CN105348205A - Method for preparing fructosazine by utilizing chitin-based biomass - Google Patents
Method for preparing fructosazine by utilizing chitin-based biomass Download PDFInfo
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- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
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Abstract
The invention relates to a method for preparing fructosazine by utilizing chitin-based biomass. The method comprises the following steps: adding a dry chitin-based biomass raw material, an imidazolium ionic liquid solution and an additive to dimethyl sulfoxide to obtain a mixture; uniformly mixing the obtained mixture to perform a reaction, wherein the mass ratio of the imidazolium ionic liquid to the chitin-based biomass raw material is 1: (2-100), and the mass ratio of the added chitin-based biomass raw material to an oxidant is 1: (1-50) to obtain an intermediate product; adding a crystallization solvent to the intermediate product, wherein the volume ratio of the intermediate product to the solvent is 1: 1 to 1: 10; completely dissolving the product; removing undissolved impurities to obtain a filter liquor; carrying out rotary evaporation concentration on the filter liquor; standing; and recrystallizing to prepare the final product. The method has the advantages of wide raw material resources, no pollution, simple preparation and high product purity.
Description
Technical field
The present invention relates to a kind of chitin kind biomass-making that utilizes for the method for fructosazine.
Technical background
Along with the continuous increase of exhaustion and the environmental protection pressure day by day of conventional fossil fuel, develop sustainable, pollution-free, reproducible substitute energy and be day by day subject to extensive concern.Biomass are as enormous amount, and cheap a kind of sustainability resource is the effective way solving current resource and energy dilemma.Chitin and partly or entirely deacetylation derivative are the important marine biomass resources of occurring in nature, annual biosynthetic chitin about 10,000,000,000 tons, that reserves are only second to cellulosic second largest biomass resource, also be the nitrogenous natural organic matter that outside occurring in nature isolating protein, quantity is maximum, occurring in nature is unique especially basic amine group polysaccharide (Nature.2015,524,155-157. nature, 2015,524,155-157; GreenChem., 2014,16,2204-2212. Green Chemistry, 2014,16,2204-2212).The nitrogenous Wood Adhesives from Biomass such as chitin kind are become some platform chemicals, and further these platform chemicals is changed into fuel or chemical meets Green Sustainable route.Design and develop effective catalyst according to Biomass Characteristics, screening green solvent system is the key of biorefinery seeking breakthrough.At present, chitin kind biomass resource all has very important purposes in multiple field: in foodstuffs industry, and chitin and soluble derivative chitosan thereof can be used as preservation agent, finings and antioxidant etc.; In field of medicaments, because chitin kind biomass toxicity is little, have good biocompatibility and degradation property, be therefore often used as medicinal slow release agent.In the recent period, chitin kind biomass are also by carrier (Chem.Common., 2010 as catalyzer, 46,5593-5595. chemical communication, 2010,46,5593-5595) and prepare magnetic gel material for sewage disposal (Chem.Commun., 2012,48,7350 – 7352. chemical communications, 2012,48,7350 – 7352).Under the pressure of crisis of resource and environmental stress, explore the focus that biomass efficient Land use models has become various countries' chemical field research.If by the chitin kind biomass resource of suitable these surpluses of approach efficiency utilization, will develop the economy and improve people's living standard to China and produce positive effect.Terrestrial organism matter resource Mierocrystalline celluloses maximum for reserves and monomeric glucose thereof are converted into bio-based chemical, as platform chemicals such as 5 – hydroxymethylfurfurals or levulinic acids, are one of most active research directions of current biomass converting field.But, by marine biomass resource chitins maximum for reserves, chitosan and corresponding monomer acetylglucosamine thereof and glucosamine orientation are converted into high added value bio-based chemical, and bibliographical information is less, as the preparation of Pyrazine nitrogen-containing heterocycle compound fructosazine.Fructosazine belongs to tobacco and to dive fragrant class material, tobacco has improve the fine and smooth degree of tobacco and increase flue gas concentration flavouring and improve the effect of inhaling taste; In addition, relevant report display fructosazine also has certain physiologically active.Fructosazine, primarily of the condensation reaction of two molecule glucosamines, all has existence in various plants, all has the fructosazine (TheJournalofOrganicChemistry of certain content in such as Chinese medicine pseudo-ginseng and tobacco, organic chemistry, 1966,31,2239-2241).In addition, Kushida etc. have studied in the methyl alcohol and sodium methoxide solution of heat, prepare fructosazine with mannosamine hydrochloride and glucosamine hydrochloride.But above-mentioned reactions steps is complicated, and the reaction times is long, subsequent step is complicated, the not high and target product selectivity difference (Chem.Pharm.Bull., 1991,39,792-794. chemicals bulletin, 1991,39,792-794) of yield.The patent of invention " a kind of method utilizing chitin kind biomass resource to prepare nitrogen-containing heterocycle compound " in our early stage, selectivity can not prepare fructosazine, generating portion deoxy fructosazine simultaneously, target product yield is low, product separation difficulty is large, the consumption of ionic-liquid catalyst is large, and the step that crystallization obtains product is complicated.
Summary of the invention
The object of the present invention is to provide a kind of raw material sources extensive, pollution-free, preparation is simple, and what product purity was high utilizes chitin kind biomass for raw material, and selectivity prepares the method for high added value nitrogen heterocyclic ring fructosazine.
Because fructosazine has special aromatic heterocycle molecular structure and biological activity, fructosazine is considered to most development potentiality and representational Novel platform compound, has a wide range of applications in multiple field such as medical chemistry and Food science.According to the market quotes of traditional Chinese medicines group, the market value of fructosazine is every milligram and can reaches 394 yuan.Therefore, design and develop efficient catalytic system and environmentally friendly solvent and additive, reproducible marine biomass resource selection is changed into some high added values nitrogenous platform chemicals fructosazine and there is very wide prospect and profound significance.
With Oxidative Dehydrogenation under conventional alkaline condition for compared with fructosazine, ionic liquid has efficiently as the application of catalyzer, green non-pollution, and many-sided advantage such as can be recycled, and receives extensive concern.As can be seen here, the more new and effective ionic liquid catalyst systems of exploitation and environmentally friendly solvent and additive are used for monose and the more complicated carbohydrate of structure, and then highly selective prepares fructosazine, has most important theories meaning and using value.
The present invention utilizes basic imidazole base ionic liquid as catalyzer, and polar aprotic solvent, as reaction medium, is oxidized and prepares fructosazine as additive application in chitin kind biomass selectivity.On the one hand, ionic liquid, as catalyzer, has the following advantages: non-volatile, colourless, odorless, pollution-free, has larger equilibrium temperature scope, good chemical stability.In addition, ionic liquid great advantage is also its designability, by its physics-chem characteristic appropriately combined adjustable of zwitterion, meets the different requirements of separation or catalysis.On the other hand, polar aprotic solvent is the environmentally friendly solvent of a class, is used as the medium much having chemical reaction.In addition, oxide compound is as additive, and such as hydrogen peroxide, environmental protection, is widely used in carbohydrate-modifying, can improve reaction preference.The chitin kind biomass degradation that the present invention relates to prepares nitrogen-containing heterocycle compound fructosazine, and reaction process is efficient, and product controls accurately and has very high using value, and production process is green.
Concrete operations of the present invention comprise the steps:
(1) by dry chitin kind biomass material, glyoxaline ion liquid solution and weight of additive sum: dimethyl sulfoxide (DMSO)=0.1-25g:1ml, the chitin kind biomass material of drying, glyoxaline ion liquid solution and additive are added in dimethyl sulfoxide (DMSO) and mixes, react 5 minutes-10 days at 20 DEG C-200 DEG C, wherein: imidazole ion liquid and chitin kind biomass material mass ratio are 1:2-100, the mass ratio adding chitin kind biomass material and oxygenant is 1:1-50, obtains intermediate product;
(2) intermediate product obtained in step (1) adds recrystallisation solvent, wherein intermediate product: product, than being 1:1-1:10, all dissolves by solvent volume, remove insoluble impurity, filtrate concentrated by rotary evaporation, leave standstill 10 hours-24 hours, recrystallization prepares product.
The chitin of to be molecular weight ranges the be 1-30 ten thousand of the chitin kind biomass as described in (1) step, molecular weight ranges is 0.1-20 ten thousand, deacetylation is the chitosan of 50%-100%, D-Glucosamine Hydrochloride, D-glucosamine sulfuric acid sylvite centre or D-glucosamine sodium sulfate salt etc.
Glyoxaline ion liquid as described in (1) step is 1-ethyl-3-methyl-imidazoles acetate ionic liquid, 1-butyl-3-methyl-imidazoles acetate ionic liquid, hydroxide 1-ethyl-3-methylimidazole ionic liquid, hydroxide 1-hexyl-3-Methylimidazole ionic liquid, 1-butyl-3-methyl-imidazoles carbonate ion liquid, 1-butyl-3-methyl-imidazoles bicarbonate ion liquid or 1-butyl-3-methyl-imidazoles Benzoate Ion liquid etc.
Glyoxaline ion liquid as above adopts two-step synthesis method preparation.The first step of the method is halogeno salt ionic liquid (the halogenated anion X of preparation containing target cationic
-=Cl
-, Br
-), wherein the preparation process of halogenated imidazole salt ion liquid is: first to purified alkyl imidazole and halogenated alkane mixing; Then control certain temperature, react under sealing agitation condition, by washing, recrystallization and underpressure distillation, obtained pure halogenated imidazole salt ion liquid; Then adopt the salt containing desired anion or acid (as Potassium ethanoate, sodium-acetate, sodium carbonate or potassium hydroxide) to carry out replacement(metathesis)reaction, obtain object ion liquid.This reaction is reacted usually under stirring at room temperature.Concrete preparation method is shown in J.Iran.Chem.Soc., Chemical Society of 2009,6,647-678. Iran, 2009,6,647-678; Org.Lett., the communication of 2005,7,3049-3052. organic chemistry, 2005,7,3049-3052.
The aqueous hydrogen peroxide solution of to be massfraction the be 30%-95% of the additive as described in (1) step, clorox, sodium hypobromite, one or more of potassium hypobromite etc.
The solvent that crystallization as described in (2) step uses is acetonitrile, ethanol, propyl alcohol, one or more in acetone.
Fructosazine belongs to tobacco and to dive fragrant class material, tobacco has improve the fine and smooth degree of tobacco and increase flue gas concentration flavouring and improve the effect of inhaling taste, also has physiologically active.Fructosazine has higher activity to the fracture of DNA than its derivative deoxy fructosazine in physiological action.Fructosazine can be prepared by the reaction of nitrogenous compound and some monose.Report fructose the earliest and amino acid reactants forms fructosazine, although react under mild conditions, the synthesis of fructosazine needs long time, is difficult to the needs meeting actual production.Fujii etc. are studied it further, and employing 2-amino-2-deoxy-D-Glucose is raw material, temperature of reaction 70 DEG C, pass into methyl alcohol (when sodium methylate is excessive) at air, through 4h back flow reaction, can fructosazine be formed, but productive rate is extremely low, be about 5.5% (J.Org.Chem., 1966,31,2239 – 2241. organic chemistry, 1966,31,2239 – 2241).In water-soluble liquid phase, adopt traditional preparation method, determine that product is mixture system, containing deoxy fructosazine and fructosazine compound, the selectivity preparing nitrogenous compound fructosazine is not high.According to bibliographical information, fructosazine has higher activity to the fracture of DNA than its derivative deoxy fructosazine in physiological action.Therefore, how to improve the selectivity of reaction, high selectivity and high yield prepare fructosazine, become key of the present invention.In addition, traditional preparation method, in aqueous, needs additional nitrogenous source, and with conventional inorganic alkali for catalyzer, the dehydration reaction of catalysis glucose or fructose is the reaction that a selectivity is very low, can produce a large amount of by products.Reaction is complicated, and reaction time is long, and efficiency is low.A large amount of use inorganic base catalyst can to environment, and catalyzer can not recycling.In addition, this kind of preparation method can cause the sepn process of a highly energy-consuming.Reaction raw materials fructose and glucose belong to edible biological matter resource, and a large amount of conversion fructose prepares nitrogenous compound, and production cost is too high, does not meet Sustainable development route.But compared with edible terrestrial organism matter resource glucose or fructose, chitin kind biomass belong to unedible renewable resources, can not threaten to the life of the mankind, and output is more, price is lower, and the reaction process that exploitation is applicable to chitin kind biomass has important meaning (GreenChem., 2014,16,2204 – 2212. Green Chemistry, 2014,16,2204 – 2212).Therefore, in the urgent need to developing new technology, from chitin kind biomass, obtain nitrogenous compound fructosazine high selectivity and high yield.
The object of this invention is to provide a kind of easy and simple to handle, the reaction can carried out under low-temp low-pressure condition, exploitation has the basic imidazole base ionic-liquid catalyst of superior catalytic performance, and the nitrogenous compound continuous production processes that a kind of facility investment of exploitation is few and energy consumption is low further.The present invention selects alkali ionic liquid to be catalyzer, dimethyl sulfoxide (DMSO) (DMSO) is solvent, take oxidic species as additive, in 20 DEG C of-200 DEG C of temperature ranges, in 5 minutes-10 days reaction times, investigated the reaction result that chitin kind biomass highly selective is converted into fructosazine.Carry out in the polytetrafluoroethylcontainer container of reaction in the Pressure vessel of a 10ml.First electricity consumption balance takes a certain amount of ionic liquid, additive, and carbohydrate and solvent DMSO are placed in the polytetrafluoroethylcontainer container of Pressure vessel in the lump.Stirring magneton is added in polytetrafluoroethylcontainer container.Reaction lid is screwed, is placed in heat conduction silicone oil.Set the temperature of heat conduction silicone oil, setting speed is 30r/min.Reaction is completed within the regular hour.When reaction arrives Preset Time, close constant temperature oil bath power switch, Pressure vessel is carefully taken out, controls clean heat conduction silicone oil, be placed in frozen water and cool rapidly, terminate reaction.Get appropriate reaction mixture, add containing interior target deuterated reagent, carry out nuclear-magnetism quantitatively, analyze feed stock conversion and product yield.Whole experimental implementation is simple, reaction conditions is gentle, High Temperature High Pressure is not needed to prepare target compound, employing ionic liquid is catalyzer, meet Green Sustainable and be separated the advantages such as simple, realizing the recovery of catalyzer, there is fructosazine good product quality, selectivity is high, yield is high, and side reaction is few and react advantage thoroughly.
According to bibliographical information, traditional purification process is column chromatography: the crude product namely obtained after reaction is by different ion exchange resin (soda acid resin or macroporous resin), washing repeatedly, adjustment potential of hydrogen, repeatedly alcohol-water recrystallization obtains comparatively pure product.Operation steps is complicated, and the purity obtaining product is low.The present invention adopts solvent extration, and because fructosazine has good water solubility, alcohol dissolubility difference is insoluble or be insoluble in the feature of non-polar organic solvent, select different solvents repeatedly extraction and recrystallization remove impurity, obtain the product of certain purity.Not only overcome the shortcoming of existing traditional preparation methods completely, also overcome catalyzer easy in inactivation and be separated
The effects of the present invention different catalysts, different solvents, reaction times, temperature of reaction and reaction mass proportioning be on the impact of fructosazine yield.First screen the ionic liquid of different acid-basicity, find that alkali ionic liquid is prepared fructosazine to chitin kind Wood Adhesives from Biomass and had promoter action, and acid and neutral ionic liquid is inoperative to reaction.From the angle of catalytic mechanism, the generation of nitrogenous compound, mainly nitrogen and carbonyl carbon generation nucleophilic addition(Adn), and then generation dehydration reaction obtains.Therefore, select suitable catalyzer, retaining nitrogen-atoms and efficiently can activating nitrogen-atoms is core of the present invention.Experiment finds, add acidic ion liquid, such as sulfonic group imidazole ion liquid is as catalyzer, and temperature of reaction is incremented to 200 DEG C from 20 DEG C, reaction times is incremented to 10d from 3h, the yield of fructosazine does not significantly change, and acidic conditions can cause the loss of nitrogen in raw material, and chitin kind biomass disproportionation easily occur and are transformed into acid, serious side reaction is caused to occur, formic acid a large amount of in product, levulinic acid exists, and then affects the yield of fructosazine.In addition, add neutral ion liquid, such as 1-butyl-3-Methylimidazole chloride salt ions liquid is as catalyzer, can not effectively activate nitrogen-atoms in raw material, thus nucleophilic addition can not occur and prepare target product.Select alkali ionic liquid, such as 1-ethyl-3-methylimidazole acetate ionic liquid is catalyzer, can suppress the generation of side reaction, and efficient catalytic chitin kind Wood Adhesives from Biomass prepares fructosazine.Under alkaline condition, prevent the loss of nitrogen-atoms on the one hand, alkaline condition can activate nitrogen-atoms on the other hand, promotes nucleophilic addition, prepares target compound.In addition, alkali ionic liquid is as catalyzer, formic acid can be suppressed, the generation of acetyl-propionic acid material, this result confirms that alkalify ionic liquid contributes to suppressing chitin kind biomass molecule to form the side reaction of small molecular acidity material, thus the chitin kind degradation facilitating structure more complicated prepares fructosazine.
Compared with traditional mineral alkali catalysis, the present invention develops the alkaline ionic liquid catalyst for fructosazine synthesis innovatively, obtains excellent catalytic performance.Although traditional inorganic base catalyst is cheap and easy to get, because of the shortcoming such as side reaction is many, corrodibility is strong, post-reaction treatment is complicated and contaminate environment is serious, does not meet the developing direction of current Green Chemistry, make it use and be restricted.Ionic liquid is also called ionic liquid at room temperature, is made up of organic cation and inorganic anion, and the salt be in a liquid state at depressed temperatures, or at room temperature, also known as low temperature molten salt.Compared with traditional inorganic base catalyst, ionic liquid has following outstanding advantage: (1) does not almost have vapour pressure, non-volatile, can be used for the reaction under high vacuum; (2) colourless, odorless, pollution-free, can be used as eco-friendly solvent and to hold concurrently catalyzer; (3) there is larger equilibrium temperature scope, good chemical stability; (4) solvability is strong, can dissolve numerous inorganics, organism, comprise macromolecular compound.Ionic liquid great advantage is its designability can be changed its physics-chem characteristic by the design of zwitterion, makes its fusing point, viscosity, density, wetting ability, thermostability, acid-basicity etc. meet the different requirements of separation or catalysis.Develop as can be seen here more economical and efficiently alkali ionic liquid catalyst system for the carbohydrate of chitin kind biomass and the more complicated complexity of structure, there is most important theories meaning and using value.
Experiment finds, alkali ionic liquid efficiently can promote that chitin kind Wood Adhesives from Biomass prepares nitrogenous compound fructosazine.Such as, when basic imidazole ionic liquid and chitin kind biomass material mass ratio are 1:2, adding of a large amount of ionic liquid, except catalysis positive reaction generates target product, also can cause serious side reaction, such as, cause raw molecule generation side reaction to produce the polymer molecule of solubility, and cause the product generated to decompose further; When basic imidazole ionic liquid and chitin kind biomass material mass ratio are 1:100, because the add-on of ionic liquid is very few, cause reaction not transform completely, target product fructosazine can not be prepared by high yield.Therefore, when basic imidazole ionic liquid and chitin kind biomass material mass ratio are between 1:2-100, the transformation efficiency of chitin kind biomass material is the highest, and the yield of product fructosazine is the highest simultaneously.In sum, alkali ionic liquid efficient catalytic chitin kind Wood Adhesives from Biomass can prepare nitrogenous compound fructosazine, but the selectivity preparing nitrogenous compound is not high, therefore, how to improve the selectivity of reaction, becomes key of the present invention.Exploitation suitable additive, joins reaction system, improves reaction preference.According to catalyst mechanism, fructosazine comes from certain embodiments and prepares.Therefore, oxygenant is incorporated in reaction system, and promote dehydrogenation reaction, highly selective obtains product fructosazine.Such as, chitin kind biomass material and the mass ratio of oxygenant be than lower than 1 time, reaction can not transform completely, and the product obtained is the mixture of fructosazine and deoxy fructosazine; When the mass ratio of chitin kind biomass material and oxygenant is greater than 1:50, the transformation efficiency of reaction raw materials obviously declines, this is owing to adding excessive oxidation class additive, the solvent DMSO of reaction system can be oxidized to dimethyl sulphide by excessive oxygenant, there is " poisoning " effect in glucosamine hydrochloride molecule simultaneously, thus suppress raw molecule next step transform, cause transformation efficiency to decline, can not high yield prepare target compound.Under the condition of excessive oxidant, serious side reaction can be there is, generate the by products such as formic acid.Therefore, when the mass ratio of chitin kind biomass material and oxygenant is between 1:1-50, efficiently can promote that glucosamine hydrochloride highly selective is converted into fructosazine.
Water is as solvent environmental protection and price is inexpensive, is optimal reaction solvent.But chitin kind biomass macromole is not soluble in water, cannot form homogeneous catalysis system, and in water-soluble liquid phase, reaction product is easily degraded further, generate the by products such as the lower acid such as levulinic acid and formic acid.Therefore, in order to suppress the carrying out of side reaction, in order to form homogeneous catalysis system.Experimental selection dissimilar polarity aprotic solvent (as DMF, DMAc, DMSO etc.), as the solvent of chitin kind Wood Adhesives from Biomass, finds that DMSO is as the solvent of chitin kind Wood Adhesives from Biomass, effectively can improve catalytic efficiency.Experiment finds that there is very important active effect adding of DMSO to reaction, can significantly improve the yield of fructosazine.DMSO has promoter action clearly to chitin kind Wood Adhesives from Biomass, its major cause have following some.First DMSO has certain weakly alkaline, be not only the effect of act as solvents in this reaction system, also likely play a part catalyzer, in carbohydrate dehydration, DMSO can serve as electron acceptor(EA) also can serve as electronics donor, thus can promote the generation of dehydration reaction.Again, DMSO can suppress the side reaction in carbohydrate dehydration effectively, as various polyreaction, to reduce the generation of soil ulmin, improves the selectivity of fructosazine.In addition, DMSO or a kind of excellent solvent, have good dissolving power to carbohydrate and product, be therefore conducive to saccharide converted.Compared to DMSO, other solvent, as DMF and DMAc polar aprotic solvent can not promote chitin kind Wood Adhesives from Biomass, mainly these solvents can not suppress the side reaction in carbohydrate dehydration effectively.As can be seen from above correlative study, compared to other solvent systems, in having machine solvent DMSO, the result of chitin kind biomass degradation is ideal, trace it to its cause, mainly because raw material chitin kind biomass can form homogeneous catalysis system, in addition fructosazine be degraded to the side reaction of the lower acids such as levulinic acid in organic solvent can be suppressed to a certain extent.
The condition of the present invention's reaction is temperature of reaction is 20 ~ 200 DEG C, and the reaction times is 5min ~ 10d, and the determination of reaction conditions needs association reaction feature and catalyst performance to consider.Experimental result shows, when reaction starts, the yield of fructosazine is lower, and along with the reaction times is increased to 10d from 5min, the yield of fructosazine continues to increase.More than after 10d when reacted, the stable yield of fructosazine, between 30% to 40%, does not significantly change.Be elevated to 200 DEG C in temperature of reaction from 20 DEG C, the transformation efficiency of glucosamine raises gradually, and the yield of fructosazine also raises gradually, and 200 DEG C time, the transformation efficiency of glucosamine is 100%, and now the yield of fructosazine also reaches maximum 40%.In temperature of reaction more than 200 DEG C, the yield of fructosazine has no raising, and raise with temperature on the contrary and reaction times prolongation, yield declines gradually.Major cause is that high temperature can cause serious side reaction, the fructosazine generated may be caused to be decomposed into other micromolecular compounds further, thus cause fructosazine yield to reduce.
According to above-mentioned experiment, can determine in investigated catalyzer and additive, alkali ionic liquid is the catalyzer uniquely having catalytic activity, and oxidic species is efficient additive.Compare with the technique of other polysaccharide conversion, alkaline ionic liquid catalyst and the acting in conjunction of oxidation class additive, have better selectivity of product, only generate fructosazine.
Advantage of the present invention is as follows:
(1) chitin kind biomass source is extensive, and rich reserves, the present invention utilizes chitin kind biomass resource to produce nitrogenous aromatic heterocycle pyrazine compounds, and production technique has potential using value.It is from the angle of Atom economy, the nitrogen element utilizing this class raw material itself to have, and prepares nitrogenous small molecules platform chemicals, develops the new way that chitin kind biomass comprehensive utilizes, has widened the raw material sources of efficient preparation bio-based chemical.
(2) fructosazine is as the platform chemicals of high added value, due to the aromatic structure that it is special, therefore has and specially causes fragrant effect, is that a kind of important spices is dived perfumery; There is again stronger physiologically active and there is pharmaceutical use simultaneously.
(3) ionic liquid is as green environment friendly catalyst, its physics-chem characteristic can be changed by the design of zwitterion, its thermostability and acid-basicity etc. are met be separated or the different requirements of catalysis, and then efficient catalytic degraded chitin kind biomass resource, prepare fructosazine.
(4) by adding suitable oxidisability additive, efficiently control response path, selectivity prepares fructosazine.After separation and purification completes, organic extractant recoverable, greatly reduces later stage separation costs, is convenient to industrialization.
Discuss in two of fructosazine and chitin kind biomass in conjunction with above, this patent proposes with reproducible ocean class chitin kind biomass as nitrogen-containing heterocycle compound fructosazine prepared by raw material, Atom economy can be improved on the one hand, namely make full use of distinctive nitrogen element in chitin kind biomass, preparation process is without the need to additional nitrogenous source; The raw material sources preparing pyrazine compounds can be widened on the other hand, reduce the dependence of its preparation process to traditional fossil resources.
Accompanying drawing illustrates:
Fig. 1 is embodiment 1,1-ethyl-3-methylimidazole acetic acid ion liquid catalyst, massfraction be 30% aqueous hydrogen peroxide solution be oxygenant, glucosamine dehydrogenation generates fructosazine reaction equation.
Fig. 2 is embodiment 1 product fructosazine
13c nuclear magnetic resonance spectrum.
Embodiment
Embodiment 1:
(1) 1-ethyl-3-methyl-imidazoles acetate ionic liquid is prepared, 0.1mol1-ethyl-3-methylimidazole bromine salt (19.1g) and 2.5mol Potassium ethanoate (245.3g) is added in 250ml flask with three necks,round bottom, add 160ml Virahol to be dissolved, stirred at ambient temperature 36h.Filter, remove insolubles, filtrate 70 DEG C of backspins steam 8h, obtain pale yellow oil, dissolve with 80ml methylene dichloride, and add activity charcoal powder stirring at room temperature 17h, filter, with and chlorination carbon washs 3 times, merging filtrate revolves and steams except desolventizing, and obtain tan solid, 70 DEG C of vacuum-dryings obtain target product.Get 1-ethyl-3-methyl-imidazoles acetate ionic liquid 10g, add the D-Glucosamine Hydrochloride that 20g molecular weight is 215.5, adding with the massfraction of the total mass numbers such as D-Glucosamine Hydrochloride is the aqueous hydrogen peroxide solution of 30%, after mixing in 80ml dimethyl sulfoxide (DMSO), 20 DEG C are reacted 10 days.
(2), after reaction terminates, at ambient temperature, get reaction product solution 10ml, add 50ml acetonitrile, extract three times.Remove insoluble impurity, filtrate concentrated by rotary evaporation, extraction agent reclaims, glyoxaline ion liquid recycling; Leave standstill 10 hours, crystallization can obtain product fructosazine, and the transformation efficiency of reaction raw materials D-Glucosamine Hydrochloride is 80%, and crystallization obtains purity >=99% of product, and the molar yield of fructosazine is 40%.
Embodiment 2:
(1) preparation method of ionic liquid and the preparation method of 1-ethyl-3-methyl-imidazoles acetate ionic liquid similar, 1-butyl-3-Methylimidazole bromine salt and Potassium ethanoate reaction is added in flask with three necks,round bottom, reactant mol ratio and reaction conditions in the same manner as in Example 1, prepare 1-butyl-3-methyl-imidazoles acetate ionic liquid.Get 1-butyl-3-methyl-imidazoles acetate ionic liquid 15g, add the D-Glucosamine Hydrochloride that 35g molecular weight is 215.5, add the sodium hypobromite with total mass numbers such as raw material D-Glucosamine Hydrochlorides, Homogeneous phase mixing in 100ml dimethyl sulfoxide (DMSO), after mixing in 100ml dimethyl sulfoxide (DMSO), 80 DEG C are reacted 10 minutes.
(2) after reaction terminates, at ambient temperature, get reaction product solution 1ml, add 10ml acetonitrile, extract five times, by dissolving of obtaining the acetonitrile of product mutually concentrated evaporate to dryness concentrate, crystallization can obtain product, the transformation efficiency of reaction raw materials D-Glucosamine Hydrochloride is 70%, and crystallization obtains purity >=98% of product, and the molar yield of fructosazine is 25%.
Embodiment 3:
(1) taking 1-ethyl-3-methylimidazole bromine salt 0.25mol (55.0g) is dissolved in 100ml methylene dichloride, add potassium hydroxide 0.25mol (14.0g), at room temperature stir 10h, filtering-depositing, revolve steaming to desolventize, product washed with diethyl ether 2-4 time, vacuum-drying 10h at 90 DEG C, can obtain hydroxide 1-ethyl-3-methylimidazole ionic liquid.Get hydroxide 1-ethyl-3-methylimidazole ionic liquid 20g, add the chitin that 200g molecular weight is 250,000, to add total mass number be raw molecule amount is the potassium hypobromite of the twice of the chitin of 250,000, after mixing in 200ml dimethyl sulfoxide (DMSO), and 200 DEG C of reactions 5 minutes.
(2) after reaction terminates, at ambient temperature, get reaction product solution 3ml, add 15ml acetonitrile extraction twice, by dissolving of obtaining the acetonitrile of product mutually concentrated evaporate to dryness concentrate, filtrate leaves standstill 15 hours, crystallization can obtain product, reaction raw materials molecular weight is the transformation efficiency of the chitin of 250,000 is 80%, and crystallization obtains purity >=97% of product, and the molar yield of fructosazine is 15%.
Embodiment 4:
(1) taking 1-hexyl-3-Methylimidazole bromine salt 0.5mol (110.0g) is dissolved in 100ml methylene dichloride, add potassium hydroxide 0.5mol (28.0g), at room temperature stir 10h, filtering-depositing, revolve steaming to desolventize, product washed with diethyl ether 2-4 time, vacuum-drying 10h at 90 DEG C, can obtain hydroxide 1-hexyl-3-Methylimidazole ionic liquid.Get hydroxide 1-hexyl-3-Methylimidazole ionic liquid 50g, add the chitin that 45g molecular weight is 300,000, to add total mass number be raw molecule amount is 35% aqueous hydrogen peroxide solution of 50 times of the chitin of 300,000, after mixing in 500ml dimethyl sulfoxide (DMSO), and 180 DEG C of reactions 1 hour.
(2) after reaction terminates, at ambient temperature, get reaction product solution 9ml, add 45ml acetonitrile, extraction once, by dissolving of obtaining the acetonitrile of product mutually concentrated evaporate to dryness concentrate, filtrate leaves standstill 20 hours, and crystallization can obtain product, and reaction raw materials molecular weight is the transformation efficiency of the chitin of 300,000 is 80%, crystallization obtains purity >=97% of product, and the molar yield of fructosazine is 12%.
Embodiment 5:
(1) 1-butyl-3-Methylimidazole bromine salt (219.1g) of 1mol is joined in 250ml there-necked flask, then 100ml Virahol is added, stirring makes it all dissolve, then 2 times amount sodium carbonate (168.0g) are added, filter after 60 DEG C of reaction 8h, filtrate is steamed 7h at 60 DEG C of backspins and is obtained pale yellow oily liquid body, and 70 DEG C of vacuum-drying 10h obtain final product 1-butyl-3-methyl-imidazoles carbonate ion liquid.Get 1-butyl-3-methyl-imidazoles carbonate ion liquid 80g, to add 60g molecular weight be 200,000 deacetylations be 64% chitosan, 50% aqueous hydrogen peroxide solution of total mass number is raw molecule amount to be 200,000 deacetylations be 40 times of the chitosan of 64%, after mixing in 800ml dimethyl sulfoxide (DMSO), 100 DEG C are reacted 9 hours.
(2) after reaction terminates, at ambient temperature, get reaction product solution 15ml, add 15ml ethanol and acetone (v/v=1:3), extract three times, by dissolving of obtaining ethanol and the acetone of product mutually concentrated evaporate to dryness concentrate, filtrate leaves standstill 20 hours, and crystallization can obtain product, and the transformation efficiency of reaction raw materials molecular weight to be 200,000 deacetylations the be chitosan of 64% is 60%, crystallization obtains purity >=95.9% of product, and the molar yield of fructosazine is 10%.
Embodiment 6:
(1) preparation method of ionic liquid and the preparation method of 1-butyl-3-methyl-imidazoles carbonate ion liquid similar, 1-butyl-3-Methylimidazole bromine salt and reaction of sodium bicarbonate is added in flask with three necks,round bottom, reactant mol ratio and reaction conditions in the same manner as in Example 5, prepare 1-butyl-3-methyl-imidazoles bicarbonate ion liquid.1-butyl-3-methyl-imidazoles bicarbonate ion liquid 70g, to add 15g molecular weight be 0.1 ten thousand deacetylations be 50% chitosan, to add total mass number be 25 times of molecular weight to be 0.1 ten thousand deacetylations be 50% chitosan mass mark be the aqueous hydrogen peroxide solution of 95%, after mixing in 500ml dimethyl sulfoxide (DMSO), 200 DEG C are reacted 6 hours.
(2) after reaction terminates, at ambient temperature, get reaction product solution 4ml, add 20ml acetonitrile, extraction once, by dissolving of obtaining the acetonitrile of product mutually concentrated evaporate to dryness concentrate, filtrate leaves standstill 12 hours, and crystallization can obtain product, and the transformation efficiency of reaction raw materials molecular weight to be 0.1 ten thousand deacetylations the be chitosan of 50% is 65%, crystallization obtains purity >=98.5% of product, and the molar yield of fructosazine is 28%.
Embodiment 7:
(1) mass concentration is prepared for join in 250ml there-necked flask by 0.75mol1-butyl-3-Methylimidazole bromine salt (164.1g), add Virahol 200ml (157g) again, stirring makes it all dissolve, add 20 times amount Sodium Benzoate (1.5mol again, 216.2g), be warmed up to 70 DEG C, filter after reaction 10h, filtrate 70 DEG C is revolved and is steamed to obtain colourless oil liquid, and 70 DEG C of vacuum-dryings obtain final product 1-butyl-3-methyl-imidazoles Benzoate Ion liquid.Get 1-butyl-3-methyl-imidazoles Benzoate Ion liquid 35g, to add 25g molecular weight be 100,000 deacetylations be 100% chitosan, the potassium hypobromite of the chitosan of 100% that adds with total mass number that be 50 times of molecular weight to be 100,000 deacetylations be, after mixing in 600ml dimethyl sulfoxide (DMSO), 170 DEG C of reactions 5 hours.
(2) after reaction terminates, at ambient temperature, get reaction product solution 5ml, add 25ml propyl alcohol and acetone (v/v=1:5), extraction once, by dissolving of obtaining propyl alcohol and the acetone of product mutually concentrated evaporate to dryness concentrate, filtrate leaves standstill 15 hours, and crystallization can obtain product, and the transformation efficiency of reaction raw materials molecular weight to be 100,000 deacetylations the be chitosan of 100% is 85%, crystallization obtains purity >=98.9% of product, and the molar yield of fructosazine is 54%.
Embodiment 8:
(1) as method preparation 1-ethyl-3-methylimidazole acetate ionic liquid in embodiment 1, get 1-ethyl-3-methylimidazole acetate ionic liquid 100g, add 1g Glucosamine sulfate potassium chloride, add the sodium hypobromite that total mass number is 45 times of raw material Glucosamine sulfate potassium chlorides, after mixing in 200ml dimethyl sulfoxide (DMSO), 150 DEG C of reactions 5 hours.
(2) after reaction terminates, at ambient temperature, get reaction product solution 15ml, add 75ml acetonitrile, extraction once, by dissolving of obtaining the acetonitrile of product mutually concentrated evaporate to dryness concentrate, filtrate leaves standstill 20 hours, and crystallization can obtain product, and the transformation efficiency of reaction raw materials Glucosamine sulfate potassium chloride is 100%, crystallization obtains purity >=99% of product, and the molar yield of fructosazine is 60%.
Embodiment 9:
(1) as method preparation 1-ethyl-3-methylimidazole acetate ionic liquid in embodiment 1, get 1-ethyl-3-methylimidazole acetate ionic liquid 20g, add 15gD-Glucosamine sulfate sodium chloride, to add total mass number be the massfraction of 30 times of raw material D-glucosamine sodium sulfate salts is the aqueous hydrogen peroxide solution of 30%, after mixing in 500ml dimethyl sulfoxide (DMSO), 80 DEG C are reacted 5 hours.
(2) after reaction terminates, at ambient temperature, get reaction product solution 12ml, add 60ml acetone, extract four times, by dissolving of obtaining the acetone of product mutually concentrated evaporate to dryness concentrate, filtrate leaves standstill 10 hours, and crystallization can obtain product, and the transformation efficiency of reaction raw materials D-glucosamine sodium sulfate salt is 100%, crystallization obtains purity >=99.5% of product, and the molar yield of fructosazine is 59%.
Claims (6)
1. utilize chitin kind biomass-making for a method for fructosazine, it is characterized in that comprising the steps:
(1) by dry chitin kind biomass material, glyoxaline ion liquid solution and weight of additive sum: dimethyl sulfoxide (DMSO)=0.1-25g:1ml, the chitin kind biomass material of drying, glyoxaline ion liquid solution and additive are added in dimethyl sulfoxide (DMSO) and mixes, react 5 minutes-10 days at 20 DEG C-200 DEG C, wherein: imidazole ion liquid and chitin kind biomass material mass ratio are 1:2-100, the mass ratio adding chitin kind biomass material and oxygenant is 1:1-50, obtains intermediate product;
(2) intermediate product obtained in step (1) adds recrystallisation solvent, wherein intermediate product: product, than being 1:1-1:10, all dissolving, removes insoluble impurity, filtrate concentrated by rotary evaporation by solvent volume, and leave standstill 10 hours-24 hours, recrystallization prepares product.
2. as claimed in claim 1 a kind of chitin kind biomass-making that utilizes for the method for fructosazine, the chitin of the chitin kind biomass that it is characterized in that described in step (1) to be molecular weight ranges be 1-30 ten thousand, molecular weight ranges is 0.1-20 ten thousand, deacetylation is the chitosan of 50%-100%, D-Glucosamine Hydrochloride, D-glucosamine sulfuric acid sylvite centre or D-glucosamine sodium sulfate salt.
3. a kind of chitin kind biomass-making that utilizes, for the method for fructosazine, is characterized in that the glyoxaline ion liquid described in step (1) is 1-ethyl-3-methyl-imidazoles acetate ionic liquid, 1-butyl-3-methyl-imidazoles acetate ionic liquid, hydroxide 1-ethyl-3-methylimidazole ionic liquid, hydroxide 1-hexyl-3-Methylimidazole ionic liquid, 1-butyl-3-methyl-imidazoles carbonate ion liquid, 1-butyl-3-methyl-imidazoles bicarbonate ion liquid or 1-butyl-3-methyl-imidazoles Benzoate Ion liquid as claimed in claim 1.
4. a kind of chitin kind biomass-making that utilizes as described in claim .3 is for the method for fructosazine, it is characterized in that described glyoxaline ion liquid adopts two-step synthesis method preparation, the first step of the method is the halogeno salt ionic liquid of preparation containing target cationic, and wherein the preparation process of halogenated imidazole salt ion liquid is: first to purified alkyl imidazole and halogenated alkane mixing; Then control certain temperature, react under sealing agitation condition, by washing, recrystallization and underpressure distillation, obtained pure halogenated imidazole salt ion liquid; Then adopt the salt containing desired anion or acid to carry out replacement(metathesis)reaction under stirring at room temperature, obtain object ion liquid.
5. as claimed in claim 1 a kind of chitin kind biomass-making that utilizes for the method for fructosazine, the aqueous hydrogen peroxide solution of the additive that it is characterized in that described in step (1) to be massfraction be 30%-95%, clorox, sodium hypobromite, one or more of potassium hypobromite.
6. a kind of chitin kind biomass-making that utilizes, for the method for fructosazine, is characterized in that the solvent that crystallization described in step (2) uses is acetonitrile, ethanol, propyl alcohol as claimed in claim 1, one or more in acetone.
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| CN112679443A (en) * | 2021-01-25 | 2021-04-20 | 大连理工大学 | Preparation method and application of fructosazine |
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| CN112679443A (en) * | 2021-01-25 | 2021-04-20 | 大连理工大学 | Preparation method and application of fructosazine |
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