CN106832324A - The preparation method of the cucurbit urea polymers with various topological structures - Google Patents
The preparation method of the cucurbit urea polymers with various topological structures Download PDFInfo
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Abstract
The present invention relates to the preparation method of the cucurbit urea polymers with various topological structures, monohydroxy Cucurbituril and double hydroxy-cucurbiturils are obtained by persulfate oxidation Cucurbituril, further reaction obtains single alkynyl Cucurbituril and double alkynyl Cucurbiturils in the presence of highly basic sodium hydride, and the cucurbit urea polymers with various topological structures are prepared by the azide-functionalized polymer of click-reaction and different structure.The polymer prepared by the method for the present invention, compound with regular structure, property is enriched, and controllability is high, in combination with advantage of the Cucurbituril in terms of self assembly, had a good application prospect in multiple fields such as basic research, drug delivery, cell loading, functional material design and biochemical analysises.
Description
Technical field
Birdsed of the same feather flock together the present invention relates to one the preparation method of compound, and in particular to a class contains the system of the polymer of cucurbit urea structure
Preparation Method, the more particularly to preparation method of Cucurbituril terminated polymer, the preparation method of Cucurbituril star-type polymer and cucurbit
The preparation method of urea trunk polymer, belongs to technical field of organic synthesis.
Background technology
Cucurbituril is the macrocyclic host molecule that a class is made up of methylene-bridged glycoluril unit, and foundation constitutes the sweet of its big ring
Urea unit quantity, its family includes cucurbit [5] urea, cucurbit [6] urea, cucurbit [7] urea, cucurbit [8] urea and cucurbit [10] urea etc.
Serial member.Used as a human subject molecule, it shows good structure selectivity and splendid with corresponding guest molecule
Bond strength.In addition, Cucurbituril steady chemical structure, bio-toxicity is low, and biocompatibility is good.Literature research shows Cucurbituril
The numerous areas such as construct in medicament transport controlled release, analysis detection, concentration and separation, new function material all to be dived by huge application
Power.However, the dissolubility of Cucurbituril extreme difference with its further application is hindered the characteristics of being difficult to functionalization.
It is not only to provide to overcome the shortcoming of Cucurbituril, performance Cucurbituril advantage to carry to construct the polymer containing cucurbit urea structure
A kind of feasible method is supplied, and can further expand the application mode and scope of Cucurbituril.For example:Document
Biomaterials, 2011,32,7687-7694 report the method that Cucurbituril is grafted hyaluronic acid, document
J.Polym.Sci.,Part A:Polym.Chem., 2015,53,1748-1752 and Chinese patent document CN104086691A is public
A kind of preparation method of the polymer containing cucurbit urea structure is opened, Chinese patent document CN103183743A discloses a kind of calabash
The preparation method of reed urea [6] (CB [6]) grafted chitosan.Additionally, document ACS Nano, 2012,6,2960-2968 and
Scientific Reports,2016,DOI:10.1038/srep20722 etc. is reported using the polymerization containing cucurbit urea structure
The method that thing further constructs supramolecular hydrogel.
However, the polymer with cucurbit urea structure reported for work both at home and abroad at present is only limitted to side chain polymer and branched polymeric
Two kinds of topological structures of thing.It is therefore desirable to the method that a class can effectively prepare the cucurbit urea polymers of various topological structures is found,
It is significant.
The content of the invention
In view of the shortcomings of the prior art, the present invention provides one kind and can effectively prepare various topological structure cucurbit urea polymers
Method, including the preparation method of Cucurbituril terminated polymer, the preparation method of Cucurbituril star-type polymer and Cucurbituril master
The preparation method of chain polymerization thing.
The Cucurbituril terminated polymer such as formula (VII) of present invention offer, formula (Ⅸ) are shown, Cucurbituril star-type polymer such as formula
(Ⅺ) shown in, shown in Cucurbituril trunk polymer such as formula (Ⅻ).
Technical scheme is as follows:
A kind of preparation method of the cucurbit urea polymers with various topological structures, including step is as follows:
(1) by Cucurbituril hydroxylating shown in formula (I), obtain containing monohydroxy Cucurbituril shown in formula (II), shown in formula (III)
The mixture of double hydroxy-cucurbiturils and other polyhydroxy Cucurbiturils;
(2) will containing monohydroxy Cucurbituril shown in formula (II), shown in formula (III) double hydroxy-cucurbiturils and other polyhydroxy calabashes
The mixture of reed urea is isolated and purified, and obtains double hydroxy-cucurbiturils shown in monohydroxy Cucurbituril shown in formula (II) and formula (III);
(3) by monohydroxy Cucurbituril shown in formula (II) under sodium hydride effect, with propargyl bromide reaction, obtain shown in formula (IV)
Single alkynyl Cucurbituril;
(4) by double hydroxy-cucurbiturils shown in formula (III) under sodium hydride effect, with propargyl bromide reaction, obtain shown in formula (V)
Double alkynyl Cucurbiturils;
(5) by single alkynyl Cucurbituril shown in formula (IV) and single azide-functionalized polymer reaction shown in formula (VI), obtain final product
Single Cucurbituril terminated polymer shown in formula (VII);Or,
(6) by single alkynyl Cucurbituril shown in formula (IV) and double azide-functionalized polymer reactions shown in formula (VIII), obtain final product
Double Cucurbituril terminated polymers shown in formula (Ⅸ);Or,
(7) by single alkynyl Cucurbituril shown in formula (IV) and star-type polymer reaction azide-functionalized shown in formula (Ⅹ), i.e.,
Obtain Cucurbituril star-type polymer shown in formula (Ⅺ);Or,
(8) by double alkynyl Cucurbiturils shown in formula (V) and double azide-functionalized polymer reactions shown in formula (VIII), obtain final product
Cucurbituril trunk polymer shown in formula (Ⅻ);
The synthesis of Cucurbituril terminated polymer:
The synthesis of Cucurbituril star-type polymer:
The synthesis of Cucurbituril trunk polymer:
In the present invention, Cucurbituril chemical constitution shown in formula (I) is as follows:
, according to the invention it is preferred to, the hydroxylated process of Cucurbituril is as follows in step (1):
Cucurbituril is distributed in water, 3,3 '-(1,8- bis- octamethylene)-bis--(1- ethyl imidazol(e)s) dibromo salt is added, is formed
Homogeneous phase solution;Resulting solution addition persulfate carries out oxidation reaction, obtains containing formula (II), formula (III) and other polyhydroxy calabashes
The mixture of reed urea;
Preferably, Cucurbituril, 3,3 '-(1,8- bis- octamethylene)-bis--(1- ethyl imidazol(e)s) dibromo salt, the matter of persulfate
Amount is than being (0.1-2):(0.05–1):(0.05–1);The ratio between the quality of Cucurbituril and the volume of water are (0.1-2):(10–100)
g/mL。
, according to the invention it is preferred to, isolate and purify process in step (2) is carried out in the chromatography column;Preferably, in chromatographic column
Filler be macroreticular resin;Further preferred mitsubishi chemical industry CHP macroreticular resins.
, according to the invention it is preferred to, in step (3), the mass ratio of monohydroxy Cucurbituril, sodium hydride and propargyl bromide is
(0.05–0.5):(0.05–0.2):(0.05–1);In step (4), the mass ratio of double hydroxy-cucurbiturils, sodium hydride and propargyl bromide
It is (0.05-0.5):(0.05–0.2):(0.05–1);
Preferably, step (3) and step (4) reaction is carried out in highly polar aprotic solvent, further preferably
, described highly polar aprotic solvent is dimethyl sulfoxide (DMSO) or N, N '-dimethyl formamide;
Preferably, the product of step (3) and step (4) is by other solvent depositions, the washing dissolved each other with reaction dissolvent
Purifying is obtained;Further preferably precipitated with methyl alcohol or acetone, washed purifying.
, according to the invention it is preferred to, step (5), (6), single azide-functionalized polymer, formula shown in (7) Chinese style (VI)
(VIII) azide-functionalized star-type polymer is end group nitrine function shown in double azide-functionalized polymer shown in and formula (Ⅹ)
The polyethylene glycol of change;
It is further preferred that single azide-functionalized polymer is α-nitrine-ω-methyl polyethylene glycol shown in formula (VI)
2000th, α-nitrine-ω-methyl Macrogol 4000.
It is further preferred that double azide-functionalized polymer shown in formula (VIII) are α, ω-nitrine polyethylene glycol 2000, α,
ω-nitrine Macrogol 4000.
It is further preferred that star-type polymer azide-functionalized shown in formula (Ⅹ) is nitrine blocks four arm polyethylene glycol
10000。
, according to the invention it is preferred to, course of reaction is as follows in step (5):
Single alkynyl Cucurbituril shown in formula (IV) is distributed in water, potassium chloride is added, insoluble matter is filtered, clarification is obtained molten
Liquid;To single azide-functionalized polymer shown in formula (VI) is added in the solution, three [1- (3- hydroxypropyls) -1H-1,2,3- are added
Triazole-4-yl] methyl alcohol reacted with the complex of stannous chloride as catalyst, and after reaction terminates, potassium chloride is removed in dialysis
And catalyst, Solutions in Freeze-drying, obtain single Cucurbituril terminated polymer shown in formula (VII);
Preferably, single alkynyl Cucurbituril, the mass ratio of potassium chloride are (0.05g -0.2):(0.05–0.1);Single alkynyl cucurbit
The ratio between the quality of urea and the volume of water are (0.05g -0.2):(10–100)g/mL;
Single azide-functionalized polymer adds the 20%- that mole is single alkynyl Cucurbituril mole shown in formula (VI)
100%;
The addition mole of catalyst is the 2%-20% of single alkynyl Cucurbituril mole.
, according to the invention it is preferred to, course of reaction is as follows in step (6):
Single alkynyl Cucurbituril shown in formula (IV) is distributed in water, potassium chloride is added, insoluble matter is filtered, clarification is obtained molten
Liquid;To double azide-functionalized polymer shown in formula (VIII) are added in the solution, three [1- (3- hydroxypropyls) -1H-1,2,3- are added
Triazole-4-yl] methyl alcohol reacted with the complex of stannous chloride as catalyst;After reaction terminates, potassium chloride is removed in dialysis
And catalyst, Solutions in Freeze-drying, obtain the polymer of double Cucurbituril end-blockings shown in formula (Ⅸ);
Preferably, single alkynyl Cucurbituril, the mass ratio of potassium chloride are (0.05g -0.2):(0.05–0.1);Single alkynyl cucurbit
The ratio between the quality of urea and the volume of water are (0.05g -0.2):(10–100)g/mL;
Double azide-functionalized polymer add the 20%- that mole is single alkynyl Cucurbituril mole shown in formula (VIII)
100%;
The addition mole of catalyst is the 2%-20% of single alkynyl Cucurbituril mole.
, according to the invention it is preferred to, course of reaction is as follows in step (7):
Single alkynyl Cucurbituril shown in formula (IV) is distributed in water, potassium chloride is added, insoluble matter is filtered, clarification is obtained molten
Liquid;To star-type polymer azide-functionalized shown in formula (Ⅹ) is added in the solution, add three [1- (3- hydroxypropyls) -1H-1,2,
3- triazole-4-yls] methyl alcohol reacted with the complex of stannous chloride as catalyst;After reaction terminates, chlorination is removed in dialysis
Potassium and catalyst, Solutions in Freeze-drying obtain the Cucurbituril star-type polymer shown in formula (Ⅺ);
Preferably, single alkynyl Cucurbituril, the mass ratio of potassium chloride are (0.05g -0.2):(0.05–0.1);Single alkynyl cucurbit
The ratio between the quality of urea and the volume of water are (0.05g -0.2):(10–100)g/mL;
Star-type polymer azide-functionalized shown in formula (Ⅹ) adds the 5%- that mole is single alkynyl Cucurbituril mole
25%;
The addition mole of catalyst is the 2%-20% of single alkynyl Cucurbituril mole.
, according to the invention it is preferred to, course of reaction is as follows in step (8):
Double alkynyl Cucurbiturils shown in formula (V) are distributed in water, potassium chloride is added, insoluble matter is filtered, clarification is obtained molten
Liquid;To double azide-functionalized polymer shown in formula (VIII) are added in the solution, three [1- (3- hydroxypropyls) -1H-1,2,3- are added
Triazole-4-yl] methyl alcohol reacted with the complex of stannous chloride as catalyst;After reaction terminates, potassium chloride is removed in dialysis
And catalyst, Solutions in Freeze-drying, obtain the Cucurbituril trunk polymer shown in formula (Ⅻ);
Preferably, single alkynyl Cucurbituril, the mass ratio of potassium chloride are (0.05g -0.2):(0.05–0.1);Single alkynyl cucurbit
The ratio between the quality of urea and the volume of water are (0.05g -0.2):(10–100)g/mL;
Double azide-functionalized polymer add the 50%- that mole is double alkynyl Cucurbituril moles shown in formula (VIII)
150%;
The addition mole of catalyst is the 2%-20% of single alkynyl Cucurbituril mole.
, according to the invention it is preferred to, reacted at 20-70 DEG C described in step (5), step (6), step (7) and step (8)
Carry out.
According to the present invention, the preparation method of the cucurbit urea polymers with various topological structures, a kind of preferred embodiment party
Case is as follows:
(1) compound shown in formula (I) is that-the 2g of Cucurbituril 0.1 is dispersed in 10-100mL ultra-pure waters, adds 0.05-1g 3,
3 '-(1,8- bis- octamethylene)-bis--(1- ethyl imidazol(e)s) dibromo salt, forms homogeneous phase solution;Resulting solution adds 0.05-1g over cures
Hydrochlorate, carries out oxidation reaction, obtains the mixture containing formula (II), formula (III) and other polyhydroxy Cucurbiturils;
(2) said mixture obtains formula (II) and the list shown in formula (III) by loading the chromatogram post separation of macroreticular resin
Hydroxy-cucurbituril and double hydroxy-cucurbiturils;
(3)-the 0.5g of compound 0.05 shown in formula (II), under the effect of 0.05-0.2g sodium hydrides, with 0.05-1g propargyl bromides
Reaction, obtains the single alkynyl Cucurbituril shown in formula (IV);
(4)-the 0.5g of compound 0.05 shown in formula (III) is anti-with 0.1-1g propargyl bromides under the effect of 0.1-0.3g sodium hydrides
Should, obtain the double alkynyl Cucurbiturils shown in formula (IV);
(5) compound 0.05g-0.2g are distributed in water shown in formula (IV), add 0.05-0.1g potassium chloride, are filtered insoluble
Thing, obtains settled solution;To single azide-functionalized polymer shown in formula (VI) is added in the solution, single azide-functionalized gathers
The mole of compound is the 20-100% of compound shown in formula (IV);Add the 2- of single azide-functionalized polymer mole
Three [1- (3- the hydroxypropyls) -1H-1,2,3- triazole-4-yls] methyl alcohol of 20mol% are with the complex of stannous chloride as catalyst
Reacted;After reaction terminates, potassium chloride and catalyst are removed in dialysis, and Solutions in Freeze-drying obtains single Cucurbituril modification shown in formula (VII)
Polymer;
(6) compound 0.05g-0.2g are distributed in water shown in formula (IV), add 0.05-0.1g potassium chloride, are filtered insoluble
Thing, obtains settled solution;To double azide-functionalized polymer shown in formula (VIII) are added in the solution, double azide-functionalized gathers
The mole of compound is the 20-100% of compound shown in formula (IV);Add the mole 2- of double azide-functionalized polymer
Three [1- (3- the hydroxypropyls) -1H-1,2,3- triazole-4-yls] methyl alcohol of 20mol% are with the complex of stannous chloride as catalyst
Reacted;After reaction terminates, potassium chloride and catalyst are removed in dialysis, and Solutions in Freeze-drying obtains double Cucurbituril modifications shown in formula (Ⅸ)
Polymer.
(7) compound 0.05g-0.2g are distributed in water shown in formula (IV), add 0.05-0.1g potassium chloride, are filtered insoluble
Thing, obtains settled solution;To the azide-functionalized star of star-type polymer azide-functionalized shown in addition formula (Ⅹ) in the solution
The mole of type polymer is the 5-25% of compound shown in formula (IV);Add azide-functionalized star-type polymer mole 2-
Three [1- (3- the hydroxypropyls) -1H-1,2,3- triazole-4-yls] methyl alcohol of 20mol% are with the complex of stannous chloride as catalyst
Reacted;After reaction terminates, potassium chloride and catalyst are removed in dialysis, and Solutions in Freeze-drying obtains the Cucurbituril modification shown in formula (Ⅺ)
Star-type polymer;
(8) compound 0.05g-0.2g are distributed in water shown in formula (V), add 0.05-0.1g potassium chloride, are filtered insoluble
Thing, obtains settled solution;To double azide-functionalized polymer shown in formula (VIII) are added in the solution, double azide-functionalized gathers
The mole of compound is the 50-150% of compound shown in formula (V);Add double azide-functionalized polymer mole 2-
Three [1- (3- the hydroxypropyls) -1H-1,2,3- triazole-4-yls] methyl alcohol of 20mol% are with the complex of stannous chloride as catalyst
Reacted;After reaction terminates, potassium chloride and catalyst are removed in dialysis, and Solutions in Freeze-drying obtains the Cucurbituril main chain shown in formula (Ⅻ)
Polymer.
In the above-mentioned preparation method of the present invention, step (5), step (6), step (7) and step (8) use traditional catalysis
Agent, such as copper sulphate are catalyzed with sodium ascorbate, and effect is poor, and are more difficult to purification.
The preparation method that the present invention is provided has advantages below:
1st, preparation method, the preparation method of Cucurbituril star-type polymer and the calabash of Cucurbituril terminated polymer are realized first
The preparation of reed urea trunk polymer.
2nd, cucurbit urea polymers are prepared using click-reaction, mild condition, reaction efficiency is high, and side reaction is few.Product
High income, purifying is easy.High income reaches 70-95%.
3rd, the molecule of biocompatibility can be derived by the method, and then synthesizes compatible with good biological
The cucurbit urea polymers of property.
4th, the Cucurbituril polymer architecture by the method synthesis is highly regular controllable.
The 5th, Cucurbituril introducing polymer can be assigned the specific function of polymer Cucurbituril, such as molecular recognition;Simultaneously
The function and application scope of Cucurbituril can also be expanded further.
6th, relative to the polymer containing other host molecules, molecule of the polymer containing cucurbit urea structure in water phase
Recognition capability is stronger, and selectivity is more preferably.
By synthetic method of the present invention, can synthesize and prepare the cucurbit urea polymers of various different structures.Profit
With the excellent molecule distinguishability of Cucurbituril, such polymer can apply to basic research, drug delivery, cell loading, work(
Can the multiple fields such as design of material and biochemical analysis.
Brief description of the drawings
Fig. 1 is the nuclear magnetic resonance that the step of the embodiment of the present invention 1 (1) obtains monohydroxy Cucurbituril (by taking cucurbit [7] urea as an example)
Hydrogen spectrogram.
Fig. 2 is the mass spectrogram that the step of the embodiment of the present invention 1 (1) obtains monohydroxy Cucurbituril (by taking cucurbit [7] urea as an example)
(with the addition of 3,3 '-(octamethylenes of 1,8- bis-)-bis--(1- ethyl imidazol(e)s) dibromo salt as support guest molecule).
Fig. 3 is the proton nmr spectra of the embodiment of the present invention 1 step (1) double hydroxy-cucurbiturils (by taking cucurbit [7] urea as an example)
Figure.
Fig. 4 is the mass spectrogram that the step of the embodiment of the present invention 1 (1) obtains double hydroxy-cucurbiturils (by taking cucurbit [7] urea as an example)
(with the addition of 3,3 '-(octamethylenes of 1,8- bis-)-bis--(1- ethyl imidazol(e)s) dibromo salt as support guest molecule).
Fig. 5 is the nuclear magnetic resonance that the step of the embodiment of the present invention 1 (2) obtains single alkynyl Cucurbituril (by taking cucurbit [7] urea as an example)
Hydrogen spectrogram.
Fig. 6 is the mass spectrogram that the step of the embodiment of the present invention 1 (2) obtains single alkynyl Cucurbituril (by taking cucurbit [7] urea as an example)
(with the addition of 3,3 '-(octamethylenes of 1,8- bis-)-bis--(1- ethyl imidazol(e)s) dibromo salt as support guest molecule).
Fig. 7 is the hydrogen nuclear magnetic resonance spectrogram that the step of the embodiment of the present invention 1 (3) obtains Cucurbituril terminated polymer.
Fig. 8 is the nuclear magnetic resonance that the step of the embodiment of the present invention 5 (2) obtains double alkynyls Cucurbituril (by taking cucurbit [7] urea as an example)
Hydrogen spectrogram.
Fig. 9 is the mass spectrogram that the step of the embodiment of the present invention 5 (2) obtains double alkynyls Cucurbituril (by taking cucurbit [7] urea as an example)
(with the addition of 3,3 '-(octamethylenes of 1,8- bis-)-bis--(1- ethyl imidazol(e)s) dibromo salt as support guest molecule).
Figure 10 is the hydrogen nuclear magnetic resonance spectrogram that the step of the embodiment of the present invention 5 (3) obtains Cucurbituril trunk polymer.
Figure 11 is the hydrogen nuclear magnetic resonance spectrogram that the embodiment of the present invention 7 obtains Cucurbituril star-type polymer.
Specific embodiment
Experimental technique used in following embodiments is conventional method unless otherwise specified.
Material used, reagent etc. in following embodiments, unless otherwise specified, commercially obtain.
Sodium hydride and ammonium persulfate in the following embodiments of the present invention are purchased from Shanghai Chemical Reagent Co., Ltd., Sinopharm Group;
Propargyl bromide, α-nitrine-ω-methyl polyethylene glycol 2000, α-nitrine-ω-methyl Macrogol 4000, α, the poly- second two of ω-nitrine
Alcohol 2000, α, ω-nitrine Macrogol 4000 and nitrine block four arm PEG20000s purchased from the lark prestige limited public affairs of science and technology
Department;Macroreticular resin CHP2OP is purchased from Mitsubishi Chemical MCI;Methyl alcohol, dimethyl sulfoxide (DMSO) and N, N '-dimethyl formamide are rich purchased from Tianjin
Space chemical reagent Co., Ltd;3,3 '-(octamethylenes of 1,8- bis-)-bis--(1- ethyl imidazol(e)s) dibromo synthesizes according to document
(Chem.Commun.,2012,48,3070–3072).Cucurbituril synthesizes (J.Org.Chem., 2001,66,8094- according to document
8100).Three [1- (3- hydroxypropyls) -1H-1,2,3- triazole-4-yls] methyl alcohol according to document synthesize (Supramol.Chem.,
2016,28,801-809)。
Embodiment 1
The preparation method of the polymer of double cucurbit [7] urea end-blockings, including step is as follows:
(1) cucurbit [7] urea 1g is dissolved in 80mL with 0.3g 3,3 '-(octamethylenes of 1,8- bis-)-bis--(1- ethyl imidazol(e)s) dibromo
In ultra-pure water, nitrogen bubble degassing half an hour.0.26g ammonium persulfates are subsequently added, 12h is reacted at 85 DEG C.It is molten after reaction terminates
Liquid, with the chromatogram post separation using filling macroreticular resin CHP 2OP, obtains formula (II) shownization through concentrated by rotary evaporation to 10mL or so
The compound 0.21g and compound shown in formula (III) of compound and 3,3 '-(octamethylenes of 1,8- bis-)-bis--(1- ethyl imidazol(e)s) dibromo
With the compound 0.10g of 3,3 '-(octamethylenes of 1,8- bis-)-bis--(1- ethyl imidazol(e)s) dibromo.
(2) the compound 0.2g of formula (II) compound is dissolved in 20mL dimethyl sulfoxide (DMSO)s and 4mL N, N '-dimethyl formamide
Mixed solution, at 0 DEG C add 0.1g sodium hydrides, react 5h.The toluene solution of 1mL propargyl bromides 80% is subsequently added, was reacted
Night.After reaction terminates, with methanol product, washing 3 times of going forward side by side obtains single alkynyl cucurbit [7] the urea 0.18g shown in formula (IV).
(3) compound 0.1g shown in formula (IV) is distributed in water, adds 0.05g potassium chloride, is filtered not after ultrasound and stirring
Molten thing, obtains settled solution.To added in the solution single azide-functionalized polymer shown in formula (VI) (α is used in this example,
ω-nitrine polyethylene glycol 2000) 0.06g.Add three [1- (3- hydroxypropyls) -1H-1,2,3- triazole-4-yls] methyl alcohol and protochloride
The common 5mg of complex of copper reacts 48h as catalyst, under nitrogen protection at 50 DEG C.After reaction terminates, dialysis purification polymerization
Thing, Solutions in Freeze-drying obtains the polymer 0.10g of double cucurbit [7] urea end-blockings shown in formula (Ⅸ).Yield is 70%.
Embodiment 2
As described in Example 1, except that polymer is α, ω-nitrine Macrogol 4000, polymer in step (3)
Consumption be 0.12g, receive the polymer 0.16g to obtain double cucurbit [7] ureas end-blockings shown in formula (Ⅸ).Yield is 84%.
Embodiment 3
As described in Example 1, except that polymer is α-nitrine-ω-methyl polyethylene glycol 2000 in step (3),
The consumption of polymer is 0.12g, receives to obtain the polymer 0.14g of double cucurbit [7] urea end-blockings shown in formula (VII).Yield is 74%.
Embodiment 4
As described in Example 1, except that polymer is α-nitrine-ω-methyl Macrogol 4000 in step (3),
The consumption of polymer is 0.24g, receives to obtain the polymer 0.27g of double cucurbit [7] urea end-blockings shown in formula (VII).Yield is 84%.
Embodiment 5
The preparation method of cucurbit [7] urea trunk polymer, including step is as follows:
(1) with step (1) in embodiment 1.
(2) the compound 0.1g of formula (III) compound is dissolved in 10mL dimethyl sulfoxide (DMSO)s and 2mL N, N '-dimethyl formamide
Mixed solution, at 0 DEG C add 0.08g sodium hydrides, react 5h.The toluene solution of 1mL propargyl bromides 80% is subsequently added, was reacted
Night.After reaction terminates, with methanol product, washing 3 times of going forward side by side obtains double alkynyl cucurbit [7] the urea 0.10g shown in formula (V).
(3) compound 0.1g shown in formula (V) is distributed in water, adds 0.05g potassium chloride, is filtered not after ultrasound and stirring
Molten thing, obtains settled solution.To added in the solution double azide-functionalized polymer shown in formula (VIII) (α is used in this example,
ω-nitrine polyethylene glycol 2000) 0.08g.Add three [1- (3- hydroxypropyls) -1H-1,2,3- triazole-4-yls] methyl alcohol and protochloride
The common 5mg of complex of copper reacts 48h as catalyst, under nitrogen protection at 50 DEG C.After reaction terminates, dialysis purification polymerization
Thing, Solutions in Freeze-drying obtains cucurbit [7] urea trunk polymer shown in formula (Ⅻ) 0.12g.Yield is 90%.
Embodiment 6
As described in Example 5, except that polymer is α, ω-nitrine Macrogol 4000, polymer in step (3)
Consumption be 0.16g, receive to obtain cucurbit [7] urea trunk polymer shown in formula (Ⅻ) 0.19g.Yield is 91%.
Embodiment 7
The preparation method of cucurbit [7] urea star-type polymer, including step is as follows:
As described in Example 1, except that polymer is that nitrine blocks four arm PEG20000s in step (3), gather
The consumption of compound is 0.07g, receives to obtain cucurbit [7] urea star-type polymer shown in formula (Ⅸ) 0.10g.Yield is 91%.
Claims (10)
1. a kind of preparation method of the cucurbit urea polymers with various topological structures, including step is as follows:
(1) by Cucurbituril hydroxylating shown in formula (I), double hydroxyls containing monohydroxy Cucurbituril shown in formula (II), shown in formula (III) are obtained
The mixture of base Cucurbituril and other polyhydroxy Cucurbiturils;
(2) will containing monohydroxy Cucurbituril shown in formula (II), shown in formula (III) double hydroxy-cucurbiturils and other polyhydroxy Cucurbiturils
Mixture isolated and purified, obtain shown in monohydroxy Cucurbituril shown in formula (II) and formula (III) double hydroxy-cucurbiturils;
(3) by monohydroxy Cucurbituril shown in formula (II) under sodium hydride effect, with propargyl bromide reaction, the list shown in formula (IV) is obtained
Alkynyl Cucurbituril;
(4) by double hydroxy-cucurbiturils shown in formula (III) under sodium hydride effect, with propargyl bromide reaction, obtain double shown in formula (V)
Alkynyl Cucurbituril;
(5) by single alkynyl Cucurbituril shown in formula (IV) and single azide-functionalized polymer reaction shown in formula (VI), formula is obtained final product
(VII) single Cucurbituril terminated polymer shown in;Or,
(6) by single alkynyl Cucurbituril shown in formula (IV) and double azide-functionalized polymer reactions shown in formula (VIII), formula is obtained final product
(Ⅸ) double Cucurbituril terminated polymers shown in;Or,
(7) by single alkynyl Cucurbituril shown in formula (IV) and star-type polymer reaction azide-functionalized shown in formula (Ⅹ), formula is obtained final product
(Ⅺ) Cucurbituril star-type polymer shown in;Or,
(8) by double alkynyl Cucurbiturils shown in formula (V) and double azide-functionalized polymer reactions shown in formula (VIII), formula is obtained final product
(Ⅻ) the Cucurbituril trunk polymer shown in;
2. the preparation method of the cucurbit urea polymers with various topological structures according to claim 1, it is characterised in that
The hydroxylated process of Cucurbituril is as follows in step (1):
Cucurbituril is distributed in water, 3,3 '-(1,8- bis- octamethylene)-bis--(1- ethyl imidazol(e)s) dibromo salt is added, forms homogeneous
Solution;Resulting solution addition persulfate carries out oxidation reaction, obtains containing formula (II), formula (III) and other polyhydroxy Cucurbiturils
Mixture;
Preferably, Cucurbituril, 3,3 '-(1,8- bis- octamethylene)-bis--(1- ethyl imidazol(e)s) dibromo salt, the mass ratio of persulfate
It is (0.1-2):(0.05–1):(0.05–1);The ratio between the quality of Cucurbituril and the volume of water are (0.1-2):(10–100)g/mL.
3. the preparation method of the cucurbit urea polymers with various topological structures according to claim 1, it is characterised in that
Isolate and purify process in step (2) is carried out in the chromatography column;Filler in chromatographic column is macroreticular resin.
4. the preparation method of the cucurbit urea polymers with various topological structures according to claim 1, it is characterised in that
In step (3), the mass ratio of monohydroxy Cucurbituril, sodium hydride and propargyl bromide is (0.05-0.5):(0.05–0.2):(0.05–
1);
In step (4), the mass ratio of double hydroxy-cucurbiturils, sodium hydride and propargyl bromide is (0.05-0.5):(0.05–0.2):
(0.05–1);
Preferably, step (3) and step (4) reaction is carried out in highly polar aprotic solvent, and described is highly polar
Aprotic solvent is dimethyl sulfoxide (DMSO) or N, N '-dimethyl formamide;
Preferably, the product of step (3) and step (4) is by other solvent depositions, the washing purifying dissolved each other with reaction dissolvent
Obtain.
5. the preparation method of the cucurbit urea polymers with various topological structures according to claim 1, it is characterised in that
Step (5), (6), double azide-functionalized polymerizations shown in single azide-functionalized polymer, formula (VIII) shown in (7) Chinese style (VI)
Azide-functionalized star-type polymer shown in thing and formula (Ⅹ) is the azide-functionalized polyethylene glycol of end group;
Preferably, single azide-functionalized polymer shown in formula (VI) be α-nitrine-ω-methyl polyethylene glycol 2000, α-nitrine-
ω-methyl Macrogol 4000;
Preferably, double azide-functionalized polymer are α, ω-nitrine polyethylene glycol 2000, α shown in formula (VIII), and ω-nitrine gathers
Ethylene glycol 4000;
Preferably, star-type polymer azide-functionalized shown in formula (Ⅹ) is that nitrine blocks four arm PEG20000s.
6. the preparation method of the cucurbit urea polymers with various topological structures according to claim 1, it is characterised in that
Course of reaction is as follows in step (5):
Single alkynyl Cucurbituril shown in formula (IV) is distributed in water, potassium chloride is added, insoluble matter is filtered, settled solution is obtained;To
Single azide-functionalized polymer shown in addition formula (VI) in the solution, addition three [1- (3- hydroxypropyls) -1H-1,2,3- triazoles -
4- yls] methyl alcohol reacted with the complex of stannous chloride as catalyst, and after reaction terminates, potassium chloride and catalysis are removed in dialysis
Agent, Solutions in Freeze-drying obtains single Cucurbituril terminated polymer shown in formula (VII);
Preferably, single alkynyl Cucurbituril, the mass ratio of potassium chloride are (0.05g -0.2):(0.05–0.1);Single alkynyl Cucurbituril
The ratio between volume of quality and water is (0.05g -0.2):(10–100)g/mL;
Single azide-functionalized polymer adds the 20%-100% that mole is single alkynyl Cucurbituril mole shown in formula (VI);
The addition mole of catalyst is the 2%-20% of single alkynyl Cucurbituril mole.
7. the preparation method of the cucurbit urea polymers with various topological structures according to claim 1, it is characterised in that
Course of reaction is as follows in step (6):
Single alkynyl Cucurbituril shown in formula (IV) is distributed in water, potassium chloride is added, insoluble matter is filtered, settled solution is obtained;To
Double azide-functionalized polymer shown in addition formula (VIII) in the solution, addition three [1- (3- hydroxypropyls) -1H-1,2,3- triazoles -
4- yls] methyl alcohol reacted with the complex of stannous chloride as catalyst;After reaction terminates, potassium chloride and catalysis are removed in dialysis
Agent, Solutions in Freeze-drying obtains the polymer of double Cucurbituril end-blockings shown in formula (Ⅸ);
Preferably, single alkynyl Cucurbituril, the mass ratio of potassium chloride are (0.05g -0.2):(0.05–0.1);Single alkynyl Cucurbituril
The ratio between volume of quality and water is (0.05g -0.2):(10–100)g/mL;
Double azide-functionalized polymer add the 20%-100% that mole is single alkynyl Cucurbituril mole shown in formula (VIII);
The addition mole of catalyst is the 2%-20% of single alkynyl Cucurbituril mole.
8. the preparation method of the cucurbit urea polymers with various topological structures according to claim 1, it is characterised in that
Course of reaction is as follows in step (7):
Single alkynyl Cucurbituril shown in formula (IV) is distributed in water, potassium chloride is added, insoluble matter is filtered, settled solution is obtained;To
Star-type polymer azide-functionalized shown in formula (Ⅹ) is added in the solution, three [1- (3- hydroxypropyls) -1H-1,2,3- tri- are added
Azoles -4- bases] methyl alcohol reacted with the complex of stannous chloride as catalyst;Reaction terminate after, dialysis remove potassium chloride and
Catalyst, Solutions in Freeze-drying obtains the Cucurbituril star-type polymer shown in formula (Ⅺ);
Preferably, single alkynyl Cucurbituril, the mass ratio of potassium chloride are (0.05g -0.2):(0.05–0.1);Single alkynyl Cucurbituril
The ratio between volume of quality and water is (0.05g -0.2):(10–100)g/mL;
Star-type polymer azide-functionalized shown in formula (Ⅹ) adds the 5%-25% that mole is single alkynyl Cucurbituril mole;
The addition mole of catalyst is the 2%-20% of single alkynyl Cucurbituril mole.
9. the preparation method of the cucurbit urea polymers with various topological structures according to claim 1, it is characterised in that
Course of reaction is as follows in step (8):
Double alkynyl Cucurbiturils shown in formula (V) are distributed in water, potassium chloride is added, insoluble matter is filtered, settled solution is obtained;To
Double azide-functionalized polymer shown in addition formula (VIII) in the solution, addition three [1- (3- hydroxypropyls) -1H-1,2,3- triazoles -
4- yls] methyl alcohol reacted with the complex of stannous chloride as catalyst;After reaction terminates, potassium chloride and catalysis are removed in dialysis
Agent, Solutions in Freeze-drying obtains the Cucurbituril trunk polymer shown in formula (Ⅻ);
Preferably, single alkynyl Cucurbituril, the mass ratio of potassium chloride are (0.05g -0.2):(0.05–0.1);Single alkynyl Cucurbituril
The ratio between volume of quality and water is (0.05g -0.2):(10–100)g/mL;
Double azide-functionalized polymer add the 50%-150% that mole is double alkynyl Cucurbituril moles shown in formula (VIII);
The addition mole of catalyst is the 2%-20% of single alkynyl Cucurbituril mole.
10. the preparation method of the cucurbit urea polymers with various topological structures according to claim 1, its feature exists
In reacted described in step (5), step (6), step (7) and step (8) is carried out at 20-70 DEG C.
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CN109161028A (en) * | 2018-08-21 | 2019-01-08 | 四川大学 | It is a kind of using Cucurbituril as the preparation method of the degradable type two-dimension polymer of structural unit |
CN111821472A (en) * | 2019-04-17 | 2020-10-27 | 中国科学院武汉物理与数学研究所 | Hyperpolarization for delivery of hydrophobic drugs129Xe magnetic resonance molecular probe |
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