CN106866458A - Azobenzene derivatives containing quaternary ammonium salt group and its preparation method and application - Google Patents
Azobenzene derivatives containing quaternary ammonium salt group and its preparation method and application Download PDFInfo
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- C07C245/08—Azo compounds, i.e. compounds having the free valencies of —N=N— groups attached to different atoms, e.g. diazohydroxides with nitrogen atoms of azo groups bound to carbon atoms of six-membered aromatic rings with the two nitrogen atoms of azo groups bound to carbon atoms of six-membered aromatic rings, e.g. azobenzene
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Abstract
The present invention relates to stimuli responsive carrier field, there is provided a kind of azobenzene derivatives containing quaternary ammonium salt group and its preparation method and application.Azobenzene derivatives containing quaternary ammonium salt group of the invention are connected to hydrophilic cationic quaternary ammonium salt group and long-chain hydrophobic alkyl at the two ends of azobenzene, and reversible conformational change be able to can occur under ultraviolet light.Can be prepared based on the azobenzene derivatives containing quaternary ammonium salt group of the invention being capable of the liposome that is responded of photic stimuli, if will be wrapped in medicine in above-mentioned liposome, the controlled release of internal drug can be then realized, mitigates side effects of pharmaceutical drugs, improve therapeutic effect.The preparation method of the azobenzene derivatives containing quaternary ammonium salt group of the invention is simple, yield is high.
Description
Technical field
The present invention relates to stimuli responsive carrier field, more particularly to a kind of azobenzene derivatives containing quaternary ammonium salt group and its
Preparation method and application.
Background technology
The breakthrough of nanometer technology generates important influence to multiple industries, especially to material science, biotechnology and
Drug therapy.Different nano-carriers, such as liposome, polymer, micella and c-based nanomaterial are just gradually being applied to medical science neck
The transport (medicine and gene) in domain, such as curative drug macromolecular.But, the transport still face of current curative drug macromolecular
Face very big challenge, because the medicament transport system required for us is preferably able to realize the timing of medicine, fixed point and quantifies
Release.To for medicament transport system, having had certain research at present, such as：By intelligent micrometer/nanometer particle
(MNPs) realize.The MNPs is referred to certain specific mode response external/internal stimulus, and then realizes internal medicine
The general name of the micrometer/nanometer particle of the controlled release of thing.Illumination can be accurate due to parameters such as its intensity, wavelength, irradiation times
Regulation, and be non-invasive to organism, thus it is possible to the MNPs that photic stimuli is responded has wide application preceding
Scape.
Accordingly, it would be desirable to a kind of being capable of the azobenzene derivatives that are responded of photic stimuli.
The content of the invention
Object of the present invention is to provide a kind of azobenzene derivatives containing quaternary ammonium salt group and preparation method thereof and should
With based on the azobenzene derivatives containing quaternary ammonium salt group, the MNPs that photic stimuli is responded can be prepared.
To achieve the above object, the invention provides a kind of azobenzene derivatives containing quaternary ammonium salt group, structural formula is as follows：
Wherein, R1It is the straight chained alkyl of C1~6；R2It is the straight chain hydrophobic alkyl of C12~16；X is COO or CONH.
To achieve these goals, present invention also offers a kind of system of the above-mentioned azobenzene derivatives containing quaternary ammonium salt group
Preparation Method, comprises the following steps：
A, compound 1 and compound 2 are reacted, obtain compound 3；
B, compound 3 and N-bromosuccinimide are dissolved in tetrachloromethane and in benzoyl peroxide under atmosphere of inert gases
There is bromination reaction under the catalysis of formyl, obtain compound 4；
C, make the substrate reactions of compound 4 and first, obtain the azobenzene derivatives containing quaternary ammonium salt group；
The structural formula of the compound 1 is as follows：
The structural formula of the compound 2 is as follows：
X2-R2；
The structural formula of the compound 3 is as follows：
The structural formula of the compound 4 is as follows：
The X1It is COOH or COCl；
The X2It is OH or NH2；
The structural formula of first substrate is：
Wherein, the X1It is COCl；The X2It is NH2；The step A is comprised the following steps：
A1, compound 1 is dissolved in dichloromethane, is subsequently adding triethylamine, obtain the first reaction solution；
A2, compound 2 is dissolved in dichloromethane, obtains the second reaction solution；
A3, by the second reaction solution instill the first reaction solution in, stirring at normal temperature is overnight；
Dichloromethane in A4, the product of removing step A3, obtains solid；
A5, solid is dissolved in dichloromethane, and is isolated and purified by column chromatography, the mobile phase is by 1:1 volume
Than the petroleum ether and dichloromethane mixed liquor prepared, compound 3 is obtained.
Wherein, the step A is further comprising the steps of：
A0, compound 5 is added into thionyl chloride, be heated to 60-70 DEG C, be stirred overnight, and then remove unreacted chlorination
Sulfoxide, obtains compound 2；
The structural formula of the compound 5 is as follows：
Wherein, 10≤n≤14.
Wherein, the step B is comprised the following steps：
B1, compound 3, N-bromosuccinimide and benzoyl peroxide are dissolved in tetrachloromethane under argon atmosphere,
Heating reflux reaction 12-72 hours；
B2, reaction system is cooled to 0 DEG C, suction filtration obtains powder；
B3, ether washing powder is used, obtain compound 4.
Wherein, the step C is comprised the following steps：
C1, compound 4 is dissolved in ethanol, adds the first substrate, back flow reaction 6-48 hours；
C2, the product of step C1 is evaporated, then with by 5:Ether and the dissolving of dichloromethane mixed liquor that 1 volume ratio is prepared,
Solids of sedimentation is collected by filtration.
Wherein, the step C is further comprising the steps of：
C3, with by 5:Ether and dichloromethane mixed liquor washing solids of sedimentation that 1 volume ratio is prepared, obtain described containing quaternary ammonium salt
The azobenzene derivatives of group.
In order to realize the purpose of the present invention, present invention also offers a kind of azobenzene containing quaternary ammonium salt group of the present invention
Application of the derivative in preparing in the photoresponse liposome of bag medicine.
Wherein, the medicine is adriamycin.
Azobenzene derivatives containing quaternary ammonium salt group of the invention the two ends of azobenzene be connected to hydrophily sun from
Sub- quaternary ammonium salt group and long-chain hydrophobic alkyl, can occur reversible conformational change under ultraviolet light, based on this
The azobenzene derivatives containing quaternary ammonium salt group of invention can prepare can the liposome that is responded of photic stimuli, if by medicine
Bag can then realize the controlled release of internal drug in above-mentioned liposome in thing, mitigate side effects of pharmaceutical drugs, and curative effect is controlled in raising
Really.The preparation method of the azobenzene derivatives containing quaternary ammonium salt group of the invention is simple, yield is high.
Brief description of the drawings
Fig. 1 is the structural formula of the azobenzene derivatives containing quaternary ammonium salt group in first embodiment of the invention.
Fig. 2 is that the present invention first is specific prepares the structure that embodiment prepares azobenzene derivatives of the gained containing quaternary ammonium salt group
Formula.
Fig. 3 is that the present invention second is specific prepares the structure that embodiment prepares azobenzene derivatives of the gained containing quaternary ammonium salt group
Formula.
Fig. 4 is that the present invention the 3rd is specific prepares the structure that embodiment prepares azobenzene derivatives of the gained containing quaternary ammonium salt group
Formula.
Fig. 5 is that the specific embodiment for preparing of the present invention the 3rd prepares azobenzene derivatives of the gained containing quaternary ammonium salt group through purple
Uv-visible absorption spectra variation diagram after outer light irradiation.
Fig. 6 is to prepare azobenzene derivatives system of the gained containing quaternary ammonium salt group based on the specific embodiment for preparing of the present invention the 3rd
The light-operated release profiles of the photoresponse liposome of standby interior bag adriamycin.
Specific embodiment
With reference to specific embodiment, the present invention is described in further detail, and following examples are to solution of the invention
Release, the invention is not limited in following examples.
In the first embodiment of the present invention, a kind of azobenzene derivatives containing quaternary ammonium salt group, structural formula such as Fig. 1 institutes
Show, wherein, R1It is the straight chained alkyl of C1~6；R2It is the straight chain hydrophobic alkyl of C12~16；X is COO or CONH.
The straight chain hydrophobic alkyl chain of one end of the azobenzene derivatives containing quaternary ammonium salt group of the invention is inserted into fat
In the phospholipid bilayer of plastid, the hydrophilic cationic quaternary ammonium salt group of the other end then can be towards outside phospholipid bilayer tunic
The aqueous solution, so as to form the arrangement of regularity in liposome, when the azobenzene derivatives containing quaternary ammonium salt group of the invention are received
When under to ultraviolet light, its conformation is reversibly changed.
Preferably, the R1It is the straight chained alkyl of C2~4, i.e. ethyl group, propyl or normal butane base.
Preferably, the R2It is the straight chain hydrophobic alkyl of C12, C14 or C16.
In the second embodiment of the present invention, a kind of method for preparing the above-mentioned azobenzene derivatives containing quaternary ammonium salt group,
Comprise the following steps：
A, compound 1 and compound 2 are reacted, obtain compound 3；
B, compound 3 and N-bromosuccinimide are dissolved in tetrachloromethane and in benzoyl peroxide under atmosphere of inert gases
There is bromination reaction under the catalysis of formyl, obtain compound 4；
C, make the substrate reactions of compound 4 and first, obtain the azobenzene derivatives containing quaternary ammonium salt group；
The structural formula of the compound 1 is as follows：
The structural formula of the compound 2 is as follows：
X2-R2；
The structural formula of the compound 3 is as follows：
The structural formula of the compound 4 is as follows：
The X1It is COOH or COCl；
The X2It is OH or NH2；
The structural formula of first substrate is：
It should be noted that the inert gas includes at least one in helium, argon gas, neon or xenon.
In a specific embodiment of the invention, the X1It is COCl；The X2It is NH2；The step A includes following step
Suddenly：
A1, compound 1 is dissolved in dichloromethane, is subsequently adding triethylamine, obtain the first reaction solution；
A2, compound 2 is dissolved in dichloromethane, obtains the second reaction solution；
A3, by the second reaction solution instill the first reaction solution in, stirring at normal temperature is overnight；
Dichloromethane in A4, the product of removing step A3, obtains solid；
A5, solid is dissolved in dichloromethane, and is isolated and purified by column chromatography, the mobile phase is by 1:1 volume
Than the petroleum ether and dichloromethane mixed liquor prepared, compound 3 is obtained.
It should be noted that in the step A, mainly as reaction dissolvent, tri-n-butylamine is catalyst to dichloromethane；Step
Rapid A4 can be realized by being vacuum dried or rotating.In addition, in this programme, the NH in COCl and compound 2 in compound 12
Reaction, so as to generate compound 3, this method with by the OH or NH in the COOH and compound 2 in compound 12Reaction life
Method into compound 3 is compared, and reaction efficiency is higher, and the yield for preparing compound 3 is higher.
On the basis of a upper specific embodiment, the present invention proposes another specific embodiment, and the step A also includes following
Step：
A0, compound 5 is added into thionyl chloride, be heated to 60-70 DEG C, be stirred overnight, and then remove unreacted chlorination
Sulfoxide, obtains compound 2；
The structural formula of the compound 5 is as follows：
Wherein, 10≤n≤14.
It should be noted that in step A0 thionyl chloride can be removed by the method such as vacuum drying or revolving.
In another specific embodiment of the invention, the step B is comprised the following steps：
B1, compound 3, N-bromosuccinimide and benzoyl peroxide are dissolved in tetrachloromethane under argon atmosphere,
Heating reflux reaction 12-72 hours；
B2, reaction system is cooled to 0 DEG C, suction filtration obtains powder；
B3, ether washing powder is used, obtain compound 4.
It should be noted that the benzoyl peroxide in step B1 is catalyst；Step B2 suction filtrations gained powder is chemical combination
The crude product of thing 4；Ether washing powder is used in step B3, mainly by ether by unreacted Impurity removal, so as to play
The effect of purifying.
In another specific embodiment of the invention, the step C is comprised the following steps：
C1, compound 4 is dissolved in ethanol, adds the first substrate, back flow reaction 6-48 hours；
C2, the product of step C1 is evaporated, then with by 5:Ether and the dissolving of dichloromethane mixed liquor that 1 volume ratio is prepared,
Solids of sedimentation is collected by filtration.
It should be noted that in step C2, the product of step C1 can be evaporated by rotating；Step C2 gained solids of sedimentation
It is the crude product of the azobenzene derivatives containing quaternary ammonium salt group of the present invention.
Based on a upper specific embodiment, the present invention proposes another specific embodiment, and the step C is further comprising the steps of：
C3, with by 5:Ether and dichloromethane mixed liquor washing solids of sedimentation that 1 volume ratio is prepared, obtain described containing quaternary ammonium salt
The azobenzene derivatives of group.
It should be noted that described press 5:The ether and dichloromethane mixed liquor that 1 volume ratio is prepared can dissolve and not occur
The impurity of reaction, so as to play a part of purification.
In the of the invention first specific preparation embodiment, the structural formula of the azobenzene derivatives containing quaternary ammonium salt group
As shown in Fig. 2 the preparation method of the azobenzene derivatives is comprised the following steps：
S01, make compound 1 (the carboxyl azobenzene of 4- methyl -4 ') and compound 2 (n-tetradecanol) in the catalysis of the concentrated sulfuric acid
With there is esterification reaction under heating condition, generation compound 3 (the n-tetradecanol carbonyl azobenzene of 4- methyl -4 ')；
S02, the n-tetradecanol carbonyl azobenzene of 4- methyl -4 ', N-bromosuccinimide and benzoyl peroxide are existed
Tetrachloromethane, heating reflux reaction 24 hours are dissolved under argon atmosphere；
S03, the reaction system of step S02 is cooled to 0 DEG C, suction filtration obtains powder；
S04, with ether washing step S03 gained powder, remove unreacted impurity, obtain (the 4- bromomethyls -4 ' of compound 4
N-tetradecanol carbonyl azobenzene)；
S05, the n-tetradecanol carbonyl azobenzene of 4- bromomethyls -4 ' is dissolved in ethanol, is subsequently adding triethylamine, back flow reaction
12 hours；
S06, solution is evaporated, then with by 5:Ether and the dissolving of dichloromethane mixed liquor that 1 volume ratio is prepared, are collected by filtration
Solids of sedimentation, obtains final product the azobenzene derivatives containing quaternary ammonium salt group shown in Fig. 2, i.e. and 4- (N, N, N- triethylamine MB)-
4 '-n-tetradecanol carbonyl azobenzene.
In the of the invention second specific preparation embodiment, the structural formula of the azobenzene derivatives containing quaternary ammonium salt group
As shown in figure 3, the preparation method of the azobenzene derivatives is comprised the following steps：
S01, make compound 1 (the carboxyl azobenzene of 4- methyl -4 ') and compound 2 (cetyl alcohol) in the catalysis of the concentrated sulfuric acid
And there is esterification reaction, generation compound 3 (4- methyl -4 '-cetyl alcohol carbonyls azobenzene) under heating condition；
S02,4- methyl -4 '-cetyl alcohol carbonyls azobenzene, N-bromosuccinimide and benzoyl peroxide are existed
Tetrachloromethane, heating reflux reaction 48 hours are dissolved under argon atmosphere；
S03, the reaction system of step S02 is cooled to 0 DEG C, suction filtration obtains powder；
S04, with ether washing step S03 gained powder, remove unreacted impurity, obtain compound 4 (4- bromomethyls -4 ' -
Cetyl alcohol carbonyl azobenzene)；
S05,4- bromomethyl -4 '-cetyl alcohol carbonyl azobenzenes are dissolved in ethanol, are subsequently adding trimethylamine, backflow is anti-
Answer 24 hours；
S06, solution is evaporated, then with by 5:Ether and the dissolving of dichloromethane mixed liquor that 1 volume ratio is prepared, are collected by filtration
Solids of sedimentation, i.e. crude product.
S07, with by 5:The ether and dichloromethane mixed liquor that 1 volume ratio is prepared wash solids of sedimentation 3 times, obtain shown in Fig. 3
Azobenzene derivatives containing quaternary ammonium salt group, i.e. 4- (N, N, N- trimethylamine MB) -4 '-cetyl alcohol carbonyl azo
Benzene.
In the of the invention 3rd specific preparation embodiment, the structural formula of the azobenzene derivatives containing quaternary ammonium salt group
As shown in figure 4, the preparation method of the azobenzene derivatives is comprised the following steps：
S01, by the carboxyl azobenzene of 2.4g4- methyl -4 ' add 10mL thionyl chlorides in, 65 DEG C are stirred overnight, and revolving is gone out
Unreacted obtains thionyl chloride, obtains 2.4g colorless oil crude products, i.e. compound 2 (the acyl chlorides azobenzene of 4- methyl -4 ')；
S02,0.56g compounds 1 (n-dodecylamine) are dissolved in 20mL dichloromethane, are subsequently adding 0.59g triethylamines, obtain
One reaction solution；
S03,1.15g colorless oils crude product (the acyl chlorides azobenzene of 4- methyl -4 ') is dissolved in 5mL dichloromethane, obtains second
Reaction solution；
S04, the second reaction solution slowly instills the first reaction solution, 25 DEG C are stirred overnight；
Dichloromethane in S05, the product of vacuum drying removing step S04, obtains yellow solid；
S06, with dichloromethane dissolving step S05 gained yellow solid, while add 200-300 mesh silica gel stirring, rotation
Loading after dichloromethane is evaporated off, plus mobile phase carries out column chromatography, the mobile phase is by 1:1 volume ratio prepare petroleum ether and
Dichloromethane mixed liquor；Obtain compound 3 (the positive 12 aminocarbonyl azobenzene of 4- methyl -4 ') 1.12g after purification；
S07, by the positive 12 aminocarbonyl azobenzene of 0.5g 4- methyl -4 ', 0.34g N-bromosuccinimides and 15mg mistakes
BP is dissolved in tetrachloromethane, heating reflux reaction 48 hours under argon atmosphere；
S08, step S07 products are cooled to 0 DEG C, suction filtration obtains yellow powder；
S09, yellow powder is washed with ether, remove unreacted impurity, obtain (the 4- bromomethyls -4 '-positive 12 of compound 4
Aminocarbonyl azobenzene)；
S10,250mg 4- bromomethyls -4 '-positive 12 aminocarbonyl azobenzene is dissolved in 6mL ethanol, is subsequently adding the fourths of 1mL tri-
Amine and 2mL ethanol, back flow reaction 24 hours；
S11, the product of step S10 is evaporated, then 5 are pressed with 20mL:Ether and dichloromethane mixed liquor that 1 volume ratio is prepared
Dissolving, is collected by filtration crocus solids of sedimentation；
S12, with 20mL press 5:Ether and dichloromethane mixed liquor washing crocus solids of sedimentation three that 1 volume ratio is prepared
It is secondary, obtain the azobenzene derivatives containing quaternary ammonium salt group shown in 120mg Fig. 4, i.e. 4- (N, N, N- tri-n-butylamine MB) -4 ' -
Positive 12 aminocarbonyl azobenzene.
It is of the invention in order to further prove the response characteristics to light of the azobenzene derivatives containing quaternary ammonium salt group of the invention
Inventor devises tests below, with chloroform or ethanol as solvent, by the azobenzene derivatives configuration containing quaternary ammonium salt group
Into about 1 μm of solution of ol/L, and its ultraviolet-visible absorption spectroscopy is determined, then with the time that ultraviolet light is different, survey each
The absorption spectrum at time point, then by the different ultraviolet light time, makees the curve of absorbance and wavelength respectively.Wherein, with
The result of the 3rd specific embodiment azobenzene derivatives of the gained containing quaternary ammonium salt group is as shown in Figure 5.As shown in figure 5, with purple
The extension of outside line irradiation time, absorbance of the azobenzene derivatives at 350nm is constantly reduced, and illustrates the azo benzenesulfonamide derivative
Thing can occur quick Trans-cis isomery, can be used as a kind of light-operated switch.
It should be noted that other azobenzene derivatives containing quaternary ammonium salt group of the invention, such as above-mentioned first is specific
Embodiment, the second specific azobenzene derivatives containing quaternary ammonium salt group for preparing gained in embodiment are prepared, in above-mentioned experiment
Result (not shown) similar with Fig. 5, illustrate that the azobenzene derivatives containing quaternary ammonium salt group of the invention can occur quickly
Trans-cis isomery, can be used as a kind of light-operated switch.
Based on the above-mentioned azobenzene derivatives containing quaternary ammonium salt group, the present inventor is also further with ultrasonic disperse
Method is prepared for photoresponse liposome, method approximately as：
By phosphatide, cholesterol, any of the above-described kind of azobenzene derivatives containing quaternary ammonium salt group according to 1:1:1 mol ratio
(each 0.02mmol) is dissolved in by 2 together:After the 20mL chloroforms and methyl alcohol mixed liquor of 1 volume ratio configuration, fully dissolving, in 37 DEG C of perseverances
Organic solvent is removed with rotary evaporator under tepidarium, round-bottomed flask bottom forms one layer of uniform lipid film.It is subsequently adding 10mL,
The citric acid solution (pH=7.4) of 300mM, lipid film aquation is got off, then with probe type ultrasonic cell crushing instrument ultrasound
30min (power 100mW, on 30s, off 30s), is subsequently placed in 37 DEG C of water-baths and places 2 hours to complete closed process.Institute
Photoresponse Liposomal suspensions must be.
Above-mentioned phosphatide is phosphatid ylcholine, phosphatidyl-ethanolamine, phosphatidic acid, phosphatidylserine, phosphatidyl glycerol, phosphatide
Acyl inositol or their compositions.
Then adriamycin (DOX) is encapsulated with pH gradient method：2mg DOX are weighed, is added in Liposomal suspensions, it is fully molten
Solution, pH to 7.4 is adjusted with 1.0M NaOH.The 000g of liposome solutions 10 is centrifuged 10min, is fallen down on probe in removing ultrasonic procedure
The titanium particle and undispersed lipid for coming, supernatant liquid are the photoresponse liposome of interior bag adriamycin.
In order to verify the light-operated releasing effect of the photoresponse liposome of bag adriamycin in gained, the present inventor's design
Another checking test.
Experimental group：The photoresponse liposome 5mL of interior bag adriamycin prepared by the above method is dispersed in 45mL pH=7.4
PBS in, then the solution of gained is placed in dark surrounds, ultraviolet light 10min, every 2 are used per hour
Hour determines the doxorubicin content being released in a PBS.
Control group, the photoresponse liposome 5mL of interior bag adriamycin prepared by the above method is dispersed in 45mL pH=7.4
PBS in, then the solution of gained is placed in dark surrounds, same every 2 hours determine a PBS
In the doxorubicin content that is released.
Experimental group, control group respectively do 3 repetitions.
With the total adriamycin in the doxorubicin content being released in each time point PBS and the PBS
The ratio of amount is ordinate, and the time is abscissa, makees curve, as a result as shown in Figure 6.
As shown in fig. 6, explanation, under ultraviolet illumination, the phospholipid bilayer of the photoresponse liposome of interior bag adriamycin
In azobenzene derivatives there is Trans-cis isomery, disturbance is caused to immobilized artificial membrane, and formed in phospholipid bilayer logical
Road, and then cause that adriamycin is released, accelerate the release of the adriamycin of the photoresponse liposome interior of interior bag adriamycin.
Therefore, the azobenzene derivatives containing quaternary ammonium salt group of the invention can photic stimuli responded, based on this hair
Liposome containing azobenzene derivatives prepared by the bright azobenzene derivatives containing quaternary ammonium salt group can be prepared into interior bag medicine
MNPs, has broad application prospects.
It should be noted that interior bag medicine of the present invention can be water soluble drug, for example：Gemcitabine hydrochloride, card
Platinum, cytarabine hydrochloride, mustine hydrochlcride, mitoxantrone hydrochloride；Or fat-soluble medicine, such as adriamycin, taxol etc..
The preferred embodiments of the present invention are these are only, the scope of the claims of the invention is not thereby limited, it is every to utilize this hair
Equivalent structure or equivalent flow conversion that bright specification and accompanying drawing content are made, or directly or indirectly it is used in other related skills
Art field, is included within the scope of the present invention.
Claims (9)
1. a kind of azobenzene derivatives containing quaternary ammonium salt group, it is characterised in that the azo benzenesulfonamide derivative containing quaternary ammonium salt group
The structural formula of thing is as follows：
Wherein, R1It is the straight chained alkyl of C1~6；R2It is the straight chain hydrophobic alkyl of C12~16；X is COO or CONH.
2. a kind of preparation method of the azobenzene derivatives containing quaternary ammonium salt group as claimed in claim 1, it is characterised in that institute
The preparation method for stating the azobenzene derivatives containing quaternary ammonium salt group is comprised the following steps：
A, compound 1 and compound 2 are reacted, obtain compound 3；
B, compound 3 and N-bromosuccinimide are dissolved in tetrachloromethane and in benzoyl peroxide under atmosphere of inert gases
Catalysis under there is bromination reaction, obtain compound 4；
C, make the substrate reactions of compound 4 and first, obtain the azobenzene derivatives containing quaternary ammonium salt group；
The structural formula of the compound 1 is as follows：
The structural formula of the compound 2 is as follows：
X2-R2；
The structural formula of the compound 3 is as follows：
The structural formula of the compound 4 is as follows：
The X1It is COOH or COCl；
The X2It is OH or NH2；
The structural formula of first substrate is：
3. the preparation method of the azobenzene derivatives containing quaternary ammonium salt group according to claim 2, it is characterised in that described
X1It is COCl；The X2It is NH2；The step A is comprised the following steps：
A1, compound 1 is dissolved in dichloromethane, is subsequently adding triethylamine, obtain the first reaction solution；
A2, compound 2 is dissolved in dichloromethane, obtains the second reaction solution；
A3, by the second reaction solution instill the first reaction solution in, stirring at normal temperature is overnight；
Dichloromethane in A4, the product of removing step A3, obtains solid；
A5, solid is dissolved in dichloromethane, and is isolated and purified by column chromatography, the mobile phase is by 1:1 volume ratio is matched somebody with somebody
The petroleum ether and dichloromethane mixed liquor of system, obtain compound 3.
4. the preparation method of the azobenzene derivatives containing quaternary ammonium salt group according to claim 3, it is characterised in that described
Step A is further comprising the steps of：
A0, compound 5 is added into thionyl chloride, is heated to 60-70 DEG C, be stirred overnight, and then remove unreacted thionyl chloride,
Obtain compound 2；
The structural formula of the compound 5 is as follows：
Wherein, 10≤n≤14.
5. the preparation method of the azobenzene derivatives containing quaternary ammonium salt group according to claim 2, it is characterised in that described
Step B is comprised the following steps：
B1, compound 3, N-bromosuccinimide and benzoyl peroxide are dissolved in tetrachloromethane under argon atmosphere, heated
Back flow reaction 12-72 hours；
B2, reaction system is cooled to 0 DEG C, suction filtration obtains powder；
B3, ether washing powder is used, obtain compound 4.
6. the preparation method of the azobenzene derivatives containing quaternary ammonium salt group according to claim 2, it is characterised in that described
Step C is comprised the following steps：
C1, compound 4 is dissolved in ethanol, adds the first substrate, back flow reaction 6-48 hours；
C2, the product of step C1 is evaporated, then with by 5:Ether and the dissolving of dichloromethane mixed liquor that 1 volume ratio is prepared, filtering
Collect solids of sedimentation.
7. the preparation method of the azobenzene derivatives containing quaternary ammonium salt group according to claim 6, it is characterised in that described
Step C is further comprising the steps of：
C3, with by 5:Ether and dichloromethane mixed liquor washing solids of sedimentation that 1 volume ratio is prepared, obtain described containing quaternary ammonium salt group
Azobenzene derivatives.
8. a kind of azobenzene derivatives containing quaternary ammonium salt group as claimed in claim 1 are preparing the photoresponse fat of interior bag medicine
Application in plastid.
9. the azobenzene derivatives containing quaternary ammonium salt group according to claim 8 are preparing the photoresponse lipid of interior bag medicine
Application in body, it is characterised in that the medicine is adriamycin.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107335383A (en) * | 2017-06-29 | 2017-11-10 | 宁德师范学院 | Soluble cation Gemini surfactant of the coupling link containing azobenzene and its preparation method and application |
| CN108484435A (en) * | 2018-04-10 | 2018-09-04 | 杨仲辉 | Modified azobenzene derivative for dyeing and finishing fabric and preparation method thereof |
| CN113321596A (en) * | 2021-06-08 | 2021-08-31 | 四川大学华西医院 | Photochromic controllable permeable small-molecule cross-linked vesicle and preparation method and application thereof |
| CN118146115A (en) * | 2024-02-21 | 2024-06-07 | 中科帅天医药(深圳)有限公司 | Azo compound, azo prodrug compound, pharmaceutical composition, high-energy-ray-responsive lipid molecule, and high-energy-ray-responsive liposome |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101117447A (en) * | 2007-03-21 | 2008-02-06 | 成都理工大学 | Method for preparing yellow cationic azobenzene dye |
| JP5137250B2 (en) * | 2007-11-29 | 2013-02-06 | 学校法人東京理科大学 | Gemini type fluorosurfactant having azobenzene skeleton as spacer and method for producing the same |
| CN106187813A (en) * | 2016-07-20 | 2016-12-07 | 江南大学 | A kind of environment-friendly preparation method thereof of the photosensitive foam controller of diphenyl diimide quaternary ammonium salt |
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2017
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- 2017-12-29 WO PCT/CN2017/120156 patent/WO2018127015A1/en active Application Filing
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107335383A (en) * | 2017-06-29 | 2017-11-10 | 宁德师范学院 | Soluble cation Gemini surfactant of the coupling link containing azobenzene and its preparation method and application |
| CN108484435A (en) * | 2018-04-10 | 2018-09-04 | 杨仲辉 | Modified azobenzene derivative for dyeing and finishing fabric and preparation method thereof |
| CN108484435B (en) * | 2018-04-10 | 2020-10-16 | 新昌县勤勉生物医药科技有限公司 | Modified azobenzene derivative for dyeing and finishing fabric and preparation method thereof |
| CN113321596A (en) * | 2021-06-08 | 2021-08-31 | 四川大学华西医院 | Photochromic controllable permeable small-molecule cross-linked vesicle and preparation method and application thereof |
| CN113321596B (en) * | 2021-06-08 | 2022-04-15 | 四川大学华西医院 | Photochromic controllable permeable small-molecule cross-linked vesicle and preparation method and application thereof |
| CN118146115A (en) * | 2024-02-21 | 2024-06-07 | 中科帅天医药(深圳)有限公司 | Azo compound, azo prodrug compound, pharmaceutical composition, high-energy-ray-responsive lipid molecule, and high-energy-ray-responsive liposome |
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| WO2018127015A1 (en) | 2018-07-12 |
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