Background technology
Neohesperidin is a kind of important flavanone compound, and its synthesis neohesperidin dihydro that is mainly used for looks into ear
A kind of novel sweetener of ketone, its sugariness is 1500~1800 times of sucrose, has sugariness height, and heat is little, and sweet taste is lasting, surely
Qualitative good, avirulent feature, it is widely used in food, medicine and feedstuff industry.At present, domestic and international market is to neohesperidin two
The demand of hydrogen chalcone increasingly increases, but the raw material of synthesis neohesperidin dihydrochalcone is but difficult to meet the need in market
Ask.
The existing method obtaining a large amount of neohesperidins mainly has extraction method and synthetic method.Extract from natural plants and separate
Neohesperidin is limited by resource and production cost.Due to the destruction of ecological environment and the over-exploitation of resource, extraction method obtains
Obtain neohesperidin and do not possess the production advantage.China's aurantiin aboundresources, cheap and easy to get, it is that Material synthesis are newly orange with aurantiin
Skin glycosides, for we providing the new method of a large amount of neohesperidins of acquisition.
The method that US3375242 discloses a kind of synthesis of neohesperidin, the method is by aurantiin and excessive isovanillin
Directly mix, synthesize neohesperidin under the catalysis of potassium hydroxide.Though the method is simple, the loss of isovanillin is huge,
The yield of reaction is low, is not suitable for industrialized production.
The method that US3947405 discloses a kind of synthesis of neohesperidin, the method is by phloroacetophenone -4 '-β-new orange peel
Glucosides(Abbreviation PN)It is dissolved in anhydrous alcohols solvent with isovanillin, under inert gas shielding, made using nafoxidine-acetic acid
For catalyst.But, the method condition is harsh, and the reaction time is long, and reaction requires to carry out under conditions of absolute, has very big
Limitation.
CN103408620A discloses a kind of synthesis technique of neohesperidin, and the method is to be dissolved in PN and isovanillin
In 98% ethanol, successively add major catalyst nafoxidine and co-catalyst acetic acid under nitrogen protection.But, the method is reacted
Process also requires that anhydrous condition, the recovery of 98% ethanol and recycling are difficult in practical operation, and the method is received
Rate highest only 86%, does not possess the advantage of industrialization.
CN101863940A discloses a kind of synthesis technique of neohesperidin, and the method is with aurantiin as raw material, first uses
Basic hydrolysis aurantiin obtains PN, then the condensation with Proline-Catalyzed PN and isovanillin, thus synthesizing neohesperidin.In the method
Although condensation step do not need anhydrous reaction condition, the alkali consumption of hydrolysing step is too big, and the pollution to environment is tight
Weight;Alkali concn is high, during hydrolysis, the side reaction that carbonyl reduction is hydroxyl easily occurs, and leads to hydrolysis yield low, and only 70%;And be catalyzed
Agent proline consumption is big, expensive, and consumption is excessive, and the cost of production is very high;Due to a large amount of interpolations of catalyst, post processing is difficult
Removed with thorough, lead to the purity of final products neohesperidin low, only 97%.
Content of the invention
The technical problem to be solved is to overcome the drawbacks described above of prior art presence, provide a kind of product pure
Degree is high, high income, and without inertia and anhydrous condition, low cost, be suitable for industrialized production is former with aurantiin to technical process
The method of material synthesis neohesperidin.
The technical solution adopted for the present invention to solve the technical problems is as follows:One kind is with aurantiin for the new orange peel of Material synthesis
The method of glycosides, comprises the following steps:
(1)Hydrolysis:Aurantiin is dissolved in aqueous alkali, heating, pressurized hydrolysis, is cooled to room temperature, with acid for adjusting pH value, cold
But crystallization, filters, and is dried, obtains hydrolysate phloroacetophenone -4 '-β-neohesperidoside;
(2)Condensation:By step(1)Gained phloroacetophenone -4 '-β-neohesperidoside is dissolved in water or organic solvent, adds
Isovanillin and histidine, back flow reaction, after reaction completely, freeze crystallization, filter, be dried, obtain neohesperidin crude product;
(3)Refined:By step(2)Gained neohesperidin crude product low carbon alcohol solution heating for dissolving, cooling crystallization, filters, filter
Biscuit is dry, obtains neohesperidin fine work.
Preferably, step(1)In, the alkali in described aqueous alkali is NaOH or potassium hydroxide, the matter of aqueous alkali
Amount concentration is 1~5%, the liquid-solid ratio of aqueous alkali and aurantiin quality(mL/g)For 8~15(More preferably 10~12).If alkali
Concentration is too low, will lead to hydrolysis not exclusively, yield is low, if the excessive concentration of alkali, will lead to the waste of alkali and neutralization acid, this
Outward, under the alkali and high temperature action of high concentration, carbonyl can be reduced to hydroxyl to the product PN of hydrolysis, leads to hydrolysis yield low;
If aqueous alkali consumption is very few, aurantiin will be led to compared with indissoluble solution and hydrolysis, if aqueous alkali consumption is excessive, will lead to anti-again
After answering liquid acid for adjusting pH value, volume is excessive, and product PN is difficult to crystallization and separates out, and yield is low.
Preferably, step(1)In, the temperature of described hydrolysis is 90~140 DEG C(More preferably 110~130 DEG C), the pressure of hydrolysis
Power is 0.01~0.40MPa(More preferably 0.1~0.3MPa), the time of hydrolysis is 0.4~1.5h(More preferably 0.5~1.0h).
Research shows, heating, pressurized hydrolysis are conducive to the C ring in flavones molecular skeleton(Pyranone structure)Beat completely at short notice
Open, under pressurized conditions, the time of hydrolysis shortens dramatically;And the concentration of alkali is relatively low, side reaction will not be induced, therefore, yield can achieve
Significantly lifted.If temperature is too low, pressure is too small or the time is too short, hydrolysis will be led to not exclusively;If temperature is too high, pressure is excessive
Or overlong time, all will result in the waste of the energy and material.
Preferably, step(1)In, the described acid for adjusting pH value is hydrochloric acid, sulfuric acid or citric acid etc., and the quality of acid is dense
Spend for 10~30%.If the concentration of acid is too low, after leading to reactant liquor acid for adjusting pH value, volume is excessive, and product PN is difficult to crystallize
Separate out, yield is low;If the excessive concentration of acid, locally acidity is too strong to easily cause solution during adjusting pH value, will destroy
The molecular structure of PN and lead to yield low.
Preferably, step(1)In, regulation pH value to 2~7(More preferably 4~6).If pH value is too low, the molecule of PN will be destroyed
Structure and lead to yield low;If pH value is too high, PN is difficult to separate out in neutrality or alkaline solution.
Preferably, step(2)In, described organic solvent be methyl alcohol, ethanol, isopropanol, n-butanol, acetone, ethyl acetate,
One of dichloromethane or chloroform etc. or two kinds;The consumption of described water or organic solvent is phloroacetophenone -4 '-β-new
5~30 times of orange peel glucosides quality(More preferably 5.2~10.0 times).If water or consumption of organic solvent are very few, PN, isovanillin and
Histidine can not fully dissolve, and condensation reaction is difficult to be smoothed out;If water or consumption of organic solvent are excessive, PN, isovanillin and
Concentration in reactant liquor for the histidine is low, and the time of reaction will extend, and reaction solution volume is excessive, and neohesperidin is difficult to fill
Analysis is brilliant.
Preferably, step(2)In, the addition of described isovanillin and histidine is to make phloroacetophenone -4 '-β-new
The mass ratio of orange peel glucosides, isovanillin and histidine is 1:0.3~0.4:0.05~0.10(More preferably 1:0.31~0.35:
0.06~0.08).Although the histidine that the inventive method is used is all amino acid with the proline used in background technology,
But also there is the difference of its essence:1)Histidine is alpha amino acid(-NH2), proline is a kind of imino acid(-NH);2)Group ammonia
In alkalescence, proline is not in alkalescence for acid;3)Histidine is polarity, hydrophilic amino acid, and proline is nonpolar, hydrophobic amino
Acid, therefore, they are far from each other in catalytic action.Histidine acts primarily as catalytic action in the reaction, and inventor's research finds,
In addition to having amino and carboxyl as other amino acid, there is imidazole group due in its molecular structure in histidine(Wherein
There is secondary amine)So as to have stronger alkalescence, the condition of alkalescence adds the synergy of secondary amine and carboxyl, meets catalysis
The condition of this reaction, additionally, the imidazole group in histidine molecule can not only be used for proton donor, but also as proton acceptor, and
It is all very fast with the speed accepting proton to confess proton, so histidine can serve as efficient catalysis in this aldol condensation
Agent.In the present invention, because histidine uses primarily as catalyst, therefore, consumption need not be excessive.
Preferably, step(2)In, the temperature of described back flow reaction is 60~95 DEG C(More preferably 80~90 DEG C), reaction
Time is 2~10h(More preferably 5~8h).If the temperature of reaction is too low or the reaction time is too short, may result in condensation reaction not
Completely;If the temperature of reaction is too high or the reaction time is long, side reaction odds will be increased, reduce the receipts of condensation reaction
Rate.
Preferably, step(2)In, the temperature of described freezing crystallization is 0~5 DEG C, and the time of crystallization is 12~24h.
Preferably, step(3)In, described low-carbon alcohols are methyl alcohol, ethanol or isopropanol etc.;The body of described low carbon alcohol solution
Long-pending concentration is 30~90%(More preferably 40~70%), the consumption of low carbon alcohol solution is 5~20 times of neohesperidin crude product quality
(More preferably 6~12 times).Select low-carbon alcohols as the foundation of dissolution solvent be:1)At different temperature, neohesperidin is in first
Dissolubility difference in alcohol, ethanol and isopropanol is larger, more conducively crystallizes;2)Methyl alcohol, ethanol and isopropanol moderate boiling point, are suitable for
In industrial production, existing certain stability, it is easily recycled again.
Preferably, step(3)In, the temperature of described heating for dissolving is 60~80 DEG C.
Preferably, step(1)In, the temperature of described cooling crystallization is room temperature, and the time of crystallization is 4~8h.
Preferably, step(3)In, the temperature of described cooling crystallization is 20~25 DEG C, and the time of crystallization is 12~24h.
The inventive method step(1)In, the yield of PN hydrolyzes theoretical value 81.96g producing PN according to 100g aurantiin
Calculate;Step(2)In, the yield of neohesperidin is condensed the theoretical value 128.32g calculating producing neohesperidin according to 100gPN.
Room temperature of the present invention is 15~25 DEG C.
The principle of the inventive method:C ring in the presence of alkali lye and high temperature, in its flavones molecular skeleton for the aurantiin(Pyrrole
Mutter ketone structure)To fully open, hydrolysis generates phloroacetophenone -4 '-β-neohesperidoside(PN), it is used in combination high temperature, pressurization
The mode of hydrolysis, the amount ratio existing process of alkali significantly reduces, and shortens hydrolysis time, and the side reaction of hydrolysis is few, therefore
Improve the yield of PN;In step of condensation, the inventive method is initiated and histidine is used as PN and isovanillin condensation
Catalyst, can meet the condition being catalyzed this reaction, serve as efficient catalyst in this aldol condensation, and reaction rate is high, consumption
Few.
The having the beneficial effect that of the inventive method:
(1)According to the white crystalline powder shape of the inventive method gained neohesperidin fine work, through high-performance liquid chromatography
Detection, the purity of gained neohesperidin may be up to 99.5 %, and impurity content is few, the high income of neohesperidin;
(2)The inventive method adopts high temperature, pressurized hydrolysis mode in hydrolysing step, has saved the consumption of alkali, when shortening reaction
Between, improve the yield of PN, the yield > 85% of hydrolysis;Select histidine as catalyst in condensation step, decrease and urge
The consumption of agent, shortens the time of reaction, condensation reaction yield > 90%;
(3)The inventive method technical process without inert gas shielding, without anhydrous response condition, due to the use of alkali and catalyst
Amount less, each step reaction high income, reduce production cost, be suitable for industrialized production.