,156.05,145.11,137.55,130.11,129.14,127.24,126.66,125.25,121.46,117.63,107.36,21.69.IR (KBr): 1638,1490,1410,1092,906,827,813,477cm
-1.MS (EI): m/z (%)=270 (5) [M
+], 242 (100), 178 (90), 152 (70), 78 (6)
Embodiment 12:6,4 '-preparation of dichloro flavones
In the 75mL ball grinder, add 1-(2 '-hydroxyl-4 '-chloro-phenyl-)-3-(4 " chloro-phenyl-)-1, the 3-propanedione (3.09g, 10mmol), (0.35g 1mmol) and silica gel (16g), adds abrading-ball to hydrogen sulfate iron again, tightens cover.Ball grinder is put into ball mill make mixture reaction 5min with the operation of the rotating speed of 1290rpm, TLC (sampling is dissolved in DMF) follows the tracks of extent of reaction.Purification procedures is with embodiment 1, obtain 6,4 '-dichloro flavones 2.62g, yield 90%.
White solid, mp:226-227 ℃.
1H NMR (400MHz, CDCl
3): δ=8.19 (s, 1H, ArH), 7.85 (d, J=8.0Hz, 2H, ArH), 7.64-7.67 (m, 1H, ArH), 7.51-7.54 (m, 3H, ArH), 6.79 (s, 1H, CH).
13C NMR (100MHz, CDCl
3): δ=176.98,162.51,154.49,138.21,134.09,131.40,129.90,129.47,127.57,125.25,124.94,119.75,107.63.IR (KBr): 1658,1492,1438,1092,906,831,664cm
-1.MS (EI): m/z (%)=290 (10) [M
+], 293 (M
++ 2,2), 262 (100), 199 (60), 163 (87)
The preparation of embodiment 13:2 '-chlorine flavones
In the 75mL ball grinder, add 1-(2 '-hydroxy phenyl)-3-(4 " chloro-phenyl-)-1, the 3-propanedione (2.75g, 10mmol), sal enixum (0.14g, 1mmol), (0.12g 1mmol) and silica gel (14g), adds abrading-ball to sodium pyrosulfate again, tightens cover.Ball grinder is put into ball mill make mixture reaction 5min with the operation of the rotating speed of 1290rpm, TLC (sampling is dissolved in DMF) follows the tracks of extent of reaction.Purification procedures is with embodiment 1, obtain 2 '-chlorine flavones 2.39g, yield 93%.
Yellow solid, mp:193-195 ℃.
1H NMR (400MHz, CDCl
3): δ=8.26 (d, J=8.0Hz, 1H, ArH), 7.62-7.71 (m, 2H, ArH), 7.39-7.53 (m, 5H, ArH), 6.67 (s, 1H, CH).
13C NMR (100MHz, CDCl
3): δ=177.96,162.47,156.50,133.81,132.75,131.69,130.69,130.52,127.00,125.60,125.22,123.72,118.09,112.89.IR (KBr): 1651,1368,1153,1066,909,767cm
-1.MS (EI): m/z (%)=256 (100) [M
+], 258 (M
++ 2,34), 228 (39), 221 (42), 165 (13), 120 (63), 92 (47)
Embodiment 14:6-methyl-4 '-preparation of chlorine flavones
In the 75mL ball grinder, add 1-(2 '-hydroxyl-4 '-aminomethyl phenyl)-3-(4 " chloro-phenyl-)-1, the 3-propanedione (2.89g, 10mmol), (0.14g 1mmol) and silica gel (15g), adds abrading-ball to sal enixum again, tightens cover.Ball grinder is put into ball mill make mixture reaction 2min with the operation of the rotating speed of 1820rpm, TLC (sampling is dissolved in DMF) follows the tracks of extent of reaction.Purification procedures is with embodiment 1, obtain 6-methyl-4 '-chlorine flavones 2.41g, yield 89%.
Faint yellow solid, mp:198-199 ℃.
1H NMR (400MHz, CDCl
3): δ=7.99 (s, 1H, ArH), 7.83 (d, J=8.4Hz, 2H, ArH), 7.43-7.51 (m, 4H, ArH), 6.76 (s, 1H, CH), 2.46 (s, 3H, CH
3).
13C NMR (100MHz, CDCl
3): δ=178.30,161.97,154.37,137.70,135.32,135.06,130.26,129.27,127.43,125.01,123.48,117.73,107.43,20.86.IR (KBr): 1643,1621,1483,1089,902,820,707cm
-1.MS (EI): m/z (%)=270 (100) [M
+], 272 (40), 242 (30), 235 (15), 134 (95), 106 (20)
The preparation of embodiment 15:4 '-methyl flavones
In the 75mL ball grinder, add 1-(2 '-hydroxy phenyl)-3-(4 " aminomethyl phenyl)-1, and the 3-propanedione (2.54g, 10mmol), (0.14g 1mmol) and silica gel (13g), adds abrading-ball to sal enixum again, tightens cover.Ball grinder is put into ball mill make mixture reaction 20min with the operation of the rotating speed of 1820rpm, TLC (sampling is dissolved in DMF) follows the tracks of extent of reaction.Purification procedures is with embodiment 1, obtain 4 '-methyl flavones 2.08g, yield 88%.
Yellow solid, mp:108-111 ℃.
1H NMR (400MHz, CDCl
3): δ=8.21 (d, J=8.0Hz, 1H, ArH), 7.78 (s, 2H, ArH), 7.65 (t, J=4.0Hz, 1H, ArH), 7.52 (s, 1H, ArH), 7.27 (s, 1H, ArH), 7.38 (t, J=8Hz, 2H, ArH), 6.76 (s, 1H, CH), 2.40 (s, 3H, CH
3).
13C NMR (100MHz, CDCl
3): δ=178.26,163.37,156.05,142.10,133.49,129.61,128.73,126.04,125.49,124.96,123.83,117.92,106.76,21.38.IR (KBr): 1637,1465,1371,1227,817,752,634cm
-1.MS (EI): m/z (%)=236 (100) [M
+], 221 (44), 120 (36), 115 (37), 104 (10), 92 (23)
Embodiment 16:6,4 '-preparation of dimethyl flavones
In the 75mL ball grinder, add 1-(2 '-hydroxyl-4 '-aminomethyl phenyl)-3-(4 " aminomethyl phenyl)-1, the 3-propanedione (2.68g, 10mmol), (0.14g 1mmol) and silica gel (14g), adds abrading-ball to sal enixum again, tightens cover.Ball grinder is put into ball mill make mixture reaction 10min with the operation of the rotating speed of 1820rpm, TLC (sampling is dissolved in DMF) follows the tracks of extent of reaction.Purification procedures is with embodiment 1, obtain 6,4 '-dimethyl flavones 2.33g, yield 93%.
White solid, mp:151-152 ℃.
1H NMR (400MHz, CDCl
3): δ=8.00 (s, 1H, ArH), 7.80 (d, J=8.0Hz, 2H, ArH), 7.44-7.50 (m, 2H, ArH), 7.31 (d, J=8.0Hz, 2H, ArH), 6.77 (s, 1H, CH), 2.46 (s, 3H, CH
3), 2.43,2.46 (s, 3H, CH
3).
13C NMR (100MHz, CDCl
3): δ=178.49,163.42,154.50,142.06,135.03,134.80,129.70,129.08,126.16,125.01,123.64,117.77,106.81,21.45,20.88.IR (KBr): 1643,1613,1483,817cm
-1.MS (EI): m/z (%)=250 (100) [M
+], 235 (30), 222 (25), 134 (80), 115 (17), 106 (17), 78 (10)
The preparation of embodiment 17:6-methyl flavones
In the 75mL ball grinder, add 1-(2 '-hydroxyl-4 '-aminomethyl phenyl)-3-phenyl-1, the 3-propanedione (2.54g, 10mmol), (0.14g 1mmol) and silica gel (13g), adds abrading-ball to sal enixum again, tightens cover.Ball grinder is put into ball mill make mixture reaction 10min with the operation of the rotating speed of 1820rpm, TLC (sampling is dissolved in DMF) follows the tracks of extent of reaction.Purification procedures obtains 6-methyl flavones 2.17g, yield 92% with embodiment 1.
Yellow solid, mp:121-122 ℃.
1H NMR (400MHz, CDCl
3): δ=8.00 (s, 1H, ArH), 7.90 (d, J=8.0Hz, 2H, ArH), 7.43-7.52 (m, 5H, ArH), 6.79 (s, 1H, CH), 2.45 (s, 3H, CH
3).
13C NMR (100MHz, CDCl
3): δ=178.46,163.14,154.43,135.10,134.90,131.78,131.42,128.92,126.16,124.93,123.51,117,76,107.31,20.85.IR (KBr): 1638,1615,1482,1359,1044,883,814,778cm
-1.MS (EI): m/z (%)=236 (100) [M
+], 208 (30), 134 (71), 106 (17), 78 (12)
Embodiment 18:6-methyl-4 '-preparation of chlorine flavones
In the 75mL ball grinder, add 1-(2 '-hydroxyl-4 '-aminomethyl phenyl)-3-(4 " chloro-phenyl-)-1, the 3-propanedione (2.89g, 10mmol), (0.14g 1mmol) and silica gel (15g), adds abrading-ball to sal enixum again, tightens cover.Ball grinder is put into ball mill make mixture reaction 10min with the operation of the rotating speed of 1920rpm, TLC (sampling is dissolved in DMF) follows the tracks of extent of reaction.Purification procedures is with embodiment 1, obtain 6-methyl-4 '-chlorine flavones 2.38g, yield 88%.
Faint yellow solid, mp:198-199 ℃.
1H NMR (400MHz, CDCl
3): δ=7.99 (s, 1H, ArH), 7.83 (d, J=8.4Hz, 2H, ArH), 7.43-7.51 (m, 4H, ArH), 6.76 (s, 1H, CH), 2.46 (s, 3H, CH
3).
13C NMR (100MHz, CDCl
3): δ=178.30,161.97,154.37,137.70,135.32,135.06,130.26,129.27,127.43,125.01,123.48,117.73,107.43,20.86.IR (KBr): 1643,1621,1483,1089,902,820,707cm
-1.MS (EI): m/z (%)=270 (100) [M
+], 272 (40), 242 (30), 235 (15), 134 (95), 106 (20)
The preparation of embodiment 19:6-nitro flavones
In the 75mL ball grinder, add 1-(2 '-hydroxyl-4 '-nitrophenyl)-3-phenyl-1, the 3-propanedione (2.85g, 10mmol), (0.14g 1mmol) and silica gel (15g), adds abrading-ball to sal enixum again, tightens cover.Ball grinder is put into ball mill make mixture reaction 10min with the operation of the rotating speed of 1290rpm, TLC (sampling is dissolved in DMF) follows the tracks of extent of reaction.Purification procedures obtains 6-nitro flavones 2.38g, yield 89% with embodiment 1.
Faint yellow solid, mp:194.6-195.1 ℃.
1H NMR (400MHz, CDCl
3): δ=9.12 (s, 1H, ArH), 8.52 (d, J=8.0Hz, 1H, ArH), 7.93-7.95 (m, 2H, ArH), 7.74 (d, J=4.0Hz, 1H, ArH), 7.55-7.63 (m, 3H, ArH), 6.90 (s, 1H, CH).
13C NMR (100MHz, CDCl
3): δ=176.67,164.15,159.08,144.86,132.39,130.78,129.30,128.15,126.45,124.11,122.52,119.84,107.89.IR (KBr): 1646,1610,1454,1340,1135,922,841,772,679,627cm
-1.MS (EI): m/z (%)=267 (100) [M
+], 267 (35), 221 (22), 165 (32), 139 (19), 102 (61)
The preparation of embodiment 20:4 '-nitro flavones
In the 75mL ball grinder, add 1-(2 '-hydroxy phenyl)-3-(4 " nitrophenyl)-1, and the 3-propanedione (2.85g, 10mmol), (0.14g 1mmol) and silica gel (15g), adds abrading-ball to sal enixum again, tightens cover.Ball grinder is put into ball mill make mixture reaction 10min with the operation of the rotating speed of 1290rpm, TLC (sampling is dissolved in DMF) follows the tracks of extent of reaction.Purification procedures is with embodiment 1, obtain 4 '-nitro flavones 2.27g, yield 85%.
Yellow solid, mp:241-243 ℃.
1H NMR (400MHz, CDCl
3): δ=8.11-8.40 (m, 5H, ArH), 7.48-7.76 (m, 3H, ArH), 6.92 (s, 1H, CH).
13C NMR (100MHz, CDCl
3): δ=177.93,160.56,156.18,149.46,137.66,134.31,127.21,125.88,125.75,124.23,123.96,118.19,108.64.IR (KBr): 1659,1520,1467,1346,1130,857,750,692cm
-1.MS (EI): m/z (%)=267 (25) [M
+], 236 (100), 208 (25), 166 (9), 115 (13), 92 (12)
Embodiment 21:6-methoxyl group-4 '-preparation of nitro flavones
In the 75mL ball grinder, add 1-(2 '-hydroxyl-4 '-p-methoxy-phenyl)-3-(4 " nitrophenyl)-1, the 3-propanedione (3.15g, 10mmol), (0.14g 0.5mmol) and silica gel (16g), adds abrading-ball to sal enixum again, tightens cover.Ball grinder is put into ball mill make mixture reaction 10min with the operation of the rotating speed of 1290rpm, TLC (sampling is dissolved in DMF) follows the tracks of extent of reaction.Purification procedures is with embodiment 1, obtain 6-methoxyl group-4 '-nitro flavones 2.73g, yield 92%.
Faint yellow solid, mp:207.1-207.8 ℃.
1H NMR (400MHz, CDCl
3): δ=8.39 (d, J=8.0Hz, 2H, ArH), 8.11 (t, J=4.0Hz, 2H, ArH), 7.61 (d, J=4.0Hz, 1H, ArH), 7.55 (d, J=8.0Hz, 1H, ArH), 7.33-7.36 (m, 1H, ArH), 6.90 (s, 1H, CH), 3.96 (s, 3H, CH
3).
13C NMR (100MHz, CDCl
3): δ=177.90,160.343,157.40,151.02,149.37,137.75,127.16,124.58,124.45,124.25,119.60,108.80,104.90,56.01.IR (KBr): 1642,1607,1518,1488,1347,1020,853,826,697cm
-1.MS (EI): m/z (%)=297 (100) [M
+], 267 (28), 150 (60), 107 (43), 79 (32)
Embodiment 22:6,4 '-preparation of dimethoxy flavone
In the 75mL ball grinder, add 1-(2 '-hydroxy phenyl)-3-phenyl-1, and the 3-propanedione (3.00g, 10mmol), (0.14g 1mmol) and silica gel (15g), adds abrading-ball to sal enixum again, tightens cover.Ball grinder is put into ball mill make mixture reaction 10min with the operation of the rotating speed of 1290rpm, TLC (sampling is dissolved in DMF) follows the tracks of extent of reaction.Purification procedures is with embodiment 1, obtain 6,4 '-dimethoxy flavone 2.65g, yield 94%.
White solid, mp:196.1-196.2 ℃.
1H NMR (400MHz, CDCl
3): δ=7.88 (d, J=12.0Hz, 2H, ArH), 7.61 (d, J=4.0Hz, 1H, ArH), 7.45 (d, J=12.0Hz, 1H, ArH), 7.29 (d, J=4.0Hz, 1H, ArH), 7.03 (d, J=8.0Hz, 2H, ArH), 6.76 (s, 1H, CH), 3.92 (s, 3H, OCH
3), 3.90 (s, 3H, OCH
3).
13C NMR (100MHz, CDCl
3): δ=178.30,163.28,162.36,156.95,151.04,127.97,124.54,124.16,123.59,119.39,114.47,105.52,104.91,55.96,55.51.IR (KBr): 1649,1608,1515,1466,1382,1268,1195,1026,827,768cm
-1.MS (EI): m/z (%)=282 (100) [M
+], 272 (35), 252 (24), 150 (96), 132 (24), 107 (29)
The preparation of embodiment 23:4-flavonol
In the 75mL ball grinder, add 1-(2 ', 4 '-dihydroxy phenyl)-3-phenyl-1, the 3-propanedione (2.56g, 10mmol), (0.14g 1mmol) and silica gel (13g), adds abrading-ball to sal enixum again, tightens cover.Ball grinder is put into ball mill make mixture reaction 10min with the operation of the rotating speed of 1290rpm, TLC (sampling is dissolved in DMF) follows the tracks of extent of reaction.Purification procedures obtains 4-flavonol 2.12g, yield 89% with embodiment 1.
White solid, mp:241.1-242.0 ℃.
1H NMR (400MHz, CDCl
3): δ=10.84 (s, 1H, OH), 8.06-8.08 (m, 2H, ArH), 7.90 (d, J=6.8Hz, 1H, ArH), 7.56-7.60 (m, 3H, ArH), 7.02 (d, J=2.0Hz, 1H, ArH), 6.94 (dd, J=2.0Hz, 7.0Hz, 1H, ArH), 6.91 (s, 1H, CH).
13C NMR (100MHz, CDCl
3): δ=176.33,162.74,161.91,157.48,131.48,131.29,129.03,126.50,126.13,116.15,115.04,106.62,102.52.IR (KBr): 3118,2593,1626,1552,1512,1454,1384,1166cm
-1.MS (EI): m/z (%)=238 (100, M
+), 237 (22), 210 (82), 136 (21), 108 (24)
Claims (10)
1. a structure is suc as formula the Mechanochemical preparation of the flavonoid compound shown in (II), described method comprises: with structure suc as formula the 1-shown in (I) (2 '-hydroxy phenyl)-3-aryl-1, the 3-propanedione is a raw material, with the hydrosulfate is catalyzer, with silica gel is grinding aid, ball-milling reaction in the closed ball milling jar; Reaction finishes the afterreaction mixture and obtains structure suc as formula the flavonoid compound shown in (II) after separation and purification; Described hydrosulfate, 1-(2 '-hydroxy phenyl)-3-aryl-1, the ratio of the amount of substance of 3-propanedione compounds is 1: 3～20;
In formula (I), the formula (II), R
1～R
9Independent separately is H, CH
3, Cl, Br, OH, OCH
3Or NO
2
2. the Mechanochemical preparation of flavonoid compound as claimed in claim 1 is characterized in that described hydrosulfate is the combination of following one or more arbitrary proportions: sal enixum, sodium pyrosulfate, magnesium hydrogen sulfate, calcium bisulfate, aluminium hydrogen sulfate, hydrogen sulfate zinc, hydrogen sulfate iron; Contain or do not contain crystal water in the structural formula of described hydrosulfate.
3. the Mechanochemical preparation of flavonoid compound as claimed in claim 2 is characterized in that described hydrosulfate is the combination of following one or more arbitrary proportions: sulfuric acid monohydrate hydrogen sodium, sal enixum, magnesium hydrogen sulfate.
4. as the Mechanochemical preparation of the described flavonoid compound of one of claim 1～3, it is characterized in that described hydrosulfate, 1-(2 '-hydroxy phenyl)-3-aryl-1, the ratio of the amount of substance of 3-propanedione compounds is 1: 4～10.
5. as the Mechanochemical preparation of the described flavonoid compound of one of claim 1～3, it is characterized in that described silica gel quality is 1-(2 '-hydroxy phenyl)-3-aryl-1,5～20 times of 3-propanedione compounds quality.
6. as the Mechanochemical preparation of the described flavonoid compound of one of claim 1～3, it is characterized in that described ball-milling reaction carries out under the speed conditions between 1290～2220rpm.
7. want the Mechanochemical preparation of 6 described flavonoid compounds as right, it is characterized in that the described reaction times is 2～20 minutes.
8. the Mechanochemical preparation of flavonoid compound as claimed in claim 7 is characterized in that the described reaction times is 5～10 minutes.
9. the Mechanochemical preparation of flavonoid compound as claimed in claim 1, it is characterized in that described separation purification method is as follows: the solvent with heat washes complete reaction mixture, filter, filtrate is steamed under boiling state and is fallen partial solvent to saturated, be cooled to room temperature, separate out solid, drying obtains flavonoid compound; Described solvent is the combination of following one or more arbitrary proportions: ethanol, methyl alcohol, ethyl acetate, methylene dichloride.
10. the Mechanochemical preparation of flavonoid compound as claimed in claim 9 is characterized in that described solvent is an ethanol.
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| CN102391058B (en) * | 2011-08-04 | 2013-06-19 | 浙江工业大学 | Method for preparing stilbene compound |
| CN102526515B (en) * | 2011-12-08 | 2013-11-13 | 浙江工业大学 | Method for extracting bamboo leaf flavone |
| CN102755312A (en) * | 2012-07-16 | 2012-10-31 | 中国科学院大连化学物理研究所 | Application of compound with flavone skeleton structure as Parkinsonism treating medicine |
| CN104945303B (en) * | 2015-06-15 | 2017-09-29 | 浙江工业大学 | preparation method of 3-alkenyl indole compound |
| EP3819283A4 (en) * | 2018-07-05 | 2022-03-16 | Unitika Ltd. | Method for producing organic compound |
| CN113308305A (en) * | 2021-06-01 | 2021-08-27 | 浙江工业大学 | Organic solvent-free combined extraction method of thyme essential oil and thyme total flavonoids |
| CN113620919B (en) * | 2021-06-18 | 2023-12-12 | 浙江工业大学 | Mechanical ball milling assisted synthesis method of 2-amino-3-cyano-4H-pyran compound |
| CN113651787B (en) * | 2021-07-28 | 2023-11-03 | 浙江工业大学 | Solvent-free ball milling-amino acid coupling synthesis method of pyran-2-ketone compound |
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| CN1221726A (en) * | 1998-11-27 | 1999-07-07 | 中国科学院上海有机化学研究所 | Diketone compound, its prodn. process and applications |
| CN1335309A (en) * | 2000-07-04 | 2002-02-13 | Basf公司 | New eka-favone and its application in preparation of cosmetic and dermatology |
| WO2006040621A1 (en) * | 2004-10-15 | 2006-04-20 | Council Of Scientific And Industrial Research | Oxy substituted flavones as antihyperglycemic and antidyslipidemic agents |
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| CN1221726A (en) * | 1998-11-27 | 1999-07-07 | 中国科学院上海有机化学研究所 | Diketone compound, its prodn. process and applications |
| CN1335309A (en) * | 2000-07-04 | 2002-02-13 | Basf公司 | New eka-favone and its application in preparation of cosmetic and dermatology |
| WO2006040621A1 (en) * | 2004-10-15 | 2006-04-20 | Council Of Scientific And Industrial Research | Oxy substituted flavones as antihyperglycemic and antidyslipidemic agents |
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