CN106800521A - Azobenzene derivatives and its preparation method and application - Google Patents
Azobenzene derivatives and its preparation method and application Download PDFInfo
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- CN106800521A CN106800521A CN201611268082.3A CN201611268082A CN106800521A CN 106800521 A CN106800521 A CN 106800521A CN 201611268082 A CN201611268082 A CN 201611268082A CN 106800521 A CN106800521 A CN 106800521A
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- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
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- C07C245/02—Azo compounds, i.e. compounds having the free valencies of —N=N— groups attached to different atoms, e.g. diazohydroxides
- C07C245/06—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
- 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 and its preparation method and application.Azobenzene derivatives of the invention are connected to hydrophilic cationic quaternary ammonium salt group and long-chain hydrophobic alkyl at the two ends of azobenzene, reversible conformational change can occur under ultraviolet light, the MNPs that photic stimuli is responded can be prepared based on azobenzene derivatives of the invention, if will be wrapped in medicine in above-mentioned MNPs, the controlled release of internal drug can then be realized, mitigate side effects of pharmaceutical drugs, improve therapeutic effect.The preparation method of azobenzene derivatives 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 and preparation method thereof and should
With.
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 and its preparation method and application, based on the azo
Benzene derivative, can prepare the MNPs that photic stimuli is responded.
To achieve the above object, the invention provides a kind of azobenzene derivatives, 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：O or NH.
Wherein, the structural formula of the azobenzene derivatives is as follows：
To achieve these goals, present invention also offers a kind of preparation method of azobenzene derivatives, the azobenzene
The structural formula of derivative 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：O or NH；
The preparation method of the azobenzene derivatives 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
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；
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 OH or NH2；
The X2It is and X1Reaction forms the COOH or COCl of X；
The structural formula of first substrate is：
Wherein, the X1It is NH2；The X2It is COCl；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, dodecanoic acid is added into thionyl chloride, be heated to 60-70 DEG C, be stirred overnight, and then remove unreacted chlorine
Change sulfoxide, obtain compound 2.
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 the azobenzene and spread out
It is biological.
In order to realize the purpose of the present invention, present invention also offers a kind of azobenzene derivatives of the present invention in preparing
Application in the photoresponse liposome of bag medicine.
Wherein, the medicine is adriamycin.
Azobenzene derivatives of the invention the two ends of azobenzene be connected to hydrophilic cationic quaternary ammonium salt group and
Long-chain hydrophobic alkyl, can occur reversible conformational change under ultraviolet light, be spread out based on azobenzene of the invention
Biology can prepare can the MNPs that is responded of photic stimuli, if will be wrapped in medicine in above-mentioned MNPs, can realize
The controlled release of internal drug, mitigates side effects of pharmaceutical drugs, improves therapeutic effect.The preparation side of azobenzene derivatives of the invention
Method is simple, yield is high.
Brief description of the drawings
Fig. 1 is that the present invention first is specific prepares the structural formula that embodiment prepares gained azobenzene derivatives.
Fig. 2 is that the present invention second is specific prepares the structural formula that embodiment prepares gained azobenzene derivatives.
Fig. 3 is that the present invention the 3rd is specific prepares the structural formula that embodiment prepares gained azobenzene derivatives.
Fig. 4 is that the specific embodiment for preparing of the present invention the 3rd prepares purple of the gained azobenzene derivatives after through ultraviolet light
Outward-visible absorption spectra variation diagram.
Fig. 5 is to prepare interior bag adriamycin prepared by gained azobenzene derivatives based on the specific embodiment for preparing of the present invention the 3rd
Photoresponse liposome light-operated release profiles.
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, structural formula is illustrated in fig. 1 shown below：
Wherein, R1It is the straight chained alkyl of C1~6；R2It is the straight chain hydrophobic alkyl of C12~16；X is：O or NH.
The straight chain hydrophobic alkyl chain of one end of azobenzene derivatives of the invention is inserted into double points of the phosphatide of liposome
In sublayer, the hydrophilic cationic quaternary ammonium salt group of the other end then can towards the aqueous solution outside phospholipid bilayer tunic, so as to
The arrangement of regularity is formed in liposome.Azobenzene derivatives of the invention can occur reversible conformation under ultraviolet light
Change, in non-irradiated with ultraviolet radiation, keep anti-configuration, after being irradiated through ultraviolet, be transformed into cis-configuration.
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 above-mentioned azobenzene derivatives 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
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；
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 OH or NH2；
The X2It is and X1Reaction forms the COOH or COCl of X；
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 NH2；The X2It is COCl；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 compound 12With the COCl in compound 2
Reaction, so as to generate compound 3, this method with by the OH or NH in compound2Generation is reacted with the COOH in compound 2
The method of 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, dodecanoic acid is added into thionyl chloride, be heated to 60-70 DEG C, be stirred overnight, and then remove unreacted chlorine
Change sulfoxide, obtain compound 2.
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 azobenzene derivatives 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 the azobenzene and spread out
It is biological.
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 is as shown in figure 1, the idol
The preparation method of pyridine derivative is comprised the following steps：
S01, make compound 1 (hydroxyazobenzene of 4- methyl -4 ') and compound 2 (n-teradecanoic acid) in the catalysis of the concentrated sulfuric acid
With there is esterification reaction under heating condition, generation compound 3 (the n-teradecanoic acid azo phenyl ester of 4- methyl -4 ')；
S02, by the n-teradecanoic acid azo phenyl ester of 4- methyl -4 ', N-bromosuccinimide and benzoyl peroxide in argon
Atmosphere is dissolved in tetrachloromethane, heating reflux reaction 24 hours under enclosing；
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-teradecanoic acid azo phenyl ester)；
S05, the n-teradecanoic acid azo phenyl ester of 4- bromomethyls -4 ' is dissolved in ethanol, is subsequently adding triethylamine, back flow reaction 12
Hour；
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 azobenzene derivatives shown in Fig. 1, i.e. 4- (N, N, N- triethylamine MB) -4 '-n-teradecanoic acid idol
Pyridine ester.
In the of the invention second specific preparation embodiment, the structural formula of the azobenzene derivatives is as shown in Fig. 2 the idol
The preparation method of pyridine derivative is comprised the following steps：
S01, make compound 1 (hydroxyazobenzene of 4- methyl -4 ') and compound 2 (Palmiticacid) in the catalysis of the concentrated sulfuric acid
And there is esterification reaction, generation compound 3 (4- methyl -4 '-Palmiticacid azos phenyl ester) under heating condition；
S02, by 4- methyl -4 '-Palmiticacid azos phenyl ester, N-bromosuccinimide and benzoyl peroxide in argon
Atmosphere is dissolved in tetrachloromethane, heating reflux reaction 48 hours under enclosing；
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 ' -
Palmiticacid azo phenyl ester)；
S05,4- bromomethyl -4 '-Palmiticacid azo phenyl esters are dissolved in ethanol, are subsequently adding trimethylamine, back flow reaction
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. 2
Azobenzene derivatives, i.e. 4- (N, N, N- trimethylamine MB) -4 '-Palmiticacid azo phenyl ester.
In the of the invention 3rd specific preparation embodiment, the structural formula of the azobenzene derivatives is as shown in figure 3, the idol
The preparation method of pyridine derivative is comprised the following steps：
S01, by 2g dodecanoic acids add 10mL thionyl chlorides in, 65 DEG C are stirred overnight, and rotate away unreacted and obtain chlorine
Change sulfoxide, obtain 2g colorless oil crude products, i.e. compound 2 (positive lauroyl chloride)；
S02,0.62g compounds 1 (aminoazabenzol of 4- methyl -4 ') are dissolved in 20mL dichloromethane, are subsequently adding 0.59g
Triethylamine, obtains the first reaction solution；
S03,0.97g colorless oils crude product (positive lauroyl chloride) is dissolved in 5mL dichloromethane, obtains the 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 lauroyl aminoazabenzol of 4- methyl -4 ') 1.12g after purification；
S07, by the positive lauroyl aminoazabenzol 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
Acylamino- azobenzene)；
S10,250mg 4- bromomethyls -4 '-positive lauroyl aminoazabenzol 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 azobenzene derivatives shown in 120mg Fig. 3, i.e. 4- (N, N, N- tri-n-butylamine MB) -4 '-positive lauroyl amino idol
Pyridine.
In order to further prove the response characteristics to light of azobenzene derivatives of the invention, the present inventor devise with
The azobenzene derivatives, with chloroform or ethanol as solvent, are configured to about 1 μm of solution of ol/L by lower experiment, and it is purple to determine it
Outer visible absorption spectra, then with the time that ultraviolet light is different, surveys the absorption spectrum of Each point in time, then by different
The ultraviolet light time, the curve of absorbance and wavelength is made respectively.Wherein, with the 3rd specific embodiment gained azobenzene derivatives
Result it is as shown in Figure 4.As shown in figure 4, with the extension of ultraviolet irradiation time, the azobenzene derivatives are at 350nm
Absorbance is constantly reduced, and illustrates that the azobenzene derivatives can occur quick Trans-cis isomery, can be light-operated as one kind
Switch.
It should be noted that other azobenzene derivatives of the invention, such as the above-mentioned first specific preparation embodiment, second
The specific azobenzene derivatives for preparing gained in embodiment, the result (not shown) similar with Fig. 4 in above-mentioned experiment illustrates this
The azobenzene derivatives of invention can occur quick Trans-cis isomery, can be used as a kind of light-operated switch.
Based on above-mentioned azobenzene derivatives, the present inventor is also prepared for photoresponse further with ultrasonic dispersion
Liposome, method approximately as：
By phosphatide, cholesterol, any of the above-described kind of azobenzene derivatives according to 1:1:1 mol ratio (each 0.02mmol) is together
It is dissolved in by 2:After the 20mL chloroforms and methyl alcohol mixed liquor of 1 volume ratio configuration, fully dissolving, steamed with rotation under 37 DEG C of waters bath with thermostatic control
Hair device removes organic solvent, and round-bottomed flask bottom forms one layer of uniform lipid film.It is subsequently adding 10mL, the citric acid solution of 300mM
(pH=7.4), lipid film aquation is got off, then with probe type ultrasonic cell crushing instrument ultrasound 30min (power 100mW, on
30s, off 30s), it is subsequently placed in 37 DEG C of water-baths and places 2 hours to complete closed process.Gained is photoresponse liposome and hangs
Liquid.
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 45mLpH=7.4's
In PBS, then the solution of gained is placed in dark surrounds, ultraviolet light 10min is used per hour, every 2 small
When determine the doxorubicin content that is released in a PBS.
Control group：The photoresponse liposome 5mL of interior bag adriamycin prepared by the above method is dispersed in 45mLpH=7.4's
In PBS, then the solution of gained is placed in dark surrounds, same every 2 hours are determined in a PBS
The doxorubicin content being 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 5.
As shown in figure 5, under ultraviolet illumination, the idol in the phospholipid bilayer of the photoresponse liposome of interior bag adriamycin
There is Trans-cis isomery in azobenzene compounds, disturbance is caused to immobilized artificial membrane, and passage is formed in phospholipid bilayer, and then
So that adriamycin is released, accelerate the release of the adriamycin of the photoresponse liposome interior of interior bag adriamycin.
Therefore, azobenzene compound of the invention can photic stimuli responded, based on azobenzene chemical combination of the invention
Liposome containing azobenzene derivatives prepared by thing can be prepared into the MNPs of interior bag medicine, have 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 (10)
1. a kind of azobenzene derivatives, it is characterised in that the structural formula of the azobenzene derivatives 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：O or NH.
2. azobenzene derivatives according to claim 1, it is characterised in that the structural formula of the azobenzene derivatives is such as
Under：
3. a kind of preparation method of azobenzene derivatives, it is characterised in that the structural formula of the azobenzene derivatives 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：O or NH；
The preparation method of the azobenzene derivatives 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；
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 OH or NH2；
The X2It is and X1Reaction forms the COOH or COCl of X；
The structural formula of first substrate is：
4. the preparation method of azobenzene derivatives according to claim 3, it is characterised in that the X1It is NH2；The X2
It is COCl；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.
5. the preparation method of azobenzene derivatives according to claim 4, it is characterised in that the step A also include with
Lower step：
A0, dodecanoic acid is added into thionyl chloride, be heated to 60-70 DEG C, be stirred overnight, and then remove unreacted protochloride
Sulfone, obtains compound 2.
6. the preparation method of azobenzene derivatives according to claim 3, it is characterised in that the step B includes following
Step：
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.
7. the preparation method of azobenzene derivatives according to claim 3, it is characterised in that the step C includes following
Step：
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.
8. the preparation method of azobenzene derivatives according to claim 7, it is characterised in that the step C also include with
Lower step：
C3, with by 5:Ether and dichloromethane mixed liquor washing solids of sedimentation that 1 volume ratio is prepared, obtain the azo benzenesulfonamide derivative
Thing.
9. application of a kind of azobenzene derivatives as claimed in claim 1 in preparing in the photoresponse liposome of bag medicine.
10. application of the azobenzene derivatives according to claim 9 in preparing in the photoresponse liposome of bag medicine, its
It is characterised by, the medicine is adriamycin.
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| CN201611268082.3A CN106800521A (en) | 2016-12-31 | 2016-12-31 | Azobenzene derivatives and its preparation method and application |
| PCT/CN2017/088353 WO2018120670A1 (en) | 2016-12-31 | 2017-06-15 | Azobenzene derivative and preparation method therefor and use thereof |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018120670A1 (en) * | 2016-12-31 | 2018-07-05 | 深圳市易特科信息技术有限公司 | Azobenzene derivative and preparation method therefor and use thereof |
| WO2018120671A1 (en) * | 2016-12-31 | 2018-07-05 | 深圳市易特科信息技术有限公司 | Liposome containing azobenzene derivative and preparation method therefor and use thereof |
| CN108484435A (en) * | 2018-04-10 | 2018-09-04 | 杨仲辉 | Modified azobenzene derivative for dyeing and finishing fabric and preparation method thereof |
| CN109490149A (en) * | 2018-11-08 | 2019-03-19 | 厦门大学 | One metal ion species in-situ check and test method |
| 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 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106692058A (en) * | 2016-12-31 | 2017-05-24 | 深圳市易特科信息技术有限公司 | Azobenzene derivative containing lipidosome as well as preparation method and application thereof |
| CN106800521A (en) * | 2016-12-31 | 2017-06-06 | 深圳市易特科信息技术有限公司 | Azobenzene derivatives and its preparation method and application |
-
2016
- 2016-12-31 CN CN201611268082.3A patent/CN106800521A/en active Pending
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2017
- 2017-06-15 WO PCT/CN2017/088353 patent/WO2018120670A1/en active Application Filing
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018120670A1 (en) * | 2016-12-31 | 2018-07-05 | 深圳市易特科信息技术有限公司 | Azobenzene derivative and preparation method therefor and use thereof |
| WO2018120671A1 (en) * | 2016-12-31 | 2018-07-05 | 深圳市易特科信息技术有限公司 | Liposome containing azobenzene derivative and preparation method therefor and use thereof |
| 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 |
| CN109490149A (en) * | 2018-11-08 | 2019-03-19 | 厦门大学 | One metal ion species in-situ check and test method |
| 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 |
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| Publication number | Publication date |
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| WO2018120670A1 (en) | 2018-07-05 |
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