CN110256606A - A kind of two ureas chitosan derivatives of nitrogen-containing heterocycle and its preparation method and application - Google Patents
A kind of two ureas chitosan derivatives of nitrogen-containing heterocycle and its preparation method and application Download PDFInfo
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- CN110256606A CN110256606A CN201910743356.7A CN201910743356A CN110256606A CN 110256606 A CN110256606 A CN 110256606A CN 201910743356 A CN201910743356 A CN 201910743356A CN 110256606 A CN110256606 A CN 110256606A
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- chitosan
- ureas
- nitrogen
- containing heterocycle
- chitosan derivatives
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- 229920001661 Chitosan Polymers 0.000 title claims abstract description 152
- 235000013877 carbamide Nutrition 0.000 title claims abstract description 115
- 150000003672 ureas Chemical class 0.000 title claims abstract description 70
- 238000002360 preparation method Methods 0.000 title claims abstract description 25
- 238000006243 chemical reaction Methods 0.000 claims abstract description 26
- 230000003078 antioxidant effect Effects 0.000 claims abstract description 14
- 239000003963 antioxidant agent Substances 0.000 claims abstract description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 77
- -1 methyl thiadiazolyl group Chemical group 0.000 claims description 53
- 239000004202 carbamide Substances 0.000 claims description 38
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 34
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 claims description 28
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 24
- 150000004676 glycans Chemical class 0.000 claims description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 18
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 16
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 16
- 229910052757 nitrogen Inorganic materials 0.000 claims description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Inorganic materials [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 claims description 14
- 125000000335 thiazolyl group Chemical group 0.000 claims description 13
- 150000003384 small molecules Chemical class 0.000 claims description 12
- 125000000623 heterocyclic group Chemical group 0.000 claims description 11
- 239000012948 isocyanate Substances 0.000 claims description 11
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 claims description 10
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 claims description 9
- ATBIAJXSKNPHEI-UHFFFAOYSA-N pyridine-3-carbonyl chloride Chemical compound ClC(=O)C1=CC=CN=C1 ATBIAJXSKNPHEI-UHFFFAOYSA-N 0.000 claims description 9
- 238000003756 stirring Methods 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 8
- 239000012065 filter cake Substances 0.000 claims description 8
- 238000004108 freeze drying Methods 0.000 claims description 8
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 8
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 6
- 239000007795 chemical reaction product Substances 0.000 claims description 6
- 238000001556 precipitation Methods 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 5
- 239000007788 liquid Substances 0.000 claims description 5
- 238000006116 polymerization reaction Methods 0.000 claims description 5
- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 claims description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 4
- 239000006185 dispersion Substances 0.000 claims description 4
- HMPUHXCGUHDVBI-UHFFFAOYSA-N 5-methyl-1,3,4-thiadiazol-2-amine Chemical class CC1=NN=C(N)S1 HMPUHXCGUHDVBI-UHFFFAOYSA-N 0.000 claims description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 3
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 3
- 229910052744 lithium Inorganic materials 0.000 claims description 3
- KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 claims description 2
- 229910021529 ammonia Inorganic materials 0.000 claims description 2
- 238000002425 crystallisation Methods 0.000 claims description 2
- 230000008025 crystallization Effects 0.000 claims description 2
- QUKGLNCXGVWCJX-UHFFFAOYSA-N 1,3,4-thiadiazol-2-amine Chemical class NC1=NN=CS1 QUKGLNCXGVWCJX-UHFFFAOYSA-N 0.000 claims 1
- 150000001263 acyl chlorides Chemical class 0.000 claims 1
- 235000019504 cigarettes Nutrition 0.000 claims 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 1
- 235000013305 food Nutrition 0.000 abstract description 9
- 239000002994 raw material Substances 0.000 abstract description 5
- 239000000126 substance Substances 0.000 abstract description 5
- 238000011161 development Methods 0.000 abstract description 3
- 239000000243 solution Substances 0.000 description 24
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 13
- 238000009777 vacuum freeze-drying Methods 0.000 description 10
- 239000000047 product Substances 0.000 description 8
- 239000000523 sample Substances 0.000 description 8
- 238000005406 washing Methods 0.000 description 8
- 238000010521 absorption reaction Methods 0.000 description 7
- 239000008367 deionised water Substances 0.000 description 7
- 229910021641 deionized water Inorganic materials 0.000 description 7
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 239000003814 drug Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- OFFFOVCCGHKJES-UHFFFAOYSA-N 4-methylthiadiazole Chemical class CC1=CSN=N1 OFFFOVCCGHKJES-UHFFFAOYSA-N 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- 239000012153 distilled water Substances 0.000 description 4
- 238000012869 ethanol precipitation Methods 0.000 description 4
- 239000011521 glass Substances 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 230000002000 scavenging effect Effects 0.000 description 4
- 238000000967 suction filtration Methods 0.000 description 4
- 239000007853 buffer solution Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 239000012488 sample solution Substances 0.000 description 3
- SNTWKPAKVQFCCF-UHFFFAOYSA-N 2,3-dihydro-1h-triazole Chemical compound N1NC=CN1 SNTWKPAKVQFCCF-UHFFFAOYSA-N 0.000 description 2
- VZWOXDYRBDIHMA-UHFFFAOYSA-N 2-methyl-1,3-thiazole Chemical compound CC1=NC=CS1 VZWOXDYRBDIHMA-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- BAWFJGJZGIEFAR-NNYOXOHSSA-N NAD zwitterion Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-N 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- XLJMAIOERFSOGZ-UHFFFAOYSA-N anhydrous cyanic acid Natural products OC#N XLJMAIOERFSOGZ-UHFFFAOYSA-N 0.000 description 2
- 238000007385 chemical modification Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 229960002163 hydrogen peroxide Drugs 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 150000004867 thiadiazoles Chemical class 0.000 description 2
- 150000003852 triazoles Chemical class 0.000 description 2
- IQFIWJDBZRZLNO-UHFFFAOYSA-N 1h-pyrazole;urea Chemical compound NC(N)=O.C=1C=NNC=1 IQFIWJDBZRZLNO-UHFFFAOYSA-N 0.000 description 1
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- RXGJTUSBYWCRBK-UHFFFAOYSA-M 5-methylphenazinium methyl sulfate Chemical compound COS([O-])(=O)=O.C1=CC=C2[N+](C)=C(C=CC=C3)C3=NC2=C1 RXGJTUSBYWCRBK-UHFFFAOYSA-M 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 206010018473 Glycosuria Diseases 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- 230000002292 Radical scavenging effect Effects 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- BKVHNXUUAWSELQ-UHFFFAOYSA-N [Cl].ClCC(=O)Cl Chemical compound [Cl].ClCC(=O)Cl BKVHNXUUAWSELQ-UHFFFAOYSA-N 0.000 description 1
- MOFINMJRLYEONQ-UHFFFAOYSA-N [N].C=1C=CNC=1 Chemical class [N].C=1C=CNC=1 MOFINMJRLYEONQ-UHFFFAOYSA-N 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000002082 anti-convulsion Effects 0.000 description 1
- 238000009452 anti-microbial packaging Methods 0.000 description 1
- 230000001857 anti-mycotic effect Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 239000002543 antimycotic Substances 0.000 description 1
- 238000011095 buffer preparation Methods 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 235000013376 functional food Nutrition 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 229950006238 nadide Drugs 0.000 description 1
- JPXMTWWFLBLUCD-UHFFFAOYSA-N nitro blue tetrazolium(2+) Chemical compound COC1=CC(C=2C=C(OC)C(=CC=2)[N+]=2N(N=C(N=2)C=2C=CC=CC=2)C=2C=CC(=CC=2)[N+]([O-])=O)=CC=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=C([N+]([O-])=O)C=C1 JPXMTWWFLBLUCD-UHFFFAOYSA-N 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000011435 rock Substances 0.000 description 1
- OARRHUQTFTUEOS-UHFFFAOYSA-N safranin Chemical compound [Cl-].C=12C=C(N)C(C)=CC2=NC2=CC(C)=C(N)C=C2[N+]=1C1=CC=CC=C1 OARRHUQTFTUEOS-UHFFFAOYSA-N 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
- A23L29/30—Foods or foodstuffs containing additives; Preparation or treatment thereof containing carbohydrate syrups; containing sugars; containing sugar alcohols, e.g. xylitol; containing starch hydrolysates, e.g. dextrin
-
- 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
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Abstract
The present invention relates to food and daily chemicals field, specifically a kind of two ureas chitosan derivatives of nitrogen-containing heterocycle and its preparation method and application.Two ureas chitosan derivatives structural formula of nitrogen-containing heterocycle is as the formula (1), the two ureas chitosan derivatives of nitrogen-containing heterocycle that the present invention is prepared are water-soluble good and have good antioxidant activity, it can be applied to prepare environmentally friendly antioxidant, and the reaction is efficient, easy to spread, required equipment and raw material are easy to get, it can be widely applied to food and daily chemicals field, lay a good foundation for the application and development of high-valued chitosan.Formula (1).
Description
Technical field
The present invention relates to food and daily chemicals field, specifically a kind of two ureas chitosan derivatives of nitrogen-containing heterocycle and its preparation
Methods and applications.
Background technique
Chitosan abundance is the unique natural cationic polysaccharide found in nature.Chitosan has excellent resist
Bacterium property, nontoxicity, film forming, biocompatibility and biodegradability, therefore, the application of chitosan receive numerous researchers
Concern, and multiple industry fields such as be widely used in agricultural, food, medicine.Especially in field of food, chitosan is edible
Property antimicrobial packaging, anti-corrosive fresh-keeping, emulsification, thickening, show good application prospect in terms of juice clarification and functional food.
But due in chitosan molecule, it is intermolecular containing ammonia key, and molecular chain structure is firm so that chitosan material compact structure,
Dissolubility is poor, is only capable of being dissolved in acid solution, greatly limits chitosan further applying in field of food.By poly- to shell
The chemical modification of sugar introduces functional groups, and the available water-soluble and preferable derivative of activity, this is to abundant chitosan
Application and development is of great significance.
Carbamide compounds are a kind of particularly important small molecular organic compounds, and it is living to be found to have good biology from it
Property come just by people from all circles ± extensive concern, urea has important use in the multiple fields such as chemistry, agricultural, medicine.Especially curing
Medicine field, carbamide derivative can be used as antiproliferative, anticancer, anticonvulsion, anti-glycosuria because having good biological characteristics
The drugs such as disease, analgesia, anti AIDS virus, antimycotic and antibacterial.But seldom studies have reported that carbamide compounds antioxidant activity,
It is restricted it in the application of field of food.
Summary of the invention
It is an object of the present invention to provide a kind of two ureas chitosan derivatives of nitrogen-containing heterocycle and its preparation method and application.
To achieve the above object, the technical scheme adopted by the invention is as follows:
A kind of two ureas chitosan derivatives of nitrogen-containing heterocycle, two ureas chitosan derivatives structural formula of nitrogen-containing heterocycle such as formula (1) institute
Show,
Formula (1)
Wherein, R is thiazolyl, thiadiazolyl group, methyl thiadiazolyl group or triazol radical；N is average degree of polymerization, and value range is 10
~1242.
A kind of preparation method of two ureas chitosan derivatives of nitrogen-containing heterocycle:
1) nicotinoyl chlorine is reacted with aqueous sodium azide and 3- pyridine isocyanates, reaction product system of reacting with amino-heterocycles is made
Small molecule urea is obtained, for use；
2) chitosan is reacted with methylchloroformate and is madeNMethoxycarbonyl group chitosan, reaction product react to obtain with amino-heterocyclesNHeterocyclic urea base enclosure glycan, for use；
3) above-mentioned gainedNHeterocyclic urea base enclosure glycan is reacted with chloracetyl chloride, reaction product again with the resulting small molecule urea of step 1)
Reaction, it is purified to obtain two ureas chitosan derivatives of nitrogen-containing heterocycle shown in formula (1).
The step 1), which disperses nicotinoyl chlorine in excessive acetone, obtains dispersion liquid, by dispersion liquid under condition of ice bath
It instills in aqueous sodium azide, the stirring under condition of ice bath is added dropwise until solution layering, upper solution is released at 60-70 DEG C
Nitrogen is put, 3- pyridine isocyanates is obtained；By gained 3- pyridine isocyanates from different amino-heterocycles in 60-70 DEG C of reaction 24-28
Then h is filtered, is recrystallized, small molecule urea can be obtained in freeze-drying；It is described difference amino-heterocycles be thiazolamine, amino -1 2-,
3,4- thiadiazoles, 2- amino -5- methyl-1,3,4- thiadiazoles or 3- amino-1,2,4-triazol.
The molar ratio of the nicotinoyl chlorine and sodium azide is 1:(5~6), the 3- pyridine isocyanates and different amino are miscellaneous
The molar ratio of ring is 1:1.5.
The step 2), which dissolves the chitosan in excessive water, to be placed under 0 DEG C of condition of ice bath, and temperature adds when being lower than 10 DEG C
Enter methanol, methylchloroformate is added when temperature is lower than 5 DEG C and is stirred to react 6~7h, during which, temperature of reaction system be maintained at 0 DEG C-
5 DEG C, system pH is maintained at 2~7, is freeze-dried filter cake after being precipitated, be filtered, washed with dehydrated alcohol after reaction, obtains
It arrivesNMethoxycarbonyl group chitosan；Then, it takesNMethoxycarbonyl group chitosan is dissolved in chloride containing lithiumN,NDimethyl acetamide is molten
In liquid, adds aminoazaheterocycles and is stirred to react 12~14 h under the conditions of 110-120 DEG C, precipitated after reaction with dehydrated alcohol,
Filter cake is freeze-dried after being filtered, washed, is obtainedNHeterocyclic urea base enclosure glycan.
The chloride containing lithiumN,NThe quality of lithium chloride final concentration of 8% in dimethylacetamide solution；The chitosan
Molar ratio with methylchloroformate is 1:(6~8), it is describedNThe molar ratio of methoxycarbonyl group chitosan and amino-heterocycles be 1:(6~
8).
The preparationN2~7 are maintained at using triethylamine regulation system pH value when methoxycarbonyl group chitosan.
The step 3) is by above-mentioned steps 2) gainedNHeterocyclic urea base enclosure glycan reacts at room temperature with chloracetyl chloride
Small molecule urea obtained by step 1) is added after reacting in 24-36 h, acetone precipitation is then directly used, after purified and freeze-drying
Obtain two ureas chitosan derivatives of nitrogen-containing heterocycle as the formula (1)；Wherein, the mole of the chloracetyl chloride isNHeterocyclic urea
1-2 times of base enclosure glycan；The mole of small molecule urea is chloroacetylationN2-3 times of heterocyclic urea base enclosure glycan.
A kind of application of two ureas chitosan derivatives of nitrogen-containing heterocycle, the two ureas chitosan derivatives of nitrogen-containing heterocycle are used
In preparing antioxidant.
A kind of intermediate compound preparing the derivative, structural formula of compound are as follows:
Wherein, R is thiazolyl, thiadiazolyl group, methyl thiadiazolyl group or triazol radical；N is average degree of polymerization, and value range is 10
~1242.
Advantage for present invention:
Urea with excellent bioactivity is integrated into the chitosan molecule of degradability by the present invention by chemical modification, is closed
At the chitosan derivative for having obtained having the advantages that the two.And antioxidant activity is carried out to obtained chitosan derivatives
Measurement, the results showed that, obtained chitosan derivatives have preferable antioxidant activity, and are eating for high-valued chitosan
The application and development of product and daily chemicals field is laid a good foundation.
(1) the compounds of this invention improves its water-soluble and bioactivity after introducing active group urea compared with chitosan,
And the pass between the antioxidant activity of chitosan derivatives and urea groups quantity, number of nitrogen atoms is had found by active testing
System, i.e. urea groups quantity is more, and antioxidant activity is better；Number of nitrogen atoms is more on urea groups, and electron-withdrawing ability is stronger, antioxygen
It is better to change activity.
(2) two ureas chitosan derivatives of nitrogen-containing heterocycle shown in present invention preparation gained formula (1), bioactivity are able to
It improves, such as: inoxidizability, this analog derivative can be used as food oxydating resistance additive.
(3) on synthesis technology this synthetic method have the advantage that equipment and raw material needed for the present invention be easy to get, cost compared with
It is low, easy to spread, and this product yield is higher, up to 60% or more.Products obtained therefrom of the present invention can be widely used for food, medicine,
The fields such as daily use chemicals.
Detailed description of the invention
Fig. 1 is the synthetic route chart of two ureas chitosan derivatives of nitrogen-containing heterocycle provided in an embodiment of the present invention.
The infrared spectrogram of Fig. 2 chitosan.
Fig. 3 embodiment of the present invention providesNThe infrared spectrogram of methoxycarbonyl group chitosan, as can be seen from Figure 3 with chitosan raw material
It compares, 1600cm-1The absorption peak for locating amino disappears, 1700cm-1There is the vibration absorption peak of methoxycarbonyl group in place, it was demonstrated that completesNThe synthesis of methoxycarbonyl group chitosan.
Fig. 4 provides for the embodiment of the present inventionNThe infrared spectrogram of thiazole ureas base enclosure glycan, from fig. 4, it can be seen that methoxycarbonyl group
In 1700cm-1Peak at left and right disappears, in 1648cm-1There is the sharp absorption peak of urea groups in place, and in fingerprint region 779cm-1Left and right
There is the vibration absorption peak of azacyclo- at place, thus provable N- (4- pyridine urea groups)-chitosan synthesis.
Fig. 5 provides for the embodiment of the present inventionNThe infrared spectrogram of thiadiazoles urea groups chitosan.
Fig. 6 provides for the embodiment of the present inventionNThe infrared spectrogram of methyl thiadiazoles urea groups chitosan.
Fig. 7 provides for the embodiment of the present inventionNThe infrared spectrogram of triazole urea groups chitosan.
Fig. 8 provides the infrared spectrogram of two ureas chitosan of thiazolyl, as seen from Figure 8, chitosan for the embodiment of the present invention
2, derivative upper urea groups are in 1634cm-1The absorption peak at place still also exists, in 1714cm-1There is the spy of small molecule urea groups in place
Absorption peak is levied, in addition, in 1536cm-1、779cm-1There is the characteristic absorption peak of pyridine ring and thiazole ring in place, thus provable
The synthesis of two ureas chitosan of thiazolyl.
Fig. 9 provides the infrared spectrogram of two ureas chitosan of thiadiazolyl group for the embodiment of the present invention.
Figure 10 provides the infrared spectrogram of two ureas chitosan of methyl thiadiazolyl group for the embodiment of the present invention.
Figure 11 provides the infrared spectrogram of two ureas chitosan of triazol radical for the embodiment of the present invention.
Specific embodiment
Below in conjunction with embodiment and attached drawing, the invention will be further elaborated.But the present invention is not limited thereto,
It is all according to this field equivalent replacement made by the disclosure of invention, all belong to the scope of protection of the present invention.
Embodiment 1
As shown in Figure 1, the synthetic route of two ureas chitosan derivatives of nitrogen-containing heterocycle, wherein average degree of polymerization n value range is
10~1242.
The present embodiment presses the above two ureas chitosan derivatives of synthetic route synthesising target compound nitrogen-containing heterocycle.
1) preparation of thiazole ureas: taking 0.89g nicotinoyl chlorine to be dispersed in 10mL acetone, slowly drips it under condition of ice bath
Enter in aqueous sodium azide (1.30g sodium azide is dissolved in 6mL deionized water), continues to stir under condition of ice bath after being added dropwise
3h is mixed, after stirring, solution is layered, is aspirated with capillary glass tube and removes lower water layer, then slowly by upper solution
Temperature is added to be maintained in 60 DEG C of flask, until no longer releasing nitrogen, then cools down and filters, obtain 3- pyridine isocyanide
Acid esters；Next 3- pyridine isocyanates obtained is reacted into 28h at 60 DEG C with 0.75g thiazolamine, then filtered, again
Thiazole ureas can be obtained in crystallization, freeze-drying.
2)NThe preparation of thiazole ureas base enclosure glycan: take 1g chitosan (referring to fig. 2, molecular weight is 2000-200000) in room
It is dissolved in 30mL distilled water, is subsequently placed under condition of ice bath under the conditions of temperature, 30mL methanol is added when temperature is lower than 10 DEG C, when
3.36mL methylchloroformate is added when temperature is lower than 5 DEG C and is stirred to react 7h, the pH of solution is during which controlled by the way that triethylamine is added dropwise
Value is 2~7, is freeze-dried filter cake after being precipitated, be filtered, washed with dehydrated alcohol after reaction, obtainsNMethoxycarbonyl group shell is poly-
Sugared (referring to Fig. 3)；Then take 1gNMethoxycarbonyl group chitosan is dissolved in the lithium chloride that 20mL mass concentration is 8%N, NDimethyl
In acetamide solution, the thiazolamine of 2.75g is then added, is stirred to react 14h under the conditions of 110 DEG C, after reaction directly
It connects and uses ethanol precipitation, after suction filtration, washing, vacuum freeze dryingNThiazole ureas base enclosure glycan (referring to fig. 4).
3) two ureas chitosan of thiazolyl: by 1 mmolNThiazole ureas base enclosure glycan and 1 mmol chloracetyl chloride are dissolved in 20
ML DMSO(dimethyl sulfoxide) in, 24 h are stirred at room temperature, and 2 mmol small molecule thiazole ureas are added after reaction,
It is reacted under the conditions of 70 DEG C for 24 hours, then uses acetone precipitation, filtered, washing, vacuum freeze drying, obtained shown in formula (1) containing thiazolyl
The target product of two ureas chitosans (referring to Fig. 8), wherein R is thiazolyl, n=10-1242.
Embodiment 2
Difference from Example 1 is:
1) preparation of thiadiazoles urea: taking 0.89g nicotinoyl chlorine to be dispersed in 10mL acetone, slowly instills it under condition of ice bath
In aqueous sodium azide (1.63g sodium azide is dissolved in 6mL deionized water), continue to stir under condition of ice bath after being added dropwise
3h, after stirring, solution is layered, is aspirated with capillary glass tube and removes lower water layer, then slowly adds upper solution
Enter temperature to be maintained in 70 DEG C of flask, it is then cooling and filter until no longer releasing nitrogen, obtain 3- pyridine isocyanic acid
Ester；Next 3- pyridine isocyanates obtained is reacted for 24 hours with 0.76g 2- amido-1,3,4-thiadiazoles at 70 DEG C, then
It filters, recrystallize, thiadiazoles urea can be obtained in freeze-drying.
2)NThe preparation of thiadiazoles urea groups chitosan: take 1g chitosan (molecular weight is 2000-200000) in room temperature condition
Under be dissolved in 30mL distilled water, be subsequently placed under condition of ice bath, when temperature be lower than 10 DEG C when be added 35mL methanol, when temperature is low
It being added when 5 DEG C and 3.82mL methylchloroformate and is stirred to react 6h, the pH value that solution is during which controlled by the way that triethylamine is added dropwise is 2~
7, filter cake is freeze-dried after being precipitated, be filtered, washed with dehydrated alcohol after reaction, is obtainedNMethoxycarbonyl group chitosan (referring to
Fig. 3)；Then take 1gNMethoxycarbonyl group chitosan is dissolved in the lithium chloride that 20mL mass concentration is 8%N, NDimethyl acetamide
In solution, the 2- amido-1,3,4-thiadiazoles of 3.70g are then added, are stirred to react 12h under the conditions of 110 DEG C, after reaction
Ethanol precipitation is directly used, after suction filtration, washing, vacuum freeze dryingNThiadiazoles urea groups chitosan (referring to Fig. 5).
3) two ureas chitosan of thiadiazolyl group: by 1 mmolNThiadiazoles urea groups chitosan and 2 mmol chloracetyl chlorides are molten
In 20 mL DMSO(dimethyl sulfoxides) in, 28 h are stirred at room temperature, and 3 mmol small molecule thiophenes are added after reaction
Diazole urea reacts for 24 hours under the conditions of 60 DEG C, then uses acetone precipitation, filters, washing, vacuum freeze drying, obtains shown in formula (1)
The target product of the two ureas chitosan containing thiadiazolyl group (referring to Fig. 9), wherein R is thiadiazolyl group, n=10-1242.
Embodiment 3
Difference from Example 1 is:
1) preparation of methyl thiadiazoles urea: 0.89g nicotinoyl chlorine is taken to be dispersed in 10mL acetone, under condition of ice bath slowly by it
It instills in aqueous sodium azide (1.79g sodium azide is dissolved in 6mL deionized water), continues under condition of ice bath after being added dropwise
3h is stirred, after stirring, solution is layered, is aspirated with capillary glass tube and removes lower water layer, then that upper solution is slow
The slow temperature that is added is maintained in 60 DEG C of flask, until no longer releasing nitrogen, is then cooled down and is filtered, it is different to obtain 3- pyridine
Cyanate；Next by 3- pyridine isocyanates obtained and 0.86g 2- amino -5- methyl-1,3,4- thiadiazoles is anti-at 60 DEG C
28h is answered, then filters, recrystallize, methyl thiadiazoles urea can be obtained in freeze-drying.
2)NThe preparation of methyl thiadiazoles urea groups chitosan: take 1g chitosan (molecular weight is 2000-200000) in room temperature
Under the conditions of be dissolved in 30mL distilled water, be subsequently placed under condition of ice bath, when temperature be lower than 10 DEG C when be added 30mL methanol, work as temperature
3.36mL methylchloroformate is added when degree is lower than 5 DEG C and is stirred to react 7h, the pH value of solution is during which controlled by the way that triethylamine is added dropwise
It is 2~7, filter cake is freeze-dried after being precipitated, be filtered, washed with dehydrated alcohol after reaction, is obtainedNMethoxycarbonyl group chitosan
(referring to Fig. 3)；Then take 1gNMethoxycarbonyl group chitosan is dissolved in the lithium chloride that 20mL mass concentration is 8%N, NDimethyl second
In amide solution, the 2- amino -5- methyl-1 of 3.16g is then added, 3,4- thiadiazoles are stirred to react under the conditions of 110 DEG C
14h directly uses ethanol precipitation after reaction, after suction filtration, washing, vacuum freeze dryingNMethyl thiadiazoles urea groups shell is poly-
Sugared (referring to Fig. 6).
3) two ureas chitosan of methyl thiadiazolyl group: by 1 mmolNMethyl thiadiazoles urea groups chitosan and 1 mmol chlorine
Chloroacetic chloride is dissolved in 20 mL DMSO(dimethyl sulfoxides) in, 32 h are stirred at room temperature, and 2 mmol are added after reaction
Small molecule methyl thiadiazoles urea reacts for 24 hours under the conditions of 70 DEG C, then uses acetone precipitation, filters, washing, vacuum freeze drying, obtains
The target product of two ureas chitosan of thiadiazolyl group containing methyl shown in formula (1) (referring to Figure 10), wherein R is methyl thiadiazoles
Base, n=10-1242.
Embodiment 4
Difference from Example 1 is:
1) preparation of triazole urea: taking 0.89g nicotinoyl chlorine to be dispersed in 10mL acetone, slowly instills it under condition of ice bath
In aqueous sodium azide (1.95g sodium azide is dissolved in 6mL deionized water), continue to stir under condition of ice bath after being added dropwise
3h, after stirring, solution is layered, is aspirated with capillary glass tube and removes lower water layer, then slowly adds upper solution
Enter temperature to be maintained in 70 DEG C of flask, it is then cooling and filter until no longer releasing nitrogen, obtain 3- pyridine isocyanic acid
Ester；Next by 3- pyridine isocyanates obtained and 0.63g 3- amino -1,2, for 24 hours, then 4- triazole is reacted at 70 DEG C
It filters, recrystallize, triazole urea can be obtained in freeze-drying.
2)NThe preparation of triazole urea groups chitosan: take 1g chitosan (molecular weight is 2000-200000) in room temperature condition
Under be dissolved in 30mL distilled water, be subsequently placed under condition of ice bath, when temperature be lower than 10 DEG C when be added 35mL methanol, when temperature is low
It being added when 5 DEG C and 3.82mL methylchloroformate and is stirred to react 6h, the pH value that solution is during which controlled by the way that triethylamine is added dropwise is 2~
7, filter cake is freeze-dried after being precipitated, be filtered, washed with dehydrated alcohol after reaction, is obtainedNMethoxycarbonyl group chitosan (referring to
Fig. 3)；Then take 1gNMethoxycarbonyl group chitosan is dissolved in the lithium chloride that 20mL mass concentration is 8%N, NDimethyl acetamide
In solution, 3- amino -1,2 of 3.08g is then added, 4- triazole is stirred to react 12h under the conditions of 110 DEG C, after reaction
Ethanol precipitation is directly used, after suction filtration, washing, vacuum freeze dryingNTriazole urea groups chitosan (referring to Fig. 7).
3) two ureas chitosan of triazol radical: by 1 mmolNTriazole urea groups chitosan and 2 mmol chloracetyl chlorides are molten
In 20 mL DMSO(dimethyl sulfoxides) in, 36 h are stirred at room temperature, and 3 mmol small molecules three are added after reaction
Nitrogen azoles urea reacts for 24 hours under the conditions of 60 DEG C, then uses acetone precipitation, filters, washing, vacuum freeze drying, obtains shown in formula (1)
The target product of the two ureas chitosan containing triazol radical (referring to Figure 11), wherein R is triazol radical, n=10-1242.
Application examples
Antioxidative Activity Determination
(1) remove superoxide anion oxidation resistance measurement: respectively measure Examples 1 to 4 in chitosan, preparationNMethoxy
Carbonyl chitosan,NThe removing superoxide anion ability of heterocyclic urea base enclosure glycan and the two ureas chitosan containing heterocycle simultaneously compares
(table 1), specifically:
By chitosan,NMethoxycarbonyl group chitosan,NThiazole ureas base enclosure glycan,NThiadiazoles urea groups chitosan,NMethyl thiazolium two
Azoles urea groups chitosan,NTriazole urea groups chitosan, two ureas chitosan of thiazolyl, two ureas chitosan of thiadiazolyl group, methyl
After two ureas chitosan vacuum freeze drying to constant weight of two ureas chitosan of thiadiazolyl group and triazol radical, by sample after above-mentioned constant weight
It is the solution of 0.2,0.4,0.8,1.6,3.2mg/mL that product use trishydroxymethylaminomethane-HCl buffer preparation concentration respectively.
The sample solution for taking 1.5 mL various concentrations sequentially adds 1.5mL trishydroxymethylaminomethane-HCl buffer solution, 0.5mL also
Originality cozymase (468 μM), 0.5mL nitro blue tetrazolium (300 μM) and 0.5mL phenazine methosulfate (60 μM), are mixed in test tube
After even, the ultimate density of sample is 0.1,0.2,0.4,0.8,1.6mg/mL in each test tube, 5min is stood at room temperature, in 560nm
Place's measurement absorbance A, control group 0.5mL trishydroxymethylaminomethane-HCl buffer solution replace Reducing Coenzyme I, blank group
1.5mL trishydroxymethylaminomethane-HCl buffer solution replaces sample solution, and sample is surveyed three times, is averaged, and calculates and removes
Superoxide anion ability.
Remove superoxide anion ability (%)=[1- (A sample-A control)/A blank] × 100.The results are shown in Table 1.
Table 1, chitosan,NMethoxycarbonyl group chitosan,NHeterocyclic urea base enclosure glycan and the two ureas chitosan containing heterocycle
It removes superoxide anion ability (%)
(2) remove hydroxyl radical free radical oxidation resistance measurement: respectively measure Examples 1 to 4 in chitosan, preparationNMethoxy
Carbonyl chitosan,NThe removing hydroxyl radical free radical ability of heterocyclic urea base enclosure glycan and the two ureas chitosan containing heterocycle simultaneously compares
(table 2), specifically:
By chitosan,NMethoxycarbonyl group chitosan,NThiazole ureas base enclosure glycan,NThiadiazoles urea groups chitosan,NMethyl thiazolium two
Azoles urea groups chitosan,NTriazole urea groups chitosan, two ureas chitosan of thiazolyl, two ureas chitosan of thiadiazolyl group, methyl
After two ureas chitosan vacuum freeze drying to constant weight of two ureas chitosan of thiadiazolyl group and triazol radical, each precise
6mL deionized water dissolving is added in 60mg, is configured to the sample mother liquor that concentration is 10mg/mL.Hydroxyl radical-scavenging experiment: point
Not Liang Qu 11.3,22.5,45,90,180 μ L sample mother liquor in test tube, add water to 1mL.Then 0.5mL is sequentially added
EDTA-Fe solution, 1mL phosphate buffer, 1mL safranine T solution and 1mL hydrogenperoxide steam generator.The end of sample solution is dense
Degree is respectively 0.025mg/mL, 0.05mg/mL, 0.1mg/mL, 0.2mg/mL, 0.4mg/mL.Meanwhile with 1mL deionized water generation
For sample as blank group, 1mL deionized water and 1mL phosphate buffer is used to replace sample and hydrogenperoxide steam generator as control
Group.Reaction system jump a queue rock uniformly after, react 30min in 37 DEG C of water-baths.After reaction, it is put into ice water and is quenched instead
It answers, the absorbance of test record 4.5mL reaction solution, sample are surveyed three times, be averaged at 520nm wavelength, are calculated and are removed hydroxyl
Free radical ability.
Scavenging hydroxyl ability (%)=(A sample-A blank)/(A control-A blank) × 100.The results are shown in Table 2.
Table 2, chitosan,NMethoxycarbonyl group chitosan,NHeterocyclic urea base enclosure glycan and the two ureas chitosan containing heterocycle
Scavenging hydroxyl ability (%)
Experimental result: raw materials of chitosan used by synthesis of derivatives of the present invention,NMethoxycarbonyl group chitosan,NThiazole ureas base enclosure
Glycan,NThiadiazoles urea groups chitosan,NMethyl thiadiazoles urea groups chitosan,NTriazole urea groups chitosan, and synthesis
Two ureas chitosan of derivative thiazolyl, two ureas chitosan of thiadiazolyl group, two ureas chitosan of methyl thiadiazolyl group and three nitrogen
Two ureas chitosan of oxazolyl removing superoxide anion ability is as shown in table 1, and scavenging hydroxyl ability is as shown in table 2, the present invention
The Scavenging activity of the synthesized chitosan derivatives containing ureas is substantially better thanNMethoxycarbonyl group chitosan and chitosan raw material, and table
Reveal certain antioxygen law, it may be assumed that the antioxidant activity of the two ureas chitosan containing heterocycle is better thanNHeterocyclic urea base enclosure is poly-
Sugar, this illustrates that the introducing of urea groups can significantly improve the antioxidant activity of chitosan derivatives, and urea groups quantity is more, antioxygen
It is better to change activity；In addition, several two ureas chitosan antioxidant activities of final product are containing two ureas shell of triazol radical from high to low
Two ureas chitosan of glycan > thiadiazolyl group containing methyl > contain two ureas chitosan of thiadiazolyl group > two ureas chitosan containing thiazolyl,
This illustrates that number of nitrogen atoms is more on small molecule urea groups, and electron-withdrawing ability is stronger, and antioxidant activity is better.
Claims (10)
1. a kind of two ureas chitosan derivatives of nitrogen-containing heterocycle, it is characterised in that: two ureas chitosan derivatives knot of nitrogen-containing heterocycle
Structure formula is as the formula (1),
Formula (1)
Wherein, R is thiazolyl, thiadiazolyl group, methyl thiadiazolyl group or triazol radical；N is average degree of polymerization, and value range is 10
~1242.
2. a kind of preparation method of two ureas chitosan derivatives of nitrogen-containing heterocycle described in claim 1, it is characterised in that:
1) nicotinoyl chlorine is reacted with aqueous sodium azide and 3- pyridine isocyanates, reaction product system of reacting with amino-heterocycles is made
Small molecule urea is obtained, for use；
2) chitosan is reacted with methylchloroformate and is madeNMethoxycarbonyl group chitosan, reaction product react to obtain with amino-heterocyclesNHeterocyclic urea base enclosure glycan, for use；
3) above-mentioned gainedNHeterocyclic urea base enclosure glycan is reacted with chloracetyl chloride, reaction product again with the resulting small molecule urea of step 1)
Reaction, it is purified to obtain two ureas chitosan derivatives of nitrogen-containing heterocycle shown in formula (1).
3. the preparation method of two ureas chitosan derivatives of nitrogen-containing heterocycle as described in claim 2, it is characterised in that: the step
Rapid 1) disperse nicotinoyl chlorine in excessive acetone obtains dispersion liquid, and dispersion liquid is instilled sodium azide water under condition of ice bath
In solution, the stirring under condition of ice bath is added dropwise until solution layering, discharges nitrogen at 60-70 DEG C for upper solution, obtain 3- pyrrole
Pyridine isocyanates；Then gained 3- pyridine isocyanates is filtered, again from different amino-heterocycles in 60-70 DEG C of reaction 24-28 h
Small molecule urea can be obtained in crystallization, freeze-drying；The difference amino-heterocycles are thiazolamine, 2- amino -1,3,4- thiadiazoles, 2-
Amino -5- methyl-1,3,4- thiadiazoles or 3- amino-1,2,4-triazol.
4. the preparation method of two ureas chitosan derivatives of nitrogen-containing heterocycle according to claim 3, it is characterised in that: the cigarette
The molar ratio of acyl chlorides and sodium azide is 1:(5~6), the 3- pyridine isocyanates is 1 from the molar ratio of different amino-heterocycles:
1.5。
5. the preparation method of two ureas chitosan derivatives of nitrogen-containing heterocycle as described in claim 2, it is characterised in that: the step
Rapid 2) dissolve the chitosan in excessive water is placed under 0 DEG C of condition of ice bath, and methanol is added when being lower than 10 DEG C in temperature, and temperature is low
Methylchloroformate is added when 5 DEG C and is stirred to react 6~7h, during which, temperature of reaction system is maintained at 0 DEG C -5 DEG C, system pH
2~7 are maintained at, filter cake is freeze-dried after being precipitated, be filtered, washed with dehydrated alcohol after reaction, is obtainedNMethoxycarbonyl group
Chitosan；Then, it takesNMethoxycarbonyl group chitosan is dissolved in chloride containing lithiumN,NIn dimethylacetamide solution, ammonia is added
Base azacyclo- is stirred to react 12~14 h under the conditions of 110-120 DEG C, is precipitated after reaction with dehydrated alcohol, after being filtered, washed
Filter cake is freeze-dried, is obtainedNHeterocyclic urea base enclosure glycan.
6. the preparation method of two ureas chitosan derivatives of nitrogen-containing heterocycle as described in claim 5, it is characterised in that: described to contain
Lithium chlorideN,NThe quality of lithium chloride final concentration of 8% in dimethylacetamide solution；The chitosan and methylchloroformate
Molar ratio is 1:(6~8), it is describedNThe molar ratio of methoxycarbonyl group chitosan and amino-heterocycles is 1:(6~8).
7. the preparation method of two ureas chitosan derivatives of nitrogen-containing heterocycle as described in claim 5, it is characterised in that: the system
It is standbyN2~7 are maintained at using triethylamine regulation system pH value when methoxycarbonyl group chitosan.
8. the preparation method of two ureas chitosan derivatives of nitrogen-containing heterocycle as described in claim 2, it is characterised in that: the step
It is rapid 3) by above-mentioned steps 2) gainedNHeterocyclic urea base enclosure glycan reacts 24-36 h with chloracetyl chloride at room temperature, wait react
Afterwards, small molecule urea obtained by addition step 1) is then directly used acetone precipitation, is obtained as the formula (1) after purified and freeze-drying
Two ureas chitosan derivatives of nitrogen-containing heterocycle；Wherein, the mole of the chloracetyl chloride isNThe 1-2 of heterocyclic urea base enclosure glycan
Times；The mole of small molecule urea is chloroacetylationN2-3 times of heterocyclic urea base enclosure glycan.
9. a kind of application of two ureas chitosan derivatives of nitrogen-containing heterocycle described in claim 1, it is characterised in that: described nitrogenous
Two ureas chitosan derivatives of heterocycle are used to prepare antioxidant.
10. a kind of intermediate compound for preparing derivative described in claim 1, it is characterised in that: structural formula of compound is as follows:
Wherein, R is thiazolyl, thiadiazolyl group, methyl thiadiazolyl group or triazol radical；N is average degree of polymerization, and value range is 10
~1242.
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| CN114014955A (en) * | 2022-01-10 | 2022-02-08 | 中国科学院烟台海岸带研究所 | N, O-carboxymethyl chitosan containing thiazole salt and preparation and application thereof |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020147318A1 (en) * | 2001-04-09 | 2002-10-10 | Cho Fu Chuan | Preparation method of water soluble carboxylmethyl chitosan having anti-lipid peroxidation ability |
| CN101121759A (en) * | 2007-07-27 | 2008-02-13 | 中国科学院海洋研究所 | Chitosan thiosemicarbazone derivatives and preparation method thereof |
| CN104250312A (en) * | 2013-06-28 | 2014-12-31 | 株式会社大赛璐 | Chitosan carbanilate-carbamido derivative preparation method |
| CN104387501A (en) * | 2014-12-03 | 2015-03-04 | 内蒙古农业大学 | Chitosan positioned acylation thiosemicarbazone derivative and preparation method thereof |
| EP3061772A1 (en) * | 2015-02-25 | 2016-08-31 | Deutsches Zentrum für Luft- und Raumfahrt e.V. | Synthesis of chitosan and chitin aerogels containing functional ureido groups |
| CN107216411A (en) * | 2017-07-18 | 2017-09-29 | 中国科学院烟台海岸带研究所 | A kind of quaternary ammonium salt of Acetylated Chitosans containing ureas and its preparation method and application |
| CN107383239A (en) * | 2017-08-28 | 2017-11-24 | 中国科学院烟台海岸带研究所 | A kind of N pyridines urea groups chitosan quaternary ammonium salt and its preparation method and application |
-
2019
- 2019-08-13 CN CN201910743356.7A patent/CN110256606B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020147318A1 (en) * | 2001-04-09 | 2002-10-10 | Cho Fu Chuan | Preparation method of water soluble carboxylmethyl chitosan having anti-lipid peroxidation ability |
| CN101121759A (en) * | 2007-07-27 | 2008-02-13 | 中国科学院海洋研究所 | Chitosan thiosemicarbazone derivatives and preparation method thereof |
| CN104250312A (en) * | 2013-06-28 | 2014-12-31 | 株式会社大赛璐 | Chitosan carbanilate-carbamido derivative preparation method |
| CN104387501A (en) * | 2014-12-03 | 2015-03-04 | 内蒙古农业大学 | Chitosan positioned acylation thiosemicarbazone derivative and preparation method thereof |
| EP3061772A1 (en) * | 2015-02-25 | 2016-08-31 | Deutsches Zentrum für Luft- und Raumfahrt e.V. | Synthesis of chitosan and chitin aerogels containing functional ureido groups |
| CN107216411A (en) * | 2017-07-18 | 2017-09-29 | 中国科学院烟台海岸带研究所 | A kind of quaternary ammonium salt of Acetylated Chitosans containing ureas and its preparation method and application |
| CN107383239A (en) * | 2017-08-28 | 2017-11-24 | 中国科学院烟台海岸带研究所 | A kind of N pyridines urea groups chitosan quaternary ammonium salt and its preparation method and application |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114014955A (en) * | 2022-01-10 | 2022-02-08 | 中国科学院烟台海岸带研究所 | N, O-carboxymethyl chitosan containing thiazole salt and preparation and application thereof |
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