CN118684799B - A kind of highly substituted fluorinated chitosan and preparation method thereof - Google Patents
A kind of highly substituted fluorinated chitosan and preparation method thereof Download PDFInfo
- Publication number
- CN118684799B CN118684799B CN202411170110.2A CN202411170110A CN118684799B CN 118684799 B CN118684799 B CN 118684799B CN 202411170110 A CN202411170110 A CN 202411170110A CN 118684799 B CN118684799 B CN 118684799B
- Authority
- CN
- China
- Prior art keywords
- chitosan
- organic
- substituted fluorinated
- sulfonic acid
- fluorinated
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 229920001661 Chitosan Polymers 0.000 title claims abstract description 123
- 238000002360 preparation method Methods 0.000 title abstract description 23
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims abstract description 22
- 239000003960 organic solvent Substances 0.000 claims abstract description 22
- 238000006243 chemical reaction Methods 0.000 claims abstract description 21
- VCYZVXRKYPKDQB-UHFFFAOYSA-N ethyl 2-fluoroacetate Chemical compound CCOC(=O)CF VCYZVXRKYPKDQB-UHFFFAOYSA-N 0.000 claims abstract description 17
- 238000000034 method Methods 0.000 claims abstract description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 15
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims abstract description 13
- 230000035484 reaction time Effects 0.000 claims abstract description 7
- 238000002156 mixing Methods 0.000 claims abstract description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 16
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 15
- 125000003277 amino group Chemical group 0.000 claims description 12
- OEBXWWBYZJNKRK-UHFFFAOYSA-N 1-methyl-2,3,4,6,7,8-hexahydropyrimido[1,2-a]pyrimidine Chemical compound C1CCN=C2N(C)CCCN21 OEBXWWBYZJNKRK-UHFFFAOYSA-N 0.000 claims description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 9
- STSCVKRWJPWALQ-UHFFFAOYSA-N TRIFLUOROACETIC ACID ETHYL ESTER Chemical compound CCOC(=O)C(F)(F)F STSCVKRWJPWALQ-UHFFFAOYSA-N 0.000 claims description 6
- 125000000542 sulfonic acid group Chemical group 0.000 claims description 6
- KYVBNYUBXIEUFW-UHFFFAOYSA-N 1,1,3,3-tetramethylguanidine Chemical compound CN(C)C(=N)N(C)C KYVBNYUBXIEUFW-UHFFFAOYSA-N 0.000 claims description 5
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 claims description 4
- SGUVLZREKBPKCE-UHFFFAOYSA-N 1,5-diazabicyclo[4.3.0]-non-5-ene Chemical compound C1CCN=C2CCCN21 SGUVLZREKBPKCE-UHFFFAOYSA-N 0.000 claims description 3
- VSTXCZGEEVFJES-UHFFFAOYSA-N 1-cycloundecyl-1,5-diazacycloundec-5-ene Chemical compound C1CCCCCC(CCCC1)N1CCCCCC=NCCC1 VSTXCZGEEVFJES-UHFFFAOYSA-N 0.000 claims description 3
- FVKFHMNJTHKMRX-UHFFFAOYSA-N 3,4,6,7,8,9-hexahydro-2H-pyrimido[1,2-a]pyrimidine Chemical compound C1CCN2CCCNC2=N1 FVKFHMNJTHKMRX-UHFFFAOYSA-N 0.000 claims description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 2
- 239000002244 precipitate Substances 0.000 claims description 2
- PVDYNYCZGYOXAF-UHFFFAOYSA-N 2-fluoroethyl acetate Chemical compound CC(=O)OCCF PVDYNYCZGYOXAF-UHFFFAOYSA-N 0.000 claims 1
- 238000006467 substitution reaction Methods 0.000 abstract description 20
- 239000002585 base Substances 0.000 abstract description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract description 10
- 239000003513 alkali Substances 0.000 abstract description 6
- 239000007789 gas Substances 0.000 abstract description 5
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 abstract description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract description 4
- 239000001301 oxygen Substances 0.000 abstract description 4
- 229910052760 oxygen Inorganic materials 0.000 abstract description 4
- 239000000126 substance Substances 0.000 description 17
- 238000004108 freeze drying Methods 0.000 description 12
- 239000000843 powder Substances 0.000 description 7
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 7
- 230000004048 modification Effects 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 238000010521 absorption reaction Methods 0.000 description 5
- 238000000502 dialysis Methods 0.000 description 5
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 3
- 239000008186 active pharmaceutical agent Substances 0.000 description 3
- 238000005917 acylation reaction Methods 0.000 description 3
- -1 cationic polysaccharide Chemical class 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- 150000002222 fluorine compounds Chemical class 0.000 description 3
- 229920002313 fluoropolymer Polymers 0.000 description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000000806 fluorine-19 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 239000004811 fluoropolymer Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 230000005311 nuclear magnetism Effects 0.000 description 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 229920002101 Chitin Polymers 0.000 description 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 1
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 1
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 1
- 238000006359 acetalization reaction Methods 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 238000005452 bending Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- MSWZFWKMSRAUBD-QZABAPFNSA-N beta-D-glucosamine Chemical group N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-QZABAPFNSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229920001222 biopolymer Polymers 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- NBVXSUQYWXRMNV-UHFFFAOYSA-N fluoromethane Chemical group FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 description 1
- 239000012761 high-performance material Substances 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 229950006780 n-acetylglucosamine Drugs 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 229920005604 random copolymer Polymers 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001228 spectrum 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
- C08B37/0024—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid beta-D-Glucans; (beta-1,3)-D-Glucans, e.g. paramylon, coriolan, sclerotan, pachyman, callose, scleroglucan, schizophyllan, laminaran, lentinan or curdlan; (beta-1,6)-D-Glucans, e.g. pustulan; (beta-1,4)-D-Glucans; (beta-1,3)(beta-1,4)-D-Glucans, e.g. lichenan; Derivatives thereof
- C08B37/0027—2-Acetamido-2-deoxy-beta-glucans; Derivatives thereof
- C08B37/003—Chitin, i.e. 2-acetamido-2-deoxy-(beta-1,4)-D-glucan or N-acetyl-beta-1,4-D-glucosamine; Chitosan, i.e. deacetylated product of chitin or (beta-1,4)-D-glucosamine; 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 relates to the technical field of fluorinated chitosan preparation, and discloses high-substituted fluorinated chitosan and a preparation method thereof, wherein the preparation method comprises the following steps: mixing chitosan and organic sulfonic acid in water, and reacting to obtain chitosan-organic sulfonate; and dissolving the chitosan-organic sulfonate in an organic solvent, and then sequentially adding ethyl fluoroacetate and organic strong base to react to prepare the high-substituted fluorinated chitosan. The high-substituted fluorinated chitosan is prepared by utilizing organic alkali to catalyze the reaction of ethyl fluoroacetate and amino in chitosan in an organic solvent. The method provided by the invention carries out homogeneous reaction under room temperature, strict anhydrous and anaerobic conditions are not needed, the reaction time is short, the substitution degree of the prepared high-substitution fluorinated chitosan reaches more than 90%, the high-substitution chitosan has strong capability of dissolving oxygen and ozone gas, and the high-substitution fluorinated chitosan is well dissolved in an organic solvent and can be further modified, so that more application scenes are expanded.
Description
Technical Field
The invention belongs to the technical field of fluorinated chitosan preparation, and particularly relates to high-substituted fluorinated chitosan and a preparation method thereof.
Background
Chitosan is a cationic polysaccharide in nature, and is formed by connecting N-acetyl-D-glucosamine and D-glucosamine units through beta-1, 4 glycosidic bonds to form a random copolymer. Chitosan is a sustainable polymer material that is readily available on an industrial scale from the second largest biopolymer, chitin. It has excellent biological activity including biocompatibility, biodegradability, low immunoreactivity, antibacterial activity, etc. Therefore, it is widely used in the fields of medicine, cosmetics, agriculture, food, biotechnology, etc. However, chitosan has a large number of hydrogen bonds within and between molecules, is insoluble in water and general organic solvents, and can be dissolved in an acidic aqueous solution or an aqueous alkali/urea solution. Thus, the synthetic modification of chitosan is usually performed in acidic aqueous solution, low temperature alkali/urea aqueous solution or heterogeneous conditions, and these reactions are performed in aqueous systems, but many reactions are performed in anhydrous solvents, such as esterification, acetalization, etc., and the modification of chitosan only in aqueous systems limits the development and utilization of chitosan materials.
Fluoropolymers, commonly referred to as fluoropolymers, are multifunctional high performance materials composed of partially or fully fluorinated monomers. Fluorinated polymers have specific properties such as biochemical inertness, low lipophilicity, super hydrophobicity, high gas solubility, etc. Because the fluorine element is the element with the highest electronegativity, the fluorine-carbon bond has high ionization energy and high oxidation potential, and the polarity of the fluorine-carbon bond is smaller than that of the hydrocarbon bond, so that the hydrophobicity of the fluorine-carbon bond is stronger, and the fluorine-carbon bond has strong surface activity in aqueous solution. In addition, the fluorocarbon bond is the strongest bond energy in the covalent bond and is difficult to break, so that the fluorocarbon chain is more stable. The material has wide application in the fields of chemical industry, pharmacy, biomedicine and the like. In recent years, various fluorides have been modified onto chitosan, usually by grafting the fluorides onto chitosan in an acidic solution using an amide reaction of carboxyl groups and amino groups, and these fluorides have been applied to antibacterial, protein drug delivery, and the like. However, the modification rate of the currently prepared fluorinated chitosan is less than 50%, and thus, it remains a challenge to prepare fluorinated chitosan with a high substitution degree.
Accordingly, the prior art is still in need of improvement and development.
Disclosure of Invention
In view of the shortcomings of the prior art, the invention aims to provide high-substituted fluorinated chitosan and a preparation method thereof, and aims to solve the problem that the substitution degree of the fluorinated chitosan prepared by the prior art is not high.
The technical scheme of the invention is as follows:
the preparation method of the high-substituted fluorinated chitosan comprises the following steps:
mixing chitosan and organic sulfonic acid in water, and reacting to obtain chitosan-organic sulfonate;
And dissolving the chitosan-organic sulfonate in an organic solvent, and then sequentially adding ethyl fluoroacetate and organic strong base to react to prepare the high-substituted fluorinated chitosan.
The preparation method of the high-substituted fluorinated chitosan comprises the step of preparing the high-substituted fluorinated chitosan, wherein the organic sulfonic acid is one of p-toluenesulfonic acid, alkyl sulfonic acid and camphorsulfonic acid.
The preparation method of the high-substituted fluorinated chitosan comprises the step of preparing the high-substituted fluorinated chitosan, wherein the ethyl fluoroacetate is one of ethyl trifluoroacetate, ethyl pentafluoroacetate and ethyl heptafluoroacetate.
The preparation method of the high-substituted fluorinated chitosan comprises the step of preparing the high-substituted fluorinated chitosan, wherein the organic strong base is one or more of N, N-diisopropylethylamine, 1, 8-diazabicyclo undec-7-ene, 1, 5-diazabicyclo [4.3.0] non-5-ene, 7-methyl-1, 5, 7-triazabicyclo [4.4.0] dec-5-ene, 1,5, 7-triazabicyclo [4.4.0] dec-5-ene and tetramethyl guanidine.
The preparation method of the high-substituted fluorinated chitosan comprises the step of sequentially adding ethyl fluoroacetate and organic strong base, wherein the reaction time is 3-5h.
The preparation method of the high-substituted fluorinated chitosan comprises the step of mixing chitosan and organic sulfonic acid in water, wherein the molar ratio of amino groups in the chitosan to sulfonic acid groups in the organic sulfonic acid is 1:1-3.
The preparation method of the high-substituted fluorinated chitosan comprises the step of preparing the high-substituted fluorinated chitosan by using an organic solvent selected from dimethyl sulfoxide, dimethylformamide and dimethylacetamide.
The invention relates to a high-substituted fluorinated chitosan, which is prepared by adopting the preparation method of the high-substituted fluorinated chitosan.
The beneficial effects are that: according to the preparation method of the high-substituted fluorinated chitosan, provided by the invention, the high-substituted fluorinated chitosan is prepared by catalyzing the reaction of ethyl fluoroacetate and amino groups in chitosan in an organic solvent by using organic alkali. The method provided by the invention carries out homogeneous reaction under room temperature, strict anhydrous and anaerobic conditions are not needed, the reaction time is short, the substitution degree of the prepared high-substitution fluorinated chitosan reaches more than 90%, the high-substitution chitosan has strong capability of dissolving oxygen and ozone gas, and the high-substitution fluorinated chitosan is well dissolved in an organic solvent and can be further modified, so that more application scenes are expanded.
Drawings
FIG. 1 is a flow chart of a preparation method of the high-substituted fluorinated chitosan.
FIG. 2 is a synthetic route diagram of the highly substituted fluorinated chitosan of the present invention.
FIG. 3 is a nuclear magnetic resonance spectrum of highly substituted fluorinated chitosan prepared in example 1-example 3 of the present invention.
FIG. 4 is a nuclear magnetic resonance spectrum of highly substituted fluorinated chitosan prepared in examples 1 to 3 of the present invention.
FIG. 5 shows nuclear magnetic resonance fluorine spectra of highly substituted fluorinated chitosan prepared in examples 1 to 3 of the present invention.
FIG. 6 is an infrared chart of the highly substituted fluorinated chitosan prepared in examples 1 to 3 of the present invention.
Detailed Description
The invention provides a high-substituted fluorinated chitosan and a preparation method thereof, and the invention is further described in detail below in order to make the purposes, technical schemes and effects of the invention clearer and more definite. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention.
The terms "first," "second," "third," "fourth" and the like in the description and in the claims and in the above drawings, if any, are used for distinguishing between similar objects and not necessarily for describing a particular sequential or chronological order. It is to be understood that the data so used may be interchanged where appropriate such that the embodiments described herein may be implemented in other sequences than those illustrated or otherwise described herein. Furthermore, the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, system, article, or apparatus that comprises a list of steps or elements is not necessarily limited to those steps or elements expressly listed or inherent to such process, method, article, or apparatus.
For easy understanding, the following describes a specific flow of an embodiment of the present invention, referring to fig. 1, a first embodiment of a method for preparing highly substituted fluorinated chitosan according to the embodiment of the present invention includes:
s10, mixing chitosan and organic sulfonic acid in water, and reacting to obtain chitosan-organic sulfonate;
S20, dissolving the chitosan-organic sulfonate in an organic solvent, and then sequentially adding ethyl fluoroacetate and organic strong base to react to prepare the high-substituted fluorinated chitosan.
In the present invention, as shown in fig. 2, since chitosan itself is insoluble in water and an organic solvent, the present invention firstly employs a reaction of chitosan and an organic sulfonic acid to form chitosan-organic sulfonate, which is soluble in an organic solvent; then dissolving the chitosan-organic sulfonate in an organic solvent, then sequentially adding ethyl fluoroacetate and organic strong base, and after the organic strong base is added, people fixedly think that chitosan can be precipitated without improving the reaction efficiency, but the experimental result shows that the organic strong base can catalyze the efficient reaction of the ethyl fluoroacetate and the amino in the chitosan in the organic solvent, so that the high-substituted fluorinated chitosan is prepared. The invention breaks through the traditional inertia thinking, and the high-substituted fluorinated chitosan is prepared by catalyzing the high-efficiency reaction of the ethyl fluoroacetate and the amino in the chitosan under the strong alkali condition. The method provided by the invention carries out homogeneous reaction under room temperature, strict anhydrous and anaerobic conditions are not needed, the reaction time is short, the substitution degree of the prepared high-substitution fluorinated chitosan reaches more than 90%, the high-substitution chitosan has strong capability of dissolving oxygen and ozone gas, and the high-substitution fluorinated chitosan is well dissolved in an organic solvent and can be further modified, so that more application scenes are expanded.
In some embodiments, the organic sulfonic acid is one of p-toluene sulfonic acid, alkyl sulfonic acid, and camphor sulfonic acid, but is not limited thereto. In this embodiment, the organic sulfonic acid is mainly used to react with chitosan, so that the generated chitosan-organic sulfonate can be dissolved in an organic solvent.
In some embodiments, in the step of mixing chitosan and organic sulfonic acid in water, the molar ratio of amino groups in the chitosan to sulfonic acid groups in the organic sulfonic acid is 1:1-3, but is not limited thereto. As an example, the molar ratio of amino groups in the chitosan to sulfonic acid groups in the organic sulfonic acid may be 1:1,1:2,1:3, etc. This example requires ensuring that the molar amount of sulfonic acid groups is greater than the amino groups in chitosan in order to allow the amino groups in chitosan to react sufficiently with the sulfonic acid groups.
In some embodiments, the ethyl fluoroacetate is one of ethyl trifluoroacetate, ethyl pentafluoroacetate and ethyl heptafluoroacetate, but is not limited thereto. In the catalysis of the organic alkali, the ethyl fluoroacetate can be subjected to acylation reaction with chitosan-organic sulfonate, so that the high-substituted fluorinated chitosan is prepared.
In some embodiments, the strong organic base is one or more of N, N-Diisopropylethylamine (DIPEA), 1, 8-diazabicyclo undec-7-ene (DBU), 1, 5-diazabicyclo [4.3.0] non-5-ene (DBN), 7-methyl-1, 5, 7-triazabicyclo [4.4.0] dec-5-ene (MTBD), 1,5, 7-triazabicyclo [4.4.0] dec-5-ene (TBD), tetramethylguanidine (TMG). The organic strong bases selected in the embodiment all show strong alkalinity, can be used as a base catalyst in the organic reaction to promote the acylation reaction, can be dissolved in various organic solvents, and can effectively catalyze the reaction under mild conditions. By way of example, DBU and TBD have greater steric hindrance and special electronic effects, which make them exhibit higher catalytic activity and selectivity in the reaction. Experiments prove that the organic strong bases can catalyze the efficient reaction of the ethyl fluoroacetate and the amino groups in the chitosan in the organic solvent, and the formed precipitate can disappear quickly, so that the high-substituted fluorinated chitosan can be prepared.
In some embodiments, the reaction time is 3 to 5 hours after the ethyl fluoroacetate and the organic strong base are sequentially added, but is not limited thereto. By way of example, the reaction time is 3h, 4h, 5h, etc.
In some embodiments, the organic solvent is one of dimethyl sulfoxide, dimethylformamide and dimethylacetamide, but is not limited thereto.
In some embodiments, there is also provided a highly substituted fluorinated chitosan prepared using the method of preparing highly substituted fluorinated chitosan of the present invention. The substitution degree of the high-substitution fluorinated chitosan prepared by the invention reaches more than 90%, the high-substitution chitosan has strong capability of dissolving oxygen and ozone gas, and can be well dissolved in an organic solvent, and further modification can be carried out, so that more application scenes are expanded.
The invention is further illustrated by the following examples:
Example 1
A method for preparing trifluoroacetyl chitosan, comprising the following steps:
1.0 g of chitosan and p-toluenesulfonic acid (according to the molar ratio (sulfonic acid/amino) =1:1) are dissolved in 60 mL water, and the white sponge is obtained by freeze-drying, thus obtaining chitosan-p-toluenesulfonate (CS-PTSA);
660 mg of CS-PTSA was dissolved in dimethyl sulfoxide, followed by addition of ethyl trifluoroacetate 1.5 mL, followed by addition of a quantity of DIPEA, reacted at room temperature for 4 hours, dialyzed for 48 hours, and lyophilized to give a yellow powder, i.e., trifluoroacetylated chitosan (TFAC).
Example 2
A preparation method of pentafluoroacetyl chitosan comprises the following steps:
1.0 g of chitosan and p-toluenesulfonic acid (according to the molar ratio (sulfonic acid/amino) =1:1) are dissolved in 60 mL water, and the white sponge is obtained by freeze-drying, thus obtaining chitosan-p-toluenesulfonate (CS-PTSA);
660 mg of CS-PTSA was dissolved in dimethyl sulfoxide, then ethyl pentafluoroacetate 1.5 mL was added, followed by a certain amount of DBU, reacted at room temperature for 4 hours, dialyzed for 48 hours, and lyophilized to give yellow powder, i.e., pentafluoroacetyl chitosan (PFPC) was obtained.
Example 3
A preparation method of heptafluoro-acetylated chitosan comprises the following steps:
1.0 g of chitosan and p-toluenesulfonic acid (according to the molar ratio (sulfonic acid/amino) =1:1) are dissolved in 60 mL water, and the white sponge is obtained by freeze-drying, thus obtaining chitosan-p-toluenesulfonate (CS-PTSA);
660 mg of CS-PTSA is dissolved in dimethyl sulfoxide, then ethyl heptafluoroacetate 1.5 mL is added, a certain amount of DBN is added, the reaction is carried out for 4 hours at room temperature, dialysis is carried out for 48 hours, and the yellow powder is obtained after freeze-drying, thus obtaining the heptafluoroacetylated chitosan (HFBC).
Example 4
A method for preparing trifluoroacetyl chitosan, comprising the following steps:
1.0 g of chitosan and alkylsulfonic acid (according to the molar ratio (sulfonic acid/amino) =2:1) are dissolved in 50 mL of water, and the white sponge is obtained by freeze-drying, thus obtaining chitosan-alkylsulfonate;
500 mg of chitosan-alkyl sulfonate is dissolved in dimethylformamide, then ethyl trifluoroacetate 2.5 mL is added, then a certain amount of DIPEA is added for reaction for 3 hours at room temperature, dialysis is carried out for 24 hours, and yellow powder is obtained by freeze-drying, thus obtaining the trifluoroacetyl chitosan.
Example 5
A method for preparing trifluoroacetyl chitosan, comprising the following steps:
1.0 g of chitosan and camphorsulfonic acid (according to the molar ratio (sulfonic acid/amino) =3:1) are dissolved in 50 mL of water, and the white sponge is obtained by freeze-drying, thus obtaining the chitosan-camphorsulfonate;
600 mg of chitosan-camphorsulfonate is dissolved in dimethylformamide, then 3.5 mL of ethyl trifluoroacetate is added, then a certain amount of TMG is added for reaction for 5 hours at room temperature, dialysis is carried out for 36 hours, and yellow powder is obtained by freeze-drying, thus obtaining the trifluoroacetyl chitosan.
Example 6
A preparation method of pentafluoroacetyl chitosan comprises the following steps:
1.0 g of chitosan and p-toluenesulfonic acid (according to the molar ratio (sulfonic acid/amino) =2:1) are dissolved in 50 mL water, and the white sponge is obtained by freeze-drying, thus obtaining chitosan-p-toluenesulfonate (CS-PTSA);
660 mg of CS-PTSA is dissolved in dimethyl sulfoxide, then ethyl pentafluoroacetate 2.5 mL is added, a certain amount of TBD is added for reaction for 5 hours at room temperature, dialysis is carried out for 48 hours, and yellow powder is obtained after freeze drying, thus obtaining the pentafluoroacetyl chitosan.
Example 7
A preparation method of heptafluoro-acetylated chitosan comprises the following steps:
1.0 g of chitosan and p-toluenesulfonic acid (according to the molar ratio (sulfonic acid/amino) =3:1) are dissolved in 60 mL water, and the white sponge is obtained by freeze-drying, thus obtaining chitosan-p-toluenesulfonate (CS-PTSA);
660 mg of CS-PTSA is dissolved in dimethyl sulfoxide, then ethyl heptafluoro acetate 2.5 mL is added, then a certain amount of MTBD is added for reaction for 5 hours at room temperature, dialysis is carried out for 48 hours, and yellow powder is obtained after freeze drying, thus obtaining the heptafluoro-acetylated chitosan.
Test example 1
The trifluoroacetyl chitosan, pentafluoroacetyl chitosan and heptafluoroacetyl chitosan prepared in examples 1-3 were dissolved in deuterated dimethyl sulfoxide, respectively, and nuclear magnetic 1H NMR、13 C NMR and 19 F NMR characterization was performed by using a Bruker ADVANCE III MHz NMR spectrometer, germany, and the results are shown in FIG. 3. From the nuclear magnetic 1 H NMR spectrum (shown in FIG. 3), it can be seen that 9.25-9.6 ppm is the chemical shift of CONH-, 4.3-4.7 is the chemical shift of H1, and that H2 chemical shift moves to low field due to the high electronegativity of fluorine, and 3.0-4.0 is the chemical shift of H2-6. from the nuclear magnetism 13 C NMR spectrum (as shown in fig. 4), 56 ppm, 60 ppm are chemical shifts of C2 and C6, 72, 75, 80 ppm are chemical shifts of C3, C5 and C4, respectively, and 100 ppm is a chemical shift of C1. 112-121 ppm is the chemical shift of CF 3 -, a quartet occurs due to F-to-C coupling. 104-110 ppm is the chemical shift of-CF 2 -and a triplet occurs due to F-to-C coupling. 157 ppm is the chemical shift of CF 3 CO-. From the nuclear magnetic 19 F NMR spectrum (as shown in FIG. 5), it can be seen that for TFAC, the chemical shift of CF 3 -is 74.5 ppm, for PFPC, the chemical shift of CF 3 -is 82.1, -121.7 is the chemical shift of-CF 2 -for HFBC, -80.0 is the chemical shift of CF 3, -126.7 is the chemical shift of CF 3CF2CF2, -119.1 is the chemical shift of CF 3CF2CF2 -. The nuclear magnetism 1H NMR、13 C NMR and 19 F NMR spectra show that the invention has successfully synthesized the fluorinated chitosan.
Further, in this example, the mass fraction of C, H, N elements in the trifluoroacetyl chitosan, pentafluoroacetyl chitosan and heptafluoroacetyl chitosan prepared in examples 1 to 3 was also measured by using a Thermo Flash 2000 element analyzer, and was used for calculating the substitution degree. The results are shown in Table 1, in which the substitution Degree (DS) of TFAC was 95%, the DS of PFPC was 97%, and the DS of HFBC was 92%. This shows that the substitution degree of the fluorinated chitosan prepared by the invention is more than 90%.
Table 1 test results
Test example 2
To further verify the structure of the highly substituted fluorinated chitosan, the present test example characterizes the infrared spectra of chitosan and the fluorinated chitosan prepared in examples 1 to 3 by infrared method, and the result is shown in FIG. 6, in which the absorption peak at 3400cm -1 is assigned to the stretching vibration peak of hydroxyl group (-OH) and amino group (-NH 2) for chitosan. The band around 1600cm -1 is attributed to the bending vibration peak of the amino group. The strong absorption peak around 1100 cm -1 corresponds to the C-O stretching vibration absorption peak of the hydroxyl group.
For fluorinated chitosan, a strong characteristic absorption peak appears at 1709 cm -1, which is a C=O stretching vibration peak, and 1159 cm -1 shows a strong characteristic absorption peak, which is a C-F stretching vibration peak. As the number of F increases, the peaks at 1159 cm -1 and 1709 cm -1 are gradually enhanced, so that the acylation reaction is successful as can be seen from the infrared result, and the high-substituted fluorinated chitosan is prepared.
It is to be understood that the invention is not limited in its application to the examples described above, but is capable of modification and variation in light of the above teachings by those skilled in the art, and that all such modifications and variations are intended to be included within the scope of the appended claims.
Claims (4)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202411170110.2A CN118684799B (en) | 2024-08-26 | 2024-08-26 | A kind of highly substituted fluorinated chitosan and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202411170110.2A CN118684799B (en) | 2024-08-26 | 2024-08-26 | A kind of highly substituted fluorinated chitosan and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN118684799A CN118684799A (en) | 2024-09-24 |
| CN118684799B true CN118684799B (en) | 2024-11-26 |
Family
ID=92778430
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202411170110.2A Active CN118684799B (en) | 2024-08-26 | 2024-08-26 | A kind of highly substituted fluorinated chitosan and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN118684799B (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104854134A (en) * | 2012-12-12 | 2015-08-19 | 索尔维特殊聚合物意大利有限公司 | Fluorinated chitosan derivatives |
| CN111848830A (en) * | 2019-04-30 | 2020-10-30 | 苏州大学 | Use of chitosan modified by fluorine-containing compound as drug carrier and preparation method thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112142917B (en) * | 2020-11-04 | 2022-12-16 | 扬州工业职业技术学院 | Modified chitosan water-based binder and preparation method thereof |
-
2024
- 2024-08-26 CN CN202411170110.2A patent/CN118684799B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104854134A (en) * | 2012-12-12 | 2015-08-19 | 索尔维特殊聚合物意大利有限公司 | Fluorinated chitosan derivatives |
| CN111848830A (en) * | 2019-04-30 | 2020-10-30 | 苏州大学 | Use of chitosan modified by fluorine-containing compound as drug carrier and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN118684799A (en) | 2024-09-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Qin et al. | Enzymic preparation of water-soluble chitosan and their antitumor activity | |
| Xie et al. | Chitin and chitosan dissolved in ionic liquids as reversible sorbents of CO 2 | |
| CN104292454B (en) | Polyethylene glycol cyclooctyne derivative | |
| US5597811A (en) | Oxirane carboxylic acid derivatives of polyglucosamines | |
| Gruškienė et al. | Quaternization of chitosan and partial destruction of the quaternized derivatives making them suitable for electrospinning | |
| Xiao et al. | Synthesis and properties of a novel crosslinked chitosan resin modified by L-lysine | |
| WO2019227525A1 (en) | Application and preparation method of chitooligosaccharide-based compound | |
| CN118684799B (en) | A kind of highly substituted fluorinated chitosan and preparation method thereof | |
| Detchprohm et al. | Synthesis of a Novel Chitin Derivative Having Oligo (ε‐caprolactone) Side Chains in Aqueous Reaction Media | |
| US8410262B2 (en) | Process for the preparation of hydroxy polymer esters and their use | |
| ES2496674T3 (en) | A process for preparing high purity polyethylene glycol aldehyde derivatives | |
| CN100494223C (en) | Synthesis method of chitosan nucleophilic NO donor modified by quaternary ammonium salt | |
| CN100535015C (en) | Aldonic acid esters, methods for producing the same, and methods for producing pharmaceutical active ingredients coupled to polysaccharides or polysaccharide derivatives on free amino groups | |
| CN106995502A (en) | Bifunctional group modified chitosan derivative and preparation method thereof | |
| CN111040003B (en) | Chitosan oligosaccharide derivative molecular imprinting functional monomer and preparation method thereof | |
| EP0737692B1 (en) | Process for derivatizing polyglucosamines | |
| CN119285811A (en) | A guanidine-containing carboxymethyl chitosan quaternary ammonium salt derivative and its preparation method and application | |
| CN104371098A (en) | Multi-branched hydrophilic polymer-isocyanate derivative | |
| Courtecuisse et al. | Synthesis of linear chitosan-block-dextran copolysaccharides with dihydrazide and dioxyamine linkers | |
| CN103877585B (en) | Chitosan derivatives nanoparticle and medicine-carried nano particles and preparation method | |
| JP2004250543A (en) | Method for producing chitosan derivative and chitosan derivative | |
| CN104031903B (en) | Method for flexible immobilization of papain by modified polyacrylonitrile resin | |
| JP4772203B2 (en) | Method for producing compound having sugar skeleton | |
| KR100381387B1 (en) | Manufacturing method of chitosan derivative | |
| CN101230198A (en) | A method for improving the stability of amylose inclusion complex solution |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |