The preparation of O-3,4- methylenedioxyphenylacetic acid ester-N- trimethyl chitin quaternary ammonium salt
With application
Technical field
The invention belongs to producing high-molecular condensation material fields, and in particular to O-3,4- methylenedioxyphenylacetic acid ester-N- front three
The preparation and application of base chitosan quaternary ammonium salt.
Background technique
It is steadily improved with the fast development of science and technology with living standards of the people, masses are to the packet with bacteriostasis property
Package material is more paid attention to.At present.Common antibacterial agent mainly has three classes in daily life: inorganic metal mineral material, organic miscellaneous
Ring antibacterial material and natural antibacterial material.Since natural antibacterial material is from nature, property safe to the human body is high and meets green
Environmental requirement, in recent years by the popular welcome of people.Therefore, the research and development of natural antibacterial agent is using also at application
The hot spot learned.
Chitosan be widespread in nature in the shell of shrimp, crab and insect and algae, mushroom cell wall among,
It is a kind of abundance, the natural polymer with multiple biological activities.In recent years, chitosan is because of its good biodegrade
Property, biocompatibility, film forming characteristics, adsorption sustained-release and stronger Antimicrobial preservative preservativity, caused extensive concern and
Pay attention to, the development and application research in fields such as environmental protection, biological medicine, food industry and chemical industry is very active.By to shell
Glycan is acylated, is alkylated, hydroxylating, aldimine groups, Sulfation, carboxy methylation, the chemical modifications such as quaternized, can
To obtain that there are the chitosan derivatives of certain functional group, effectively improve its performance.Some researches show that carry out N to chitosan
The methylation of position can be effectively improved its water-soluble and raising anti-microbial property (Vallapa N, Wiarachai O, Thongchul
N,et al.Enhancing antibacterial activity of chitosan surface by heterogeneous
quaternization[J].Carbohydrate Polymers,2011,83(2):868-875)。
Aromatic acid, is a kind of organic compound with very strong bacteriostatic activity, and esterification products can be used as drug or anti-corrosion
Agent uses, and capable of effectively inhibiting the effect of fungi, bacterium, fungus growth, (Xie Zongbo, Jiang Guofang, Liao Fusheng wait para hydroxybenzene first
The synthesis of sour isobutyl ester and bacteriostatic activity [J] food industry science and technology, 2007,27 (12): 144-145.).Therefore, by day
It carries out carrying out esterification introducing 3,4- methylenedioxyphenylacetic acid ester on trimethyl quaternary ammonium salt and hydroxyl on the amino of right chitosan,
A modification of chitosan derivative with double bacteria resistance function groups is obtained, this water solubility and antibacterial work for enhancing chitosan
Property there is very obvious action.
Summary of the invention
For the disadvantage for overcoming chitosan macromolecular not soluble in water, the primary purpose of the present invention is that providing a kind of novel
Water-solubility chitosan derivative with antibacterial effect: O-3,4- methylenedioxyphenylacetic acid ester-N- trimethyl chitin quaternary ammonium
Salt;
Another object of the present invention is to provide above-mentioned O-3,4- methylenedioxyphenylacetic acid ester-N- trimethyl chitin seasons
The preparation method of ammonium salt;
A further object of the present invention is to provide above-mentioned O-3,4- methylenedioxyphenylacetic acid ester-N- trimethyl chitin seasons
The application of ammonium salt.
The purpose of the invention is achieved by the following technical solution:
A kind of O-3,4- methylenedioxyphenylacetic acid ester-N- trimethyl chitin quaternary ammonium salt, shown in structure such as formula (1):
Wherein, the molecular weight of the O-3,4- methylenedioxyphenylacetic acid ester-N- trimethyl chitin quaternary ammonium salt be 3.0 ×
105~5 × 105, n be 250~600 natural number.
The present invention also provides a kind of preparations of O-3,4- methylenedioxyphenylacetic acid ester-N- trimethyl chitin quaternary ammonium salt
Method includes the following steps:
(1) using chitosan, formaldehyde and formic acid as starting material, prepared by microwave reaction chitosan schiff-base;Again with iodomethane
It reacts and N, N, N- trimethyl chitin is made;
(2) 3,4- (methylene-dioxy) phenylacetic acid is added in thionyl chloride in 4 DEG C of ice bath stirring conditions, oil bath is gradually
Until back flow reaction occurs, vacuum distillation obtains 3,4- methylenedioxyphenylacetic acid acyl chlorides for heating;Step (1) is prepared
N, N, N- trimethyl chitin are dissolved completely in Loprazolam, and it is sub- that 3 prepared, 4- is added dropwise dropwise under 4 DEG C of condition of ice bath
Methylenedioxy group phenylacetic acid acyl chlorides, is slowly warming up to 20~35 DEG C, the reaction was continued 12~48h.Acetone is added to the end of reacting to carry out
It precipitates, is transferred to bag filter after precipitating deionized water stirring and dissolving, dialyse, be freeze-dried in deionized water, obtain institute
The O-3,4- methylenedioxyphenylacetic acid ester-N- trimethyl chitin quaternary ammonium salt stated.
Preferably, chitosan described in step (1) be deacetylation be 99%, viscosity average molecular weigh be 100000Da's
Chitosan;The mass ratio of the chitosan and iodomethane reaction is 1:(5~20).
Preferably, microwave reaction described in step (1) are as follows: microwave power be 600~900W, reaction temperature be 50~80
30~60min is stirred to react under conditions of DEG C.
Preferably, the mass ratio of 3,4- (methylene-dioxy) phenylacetic acid and thionyl chloride described in step (2) be 1:(5~
20)。
Preferably, the reaction temperature control of 3,4- (methylene-dioxy) phenylacetic acid and thionyl chloride described in step (2) exists
160~200 DEG C.
Preferably, N described in step (2), N, N- trimethyl chitin and 3,4- methylenedioxyphenylacetic acid acyl chlorides are matter
Amount is than being 1:(5~20).
Preferably, N described in step (2), N, N- trimethyl chitin and 3,4- methylenedioxyphenylacetic acid acyl chlorides it is anti-
Answering temperature is 25~40 DEG C, and the reaction time is for 24 hours.
Above-mentioned O-3,4- methylenedioxyphenylacetic acid ester-N- trimethyl chitin quaternary ammonium salt is in antibacterial medical material, day
With the application in chemicals and packaging material for food field.
With 3,4- (methylene-dioxy) phenylacetic acid, for raw material, 3,4- methylene two is prepared by acyl chloride reaction in the present invention
Oxygroup phenylacetic acid acyl chlorides, then with N, N, N- trimethyl chitin has 2 in the raw esterification of Loprazolam solution relaying supervention
Together, O-3 is prepared in the group bonding for having antibacterial bioactivity, and 4- methylenedioxyphenylacetic acid ester-N- front three base enclosure is poly-
Sugared quaternary ammonium salt, to obtain better bacteriostatic activity.
The preparation process schematic diagram of O-3,4- methylenedioxyphenylacetic acid ester-N- trimethyl chitin quaternary ammonium salt of the present invention is such as
Shown in Fig. 1.
The present invention has the following advantages and effects with respect to the prior art:
Chitosan derivatives O-3,4- methylenedioxyphenylacetic acid ester-N- trimethyl chitin quaternary ammonium of the present invention
Salt, trimethyl group has been accessed in chitosan N to be improved the water solubility of chitosan and enhances biocidal property, and is drawn at O
Aromatic esters group is entered, has further enhanced the antibacterial activity and hydrophily of chitosan, two kinds of active groups are effectively combined
Together, synergetic is mutually generated, the more single chitosan quaternary ammonium salt of antibiotic property or chitosan are good, expand chitosan
Application range.
Detailed description of the invention
Fig. 1 is the preparation process schematic diagram of O-3,4- methylenedioxyphenylacetic acid ester-N- trimethyl chitin quaternary ammonium salt.
Specific embodiment
Below in conjunction with attached drawing, the present invention is described in detail.
Each starting material is commercially available or prepares according to art methods in preparation method of the present invention.At this
In embodiment, N, N, N- trimethyl chitin synthesis can according to the prior art it has been reported that method obtain (Xu T, Xin
M,Li M,etal.Synthesis,characterization,and antibacterial activity of N,O-
quaternary ammonium chitosan[J].Carbohydrate research,2011,346(15):2445-
2450).3,4- methylenedioxyphenylacetic acid acyl chlorides can refer to the prior art and it has been reported that method obtain (Qiao Zhen, Hou Shicong,
Synthesis [J] chemical reagent of the .1,1- such as Bian Qinghua ferrocenedicarboxylic acid and 1,1- ferrocenedicarboxylic acid acyl chlorides, 2003,25 (5):
299-300;Wang Feng, willow wave, Wang Limin wait .Yb (OTf)3Catalytic solid phosgene is to organic acid chlorideization reaction [J] application
Chemistry, 2010,27 (04): 390-393), but N, N, N- trimethyl chitin and 3,4- methylenedioxyphenylacetic acid acyl chlorides obtain
It must be not limited to this kind of mode.
Embodiment 1
A kind of O-3,4- methylenedioxyphenylacetic acid ester-N- trimethyl chitin quaternary ammonium salt, preparation method are as follows:
(1) chitosan of 3g is dissolved in the formic acid of 200mL deionized water and 20mL, stirring is warming up to 50 DEG C, is added
The formalin of 15mL is transferred to after mixing in microwave normal pressure reactor, and it is anti-to 600W temperature 50 C to adjust microwave power
Answer 60min;PH is adjusted to alkalinity with the NaOH solution of 15% mass fraction, is filtered, is washed to neutrality, is added to 50mL after drying
In n-methyl-2-pyrrolidone, 15mL iodomethane, 50 DEG C of reaction 96h are added;V (ether)/V (ethyl alcohol) of two volumes is added
=1:1 mixed solvent is precipitated, and N, N, N- trimethyl chitin is made using being freeze-dried after deionized water dialysis.
N can be obtained by being detected by x-ray photoelectron spectroscopy (XPS) to sample, N, N- trimethyl chitin it is quaternized
Degree of substitution is 55%.
(2) 3,4- (methylene-dioxy) phenylacetic acid for pipetting 5g is added to the chlorination of 25mL under the conditions of 4 DEG C of ice bath stirrings
In sulfoxide, it is gradually heated to 160 DEG C after 4 DEG C of ice bath stirring 0.5h the reaction was continued 8h, component is collected in vacuum distillation, and to obtain 3,4- (sub-
Methylenedioxy group) phenylacetic acid acyl chlorides.The N of 1g, N are weighed, N- trimethyl chitin is added to 10mL's under the conditions of 4 DEG C of ice bath stirrings
In Loprazolam, to which 3,4- (methylene-dioxy) phenylacetic acid acyl chlorides of 5mL is added dropwise dropwise after completely dissolution, it is to slowly warm up to 25
DEG C, the reaction was continued for 24 hours.With ethanol precipitation and repeatedly after washing, deionized water dialysis, freeze-drying obtains product 3,4- (methylene two
Oxygroup) phenylacetate-N- trimethyl chitin quaternary ammonium salt.
Nuclear magnetic resonance is carried out to product O-3,4- (methylene-dioxy) phenylacetate-N- trimethyl chitin quaternary ammonium salt1H points
Analysis, can be calculated its esterification degree is 31%.
Embodiment 2
A kind of O-3,4- methylenedioxyphenylacetic acid ester-N- trimethyl chitin quaternary ammonium salt, preparation method are as follows:
(1) chitosan of 3g is dissolved in the formic acid of 200mL deionized water and 20mL, stirring is warming up to 50 DEG C, is added
The formalin of 30mL is transferred to after mixing in microwave normal pressure reactor, and it is anti-to 700W temperature 60 C to adjust microwave power
Answer 50min;PH is adjusted to alkalinity with the NaOH solution of 15% mass fraction, is filtered, is washed to neutrality, is added to 50mL after drying
In n-methyl-2-pyrrolidone, 30mL iodomethane, 60 DEG C of reaction 72h are added;V (ether)/V (ethyl alcohol) of two volumes is added
=1:1 mixed solvent is precipitated, and N, N, N- trimethyl chitin is made using being freeze-dried after deionized water dialysis.
N can be obtained by being detected by x-ray photoelectron spectroscopy (XPS) to sample, N, N- trimethyl chitin it is quaternized
Degree of substitution is 64%.
(2) 3,4- (methylene-dioxy) phenylacetic acid for pipetting 5g is added to the chlorination of 50mL under the conditions of 4 DEG C of ice bath stirrings
In sulfoxide, it is gradually heated to 170 DEG C after 4 DEG C of ice bath stirring 0.5h the reaction was continued 8h, component is collected in vacuum distillation, and to obtain 3,4- (sub-
Methylenedioxy group) phenylacetic acid acyl chlorides.The N of 1g, N are weighed, N- trimethyl chitin is added to 10mL's under the conditions of 4 DEG C of ice bath stirrings
In Loprazolam, to which 3,4- (methylene-dioxy) phenylacetic acid acyl chlorides of 50mL is added dropwise dropwise after completely dissolution, it is to slowly warm up to 30
DEG C, the reaction was continued for 24 hours.With ethanol precipitation and repeatedly after washing, deionized water dialysis, freeze-drying obtains product 3,4- (methylene two
Oxygroup) phenylacetate-N- trimethyl chitin quaternary ammonium salt.
Nuclear magnetic resonance is carried out to product O-3,4- (methylene-dioxy) phenylacetate-N- trimethyl chitin quaternary ammonium salt1H points
Analysis, can be calculated its esterification degree is 43%.
Embodiment 3
A kind of O-3,4- methylenedioxyphenylacetic acid ester-N- trimethyl chitin quaternary ammonium salt, preparation method are as follows:
(1) chitosan of 3g is dissolved in the formic acid of 200mL deionized water and 20mL, stirring is warming up to 50 DEG C, is added
The formalin of 40mL is transferred to after mixing in microwave normal pressure reactor, and it is anti-to 800W temperature 70 C to adjust microwave power
Answer 40min;PH is adjusted to alkalinity with the NaOH solution of 15% mass fraction, is filtered, is washed to neutrality, is added to 50mL after drying
In n-methyl-2-pyrrolidone, 45mL iodomethane, 70 DEG C of reaction 48h are added;V (ether)/V (ethyl alcohol) of two volumes is added
=1:1 mixed solvent is precipitated, and N, N, N- trimethyl chitin is made using being freeze-dried after deionized water dialysis.
N can be obtained by being detected by x-ray photoelectron spectroscopy (XPS) to sample, N, N- trimethyl chitin it is quaternized
Degree of substitution is 72%.
(2) 3,4- (methylene-dioxy) phenylacetic acid for pipetting 5g is added to the chlorination of 75mL under the conditions of 4 DEG C of ice bath stirrings
In sulfoxide, it is gradually heated to 180 DEG C after 4 DEG C of ice bath stirring 0.5h the reaction was continued 8h, component is collected in vacuum distillation, and to obtain 3,4- (sub-
Methylenedioxy group) phenylacetic acid acyl chlorides.The N of 1g, N are weighed, N- trimethyl chitin is added to 10mL's under the conditions of 4 DEG C of ice bath stirrings
In Loprazolam, to which 3,4- (methylene-dioxy) phenylacetic acid acyl chlorides of 75mL is added dropwise dropwise after completely dissolution, it is to slowly warm up to 35
DEG C, the reaction was continued for 24 hours.With ethanol precipitation and repeatedly after washing, deionized water dialysis, freeze-drying obtains product 3,4- (methylene two
Oxygroup) phenylacetate-N- trimethyl chitin quaternary ammonium salt.
Nuclear magnetic resonance is carried out to product O-3,4- (methylene-dioxy) phenylacetate-N- trimethyl chitin quaternary ammonium salt1H points
Analysis, can be calculated its esterification degree is 49%.
Embodiment 4
A kind of O-3,4- methylenedioxyphenylacetic acid ester-N- trimethyl chitin quaternary ammonium salt, preparation method are as follows:
(1) chitosan of 3g is dissolved in the formic acid of 200mL deionized water and 20mL, stirring is warming up to 50 DEG C, is added
The formalin of 50mL is transferred to after mixing in microwave normal pressure reactor, and it is anti-to 80 DEG C of 900W temperature to adjust microwave power
Answer 30min;PH is adjusted to alkalinity with the NaOH solution of 15% mass fraction, is filtered, is washed to neutrality, is added to 50mL after drying
In n-methyl-2-pyrrolidone, 60mL iodomethane is added, 80 DEG C of reactions are for 24 hours;V (ether)/V (ethyl alcohol) of two volumes is added
=1:1 mixed solvent is precipitated, and N, N, N- trimethyl chitin is made using being freeze-dried after deionized water dialysis.
N can be obtained by being detected by x-ray photoelectron spectroscopy (XPS) to sample, N, N- trimethyl chitin it is quaternized
Degree of substitution is 85%.
(2) 3,4- (methylene-dioxy) phenylacetic acid for pipetting 5g is added to the chlorination of 100mL under the conditions of 4 DEG C of ice bath stirrings
In sulfoxide, it is gradually heated to 200 DEG C after 4 DEG C of ice bath stirring 0.5h the reaction was continued 8h, component is collected in vacuum distillation, and to obtain 3,4- (sub-
Methylenedioxy group) phenylacetic acid acyl chlorides.The N of 1g, N are weighed, N- trimethyl chitin is added to 10mL's under the conditions of 4 DEG C of ice bath stirrings
In Loprazolam, to which 3,4- (methylene-dioxy) phenylacetic acid acyl chlorides of 100mL is added dropwise dropwise after completely dissolution, it is to slowly warm up to 40
DEG C, the reaction was continued for 24 hours.With ethanol precipitation and repeatedly after washing, deionized water dialysis, freeze-drying obtains product 3,4- (methylene two
Oxygroup) phenylacetate-N- trimethyl chitin quaternary ammonium salt.
Nuclear magnetic resonance is carried out to product O-3,4- (methylene-dioxy) phenylacetate-N- trimethyl chitin quaternary ammonium salt1H points
Analysis, can be calculated its esterification degree is 60%.
The test of embodiment 5, O-3,4- (methylene-dioxy) phenylacetate-N- trimethyl chitin quaternary ammonium salt anti-microbial property
The bacteriostatic activity of O-3,4- (methylene-dioxy) phenylacetate-N- trimethyl chitin quaternary ammonium salt of the present invention
Measurement: O-3,4- (methylene-dioxy) phenylacetate-N- trimethyl chitin quaternary ammonium salt sample is determined using culture medium diffusion method
To the antibacterial activity of gram-positive bacteria staphylococcus aureus and Gram-negative bacteria Escherichia coli.According to " disinfection technology rule
Model 2006 " in judgement to bacteriostasis: antibacterial circle diameter, which is greater than 20mm, indicates there is strong fungistatic effect, inhibition zone 10mm~
20mm is moderate antibacterial, inhibition zone be less than 10mm be it is weak antibacterial, inhibition zone has biocidal property to determine the suppression of compound in 7mm
Bacterium effect.Nutrient broth dilution method measures raw materials of chitosan, N, N, N- trimethyl chitin quaternary ammonium salt and O-3 of the present invention,
4- (methylene-dioxy) phenylacetate-N- trimethyl chitin quaternary ammonium salt presses down Escherichia coli and the minimum of staphylococcus aureus
Bacteria concentration (MIC), data are shown in Table 1.
1. chitosan of table, N, N, N- trimethyl chitin quaternary ammonium salt and O- imidazate-N- trimethyl chitin quaternary ammonium salt are anti-
Bacterium the performance test results
By antibacterial circle diameter experimental data in table it is found that product O-3 of the present invention, 4- (methylene-dioxy) phenylacetate-N-
Antibacterial work of the trimethyl chitin quaternary ammonium salt to gram-positive bacteria staphylococcus aureus and Gram-negative bacteria Escherichia coli
With being significantly stronger than unmodified chitosan;It is a kind of biomass antibacterial material that fungistatic effect is excellent, can be widely used for antibacterial doctor
Numerous application fields such as drug material, domestic chemical products and food packaging.
The foregoing description of the disclosed embodiments enables those skilled in the art to implement or use the present invention.
Various modifications to these embodiments will be readily apparent to those skilled in the art, as defined herein
General Principle can be realized in other embodiments without departing from the spirit or scope of the present invention.Therefore, of the invention
It is not intended to be limited to the embodiments shown herein, and is to fit to and the principles and novel features disclosed herein phase one
The widest scope of cause.