CN116874644A - Process for preparing carboxyl-beta-cyclodextrin derivative - Google Patents
Process for preparing carboxyl-beta-cyclodextrin derivative Download PDFInfo
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- cyclodextrin
- carboxyl
- cyclodextrin derivative
- carboxy
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- 238000004519 manufacturing process Methods 0.000 title claims description 5
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical class OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 claims abstract description 38
- 238000002360 preparation method Methods 0.000 claims abstract description 16
- 229920000858 Cyclodextrin Polymers 0.000 claims description 34
- 239000001116 FEMA 4028 Substances 0.000 claims description 30
- 229960004853 betadex Drugs 0.000 claims description 30
- 235000011175 beta-cyclodextrine Nutrition 0.000 claims description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 19
- 239000007800 oxidant agent Substances 0.000 claims description 18
- 230000001590 oxidative effect Effects 0.000 claims description 14
- 239000003054 catalyst Substances 0.000 claims description 13
- 150000002500 ions Chemical class 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 9
- 239000011259 mixed solution Substances 0.000 claims description 9
- 238000010438 heat treatment Methods 0.000 claims description 8
- 239000012425 OXONE® Substances 0.000 claims description 7
- HJKYXKSLRZKNSI-UHFFFAOYSA-I pentapotassium;hydrogen sulfate;oxido sulfate;sulfuric acid Chemical group [K+].[K+].[K+].[K+].[K+].OS([O-])(=O)=O.[O-]S([O-])(=O)=O.OS(=O)(=O)O[O-].OS(=O)(=O)O[O-] HJKYXKSLRZKNSI-UHFFFAOYSA-I 0.000 claims description 7
- 238000002390 rotary evaporation Methods 0.000 claims description 7
- 230000035484 reaction time Effects 0.000 claims description 4
- 229910002651 NO3 Inorganic materials 0.000 claims description 3
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 3
- 238000000746 purification Methods 0.000 claims description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 description 16
- -1 cyclic oligosaccharides Chemical class 0.000 description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- 238000004566 IR spectroscopy Methods 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 229940097362 cyclodextrins Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 238000002329 infrared spectrum Methods 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- CUJVBAPGYBSBHJ-YWBSARSQSA-N 2-[[(1R,3R,5R,6S,8R,10R,11S,13R,15R,16S,18R,20R,21R,23R,25R,26R,28R,30R,31R,33R,35R,36R,37R,38R,39R,40R,41R,42R,43R,44R,45R,46R,47R,48R,49R)-36,38,40,42-tetrakis(carboxymethoxy)-10,15-bis(carboxymethoxymethyl)-37,39,41,43,44,45,46,47,48,49-decahydroxy-20,25,30,35-tetrakis(hydroxymethyl)-2,4,7,9,12,14,17,19,22,24,27,29,32,34-tetradecaoxaoctacyclo[31.2.2.23,6.28,11.213,16.218,21.223,26.228,31]nonatetracontan-5-yl]methoxy]acetic acid Chemical compound OC[C@H]1O[C@@H]2O[C@H]3[C@H](O)[C@@H](O)[C@H](O[C@@H]3COCC(O)=O)O[C@H]3[C@H](O)[C@@H](O)[C@H](O[C@@H]3COCC(O)=O)O[C@H]3[C@H](O)[C@@H](O)[C@H](O[C@@H]3COCC(O)=O)O[C@@H]3[C@@H](CO)O[C@H](O[C@@H]4[C@@H](CO)O[C@H](O[C@@H]5[C@@H](CO)O[C@H](O[C@H]1[C@H](OCC(O)=O)[C@H]2O)[C@H](O)[C@H]5OCC(O)=O)[C@H](O)[C@H]4OCC(O)=O)[C@H](O)[C@H]3OCC(O)=O CUJVBAPGYBSBHJ-YWBSARSQSA-N 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 108700035208 EC 7.-.-.- Proteins 0.000 description 1
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- VILAVOFMIJHSJA-UHFFFAOYSA-N dicarbon monoxide Chemical compound [C]=C=O VILAVOFMIJHSJA-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000006266 etherification reaction Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical class [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 1
- 235000003891 ferrous sulphate Nutrition 0.000 description 1
- 239000011790 ferrous sulphate Substances 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 description 1
- 229910000359 iron(II) sulfate Inorganic materials 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- FDRCDNZGSXJAFP-UHFFFAOYSA-M sodium chloroacetate Chemical compound [Na+].[O-]C(=O)CCl FDRCDNZGSXJAFP-UHFFFAOYSA-M 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 125000004964 sulfoalkyl group Chemical group 0.000 description 1
- 125000000542 sulfonic acid group Chemical group 0.000 description 1
- 239000002344 surface layer Substances 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
- C08B37/0009—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid alpha-D-Glucans, e.g. polydextrose, alternan, glycogen; (alpha-1,4)(alpha-1,6)-D-Glucans; (alpha-1,3)(alpha-1,4)-D-Glucans, e.g. isolichenan or nigeran; (alpha-1,4)-D-Glucans; (alpha-1,3)-D-Glucans, e.g. pseudonigeran; Derivatives thereof
- C08B37/0012—Cyclodextrin [CD], e.g. cycle with 6 units (alpha), with 7 units (beta) and with 8 units (gamma), large-ring cyclodextrin or cycloamylose with 9 units or more; Derivatives thereof
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
Abstract
The invention provides a preparation process of a carboxyl-beta-cyclodextrin derivative, which relates to the technical field of beta-cyclodextrin derivatives.
Description
Technical Field
The invention belongs to the technical field of beta-cyclodextrin derivatives, and particularly relates to a preparation process of a carboxyl-beta-cyclodextrin derivative.
Background
Cyclodextrins (CDs) are cyclic oligosaccharides formed from D-glucose molecules linked by 1, 4-glycosidic linkages and are the product of the action of cyclodextrin glucose translocases obtained by culturing starch with Bacillus alkalophilus. The structure is annular hollow cylinder, has hydrophobic inner cavity and hydrophilic outer surface layer, and thus presents a series of special properties, such as forming inclusion compound with some small molecules, improving chemical and physical properties of small molecules. Common cyclodextrins are composed of 6, 7, 8 glucose molecules, α -CD, β -CD and γ -CD, respectively. Wherein the cavity size in beta-CD is moderate and therefore most commonly used. However, there are many limitations to the use of beta-CD in medicine, such as low water solubility, and only 18.6mg/mL at normal temperature. The reason for this is: beta-CD has 7 primary hydroxyl groups and 14 secondary hydroxyl groups at two ends of the cylinder, and the intramolecular hydrogen bond prevents the hydration of water molecules, so that the water solubility of the beta-CD is reduced. The physical and chemical properties, particularly the water solubility, of the beta-CD molecules can be significantly changed by modifying the hydroxyl groups, such as introducing methyl, ethyl, hydroxypropyl, sulfonic acid groups and the like into the beta-CD molecules and destroying the formation of hydrogen bonds in the beta-CD molecules. The hydrophilic beta-CD derivative can be included with various medicines, so that the solubility of insoluble medicines is increased, and the toxicity and the irritation are reduced. To overcome the disadvantages of beta-CD, a series of beta-CD derivatives, such as various derivatives of alkylation (methylation), hydroxyalkylation (hydroxypropyl), sulfoalkyl etherification (sulfobutyl), and the like, are synthesized, wherein two important derivatives of hydroxypropyl-beta-CD and sulfobutyl ether-beta-CD are widely used. Therefore, it is important to develop other types of β -CD derivatives. Process for the preparation of a beta-cyclodextrin with an amino group-containing compound by the coupling of epichlorohydrin under alkaline conditions
In the prior art, literature (Dai Rongji, etc. beta-cyclodextrin derivatives containing amino groups and carboxyl groups are synthesized and performance is tested, university of Beijing university report, 1998,18,159-164.) reports the synthesis of beta-cyclodextrin derivatives containing carboxyl groups, namely sodium chloroacetate is used as a raw material, and carboxymethyl-beta-cyclodextrin is synthesized in sequence under alkaline and acidic conditions; the synthesis of carboxy beta-cyclodextrin derivatives has been reported in literature (Li Junhua et al, preparation and property studies of carboxy beta-cyclodextrin derivatives and their ferrocene complexes, spectral laboratory, 2010,27, 1059-1063.) the preparation of beta-cyclodextrin from a carbonyl beta-cyclodextrin followed by the reaction of the carbonyl beta-cyclodextrin with glycine to form carboxymethyl amino beta-cyclodextrin derivatives, but in the prior art described above, several different steps are required to produce the desired product, resulting in a complex reaction process.
Disclosure of Invention
In view of the above, the present invention provides a method for preparing a carboxy- β -cyclodextrin derivative with a simple preparation process.
The technical scheme adopted for solving the technical problems is as follows:
a process for preparing the derivative of carboxyl-beta-cyclodextrin includes such steps as preparing the derivative of carboxyl-beta-cyclodextrin,
s1: the beta-cyclodextrin reacts under heating in the presence of an oxidant, a catalyst and water to generate a mixed solution containing the carboxyl-beta-cyclodextrin derivative;
s2: carrying out post-treatment on the mixed solution containing the carboxyl-beta-cyclodextrin derivative to obtain the carboxyl-beta-cyclodextrin derivative;
the synthetic route is as follows:
preferably, in the step S1: the oxidant is potassium monopersulfate.
Preferably, in the step S1: the heating reaction time is 2-72 h.
Preferably, in the step S1: the molar ratio of the beta-cyclodextrin to the oxidant is 1:1-10.
Preferably, in the step S1: it is also necessary to add a catalyst in the form of Fe ion, zn ion, co ion, chloride, sulfate or nitrate.
Preferably, the catalyst is used in an amount of 1% to 10% of the amount of the oxidizing agent.
Preferably, in the step S2: the post-treatment is as follows: and (3) performing rotary evaporation, vacuum concentration and purification on the mixed solution containing the carboxyl-beta-cyclodextrin derivative to obtain the carboxyl-beta-cyclodextrin derivative.
Compared with the prior art, the invention has the beneficial effects that:
the carboxyl-beta-cyclodextrin derivative prepared by the invention directly converts hydroxymethyl into carboxyl, has high water solubility and wider application, and the preparation process uses water as a solvent, and under the action of a catalyst, the oxidant oxidizes the hydroxymethyl in the beta-cyclodextrin into carboxyl, so that the preparation process is simple and convenient, an organic solvent is not used, and the treatment process meets the requirements of safety and environmental protection.
Drawings
FIG. 1 is an infrared spectrum of a carboxy-beta-cyclodextrin derivative.
FIG. 2 is an infrared spectrum of beta-cyclodextrin.
FIG. 3 is a nuclear magnetic resonance spectrum of a carboxyl-beta-cyclodextrin derivative.
FIG. 4 is a nuclear magnetic resonance spectrum of beta-cyclodextrin.
Detailed Description
The technical scheme and technical effects of the embodiments of the present invention are further described in detail below with reference to the accompanying drawings.
A process for preparing the derivative of carboxyl-beta-cyclodextrin includes such steps as preparing the derivative of carboxyl-beta-cyclodextrin,
s1: the beta-cyclodextrin reacts under heating in the presence of an oxidant and water to generate a mixed solution containing the carboxyl-beta-cyclodextrin derivative;
s2: carrying out post-treatment on the mixed solution containing the carboxyl-beta-cyclodextrin derivative to obtain the carboxyl-beta-cyclodextrin derivative; dissolving a certain amount of beta-cyclodextrin in a proper amount of water, adding an oxidant and an auxiliary catalyst, heating to react, removing water by vacuum rotary evaporation after the reaction is finished, dissolving residues by a proper amount of N, N-dimethylformamide, filtering, and performing vacuum rotary evaporation on the filtrate to obtain the carboxyl-beta-cyclodextrin derivative.
The synthetic route is as follows:
compared with the prior art, the invention has the beneficial effects that:
the carboxyl-beta-cyclodextrin derivative provided by the invention directly converts hydroxymethyl into carboxyl, has high water solubility and is more widely applicable.
The preparation process uses water as a solvent, and under the action of a catalyst, the hydroxymethyl in the beta-cyclodextrin is oxidized into carboxyl by an oxidant, so that the preparation process is simple and convenient, an organic solvent is not used, and the treatment process meets the requirements of safety and environmental protection.
Further, in the step S1: the oxidant is potassium monopersulfate.
Further, in the step S1: the heating reaction time is 2-72 h.
Further, in the step S1: the molar ratio of the beta-cyclodextrin to the oxidant is 1:1-10.
Further, in the step S1: it is also necessary to add a catalyst in the form of a chloride, sulfate or nitrate, which is Fe ion, zn ion, co ion, to promote the reaction.
Further, the catalyst is used in an amount of 1% -10% of the amount of the oxidant.
Further, in the step S2: the post-treatment is as follows: and (3) performing rotary evaporation, vacuum concentration and purification on the mixed solution containing the carboxyl-beta-cyclodextrin derivative to obtain the carboxyl-beta-cyclodextrin derivative.
For ease of understanding, the invention is further illustrated by the following examples:
embodiment one:
1g of beta-cyclodextrin and 5g of potassium monopersulfate are weighed, 20mL of water is added, the temperature is raised to 80 ℃ under stirring, TLC (thin layer chromatography) is used for detecting the reaction progress, beta-cyclodextrin is used as a reference, the stirring reaction is carried out for a certain time, and the occurrence of new points is observed. The experimental results are shown in Table 1, if new spots are generated, the reaction solution is cooled, water is removed by vacuum rotation of a rotary evaporator, residues are dissolved by 5mLN, N-dimethylformamide, insoluble substances are removed by filtration, the filtrate is concentrated in vacuum by the rotary evaporator to obtain a crude product of the carboxyl-beta-cyclodextrin derivative, and the crude product is purified by a C18 reverse packed column to obtain the carboxyl-beta-cyclodextrin derivative.
TABLE 1
Embodiment two:
weighing 1g of beta-cyclodextrin, 5g of potassium monopersulfate, 0.5g of ferrous sulfate, adding 20mL of water, heating to 80 ℃ under stirring, detecting the reaction progress by TLC, taking beta-cyclodextrin as a reference, and stirring for reaction for 6 hours, wherein a new point appears; the reaction mixture was cooled again, water was removed by rotary evaporation under vacuum, the residue was dissolved in 5mLN, N-dimethylformamide, insoluble matter was removed by filtration, and the filtrate was concentrated under vacuum by rotary evaporation to give a crude carboxyl- β -cyclodextrin derivative, which was purified by a C18 reverse packed column to give a carboxyl- β -cyclodextrin derivative in a yield of 46% (0.48 g).
Comparative example one:
2mL of hydrogen peroxide (30 wt.% in H2O) is measured, 20mL of water is added, 1g of beta-cyclodextrin is added, the temperature is raised to 80 ℃ under stirring, the reaction is carried out for 6 hours, TLC (thin layer chromatography) detects the reaction progress, beta-cyclodextrin is used as a contrast, no new point exists, and no reaction is indicated.
As can be seen from the first and second examples, the catalyst is added to promote the reaction, so that the reaction rate is greatly increased, the reaction is facilitated, and the yield is greatly increased.
From examples one and comparative example one, it is seen that when the oxidizing agent is potassium monopersulfate, the oxidation reaction can occur although the reaction time is long, and there is a new point, but when the oxidizing agent is hydrogen peroxide, no new point is formed, beta-cyclodextrin cannot be oxidized, the desired product cannot be produced, and it is seen that not all the oxidizing agent can cause the reaction to occur.
The product obtained in example two was characterized by infrared spectroscopy (IR) and Nuclear Magnetic Resonance (NMR), IR (KBr)/cm -1 :3420,2927,2492, 1739 (c=o), 1637,1191,853, 600s, wherein 1739 is the carbonyl peak of the carboxyl group, which is not present in the starting β -cyclodextrin, see fig. 1 and 2. In the nuclear magnetic NMR carbon spectrum, 175.4ppm of the carboxyl-beta-cyclodextrin derivative appears, which is the carbonyl carbon peak of carboxyl, and the raw material beta-cyclodextrin does not have the peak, as shown in figures 3 and 4. The infrared spectrogram and the nuclear magnetic carbon spectrogram show that the potassium monopersulfate oxidizes the hydroxymethyl in the beta-cyclodextrin into carboxyl under the action of a catalyst.
In addition, the solubility in water was measured, and it was found that the solubility of the carboxy- β -cyclodextrin derivative was 276mg/mL, which was approximately 15-fold higher than that of β -cyclodextrin.
The foregoing disclosure is illustrative of the preferred embodiments of the present invention, and is not to be construed as limiting the scope of the invention, as it is understood by those skilled in the art that all or part of the above-described embodiments may be practiced with equivalents thereof, which fall within the scope of the invention as defined by the appended claims.
Claims (7)
1. A preparation process of a carboxyl-beta-cyclodextrin derivative is characterized by comprising the following steps of: comprises the steps of,
s1: the beta-cyclodextrin reacts under heating in the presence of an oxidant, a catalyst and water to generate a mixed solution containing the carboxyl-beta-cyclodextrin derivative;
s2: carrying out post-treatment on the mixed solution containing the carboxyl-beta-cyclodextrin derivative to obtain the carboxyl-beta-cyclodextrin derivative;
the synthetic route is as follows:
2. a process for the preparation of a carboxy- β -cyclodextrin derivative according to claim 1, wherein: in the step S1: the oxidant is potassium monopersulfate.
3. A process for the preparation of a carboxy- β -cyclodextrin derivative according to claim 1, wherein: in the step S1: the heating reaction time is 2-72 h.
4. A process for the preparation of a carboxy- β -cyclodextrin derivative according to claim 1, wherein: in the step S1: the molar ratio of the beta-cyclodextrin to the oxidant is 1:1-10.
5. A process for the preparation of a carboxy- β -cyclodextrin derivative according to claim 1, wherein: in the step S1: it is also necessary to add a catalyst in the form of Fe ion, zn ion, co ion, chloride, sulfate or nitrate.
6. The process for preparing a carboxy- β -cyclodextrin derivative according to claim 5, wherein: the dosage of the catalyst is 1% -10% of that of the oxidant.
7. A process for the preparation of a carboxy- β -cyclodextrin derivative according to claim 1, wherein: in the step S2: the post-treatment is as follows: and (3) performing rotary evaporation, vacuum concentration and purification on the mixed solution containing the carboxyl-beta-cyclodextrin derivative to obtain the carboxyl-beta-cyclodextrin derivative.
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