CN108034009A - One kind contains more structure functional group chitosan analog derivatives and preparation method - Google Patents
One kind contains more structure functional group chitosan analog derivatives and preparation method Download PDFInfo
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- 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
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Abstract
The present invention is to provide one kind to contain more structure functional group chitosan analog derivatives and preparation method.First chitosan is protected for 6 using triphenylchloromethane; reacted again with phenyl isocyanate or the phenyl isocyanate with side base; finally to chitosan 6 be deprotected, obtain 2 phenylurea of chitosan class, 3 carbanilate, 6 hydroxy derivatives.The present invention directly protects 6 hydroxyls of chitosan using one-step method, avoids loss and accessory substance during multi-step reaction may be brought；Prepared 6 hydroxyls of chitosan analog derivative can be modified further, be used to prepare the more diversified chitosan analog derivative of structure.
Description
Technical field
The present invention relates to a kind of chitosan analog derivative, the present invention also relates to be a kind of chitosan analog derivative
Preparation method.The chitosan class for containing side base not of the same race while specifically a kind of chemical modification based on regioselectivity is spread out
Biology and synthetic method.
Background technology
Regioselectivity chemical modification method refers under certain reaction condition, due to each position reaction activity in molecule
Difference, modification group can be repaiied preferentially with the radical reaction at reactivity higher position so as to fulfill the selectivity to the position
Decorations.So far, regioselectivity chemical modification has been widely used in polysaccharide such as cellulose and amylose class derives
The preparation of thing.The 2 of cellulose and amylose, are respectively the different hydroxyl of reactivity on 3,6- positions, by introducing protection group
Group's such as trityl group preferentially modifies 6- most active hydroxyl groups, and unprotected hydroxyl can be modified further by other groups.
1993, Kaida and Okamoto et al. the 6- positions hydroxyl of cellulose and starch is carried out using trityl group modification protection and
Deprotection, control have synthesized novel cellulose class and starch analog derivative of two major classes with side base not of the same race and have been prepared into
Chiral stationary phase.Research is found：The chiral resolution ability of Cellulose based CSP depends primarily upon drug enantiomer in itself
Structure and properties, and side base of the cellulose derivative on 2,3,6- positions in itself is very complicated to the influence of recognition capability.Remove
Outside this, for starch chiral stationary phase, its chiral resolution ability is heavily dependent on 2, the 3- positions of starch
Side base species, and the influence of 6- is smaller.This be regioselectivity chemical modification method be applied to first cellulose family and
The preparation of starch analog derivative, it successfully discloses chiral resolution of the chiral stationary phase on HPLC prepared by the analog derivative
Mechanism, this has weight for the targetedly design for splitting different pharmaceutical enantiomer and carrying out chiral stationary phase with preparing
Want meaning.
Chitosan is only second to the deacetylated of the second largest natural biological macromolecular chitin of cellulose as resource on the earth
Change product, itself is nontoxic, and possesses the performances such as good biocompatibility, antibiotic property, degradability, therefore extensive
Applied to multiple fields such as medicine, food, environmental protection, agricultural chemicalses.However, chitosan is in water and most organic solvents
Dissolubility it is poor so that it is subject to a definite limitation among practical application, therefore, it is necessary to carry out certain chemical modification to it.
For chitosan in addition to being amino on sugar unit 2- positions, other structures are similar with the structure of cellulose, therefore, area
Field selectivity chemical modification method can be applied equally to the modification of chitosan and its preparation of derivative.1991,
Nishimura etc. first using phthalic anhydride in N,N-dimethylformamide dicyandiamide solution to chitosan 2- repair
Decorations, then under conditions of using pyridine as solvent in the introducing trityl groups of chitosan 6- as blocking group, further, adopt
Reacted with 3- hydroxyls of acid anhydrides and chitosan, synthesized the chitosan class derivative for possessing side base not of the same race on 2,3,6- positions
Thing.2015, Bai Zhengwu et al. reported the preparation method of chitosan-alkyl urea, first using chitosan in methyl alcohol with chlorine
Methyl formate reacts, and accesses methoxy methyl acyl group in 2-, is then reacted in n,N-dimethylacetamide solvent with amine.It is made
The chitosan analog derivative substitution value obtained is high, compound with regular structure.In addition, to 3-, 6- further modifications of the analog derivative, so that it may make
It is standby go out new functional high molecule material.2016, applicant modified 2- by adjacent benzene two using a series of phenyl isocyanates
The chitosan that carboximide is modified and protected, having synthesized 5 kinds of sugar units 2- has a phthalimide, and 3,6- at the same time
With 4 kinds of different carbanilate groups (2- chlorine, 3- chlorine, 4- chlorine and the carbanilate of 3,5- dichloros substitution) and
A kind of chitosan analog derivative of unsubstituted carbanilate group.These derivatives be fixed against substituent position and
Structure difference shows the chiral recognition of uniqueness.Reported above is all to introduce substituent first on amino to carry out region
Method for selective synthesis, is repaiied for being introduced directly into blocking group progress regioselectivity chemistry using one-step method on 6- hydroxyls
The method of decorations has not yet to see report, and the method has important meaning to the species for expanding chitosan analog derivative with application range
Justice.
The content of the invention
Containing for intermediate can be prepared it is an object of the invention to provide a kind of as chitosan class chiral stationary phase etc.
You Duo structures functional group chitosan analog derivative.The present invention also aims to provide one kind can to derive chitosan class
Hydroxyl on the 6- positions of thing retains the preparation method containing more structure functional group chitosan analog derivatives of higher reactivity.
The present invention's has such as lower structure containing more structure functional group chitosan analog derivatives：
Wherein, R represents phenyl or the phenyl with substituent, and the substituent is 1 to 4, when the number of substituent is big
When 1, each substituent is identical or differs, and the substituent is halogen atom, alkyl, alkoxy, nitro, amino or alkane sulphur
Base.
The present invention the preparation method containing more structure functional group chitosan analog derivatives be：
First chitosan is protected for 6- using triphenylchloromethane, then with phenyl isocyanate or with side base benzene
Based isocyanate react, finally to chitosan 6- be deprotected, obtaining structural formula is's
Chitosan class -2- phenylurea -3- carbanilate -6- hydroxy derivatives, wherein, R represents phenyl or with substituent
Phenyl, the substituent are 1 to 4, and when the number of substituent is more than 1, each substituent is identical or differs, the substituent
For halogen atom, alkyl, alkoxy, nitro, amino or alkylthio group.
The preparation method containing more structure functional group chitosan analog derivatives of the present invention can also include：
1st, it is described protection is carried out to chitosan 6- using triphenylchloromethane to specifically include：Take complete deacetylated shell
Glycan is swollen in 60~100 DEG C of vacuum drying, addition reaction dissolvent, is added hydrogen bond remover at room temperature, is added triphen
Base chloromethanes, reaction temperature for 80~100 DEG C reaction 6-24h, by reaction product instill isolation solvent in, obtain chitosan-
6-OTr。
2nd, it is described to be specifically included with phenyl isocyanate or the phenyl isocyanate reaction with side base：Take chitosan 6-
OTr, adds reaction dissolvent and is swollen, add hydrogen bond remover at room temperature, adds phenyl isocyanate or has side base
Phenyl isocyanate, is 40~150 DEG C of reactions in reaction temperature, the reaction time is 0.5~24h, and reaction product is instilled and is isolated
In solvent, chitin-2-phenylurea-3- carbanilates-6-OTr is obtained.
3rd, it is described deprotection is carried out to chitosan 6- to specifically include：Take chitin-2-phenylurea-3- phenylcarbamic acids
Ester -6-OTr, adds concentrated hydrochloric acid and methanol, is 30~70 DEG C of reactions in reaction temperature, the reaction time is 12~24h, and reaction is produced
Thing is instilled in isolation solvent, obtains chitin-2-phenylurea-3- carbanilate-6- hydroxyls.
4th, the molal weight of the triphenylchloromethane added is 1.5~3 times of molal weight of 6- hydroxyls of chitosan.
5th, the molal weight of the phenyl isocyanate added or the phenyl isocyanate with side base is the 2- positions of chitosan
1.5~3 times of amino and 3- hydroxyl total moles quality.
6th, with side base phenyl isocyanate be selected from 4- methoxyphenyl isocyanates, 4- ethylphenyls isocyanates,
4- methylphenyl isocyanates, 4- fluorophenylisocyanates, 4- chlorophenyl isocyanates, 4- bromophenyl isocyanates, 4- nitros
Phenyl isocyanate, 2- chlorophenyl isocyanates, 2- methylphenyl isocyanates, 3- chlorophenyl isocyanates, 3- aminomethyl phenyls
Isocyanates, 3,5- dichlorophenyl isocyanates or 3,5- dimethylphenyl isocyanates.
Chitosan as reaction raw materials is completely deacetylated chitosan, and molecular weight is 50000~300000.
In the protection of the 6- hydroxyls of chitosan, triphenylchloromethane is directly to completely deacetylated chitosan 6-
Position is modified, and one-step method introduces trityl group as blocking group.
It is 0.013~0.025g/mL that reaction dissolvent is added in chitosan or chitosan analog derivative and is made into mass concentration, instead
It is dimethyl sulfoxide (DMSO) (DMSO) to answer solvent.
The hydrogen bond remover is lithium chloride, and wherein the concentration of lithium chloride is 0.075~0.100g/mL.
The mixed proportion that concentrated hydrochloric acid and methanol mixed solvent are added in chitosan analog derivative is 1:32.
One or more of the isolation solvent in methanol, isopropanol and ethyl acetate described in each step.
What is obtained is chitosan class -2- phenylurea -3- carbanilate -6- hydroxy derivatives.
The present invention is based on regioselectivity chemical modification method, utilizes each position substituent on chitosan glucose unit
The difference of reactivity, using chitosan, triphenylchloromethane and has the phenyl isocyanate of side base as primary raw material, control
Synthesize 2- bit aminos on chitosan and be fully converted to phenylurea and carbanilate, while 6- respectively with 3- hydroxyls
For the chitosan analog derivative of hydroxyl.Such chitosan analog derivative is still retained higher anti-due to the hydroxyl on 6- positions
Should activity, to after its further modification just can systematic function high molecular material, therefore many materials such as chitosan can be used as
Class chiral stationary phase prepares intermediate.
The beneficial effects of the present invention are：
1. present invention chitosan class -2- phenylureas -3- carbanilate -6- hydroxy derivatives structures obtained above
Regular, substitution value is high, and 2- bit aminos are fully converted to phenylurea and carbanilate respectively with 3- hydroxyls on chitosan,
6- are hydroxyl at the same time, and derivative, which remains unchanged, retains higher reactivity.
2. the present invention uses one-step method, it is introduced directly into trityl group and 6- hydroxyls of chitosan is protected, avoid
Loss and side reaction during multi-step reaction may be brought.
3. a series of chitosan analog derivatives provided by the invention, it is active group hydroxyl at 6-, it is further repaiied
, can be with preparation structure and the more diversified novel chitosan analog derivative of species after decorations.
Brief description of the drawings
Fig. 1 is the chitosan -6-OTr's prepared by step of the embodiment of the present invention (1)1H-NMR spectrum.
Fig. 2 is chitin-2-(3,5- 3,5-dimethylphenyl urea)-3- (3,5- bis- prepared by step of the embodiment of the present invention (2)
Methyl phenyl carbamate) -6-OTr infrared spectrogram.
Fig. 3 is chitin-2-(3,5- 3,5-dimethylphenyl urea)-3- (3,5- bis- prepared by step of the embodiment of the present invention (3)
Methyl phenyl carbamate) -6- hydroxyls1H-NMR spectrum.
Fig. 4 is reaction equation according to the present invention.
Fig. 5 is the phenyl of preferable substituent.
Embodiment
What the present invention synthesized is that a kind of new chitosan class -2- phenylurea -3- carbanilate -6- hydroxyls derive
Thing, the structure of the chitosan analog derivative can be as shown in Equation 1.
Reaction equation according to the present invention is as described in Figure 4.In above-mentioned formula 1 and Fig. 4 wherein, R represents phenyl or optionally
The phenyl of substituent.Substituent can be the appropriate location of phenyl ring, such as 2-, 3-, 4-, 5-, and/or 6- etc..Substituent
Number can be 1,2,3 or 4, preferably 1-2.Each substituent on the phenyl can be identical or different, can
With selected from hydrogen atom, halogen atom, alkyl, alkoxy, nitro, amino, alkylthio group etc..It is preferably C as alkyl1-12Alkyl,
More preferably C1-6Alkyl, more preferably C1-4Alkyl (such as methyl, ethyl).As alkoxy, preferably C1-12Alkoxy, more preferably
C1-6Alkoxy, more preferably C1-4Alkoxy (such as methoxyl group, ethyoxyl).Can be fluorine atom, chlorine original as halogen atom
Son, bromine atoms, iodine atom, are preferably fluorine atom, chlorine atom and bromine atoms.As alkylthio group, preferably C1-12Alkylthio group, more preferably
C1-6Alkylthio group, more preferably C1-4Alkylthio group (such as methyl mercapto, ethylmercapto group).
Preferably, R represent optionally substituted by 1 or 2 halogen atoms phenyl, optionally by 1 or 2 C1-4Alkyl (such as
Methyl, ethyl) substitution phenyl, optionally by 1 or 2 C1-4Alkoxy (such as methoxyl group, ethyoxyl) substitution phenyl or
Phenyl optionally substituted by 1 or 2 nitros etc..
Further, R is preferably the group described in Fig. 5.
The preparation method of the chitosan analog derivative, comprises the following steps：
(1) protection of chitosan 6- hydroxyls；
(2) preparation of chitosan class -2- phenylureas -3- carbanilate -6-OTr derivatives；
(3) deprotection of chitosan 6- hydroxyls.
In step (1) of the present invention, as chitosan raw material, it is preferred to use completely deacetylated chitosan.Chitosan is former
The molecular weight of material preferably 30000~600000, more preferably 50000~300000.
In step (1) of the present invention, reaction dissolvent is added to be swollen in chitosan raw material before reaction.Swelling time is excellent
When selecting 10-60 small, when preferably 24-55 is small, when further preferred 40-48 is small.
Further, it is preferable to before the reaction, before being particularly swollen, chitosan raw material is dried in vacuo in high temperature, temperature
Degree is preferably 60-100 DEG C, more preferably 70-90 DEG C, further preferred 80 DEG C or so.When drying time is preferably 1-20 small, more
When preferably 4-10 is small, when more preferably 4-6 is small.
In step (1) of the present invention, the amount of the triphenylchloromethane added as reaction, the triphenylchloromethane of addition rubs
Your quality is preferably 1.5-3 times of the molal weight of 6- hydroxyls of chitosan, more preferably 2.0-3 times, further preferred 2.5-3
Times.
It is further excellent when more preferably 12-24 is small when preferably 0.5-36 is small as the reaction time in step (1) of the present invention
When selecting 20-24 small.
In step (1) of the present invention, as reaction temperature, suitably reacted at high temperature, preferably 50-120 DEG C, more preferably
75-105 DEG C, further preferred 80-100 DEG C.
In step (2) of the present invention, as phenyl isocyanate or with side chain phenyl isocyanate, be preferably formula (2)
The shown phenyl isocyanate having with the corresponding groups of R shown in formula (1).
In formula (2), groupRepresent the group identical with the R in formula (1).R1Correspond to institute in group R
The benzene ring hydrogen or substituent stated.
In step (2) of the present invention, preferable phenyl isocyanate or the phenyl isocyanate example with side chain are selected from benzene
Based isocyanate, 4- methoxyphenyl isocyanates, 4- ethylphenyls isocyanates, 4- methylphenyl isocyanates, 4- fluorobenzene
Based isocyanate, 4- chlorophenyl isocyanates, 4- bromophenyl isocyanates, 4- nitrophenyl isocyanates, 2- chlorphenyl isocyanides
Acid esters, 2- methylphenyl isocyanates, 3- chlorophenyl isocyanates, 3- methylphenyl isocyanates, 3,5- dichlorophenyl isocyanides
One or more in acid esters and 3,5- dimethylphenyl isocyanates.
In step (2) of the present invention, the phenyl isocyanate added as reaction or the phenyl isocyanate with side chain
The molal weight of amount, the phenyl isocyanate of addition or the phenyl isocyanate with different side chains is preferably 2- ammonia of chitosan
1.5-3 times of the total moles quality of base and 3- hydroxyls, more preferably 2.0-3 times, further preferred 2.5-3 times.
It is further excellent when more preferably 0.5-20 is small when preferably 0.5-24 is small as the reaction time in step (2) of the present invention
When selecting 1-12 small.
In step (2) of the present invention, as reaction temperature, suitably reacted at high temperature, preferably 40-150 DEG C, more preferably
55-105 DEG C, further preferred 60-100 DEG C.
In step (1)-(2) of the present invention, reaction preferably carries out in a solvent, is preferably that dimethyl is sub- as reaction dissolvent
Sulfone, such as anhydrous dimethyl sulphoxide.
In step (1)-(2) of the present invention, before the reaction, hydrogen bond remover is optionally added into, is preferably stirred.Hydrogen bond disappears
Except agent is preferably lithium chloride.When mixing time is preferably 1-20 small, when preferably 3-15 is small, when more preferably 4-12 is small.
In step (3) of the present invention, the concentrated hydrochloric acid and the volume ratio of methanol that are added as reaction are preferably 1：20~50, it is more excellent
Select 1：20~35, further preferred 1：30~35.
In step (3) of the present invention, as the reaction time, when preferably 1-24 is small, when more preferably 12-24 is small, further preferably
When 20-24 is small.
Above steps carries out optionally under the conditions of non-active gas.The non-active gas can be selected from nitrogen, helium
And argon gas.Preferably nitrogen.
After completion of the reaction, optionally reaction solution is added in isolation solvent, forms the precipitation analysis of chitosan analog derivative
Go out.Reaction solution is preferably 1 with the volume ratio for isolating solvent：2~40, more preferably 1：5~30, further preferred 1：10~20.
Isolation solvent is preferably selected from the one or more in ether, methanol, ethyl acetate, isopropyl.
Optionally vacuum drying 24~60 at 35-100 DEG C, preferably 40-80 DEG C, more preferably 60-80 DEG C is deposited in by what is obtained
Hour, when preferably 40-48 is small.
Specifically, preparation method of the invention may comprise steps of：
(1) protection of chitosan 6- hydroxyls：Complete deacetylated chitosan is taken in 60-100 DEG C of vacuum drying, addition
Reaction dissolvent is swollen, and adds hydrogen bond remover at room temperature, adds triphenylchloromethane, is 80-100 DEG C in reaction temperature
6-24h is reacted, reaction product is instilled in isolation solvent, obtains chitosan -6-OTr.
(2) preparation of chitosan class -2- phenylureas -3- carbanilate -6-OTr derivatives：Obtained to step (1)
Chitosan 6-OTr in add reaction dissolvent and be swollen, add hydrogen bond remover at room temperature, add the phenyl isocyanide
Acid esters or the phenyl isocyanate with side base, are 40-150 DEG C of reaction in reaction temperature, reaction time 0.5-24h will be anti-
Answer product to instill in isolation solvent, obtain chitosan 2- phenylurea -3- carbanilates -6-OTr.
(3) deprotection of chitosan 6- hydroxyls：The chitin-2 obtained to step (2)-phenylurea -3- phenyl amino first
Methanol and concentrated hydrochloric acid are added in acid esters -6-OTr, is 30-70 DEG C of reaction in reaction temperature, reaction time 12-24h, will react
Product is instilled in isolation solvent, obtains chitin-2-phenylurea-3- carbanilate-6- hydroxyls.
For example, the preparation method of the present invention can be carried out as follows：
(1) protection of chitosan 6- hydroxyls：Under vacuum high-temperature, the completely deacetylated chitosan raw material 4-6 of stirring
Hour, when the lower addition anhydrous dimethyl sulphoxide swelling chitosan 24-48 of non-active gas protection is small, anhydrous chlorination is added at room temperature
When lithium 4-12 is small, under high temperature non-active gas, triphenylchloromethane reaction 1-36h is added.It is afterwards that chitosan analog derivative is anti-
Answer solution to instill dropwise in isolation solvent to be isolated, separate out chitosan analog derivative, carrying out centrifugation using centrifuge obtains shell
Glycan analog derivative, when vacuum drying 24-48 is small at 40-80 DEG C.Obtain chitosan -6-OTr.
(2) preparation of chitosan class -2- phenylureas -3- carbanilate -6-OTr derivatives：Step (1) is taken to obtain
Chitosan 6-OTr, the protection of high temperature non-active gas is lower add anhydrous dimethyl sulphoxide swelling chitosan 24-48 it is small when, room temperature
When lower addition anhydrous lithium chloride 4-12 is small, under high temperature non-active gas, adds the phenyl isocyanate with different side chains and react
1-24h.Chitosan analog derivative reaction solution is instilled dropwise afterwards in isolation solvent and isolated, separated out chitosan class and derive
Thing, carries out centrifugation using centrifuge and obtains chitosan analog derivative, when vacuum drying 24-48 is small at 40-80 DEG C.Obtain shell
Glycan 2- phenylurea -3- carbanilates -6-OTr.
(3) deprotection of chitosan 6- hydroxyls：Take chitin-2-phenylurea-3- phenyl amino first that step (2) obtains
Acid esters -6-OTr, under non-active gas protection, it is 1 to add volume ratio：30~35 concentrated hydrochloric acid and methanol mixed solvent, in 30-
12-24h is reacted at 70 DEG C, chitosan analog derivative reaction solution is instilled dropwise afterwards in isolation solvent and is isolated, used
Centrifuge carries out centrifugation and obtains chitosan analog derivative, when vacuum drying 24-48 is small at 40-80 DEG C.Obtain chitin-2-
Phenylurea -3- carbanilate -6- hydroxyls.
The present invention can use nuclear magnetic resonance spectroscopy to carry out test analysis to obtained chitosan analog derivative, determine its knot
Whether structure and 2- bit aminos are fully converted to phenylurea and carbamate with 3- hydroxyls, and whether 6- be hydroxyl.
The present invention is described in more detail with embodiment below, but the present invention is not limited thereto.
Chitin-2-(3,5- 3,5-dimethylphenyl urea)-3- (3,5- dimethylphenylcarbamate)-6- hydroxy derivatives
Synthesis step：
(1) protection of chitosan 6- hydroxyls.
A. at 80 DEG C, the completely deacetylated chitosans (molecular weight 50000~300000) of 0.20g, stir and vacuum
Dry 4h.
B. under nitrogen protection, 12mL anhydrous dimethyl sulphoxides (DMSO) is added, are swollen 48h.
C. at room temperature, 0.60g lithium chlorides are added, stir 4h.
D. at 100 DEG C, nitrogen protection, adding triphenylchloromethane 0.70g, (molal weight is 2.0 times of 6- hydroxyls
Amount), react 24h.
E. above-mentioned solution is added drop-wise in 200mL ethyl acetate/isopropanol (V/V, 70/30) using dropper, separates out shell and gather
Carbohydrate derivative sediment.
F. centrifuged using centrifuge, and with a large amount of ethyl acetate washed products in centrifugal process.
G. at 60 DEG C, 48h is dried in vacuo, that is, obtains the chitosan -6-OTr derivatives that yield is 84.49%.
1H-NMR spectrum is as shown in Figure 1：1H-NMR (500MHz, 80 DEG C, deuterated DMSO, δ/ppm)：3.78-5.08 (m,
7H, Glucose-H), 7.26 (s, 15H, Phenyl-H).Shell can be illustrated by occurring phenyl peak at ppm=7.26 from nuclear-magnetism figure
Glycan 6- is modified and protected by trityl group.
(2) preparation of chitosan class -2- phenylureas -3- carbanilate -6-OTr derivatives.
A. the chitosan analog derivative 0.20g that step (1) obtains is taken.
B. under nitrogen protection, 8mL anhydrous dimethyl sulphoxides (DMSO) is added, are swollen 48h.
C. at room temperature, 0.60g lithium chlorides are added, stir 4h.
D. at 80 DEG C, nitrogen protection, adding 3,5- dimethylphenyl isocyanates 0.32mL, (molal weight is 2- ammonia
2.5 times of amounts of the total moles quality of base and 3- hydroxyls), react 24h.
E. above-mentioned solution is added drop-wise in 160mL methanol solvates using dropper, separates out chitosan analog derivative sediment.
F. centrifuged using centrifuge, and with a large amount of methanol washed products in centrifugal process.
G. at 60 DEG C, 48h is dried in vacuo, that is, obtains chitin-2-phenylurea-3- phenylaminos that yield is 62.09%
Carbamate -6-OTr derivatives.
1H-NMR spectrum is as shown in Figure 2：1H-NMR (400MHz, 80 DEG C, deuterated DMSO, δ/ppm)：2.13 (s, 12H ,-
CH3), 3.63-4.94 (m, 7H, Glucose-H), 6.56-6.98 (d, 21H, Phenyl-H), 5.89 (s, 1H, Urea-H),
7.94 (s, 1H, Urea-H), 8.78 (s, 1H, Carbamate-H).
(3) deprotection of chitosan 6- hydroxyls.
A. the chitosan analog derivative 0.20g that step (2) obtains is taken.
B. at 50 DEG C, nitrogen protection, adds methanol/HCl (V/V, 97/3) 12mL, reacts 24h.
C. said mixture is added drop-wise in 200mL methanol using dropper, stirs 0.5h.
D. centrifuged using centrifuge, and washed product to neutrality with a large amount of methanol in centrifugal process.
E. at 60 DEG C, 48h is dried in vacuo, that is, obtains chitin-2-(3,5- 3,5-dimethylphenyls that yield is 78.06%
Urea) -3- (3,5- dimethylphenylcarbamate) -6- hydroxy derivatives
1H-NMR spectrum is as shown in Figure 3：1H-NMR (400MHz, 80 DEG C, deuterated DMSO, δ/ppm)：2.15 (s, 12H ,-
CH3), 3.32-4.88 (m, 8H, Glucose-H), 6.49-7.00 (d, 6H, Phenyl-H), 5.92 (s, 1H, Urea-H),
8.04 (s, 1H, Urea-H), 8.80 (s, 1H, Carbamate-H).By the peak area of proton peak it may be concluded that reaction
Replacement rate is more than 80%.
Claims (10)
1. one kind contains more structure functional group chitosan analog derivatives, it is characterized in that with such as lower structure：
Wherein, R represents phenyl or the phenyl with substituent, and the substituent is 1 to 4, when the number of substituent is more than 1
When, each substituent is identical or differs, and the substituent is halogen atom, alkyl, alkoxy, nitro, amino or alkylthio group.
2. a kind of preparation method containing more structure functional group chitosan analog derivatives, it is characterized in that：First use triphenyl chloromethane
Alkane protects chitosan for 6-, then is reacted with phenyl isocyanate or the phenyl isocyanate with side base, finally to shell
Glycan 6- is deprotected, and is obtained structural formula and isChitosan class -2- phenylurea -3- phenyl
Carbamate -6- hydroxy derivatives, wherein, R represents phenyl or the phenyl with substituent, and the substituent is 1 to 4,
When substituent number be more than 1 when, each substituent is identical or differs, the substituent for halogen atom, alkyl, alkoxy,
Nitro, amino or alkylthio group.
3. the preparation method according to claim 2 containing more structure functional group chitosan analog derivatives, it is characterized in that：Institute
State and protection is carried out to chitosan 6- using triphenylchloromethane specifically include：Take complete deacetylated chitosan 60~
100 DEG C of vacuum drying, add reaction dissolvent and are swollen, add hydrogen bond remover at room temperature, add triphenylchloromethane,
Reaction temperature is 80~100 DEG C of reaction 6-24h, and reaction product is instilled in isolation solvent, obtains chitosan -6-OTr.
4. the preparation method according to claim 2 containing more structure functional group chitosan analog derivatives, it is characterized in that：Institute
State with phenyl isocyanate or the reaction of the phenyl isocyanate with side base specifically includes：Chitosan 6-OTr is taken, it is molten to add reaction
Agent is swollen, and adds hydrogen bond remover at room temperature, adds phenyl isocyanate or the phenyl isocyanate with side base,
Reaction temperature is 40~150 DEG C of reactions, and the reaction time is 0.5~24h, and reaction product is instilled in isolation solvent, shell is obtained and gathers
Sugar -2- phenylurea -3- carbanilates -6-OTr.
5. the preparation method according to claim 2 containing more structure functional group chitosan analog derivatives, it is characterized in that：Institute
State and deprotection is carried out to chitosan 6- specifically include：Chitin-2-phenylurea-3- carbanilate-6-OTr are taken, are added
Enter concentrated hydrochloric acid and methanol, be 30~70 DEG C of reactions in reaction temperature, the reaction time is 12~24h, and reaction product is instilled and is isolated
In solvent, chitin-2-phenylurea-3- carbanilate-6- hydroxyls are obtained.
6. the preparation method containing more structure functional group chitosan analog derivatives according to claim 2 to 5 any one,
It is characterized in that：The molal weight of the triphenylchloromethane of addition is 1.5~3 times of the molal weight of 6- hydroxyls of chitosan.
7. the preparation method containing more structure functional group chitosan analog derivatives according to claim 2 to 5 any one,
It is characterized in that：The phenyl isocyanate of addition or with side base phenyl isocyanate molal weight be chitosan 2- positions ammonia
1.5~3 times of base and 3- hydroxyl total moles quality.
8. the preparation method containing more structure functional group chitosan analog derivatives according to claim 2 to 5 any one,
It is characterized in that：Phenyl isocyanate with side base is selected from 4- methoxyphenyl isocyanates, 4- ethylphenyls isocyanates, 4-
Methylphenyl isocyanate, 4- fluorophenylisocyanates, 4- chlorophenyl isocyanates, 4- bromophenyl isocyanates, 4- nitrobenzenes
Based isocyanate, 2- chlorophenyl isocyanates, 2- methylphenyl isocyanates, 3- chlorophenyl isocyanates, 3- aminomethyl phenyls are different
Cyanate, 3,5- dichlorophenyl isocyanates or 3,5- dimethylphenyl isocyanates.
9. the preparation method according to claim 6 containing more structure functional group chitosan analog derivatives, it is characterized in that：Tool
It is different that the phenyl isocyanate for having side base is selected from 4- methoxyphenyl isocyanates, 4- ethylphenyls isocyanates, 4- aminomethyl phenyls
Cyanate, 4- fluorophenylisocyanates, 4- chlorophenyl isocyanates, 4- bromophenyl isocyanates, 4- nitrophenyl isocyanates,
2- chlorophenyl isocyanates, 2- methylphenyl isocyanates, 3- chlorophenyl isocyanates, 3- methylphenyl isocyanates, 3,5-
Dichlorophenyl isocyanate or 3,5- dimethylphenyl isocyanates.
10. the preparation method according to claim 7 containing more structure functional group chitosan analog derivatives, it is characterized in that：
Phenyl isocyanate with side base is selected from 4- methoxyphenyl isocyanates, 4- ethylphenyls isocyanates, 4- aminomethyl phenyls
Isocyanates, 4- fluorophenylisocyanates, 4- chlorophenyl isocyanates, 4- bromophenyl isocyanates, 4- nitrobenzophenone isocyanic acids
Ester, 2- chlorophenyl isocyanates, 2- methylphenyl isocyanates, 3- chlorophenyl isocyanates, 3- methylphenyl isocyanates, 3,
5- dichlorophenyl isocyanates or 3,5- dimethylphenyl isocyanates.
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|---|---|---|---|---|
| CN104250312A (en) * | 2013-06-28 | 2014-12-31 | 株式会社大赛璐 | Chitosan carbanilate-carbamido derivative preparation method |
| CN104311700A (en) * | 2014-10-29 | 2015-01-28 | 武汉工程大学 | Chitosan-bi(aryl-carbamate)-(amide) and preparation method thereof |
| CN104877034A (en) * | 2015-05-08 | 2015-09-02 | 长春理工大学 | Fullerene cellulose derivative used as chiral stationary phase material and preparation method of fullerene cellulose derivative |
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2017
- 2017-10-20 CN CN201710996810.0A patent/CN108034009A/en active Pending
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|---|---|---|---|---|
| CN104250312A (en) * | 2013-06-28 | 2014-12-31 | 株式会社大赛璐 | Chitosan carbanilate-carbamido derivative preparation method |
| CN104311700A (en) * | 2014-10-29 | 2015-01-28 | 武汉工程大学 | Chitosan-bi(aryl-carbamate)-(amide) and preparation method thereof |
| CN104877034A (en) * | 2015-05-08 | 2015-09-02 | 长春理工大学 | Fullerene cellulose derivative used as chiral stationary phase material and preparation method of fullerene cellulose derivative |
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