CN102351921A - Preparation method of neohesperidin dihydrochalcone - Google Patents
Preparation method of neohesperidin dihydrochalcone Download PDFInfo
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- CN102351921A CN102351921A CN2011102438680A CN201110243868A CN102351921A CN 102351921 A CN102351921 A CN 102351921A CN 2011102438680 A CN2011102438680 A CN 2011102438680A CN 201110243868 A CN201110243868 A CN 201110243868A CN 102351921 A CN102351921 A CN 102351921A
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Abstract
The invention discloses a preparation method of neohesperidin dihydrochalcone, comprising the following steps of: (1) dissolving potassium hydroxide or sodium hydroxide in water with stirring so as to prepare 3-6% of an alkaline solution; (2) adding neohesperidin into the alkaline solution with stirring for dissolution, wherein the ratio of neohesperidin to the alkaline solution is 1: 5-8; (3) adding raneys nickel which accounts for 5-8 wt% the weight of neohesperidin after stirring and dissolving, carrying out a hydrogenation reaction at the hydrogen pressure of 0.01-0.1 MPa, stirring, and reacting for 4-6 hours to obtain a reaction solution; (4) adjusting the pH of the reaction solution to pH 7-7.5 by the use of hydrochloric acid, staying for 24-28 hours, and filtering out crystal solids to obtain the neohesperidin dihydrochalcone crude product. The preparation method disclosed in the invention requires no large pressure to carry out the hydrogenation reaction, is less dangerous, and is convenient for industrial production.
Description
Technical field
The present invention relates to a kind of botanical drug substance hydrogenation process, more specifically, particularly relate to the neohesperidin technology for preparing neohesperidin dihydrochalcone for basic raw material hydrogenation.
Background technology
Neohesperidin dihydrochalcone is the flavone derivative that the neohesperidin hydrogenation that extraction from natural oranges and tangerines obtains is formed.The neohesperidin dihydrochalcone molecular formula is C
28H
38O
15, molecular weight is 612.58, its structural formula is:
As far back as 1963, people such as Horowitz just found that neohesperidin dihydrochalcone has the intensive sweet taste.Its characteristics are sugariness big (sweetness of cane sugar 1500～1800 times), clean taste, and pleasant impression is lasting, and has the effect of splendid shielding bitter taste.Hydrolysis takes place in the glycosyl of NHDC in vivo, and glycosyl is participated in metabolism hardly, so NHDC heat energy value is lower, less than 8.36J/g, can be used as the low-energy food sweeting agent.People carried out toxicological test to it at present, and on the basis of existing toxicological test, had established its sweetening agent status.1997, neohesperidin dihydrochalcone was listed in " foodstuff additive use hygienic standard " amendments by China Ministry of Health, can be used for foodstuffs industry.
The method for preparing at present the neohesperidin dihydrochalcone phenyl styryl ketone mainly is to carry out under greater than the pressure of 2.0MPa at pressure; Usually used catalyzer carries out hydrogenation for relatively more expensive palladium carbon in the reaction, and this kind catalyzer is not easy to be recycled and industrialization production.Mostly the solvent that common hydrogenation is used is the basic solution of methyl alcohol, ethanol, water.
So this method is dangerous big, product yield is not high, and environmental pollution is arranged, and causes present method to be unfavorable for industrialization production like this.
Summary of the invention
The objective of the invention is to overcome the deficiency of above-mentioned existence, it is simple to the object of the present invention is to provide a kind of processing condition to require, and easy to operate, yield is high, and is with low cost, pollutes little neohesperidin dihydrochalcone preparation technology.
Technical scheme of the present invention is following:
A kind of preparation method of neohesperidin dihydrochalcone, said preparation method comprises the steps:
(1) potassium hydroxide or sodium hydroxide under agitation are dissolved in the water, are made into mass percentage concentration and are 3～6% basic solution;
(2) then neohesperidin is added under agitation condition in the said basic solution, the usage ratio of said neohesperidin and said basic solution is 1: 5～8, stirring and dissolving;
(3) add Raney's nickel after the stirring and dissolving, the consumption of wherein said Raney's nickel is 5～8% of a neohesperidin quality, carries out hydrogenation under 0.01～0.1MPa hydrogen pressure, begins then to stir, and reaction 4～6h gets reaction solution;
(4) reaction solution is transferred to pH7～7.5 with hydrochloric acid, leave standstill 24～28 hours after, crystalline solid is leached, the neohesperidin dihydrochalcone crude product.
Another aspect of the present invention; Said preparation method further comprises: with said neohesperidin dihydrochalcone crude product with 5～8 times of purified water heating for dissolving; And with the gac processing of decolouring; Filtered while hot; Crystallisation by cooling 24～28 hours; The leaching crystal, 100 ± 10 ℃ of vacuum-dryings got the neohesperidin dihydrochalcone finished product in 3～5 hours.
Another aspect of the present invention, said gac are 8～10% of neohesperidin dihydrochalcone crude product quality.
Another aspect of the present invention, basic solution mass percentage concentration described in the said step 1 is 3%.
Another aspect of the present invention, the usage ratio of neohesperidin and said basic solution described in the said step 2 is 1: 5.
Another aspect of the present invention, the consumption of Raney's nickel described in the said step 3 is 5% of a neohesperidin quality.
Another aspect of the present invention, hydrogen pressure described in the said step 3 is 0.01～0.02MPa.
Another aspect of the present invention transfers to neutrality with reaction solution with hydrochloric acid in the said step 4.
Preparing method of the present invention obtains yield >=85% of neohesperidin dihydrochalcone, purity >=96.5%.The prepared neohesperidin dihydrochalcone of the present invention passes through infrared spectra, and high performance liquid phase etc. characterize evaluation, and consistent with the characterization data of 2010 editions European Pharmacopoeias, spectrogram is seen description of drawings.
The present invention is a starting raw material with the natural plant raw material neohesperidin, and through the basic solution open loop, Raney's nickel is a hydrogenation catalyst, under the low pressure hydrogen condition, carries out hydrogenation, can obtain high yield, high-quality neohesperidin dihydrochalcone.
Beneficial effect of the present invention is: preparation method disclosed by the invention does not need to carry out hydrogenation under the bigger condition of pressure, and is dangerous little, is convenient to industrialization production; With water is solvent, and cost is low, non-environmental-pollution; With the Raney's nickel is hydrogenation catalyst, with low cost, recyclable utilization; The neohesperidin dihydrochalcone product yield is high, and quality is good, and production operation is simple.
Description of drawings
Fig. 1, neohesperidin dihydrochalcone infrared spectra;
Fig. 2, neohesperidin dihydrochalcone high performance liquid phase spectrogram.
Embodiment
Present embodiment prepares the method for operating of neohesperidin dihydrochalcone to carry out according to following two steps: the preparation of neohesperidin dihydrochalcone crude product: 9g potassium hydroxide or NaOH under agitation are dissolved in pour in the 2000ml round-bottomed flask in the 150ml running water; Under stirring condition, add the 30g neohesperidin in this alkali lye then; After the stirring and dissolving; Add the 1.5g Raney's nickel; Begin to stir; 0.01 carry out hydrogenation under the～0.02MPa Hydrogen Vapor Pressure; Reacted 5 hours; After reaction finishes reactant liquor is transferred between the pH7.2 with hydrochloric acid; To there be a large amount of yellow solids to separate out; After leaving standstill 26 hours; Crystalline solid is leached, get the neohesperidin dihydrochalcone crude product.
The preparation of neohesperidin dihydrochalcone finished product: with the neohesperidin dihydrochalcone crude product with 150ml purified water heating for dissolving after; Add the processing of decolouring of 3g gac; Filtered while hot; Crystallisation by cooling 25 hours; The leaching crystal, 100 ± 10 ℃ of vacuum-dryings got the neohesperidin dihydrochalcone finished product in 3.5 hours.Yield >=85%, purity >=96.5%.
Present embodiment prepares the method for operating of neohesperidin dihydrochalcone to carry out according to following two steps: the preparation of neohesperidin dihydrochalcone crude product: 1.5kg potassium hydroxide or NaOH under agitation are dissolved in pour in the hydrogenation still in the 25kg running water; Add 5kg neohesperidin stirring condition in this alkali lye down then; After the stirring and dissolving; Add new 0.3kg Raney's nickel; Begin to stir; 0.01 carry out hydrogenation under the～0.02MPa Hydrogen Vapor Pressure; Reacted 5.5 hours; After reaction finishes reactant liquor is transferred between the pH7.5 with hydrochloric acid; To there be a large amount of yellow solids to separate out; After leaving standstill 26 hours; Crystalline solid is leached, get the neohesperidin dihydrochalcone crude product.
The preparation of neohesperidin dihydrochalcone finished product: with the neohesperidin dihydrochalcone crude product with 25L purified water heating for dissolving after; Add the gac processing of decolouring; Filtered while hot; Crystallisation by cooling 24 hours; The leaching crystal, 100 ± 10 ℃ of vacuum-dryings got the neohesperidin dihydrochalcone finished product in 4 hours.Yield >=85%, purity >=96.5%.
Present embodiment prepares the method for operating of neohesperidin dihydrochalcone to carry out according to following two steps: the preparation of neohesperidin dihydrochalcone crude product: 15kg potassium hydroxide or NaOH under agitation are dissolved in pour in the hydrogenation still in the 300kg running water; Add 50kg neohesperidin stirring condition in this alkali lye down then; After the stirring and dissolving; Add new 3.0kg Raney's nickel; Begin to stir; 0.01 carry out hydrogenation under the～0.02MPa Hydrogen Vapor Pressure; Reacted 6.0 hours; After reaction finishes reactant liquor is transferred between the pH7 with hydrochloric acid; To there be a large amount of yellow solids to separate out; After leaving standstill 25 hours; Crystalline solid is leached, get the neohesperidin dihydrochalcone crude product.
The preparation of neohesperidin dihydrochalcone finished product: with the neohesperidin dihydrochalcone crude product with 250L purified water heating for dissolving after; Add the gac processing of decolouring; Filtered while hot; Crystallisation by cooling 25 hours; The leaching crystal, 100 ± 10 ℃ of vacuum-dryings got the neohesperidin dihydrochalcone finished product in 4.5 hours.Yield >=85%, purity >=96.5%.
So far invention has been described to have combined embodiment.Be familiar with those skilled in the art and should be appreciated that under situation about not departing from the scope of the present invention with spirit, can easily make various other modifications said embodiment.Therefore, the scope that Rights attached thereto require is not limited to above-mentioned explanation, but broadly construe requirement.
Claims (8)
1. the preparation method of a neohesperidin dihydrochalcone, it is characterized in that: said preparation method comprises the steps:
(1) potassium hydroxide or sodium hydroxide under agitation are dissolved in the water, are made into mass percentage concentration and are 3～6% basic solution;
(2) then neohesperidin is added under agitation condition in the said basic solution, the usage ratio of said neohesperidin and said basic solution is 1: 5～8, stirring and dissolving;
(3) add Raney's nickel after the stirring and dissolving, the consumption of wherein said Raney's nickel is 5～8% of a neohesperidin quality, carries out hydrogenation under 0.01～0.1MPa hydrogen pressure, begins then to stir, and reaction 4～6h gets reaction solution;
(4) reaction solution is transferred to pH7～7.5 with hydrochloric acid, leave standstill 24～28 hours after, crystalline solid is leached, the neohesperidin dihydrochalcone crude product.
2. preparation method as claimed in claim 1; It is characterized in that: said preparation method further comprises: with said neohesperidin dihydrochalcone crude product with 5～8 times of purified water heating for dissolving; And with the gac processing of decolouring; Filtered while hot; Crystallisation by cooling 24～28 hours; The leaching crystal, 100 ± 10 ℃ of vacuum-dryings got the neohesperidin dihydrochalcone finished product in 3～5 hours.
3. preparation method as claimed in claim 2 is characterized in that: said gac is 8～10% of a neohesperidin dihydrochalcone crude product quality.
4. preparation method as claimed in claim 1 is characterized in that: basic solution mass percentage concentration described in the said step 1 is 3%.
5. preparation method as claimed in claim 1 is characterized in that: the usage ratio of neohesperidin and said basic solution described in the said step 2 is 1: 5.
6. preparation method as claimed in claim 1 is characterized in that: the consumption of Raney's nickel described in the said step 3 is 5% of a neohesperidin quality.
7. preparation method as claimed in claim 1 is characterized in that: hydrogen pressure described in the said step 3 is 0.01～0.02MPa.
8. preparation method as claimed in claim 1 is characterized in that: in the said step 4 reaction solution is transferred to neutrality with hydrochloric acid.
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103461951A (en) * | 2013-09-04 | 2013-12-25 | 湖南康麓生物科技有限公司 | Compound sweetener with taste modifying function and preparation method thereof |
| CN103772455A (en) * | 2014-02-12 | 2014-05-07 | 李玉山 | Preparation process of naringin dihydrochalcone |
| CN103804439A (en) * | 2014-03-01 | 2014-05-21 | 张家港威胜生物医药有限公司 | Synthesis method for neohesperidin dihydrochalcone |
| CN103880896A (en) * | 2014-01-21 | 2014-06-25 | 东莞广州中医药大学中医药数理工程研究院 | New dihydrogen chalcone glycosides compound separated from lithocarpus polystachyus and preparation method thereof |
| CN104211737A (en) * | 2014-01-04 | 2014-12-17 | 西南科技大学 | Neosperidin dihydrochalcone crystal and preparation method thereof |
| CN106220694A (en) * | 2016-08-05 | 2016-12-14 | 湖南华诚生物资源股份有限公司 | A kind of preparation method of NHDC |
| CN110498821A (en) * | 2019-08-22 | 2019-11-26 | 湖南省农产品加工研究所 | A method of synthesis neohesperidin dihydrochalcone |
| CN110863025A (en) * | 2019-12-05 | 2020-03-06 | 陕西嘉禾生物科技股份有限公司 | Synthetic method of phlorizin |
| CN114280205A (en) * | 2021-12-29 | 2022-04-05 | 广州健顺生物医药研究院有限公司 | Method for efficiently preparing neohesperidin dihydrochalcone |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1443310A (en) * | 1974-01-03 | 1976-07-21 | Gi Audan Cie Sa L | Process for the production of neohesperidine dihydrochalcone |
| CN1305743A (en) * | 2000-12-27 | 2001-08-01 | 中国科学院广州化学研究所 | Process for synthesizing dihydrochalcone-type sweetening agent |
-
2011
- 2011-08-23 CN CN2011102438680A patent/CN102351921A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1443310A (en) * | 1974-01-03 | 1976-07-21 | Gi Audan Cie Sa L | Process for the production of neohesperidine dihydrochalcone |
| CN1305743A (en) * | 2000-12-27 | 2001-08-01 | 中国科学院广州化学研究所 | Process for synthesizing dihydrochalcone-type sweetening agent |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103461951A (en) * | 2013-09-04 | 2013-12-25 | 湖南康麓生物科技有限公司 | Compound sweetener with taste modifying function and preparation method thereof |
| CN103461951B (en) * | 2013-09-04 | 2015-05-20 | 湖南康麓生物科技有限公司 | Compound sweetener with taste modifying function and preparation method thereof |
| CN104211737A (en) * | 2014-01-04 | 2014-12-17 | 西南科技大学 | Neosperidin dihydrochalcone crystal and preparation method thereof |
| CN103880896A (en) * | 2014-01-21 | 2014-06-25 | 东莞广州中医药大学中医药数理工程研究院 | New dihydrogen chalcone glycosides compound separated from lithocarpus polystachyus and preparation method thereof |
| CN103880896B (en) * | 2014-01-21 | 2016-08-17 | 东莞广州中医药大学中医药数理工程研究院 | Lithocarpus polystachyus (wall) Rehd separates novel dihydrochalcone glycosides compound and preparation method thereof |
| CN103772455A (en) * | 2014-02-12 | 2014-05-07 | 李玉山 | Preparation process of naringin dihydrochalcone |
| CN103804439A (en) * | 2014-03-01 | 2014-05-21 | 张家港威胜生物医药有限公司 | Synthesis method for neohesperidin dihydrochalcone |
| CN106220694A (en) * | 2016-08-05 | 2016-12-14 | 湖南华诚生物资源股份有限公司 | A kind of preparation method of NHDC |
| CN106220694B (en) * | 2016-08-05 | 2019-03-26 | 湖南华诚生物资源股份有限公司 | A kind of preparation method of neohesperidin dihydrochalcone |
| CN110498821A (en) * | 2019-08-22 | 2019-11-26 | 湖南省农产品加工研究所 | A method of synthesis neohesperidin dihydrochalcone |
| CN110863025A (en) * | 2019-12-05 | 2020-03-06 | 陕西嘉禾生物科技股份有限公司 | Synthetic method of phlorizin |
| CN114280205A (en) * | 2021-12-29 | 2022-04-05 | 广州健顺生物医药研究院有限公司 | Method for efficiently preparing neohesperidin dihydrochalcone |
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Address after: 510000 No. 663, Wenquan Avenue, Conghua hot spring town, Guangdong, Guangzhou Applicant after: Guangzhou Hanfang Pharmaceutical Co., Ltd. Address before: 510515 No. 663, Wenquan Avenue, Conghua, Guangdong, Guangzhou Applicant before: Hanfang Modem Chinese Traditional Medicine Research Development Co., Ltd., Guang |
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Application publication date: 20120215 |