CN104031017A - Synthesis method of flavanone - Google Patents
Synthesis method of flavanone Download PDFInfo
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- CN104031017A CN104031017A CN201310069098.1A CN201310069098A CN104031017A CN 104031017 A CN104031017 A CN 104031017A CN 201310069098 A CN201310069098 A CN 201310069098A CN 104031017 A CN104031017 A CN 104031017A
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- flavanone
- acid
- generalformulaicompound
- synthetic method
- compound
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- 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 relates to a synthesis method of flavanone, especially hydroxyflavanone. The method employs substituted phenol and substituted cinnamic acid as raw materials to undergo acylation and ring-closing reaction under the action of an acidic dehydrating agent, thus obtaining the corresponding flavanone. Compared with traditional multistep methods, the method has the characteristics of high carbon atom utilization rate and high product purity, is suitable for pharmaceutical grade use, and also can be used for further synthesis of flavone.
Description
Technical field
The present invention relates to a kind of synthetic method of flavanone, especially a kind of synthetic method of hydroxyl flavanone.
Background technology
Flavanone kind composition, be commonly called as flavanone, have antibacterial, anti-inflammatory, anticancer, spasmolysis, cholagogic, prevention and treatment hepatopathy, anti-platelet clotting, the effect of anti-congee sample arteriosclerosis, clinical application is infected in treatment bacterium, calm, anticancer class is important natural product class effective component.For example naringenin is the glucoside unit of naringin; belong to flavanone kind composition; often in the nucleocapsid of Anacardiaceae plant stalk tree fruit etc., oriental cherry bud, plum blossom flower bud, extract; there is stronger cough-suppressing phlegm-dispelling functions; the ear edge edema of IPR, vLPR is produced effectively and suppressed; aspect anti-inflammatory, there is certain exploitation and be worth, can be widely used in the fields such as medicine, food.Its production technique is mainly completed by operations such as alcohol extracting, extraction, chromatography, crystallizations, but because content is low, extraction cost is high, and output is few, cannot meet the demand of field of medicaments.Hu Lihong etc. chemistry circular (2003, (1), 12-32) in, system summary existing artificial synthesis, the first closes from the cinnamophenone of hydroxyl protection the flavanone that ring obtains hydroxyl protection, for example 5,7,4 '-trimethoxy flavanone.Then with strong acid condition demethylation, obtain trihydroxy-compound, i.e. naringenin.It two is gram methods of paying, the phosphorus oxychloride of take generates corresponding acyl chlorides as chloride reagent makes substituted cinnamic acid, the aluminum chloride of take makes it and fortified phenol closes ring as catalyzer, as what Li Wenxin was announced in patent CN1296948, pay gram legal system for 5,7-dihydroxyl-4 '-benzyloxy flavanone, but the method is verified discovery through the inventor, in reaction, can there is the esterification products of phenolic hydroxyl group, only having a small amount of is target product.It three is the mono-acidylate methods of Hoesch; 2-cyano group cinnamyl nitrile and phenol acidylate, hydrolysis, decarboxylation, pass ring under zinc chloride-hydrogenchloride catalytic condition obtain flavanone; such as Chen person of outstanding talent, wait the flavanone synthetic method (SCI with improvement of report; 1987; 8(10); 914-6) prepared ten kinds of flavanone, but the reaction that generates 2-cyano group cinnamyl nitrile cannot generally be suitable for regard to being subject to the substituent remarkably influenced of aromatic aldehyde, 4 '-hydroxyl-2-cyano group cinnamyl nitrile is just difficult to synthesize.It four is polyphosphoric acid methods, with fortified phenol and styracin, carrying out condensation reaction under the catalysis of polyphosphoric acid obtains, experimental results show that, if take Phloroglucinol as raw material, one-tenth ring selectivity under this reaction conditions is lower, often obtain a part of having a double meaning ring product or positional isomers, in causing reacting, principal product content is low, is difficult for separation and purification and goes out principal product.
Summary of the invention
The inventor is through attempting and exploring, found take that fortified phenol and substituted cinnamic acid are as raw material, under new acidic dehydration agent effect, single stage method directly obtains the synthetic method of generalformulaⅰcompound, specifically take general formula II compound and general formula III compound is raw material, under the acidic dehydration agent vitriol oil or tosic acid effect, react, directly obtained generalformulaⅰcompound.
R in formula I, II and III
1-R
9h, hydroxyl, C respectively do for oneself
1-C
4alkyl, C
1-C
4alkoxyl group, benzyloxy, halogen atom.
General formula II compound can be phenol, Resorcinol, meta-methoxy phenol, Phloroglucinol or 3,5 ?syringol, be particularly preferably Phloroglucinol; General formula III compound be 4 ?hydroxycinnamic acid, 4 ?methoxy cinnamic acid, 3,4 ?dihydroxycinnamic acid or 3 ?Jia Yang Ji ?4 ?hydroxycinnamic acid.
In this synthetic method, can use arbitrarily inert solvent, use inert solvent can increase the solubleness of organic raw material, reduce the viscosity of reaction mixture, for example tetrahydrofuran (THF), 1,4 ?dioxane, dimethyl sulfoxide (DMSO), tetramethylene sulfone, chlorobenzene etc.
The range of reaction temperature of this synthetic method be 35 ?130 ℃.
Work as R
1-R
9in while being hydroxyl and H, R for example
1, R
3, R
7for hydroxyl, R
2, R
4, R
5, R
6, R
8, R
9during for H, generalformulaⅰcompound is naringenin, and this synthetic method has been avoided the loaded down with trivial details poor efficiency of a plurality of steps such as the upper protection, deprotection of cinnamophenone route; Meanwhile, and take the method that polyphosphoric acid is dewatering agent and compare, effectively reduce the side reaction in reaction, improved carbon atom utilization ratio high, product purity is high.
Specific embodiment
Synthesizing of embodiment 1 naringenin
Phloroglucinol 12.6g, 4-hydroxycinnamic acid 16.4g, tetrahydrofuran (THF) 100g, 98% vitriol oil 20g, keep temperature 50 C reaction 6 hours, reclaim under reduced pressure tetrahydrofuran (THF), residuum drops in 200g frozen water, filter precipitate, fully washing, is dried to obtain 23.1g off-white color solid, HPLC purity assay 98.50%, yield 85%, fusing point: 247-250 ℃.Proton nmr spectra proves target compound.
Embodiment 25,7-dihydroxyl-4 '-benzyloxy flavanone synthetic
Phloroglucinol 12.6g, 4-benzyloxy styracin 25.5g, methyl-sulphoxide 25g; tosic acid 1.8g, nitrogen protection, keeps 120 ℃ of reactions of temperature 10 hours; in process, there is moisture to steam, reclaim under reduced pressure methyl-sulphoxide, residuum drops in 200g water; filter precipitate; fully washing, is dried to obtain 27.2g off-white color solid, HPLC purity assay 98.80%; yield 75%, proton nmr spectra proves target compound.
Embodiment 35,7,4 '-trihydroxy--3 '-methoxyl group flavanone synthetic
Phloroglucinol 12.6g, ferulic acid 19.5g, 1; 4-dioxane 50g, vitriol oil 15g, nitrogen protection; keep temperature 60 C reaction 5 hours, reaction solution drops in 250g frozen water, filters precipitate; fully washing; be dried to obtain 24.2g off-white color solid, HPLC purity assay 98.0%, yield 80%; fusing point: 220-222 ℃, proton nmr spectra proves target compound.
Synthesizing of comparative example's naringenin
Phloroglucinol 12.6g, 4-hydroxycinnamic acid 16.4g, the polyphosphoric acid 80g of content 82%, keeps 100 ℃ of reactions of temperature 6 hours, and reaction mixture drops in 300g frozen water, filter precipitate, fully washing, is dried to obtain 20.1g off-white color solid, and HPLC-MS analyzes naringenin content 80.50%, having a double meaning ring product content 15.2%, Phloroglucinol content 3.1%.
Claims (3)
1. the synthetic method of generalformulaⅰcompound, is characterized by that to take general formula II compound and general formula III compound be raw material, under the effect of the acidic dehydration agent vitriol oil or tosic acid, reacts, and directly obtains generalformulaⅰcompound,
R wherein
1-R
9h, hydroxyl, C respectively do for oneself
1-C
4alkyl, C
1-C
4alkoxyl group, benzyloxy, halogen atom.
2. according to the synthetic method of the generalformulaⅰcompound of claim 1, its formula of II compound is selected from Resorcinol, Phloroglucinol, meta-methoxy phenol or 3,5 ?syringol; General formula III compound be selected from 4 ?hydroxycinnamic acid, 4 ?methoxy cinnamic acid, 4 ?methoxy cinnamic acid, 3,4 ?dihydroxycinnamic acid or 3 ?Jia Yang Ji ?4 ?hydroxycinnamic acid.
3. according to the synthetic method of the generalformulaⅰcompound of claim 1, range of reaction temperature be 35 ?130 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201310069098.1A CN104031017A (en) | 2013-03-05 | 2013-03-05 | Synthesis method of flavanone |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201310069098.1A CN104031017A (en) | 2013-03-05 | 2013-03-05 | Synthesis method of flavanone |
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| CN104031017A true CN104031017A (en) | 2014-09-10 |
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| CN201310069098.1A Pending CN104031017A (en) | 2013-03-05 | 2013-03-05 | Synthesis method of flavanone |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104926773A (en) * | 2015-06-04 | 2015-09-23 | 河南科技大学 | Method for extracting flavanone framework compounds in spina gleditsiae and application of flavanone framework compounds |
| CN111170979A (en) * | 2020-01-06 | 2020-05-19 | 厦门大学 | Preparation method of bioactive compound (S) -2- (4-hydroxyphenyl) -7-methoxy flavanone in Zhangzhou narcissus |
| CN115160280A (en) * | 2022-06-07 | 2022-10-11 | 贵州农业职业学院 | Method for synthesizing flavanone compound |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1296948A (en) * | 1999-11-22 | 2001-05-30 | 华中师范大学 | Synthesis and application of 5,7-dihydroxy-4'-benzyloxyflavanone |
| CN1548439A (en) * | 2003-05-09 | 2004-11-24 | 中国医学科学院药物研究所 | Prepn of racemized and optically active poon essence A and its analog |
| CN101100470A (en) * | 2006-07-07 | 2008-01-09 | 中国医学科学院药物研究所 | Tetranuclear bipyrane coumarin compound |
-
2013
- 2013-03-05 CN CN201310069098.1A patent/CN104031017A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1296948A (en) * | 1999-11-22 | 2001-05-30 | 华中师范大学 | Synthesis and application of 5,7-dihydroxy-4'-benzyloxyflavanone |
| CN1548439A (en) * | 2003-05-09 | 2004-11-24 | 中国医学科学院药物研究所 | Prepn of racemized and optically active poon essence A and its analog |
| CN101100470A (en) * | 2006-07-07 | 2008-01-09 | 中国医学科学院药物研究所 | Tetranuclear bipyrane coumarin compound |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104926773A (en) * | 2015-06-04 | 2015-09-23 | 河南科技大学 | Method for extracting flavanone framework compounds in spina gleditsiae and application of flavanone framework compounds |
| CN111170979A (en) * | 2020-01-06 | 2020-05-19 | 厦门大学 | Preparation method of bioactive compound (S) -2- (4-hydroxyphenyl) -7-methoxy flavanone in Zhangzhou narcissus |
| CN111170979B (en) * | 2020-01-06 | 2022-02-08 | 厦门大学 | Preparation method of bioactive compound (S) -4' -hydroxy-7-methoxy flavanone in Zhangzhou narcissus |
| 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 |
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Application publication date: 20140910 |