CN108164569A - It is a kind of using β-CD as the dendritic macromole and its synthetic method of core - Google Patents

Abstract

The present invention relates to a dendritic macromolecule with β-CD as the core and a synthesis method thereof, using β-CD, 2-chloropropionyl chloride, sodium azide, 5-hexynoic acid, and dibromoneopentyl glycol as raw materials , DMF, NMP, toluene, tetrahydrofuran, dichloromethane as solvents, N,N,N',N,'N"-pentamethyldiethylenetriamine (PMDETA) as ligands under mild reaction conditions Synthesized within a short time. Under the situation that does not need special equipment, the β-CD-b2-Br ₈₄ that reacts obtains the 2nd generation dendrimer of 84 modifiable end group functional groups. The dendrimer synthesized is enriched The field of topological structure of organic matter provides more options for the application of dendrimers in the fields of catalysis, molecular recognition, nanomaterials, and guest small molecule encapsulation.

Description

A kind of dendritic macromolecule with β-CD as core and its synthesis method

technical field

The invention belongs to the field of dendritic macromolecules, and relates to a dendritic macromolecule with β-CD as the core and a synthesis method thereof. Specifically, the β-CD is used as the core, and 21 hydroxyl groups on CD are modified to contain polysaccharides. dendrimers with functional groups β-CD-b2-Br ₈₄ .

Background technique

Designing and synthesizing dendrimers with multiple modifiable groups is an effective prerequisite for preparing various functional dendrimers.

Literature 1 "Ornelas C, Ruiz Aranzaes J, Cloutet E, et al. Click Assembly of 1,2,3‐Triazole‐Linked Dendrimers, Including Ferrocenyl Dendrimers, Which SenseBoth Oxo Anions and Metal Cations[J]. AngewandteChemie, 2007, 119 (6):890-895." announced a kind of azido-terminated dendrimers prepared by click reaction and nucleophilic substitution reaction, and finally carried out click reaction with ferrocene with alkynyl-terminated group to synthesize composite metal dendron Molecules are used as redox sensors.

Document 2 "Deraedt C, Pinaud N, Astruc D. Recyclable catalytic dendrimernanoreactor for part-per-million CuI catalysis of "click" chemistry in water[J].Journal of the American Chemical Society,2014,136(34):12092- 12098." announced a method of synthesizing a water-soluble dendrimer through a click reaction, using the nitrogen atom in the 1,4-disubstituted-1,2,3-triazole ring produced by the click reaction and the monovalent copper The ions are coordinated to form a water-soluble catalyst for the click reaction.

β-CD is a hollow cyclic oligosaccharide, which is easy to obtain. β-CD molecules have 7 primary hydroxyl groups on the narrow side and 14 secondary hydroxyl groups on the wide side. Therefore, the 21 hydroxyl groups on β-CD can be modified to synthesize new macromolecules. In view of the tight structure of dendrimers and the existence of a large number of holes. These cavities have the ability to entrap guest molecules. Therefore, dendrimers have broad application prospects in molecular catalysis, self-assembly of nanomaterials, drug entrapment and release, and targeted cancer cell therapy. The present invention uses β-CD as the core to design and synthesize dendritic molecules. The use of β-CD as the core is beneficial to produce more branched structures and cavities in the molecule under the premise of fewer synthesis steps, which may result in more Strong carrying capacity.

Contents of the invention

technical problem to be solved

In order to avoid the deficiencies of the prior art, the present invention proposes a dendritic macromolecule with β-CD as the core and its synthesis method. The dendritic macromolecular material has the following advantages: the surface can be modified with many functional groups The cycle is short and the post-processing is simple. The types of dendrimers are enriched, and more choices are provided for the application of dendrimers in the field of functional polymers.

Technical solutions

A dendritic macromolecule with β-CD as the core, characterized in that: with β-CD as the core, the 21 hydroxyl groups on the CD are all modified and contain multiple functional groups. Dendritic macromolecule β-CD-b2 -Br ₈₄ , the structure is as follows:

The structural characteristics of the multifunctional monomer ABMP in the synthesis process are:

A method for preparing the dendrimer with β-CD as the core, characterized in that the steps are as follows:

Step 1: react 21Cl-β-CD and sodium azide in N,N-dimethylformamide DMF as the solvent temperature, and react at 25°C-30°C for 48h-60h to obtain 21N ₃ -β-CD; The mol ratio of described sodium azide, 21Cl-β-CD is 42: 1, and the consumption ratio of DMF and 21Cl-β-CD is 3 milliliters: 1 gram;

Step 2: Dissolve 5-hexynoic acid in toluene, then add dibromoneopentyl glycol and a catalytic amount of p-toluenesulfonic acid p-TSA, then place the reaction in a Dean-StarK apparatus at 120°C to 123 Reflux in an oil bath at °C for 8h to 10h to obtain the multifunctional monomer ABMP; the molar ratio of 5-hexynoic acid, dibromoneopentyl glycol, and p-toluenesulfonic acid p-TSA is 1:7: 0.04, the ratio of the amount of toluene to 5-hexynoic acid is 40 ml: 1 g;

Step 3: Dissolve the multifunctional monomer ABMP and the ligand N,N,N',N,'N"-pentamethyldiethylenetriamine PMDETA in DMF, remove oxygen by air blowing, and then Add 21N ₃ -β-CD and CuBr under the protection of nitrogen, and continue to deoxygenate by blowing gas; then seal it under the protection of argon, and place it at 25°C-35°C for 40min-1h to obtain the first-generation branched product β-CD-b1-Br ₄₂ ; the molar ratio of 21N ₃ -β-CD, ABMP, CuBr, PMDETA is 1: 1.2: 1: 2, the amount ratio of DMF to 21N ₃ -β-CD is 30 ml: 1 gram;

Step 4: Dissolve the first-generation branched product β-CD-b1-Br ₄₂ and sodium azide in DMF, deoxygenate by air blowing, then seal under the protection of argon, and place at 70°C to 80°C The reaction was carried out for 12h-14h to obtain; the molar ratio of β-CD-b1-Br ₄₂ and sodium azide was 1:50.4, and the ratio of DMF to β-CD-b1-Br ₄₂ was 10ml:1g;

Step 5: Dissolve the multifunctional monomer ABMP and the ligand N,N,N',N,'N"-pentamethyldiethylenetriamine PMDETA in DMF, remove oxygen by air blowing, and then Add the first-generation branched product β-CD-b1-(N ₃ ) ₄₂ and CuBr treated in step 4 under the protection of nitrogen, and continue to deoxygenate by blowing gas; then seal it under the protection of argon, and place it at 25 ° C ~ 35 The second-generation dendrimer β-CD-b2-Br ₈₄ is obtained by reacting for 1h to 1.5h at ℃; the molar ratio of β-CD-b1-(N ₃ ) ₄₂ , ABMP, CuBr, and PMDETA is 1: 1.2: 1: 2, the dosage ratio of DMF and β-CD-b1-(N ₃ ) ₄₂ is 30ml: 1g.

The 21Cl-β-CD in the step 1 is obtained by the synthetic reaction of 2-chloropropionyl chloride and β-CD.

The step 1 is reacted at 25°C to 30°C for 48h to 60h, after the reaction is completed, ethyl acetate is added, washed with an aqueous solution containing sodium chloride; the organic layer is collected, dried by adding anhydrous sodium sulfate, and used in Anhydrous sodium sulfate and color were removed through a permanent alumina column; then an appropriate amount of tetrahydrofuran was added, precipitated in n-hexane and purified 2 to 3 times to obtain a white solid product, 21N ₃ -β-CD.

After the reflux of step 2 for 8h to 10h is completed, the reaction system is cooled to room temperature, the solid is removed by filtration, and the solvent is removed under reduced pressure; the obtained crude product is purified with a silica gel column, using a mixed solvent of dichloromethane and ether as the eluent; The solvent was removed under reduced pressure to obtain a colorless liquid product, the polyfunctional monomer ABMP, which was vacuum-dried at room temperature to constant weight; the volume ratio of dichloromethane and diethyl ether was 10:1.

In step 3, react at 25°C to 35°C for 40min to 1h after the reaction is completed, dilute with dichloromethane, then wash with a mixed solution of ammonium chloride and sodium chloride, and then continue to wash with an aqueous solution containing sodium chloride , adding tetrahydrofuran to help dissolve each time before washing, the amount of tetrahydrofuran is such that the volume of tetrahydrofuran and dichloromethane is less than 0.25; then the obtained organic solution is dried with anhydrous sodium sulfate, filtered and the solvent is removed under reduced pressure; the obtained product is dissolved in tetrahydrofuran and precipitated in Purified in n-hexane to obtain the white solid product β-CD-b1-Br ₄₂ .

The step 4 is placed under the condition of 70°C-80°C for 12h-14h. After the reaction is completed, after the system is cooled to room temperature, dichloromethane is added to dilute, and then washed with an aqueous solution containing sodium chloride, and tetrahydrofuran is added before each washing. Solubilization, the amount of tetrahydrofuran used is that the volume ratio of tetrahydrofuran to dichloromethane is less than 0.25; the obtained organic phase is dried with anhydrous sodium sulfate, filtered, and the solvent is removed under reduced pressure. The obtained product is dissolved in tetrahydrofuran, precipitated in n-hexane and purified to obtain a white solid product β-CD-b1-(N ₃ ) ₄₂ , dried in vacuum at room temperature to constant weight.

The step 5 is reacted at 25°C-35°C for 1h-1.5h after the reaction is completed, diluted with dichloromethane, washed with a mixed solution containing ammonium chloride and sodium chloride, and then continued with an aqueous solution containing sodium chloride Washing with water, adding tetrahydrofuran to help dissolve before each washing, the amount of tetrahydrofuran is such that the volume ratio of tetrahydrofuran to dichloromethane is less than 0.25; the obtained organic solution is dried with anhydrous sodium sulfate, filtered, and the solvent is removed under reduced pressure. The obtained product is dissolved in tetrahydrofuran and precipitated in The second-generation dendrimer β-CD-b2-Br ₈₄ was purified in n-hexane as a white solid, which was vacuum-dried at room temperature to constant weight.

Beneficial effect

The present invention proposes a dendritic macromolecule with β-CD as the core and a synthetic method thereof, using β-CD, 2-chloropropionyl chloride, sodium azide, 5-hexynoic acid, and dibromoneopentyl glycol as Raw materials, DMF, NMP, toluene, tetrahydrofuran, dichloromethane as solvent, N,N,N',N,'N"-pentamethyldiethylenetriamine (PMDETA) as ligand in mild reaction conditions Synthesis in a short period of time. Without the need for special equipment, the β-CD-b2-Br ₈₄ obtained by the reaction is a dendrimer with 84 modifiable terminal functional groups. The synthesized dendrimer is abundant It breaks the field of organic topological structure, and provides more choices for the application of dendrimers in the fields of catalysis, molecular recognition, nanomaterials, and guest small molecule entrapment.

Description of drawings

Figure 1 is a synthesis process diagram of β-CD-b2-Br ₈₄ dendrimer core

Figure 2 is a synthesis process diagram of multifunctionality monomer ABMP

Figure 3 is a synthesis process diagram of β-CD-b2-Br ₈₄ dendrimers

Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 are infrared spectra of various generations of dendrimers and multifunctional monomers

Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 Fig. 15 are NMR spectra of various generations of dendrimers and multifunctional monomers

Figure 16 is the GPC gel permeation chromatograms of various generations of dendrimers

Detailed ways

Now in conjunction with embodiment, accompanying drawing, the present invention will be further described:

The invention provides a dendritic macromolecule with β-CD as the core. The dendritic macromolecular material has the following advantages: many functional groups that can be modified on the surface, short reaction period and simple post-treatment. The types of dendrimers are enriched, and more choices are provided for the application of dendrimers in the field of functional polymers.

The dendritic macromolecule is prepared by taking β-CD as the core of the dendritic molecule, and the small molecule multifunctional monomer as the branching point, and is prepared through two click reactions and two nucleophilic substitution reactions.

Example 1:

Step 1: Add 9.4g (74mmol) 2-chloropropionyl chloride and 1.0g (18.5mmol OH) β-CD to 20mL of N-methylpyrrolidone solvent, and react at a temperature of 25°C to 30°C for 48h ; Add ethyl acetate after the completion of the reaction, washed three times with aqueous solution containing sodium chloride. The organic layer was collected, and after drying by adding anhydrous sodium sulfate, anhydrous sodium sulfate and color were removed with a neutral alumina column. Then tetrahydrofuran was added, and the precipitate was purified twice in n-hexane to obtain the white solid product 21N ₃ -β-CD. The product was dried to constant weight under vacuum at room temperature. The molar ratio of sodium azide to 21Cl-β-CD is 42:1; the ratio of DMF to 21Cl-β-CD is 3 (ml): 1 (gram). The yield was 72.8%.

Step 2: Dissolve 1g (8.92mmol) of 5-hexynoic acid in 40mL of toluene, then add 16.35g (62.4mmol) of dibromoneopentyl glycol and 0.068g (0.54mmol) of p-TSA, then the mixture is placed in Dean- Reflux in an oil bath at 120°C for 8 hours under StarK device conditions. After the reaction, the reaction system was cooled to room temperature, the solid was removed by filtration, and the solvent was removed under reduced pressure. The obtained crude product was purified with a silica gel column, using a mixed solvent of dichloromethane/diethyl ether (volume ratio 10:1) as the eluent. The solvent was removed under reduced pressure to obtain a colorless liquid product, multifunctional monomer ABMP, which was vacuum-dried at room temperature to constant weight. The molar ratio of described 5-hexynoic acid, dibromoneopentyl glycol, p-toluenesulfonic acid is 1:7:0.04; The consumption ratio of toluene and 5-hexynoic acid is 40 (ml): 1 (gram) . The yield was 78%.

Step 3: 1.41g (3.97mmol) ABMP and 1.15g (6.61mmol) PMDETA were dissolved in 15ml of DMF, the solution was stirred at room temperature and passed through argon for 30min, during which time ultrasound was added 3 times, and then 0.5g was added under the protection of argon (3.31mmol N3)21N3-β-CD and 0.47g (3.31mmol) CuBr were flushed with argon for 20 minutes, the reaction bottle was sealed, and reacted at 25°C for 40 minutes. After the reaction, dilute with dichloromethane, wash with water 3 to 5 times with a mixed solution containing a certain amount of ammonium chloride and sodium chloride, and then continue to wash with water for 2 times with an aqueous solution containing a certain amount of sodium chloride. Add tetrahydrofuran to aid dissolution, and the amount of tetrahydrofuran used is that the volume of tetrahydrofuran/dichloromethane is less than 0.25. The resulting organic solution was dried over anhydrous sodium sulfate, filtered and the solvent was removed under reduced pressure. The obtained product was dissolved in an appropriate amount of tetrahydrofuran, precipitated in n-hexane and purified twice. The resulting white solid product β-CD-b1-Br ₄₂ was vacuum-dried at room temperature to constant weight. The molar ratio of 21N ₃ -β-CD, ABMP, CuBr, N,N,N',N,'N"-pentamethyldiethylenetriamine (PMDETA) is 1:1.2:1:2; The ratio of DMF to 21N ₃ -β-CD is 30 (mL): 1 (g), and the yield is 70%.

Step 4: 1 g (3.94 mmol Br) of β-CD-b1-Br ₄₂ was dissolved in 10 ml of DMF, and then 0.31 g (4.73 mmol) of NaN ₃ was added. The reaction mixture was ventilated with argon for 20 min at room temperature, the reaction bottle was sealed, and the reaction was placed at 70° C. for 12 h. After the reaction is over, after the system is cooled to room temperature, dichloromethane is added to dilute, and then washed three times with an aqueous solution containing sodium chloride, and tetrahydrofuran is added before each washing to aid dissolution. The resulting organic phase was dried over anhydrous sodium sulfate, filtered and the solvent was removed under reduced pressure. The resulting product was dissolved in an appropriate amount of tetrahydrofuran, precipitated in n-hexane and purified twice. The resulting white solid product β-CD-b1-(N ₃ ) ₄₂ was dried under vacuum at room temperature to constant weight. The molar ratio of β-CD-b1-Br ₄₂ to sodium azide is 1:50.4; the ratio of DMF to β-CD-b1-Br ₄₂ is 10 (mL): 1 (g). The yield was 76%.

Step 5: 0.99g (2.78mmol) ABMP and 0.8g (4.63mmol) PMDETA were dissolved in 15ml of DMF, and the reaction solution was passed through argon for 30min at room temperature, during which time ultrasound was added 3 times, and then 0.5g was added under the protection of argon (2.32mmolN ₃ )β-CD-b1-(N ₃ ) ₄₂ and 0.33g (2.32mmol)CuBr were passed through argon for 20min, the reaction bottle was sealed and reacted at 25°C for 1h. After the reaction, dilute with dichloromethane, first wash with water 3 times with a mixed solution containing ammonium chloride and sodium chloride, then continue to wash with water for 2 times with an aqueous solution containing sodium chloride, add tetrahydrofuran to aid dissolution before each wash, tetrahydrofuran The dosage is less than 0.25 volume of tetrahydrofuran/dichloromethane. The resulting organic solution was dried over anhydrous sodium sulfate, filtered and the solvent was removed under reduced pressure. The obtained product was dissolved in an appropriate amount of tetrahydrofuran, precipitated in n-hexane and purified twice. The second-generation dendrimer β-CD-b2-Br ₈₄ was obtained as a white solid, which was vacuum-dried at room temperature to constant weight. The molar ratio of β-CD-b1-(N ₃ ) ₄₂ , ABMP, CuBr, N,N,N',N,'N"-pentamethyldiethylenetriamine (PMDETA) is 1:1.2 : 1: 2; the ratio of DMF to β-CD-b1-(N ₃ ) ₄₂ is 30 (mL): 1 (g). Yield: 68%.

Example 2:

Step 1: Add 9.4g (74mmol) 2-chloropropionyl chloride and 1.0g (18.5mmol OH) β-CD to 20mL of N-methylpyrrolidone solvent, and react at a temperature of 30°C for 60h; the reaction is complete After that, ethyl acetate was added and washed three times with aqueous solution containing sodium chloride. The organic layer was collected, and after drying by adding anhydrous sodium sulfate, anhydrous sodium sulfate and color were removed with a neutral alumina column. Then tetrahydrofuran was added, and the precipitate was purified three times in n-hexane to obtain the white solid product 21N ₃ -β-CD. The product was dried to constant weight under vacuum at room temperature. The molar ratio of sodium azide to 21Cl-β-CD is 42:1; the ratio of DMF to 21Cl-β-CD is 3 (ml): 1 (gram). The yield was 72.8%.

Step 2: Dissolve 1g (8.92mmol) of 5-hexynoic acid in 40mL of toluene, then add 16.35g (62.4mmol) of dibromoneopentyl glycol and 0.068g (0.54mmol) of p-TSA, then the mixture is placed in Dean- Reflux in an oil bath at 123°C for 10h under StarK device conditions. After the reaction, the reaction system was cooled to room temperature, the solid was removed by filtration, and the solvent was removed under reduced pressure. The obtained crude product was purified with a silica gel column, using a mixed solvent of dichloromethane/diethyl ether (volume ratio 10:1) as the eluent. The solvent was removed under reduced pressure to obtain a colorless liquid product, multifunctional monomer ABMP, which was vacuum-dried at room temperature to constant weight. The molar ratio of described 5-hexynoic acid, dibromoneopentyl glycol, p-toluenesulfonic acid is 1:7:0.04; The consumption ratio of toluene and 5-hexynoic acid is 40 (ml): 1 (gram) . The yield was 78%.

Step 3: 1.41g (3.97mmol) ABMP and 1.15g (6.61mmol) PMDETA were dissolved in 15ml of DMF, the solution was stirred at room temperature and passed through argon for 30min, during which time ultrasound was added 3 times, and then 0.5g was added under the protection of argon (3.31mmol N3)21N3-β-CD and 0.47g (3.31mmol) CuBr, continue flushing with argon for 20min, seal the reaction bottle, and react at 25°C to 35°C for 1h. After the reaction is finished, dilute with dichloromethane, wash with a mixed solution containing ammonium chloride and sodium chloride for 3 to 5 times, then continue to wash with water for 3 times with an aqueous solution containing sodium chloride, and add tetrahydrofuran to aid dissolution before each washing , the amount of tetrahydrofuran is THF/dichloromethane volume less than 0.25. The resulting organic solution was dried over anhydrous sodium sulfate, filtered and the solvent was removed under reduced pressure. The obtained product was dissolved in tetrahydrofuran, precipitated in n-hexane and purified three times. The resulting white solid product β-CD-b1-Br ₄₂ was vacuum-dried at room temperature to constant weight. The molar ratio of 21N ₃ -β-CD, ABMP, CuBr, N,N,N',N,'N"-pentamethyldiethylenetriamine (PMDETA) is 1:1.2:1:2; The ratio of DMF to 21N ₃ -β-CD is 30 (mL): 1 (g), and the yield is 70%.

Step 4: 1 g (3.94 mmol Br) of β-CD-b1-Br ₄₂ was dissolved in 10 ml of DMF, and then 0.31 g (4.73 mmol) of NaN ₃ was added. The reaction mixture was ventilated with argon for 20 min at room temperature, the reaction bottle was sealed, and the reaction was placed at 80° C. for 14 h. After the reaction is over, after the system is cooled to room temperature, dichloromethane is added to dilute, and then washed three times with an aqueous solution containing sodium chloride, and tetrahydrofuran is added before each washing to aid dissolution. The resulting organic phase was dried over anhydrous sodium sulfate, filtered and the solvent was removed under reduced pressure. The resulting product was dissolved in tetrahydrofuran, precipitated in n-hexane and purified 2 to 3 times. The resulting white solid product β-CD-b1-(N ₃ ) ₄₂ was dried under vacuum at room temperature to constant weight. The molar ratio of β-CD-b1-Br ₄₂ to sodium azide is 1:50.4; the ratio of DMF to β-CD-b1-Br ₄₂ is 10 (mL): 1 (g). The yield was 76%.

Step 5: 0.99g (2.78mmol) ABMP and 0.8g (4.63mmol) PMDETA were dissolved in 15ml of DMF, and the reaction solution was passed through argon for 30min at room temperature, during which time ultrasound was added 3 times, and then 0.5g was added under the protection of argon (2.32mmolN ₃ )β-CD-b1-(N ₃ ) ₄₂ and 0.33g (2.32mmol)CuBr were passed through argon for 20min, the reaction bottle was sealed, and the reaction was carried out at 35°C for 1.5h. After the reaction is over, dilute with dichloromethane, wash with water 5 times with a mixed solution containing ammonium chloride and sodium chloride, then continue to wash with water for 3 times with an aqueous solution containing sodium chloride, and add tetrahydrofuran to aid dissolution before each washing. The dosage is less than 0.25 volume of tetrahydrofuran/dichloromethane. The resulting organic solution was dried over anhydrous sodium sulfate, filtered and the solvent was removed under reduced pressure. The obtained product was dissolved in an appropriate amount of tetrahydrofuran, precipitated in n-hexane and purified three times. The second-generation dendrimer β-CD-b2-Br ₈₄ was obtained as a white solid, which was vacuum-dried at room temperature to constant weight. The molar ratio of β-CD-b1-(N ₃ ) ₄₂ , ABMP, CuBr, N,N,N',N,'N"-pentamethyldiethylenetriamine (PMDETA) is 1:1.2 : 1: 2; the ratio of DMF to β-CD-b1-(N ₃ ) ₄₂ is 30 (mL): 1 (g). Yield: 68%.

Example 3:

Step 1: Add 9.4g (74mmol) 2-chloropropionyl chloride and 1.0g (18.5mmol OH) β-CD to 20mL of N-methylpyrrolidone solvent, and react at a temperature of 28°C for 60h; the reaction is complete After that, ethyl acetate was added and washed three times with aqueous solution containing sodium chloride. The organic layer was collected, and after drying by adding anhydrous sodium sulfate, anhydrous sodium sulfate and color were removed with a neutral alumina column. Then tetrahydrofuran was added, and the precipitate was purified three times in n-hexane to obtain the white solid product 21N ₃ -β-CD. The product was dried to constant weight under vacuum at room temperature. The molar ratio of sodium azide to 21Cl-β-CD is 42:1; the ratio of DMF to 21Cl-β-CD is 3 (ml): 1 (gram). The yield was 72.8%.

Step 2: Dissolve 1g (8.92mmol) of 5-hexynoic acid in 40mL of toluene, then add 16.35g (62.4mmol) of dibromoneopentyl glycol and 0.068g (0.54mmol) of p-TSA, then the mixture is placed in Dean- Reflux in an oil bath at 123°C for 10h under StarK device conditions. After the reaction, the reaction system was cooled to room temperature, the solid was removed by filtration, and the solvent was removed under reduced pressure. The obtained crude product was purified with a silica gel column, using a mixed solvent of dichloromethane/diethyl ether (volume ratio 10:1) as the eluent. The solvent was removed under reduced pressure to obtain a colorless liquid product, multifunctional monomer ABMP, which was vacuum-dried at room temperature to constant weight. The molar ratio of described 5-hexynoic acid, dibromoneopentyl glycol, p-toluenesulfonic acid is 1:7:0.04; The consumption ratio of toluene and 5-hexynoic acid is 40 (ml): 1 (gram) . The yield was 78%.

Step 3: 1.41g (3.97mmol) ABMP and 1.15g (6.61mmol) PMDETA were dissolved in 15ml of DMF, the solution was stirred at room temperature and passed through argon for 30min, during which time ultrasound was added 3 times, and then 0.5g was added under the protection of argon (3.31mmol N3)21N3-β-CD and 0.47g (3.31mmol) CuBr, continue flushing with argon for 20 minutes, seal the reaction bottle, and react at 35°C for 40 minutes to 1 hour. After the reaction is over, dilute with dichloromethane, wash with water 5 times with a mixed solution containing ammonium chloride and sodium chloride, then continue to wash with water for 3 times with an aqueous solution containing sodium chloride, and add tetrahydrofuran to aid dissolution before each washing. The dosage is less than 0.25 volume of tetrahydrofuran/dichloromethane. The resulting organic solution was dried over anhydrous sodium sulfate, filtered and the solvent was removed under reduced pressure. The obtained product was dissolved in tetrahydrofuran, precipitated in n-hexane and purified three times. The resulting white solid product β-CD-b1-Br ₄₂ was vacuum-dried at room temperature to constant weight. The molar ratio of 21N ₃ -β-CD, ABMP, CuBr, N,N,N',N,'N"-pentamethyldiethylenetriamine (PMDETA) is 1:1.2:1:2; The ratio of DMF to 21N ₃ -β-CD is 30 (mL): 1 (g), and the yield is 70%.

Step 4: 1 g (3.94 mmol Br) of β-CD-b1-Br ₄₂ was dissolved in 10 ml of DMF, and then 0.31 g (4.73 mmol) of NaN ₃ was added. The reaction mixture was ventilated with argon for 20 min at room temperature, the reaction bottle was sealed, and the reaction was placed at 78° C. for 14 h. After the reaction is over, after the system is cooled to room temperature, dichloromethane is added to dilute, and then washed three times with an aqueous solution containing sodium chloride, and tetrahydrofuran is added before each washing to aid dissolution. The resulting organic phase was dried over anhydrous sodium sulfate, filtered and the solvent was removed under reduced pressure. The obtained product was dissolved in tetrahydrofuran, precipitated in n-hexane and purified three times. The resulting white solid product β-CD-b1-(N ₃ ) ₄₂ was dried under vacuum at room temperature to constant weight. The molar ratio of β-CD-b1-Br ₄₂ to sodium azide is 1:50.4; the ratio of DMF to β-CD-b1-Br ₄₂ is 10 (mL): 1 (g). The yield was 76%.

Step 5: 0.99g (2.78mmol) ABMP and 0.8g (4.63mmol) PMDETA were dissolved in 15ml of DMF, and the reaction solution was passed through argon for 30min at room temperature, during which time ultrasound was added 3 times, and then 0.5g was added under the protection of argon (2.32mmolN ₃ )β-CD-b1-(N ₃ ) ₄₂ and 0.33g (2.32mmol)CuBr were passed through argon for 20min, the reaction bottle was sealed, and the reaction was carried out at 35°C for 1.5h. After the reaction is over, dilute with dichloromethane, wash with water 5 times with a mixed solution containing ammonium chloride and sodium chloride, then continue to wash with water for 3 times with an aqueous solution containing sodium chloride, and add tetrahydrofuran to aid dissolution before each washing. The dosage is less than 0.25 volume of tetrahydrofuran/dichloromethane. The resulting organic solution was dried over anhydrous sodium sulfate, filtered and the solvent was removed under reduced pressure. The obtained product was dissolved in tetrahydrofuran, precipitated in n-hexane and purified three times. The second-generation dendrimer β-CD-b2-Br ₈₄ was obtained as a white solid, which was vacuum-dried at room temperature to constant weight. The molar ratio of β-CD-b1-(N ₃ ) ₄₂ , ABMP, CuBr, N,N,N',N,'N"-pentamethyldiethylenetriamine (PMDETA) is 1:1.2 : 1: 2; the ratio of DMF to β-CD-b1-(N ₃ ) ₄₂ is 30 (mL): 1 (g). Yield: 68%.

Embodiment 4:

Step 1: Add 9.4g (74mmol) 2-chloropropionyl chloride and 1.0g (18.5mmol OH) β-CD to 20mL of N-methylpyrrolidone solvent, and react at a temperature of 29°C for 50h; the reaction is complete After that, ethyl acetate was added and washed three times with aqueous solution containing sodium chloride. The organic layer was collected, and after drying by adding anhydrous sodium sulfate, anhydrous sodium sulfate and color were removed with a neutral alumina column. Then tetrahydrofuran was added, and the precipitate was purified three times in n-hexane to obtain the white solid product 21N ₃ -β-CD. The product was dried to constant weight under vacuum at room temperature. The molar ratio of sodium azide to 21Cl-β-CD is 42:1; the ratio of DMF to 21Cl-β-CD is 3 (ml): 1 (gram). The yield was 72.8%.

Step 2: Dissolve 1g (8.92mmol) of 5-hexynoic acid in 40mL of toluene, then add 16.35g (62.4mmol) of dibromoneopentyl glycol and 0.068g (0.54mmol) of p-TSA, then the mixture is placed in Dean- Reflux in an oil bath at 120°C for 7 hours under StarK device conditions. After the reaction, the reaction system was cooled to room temperature, the solid was removed by filtration, and the solvent was removed under reduced pressure. The obtained crude product was purified with a silica gel column, using a mixed solvent of dichloromethane/diethyl ether (volume ratio 10:1) as the eluent. The solvent was removed under reduced pressure to obtain a colorless liquid product, multifunctional monomer ABMP, which was vacuum-dried at room temperature to constant weight. The molar ratio of described 5-hexynoic acid, dibromoneopentyl glycol, p-toluenesulfonic acid is 1:7:0.04; The consumption ratio of toluene and 5-hexynoic acid is 40 (ml): 1 (gram) . The yield was 78%.

Step 3: 1.41g (3.97mmol) ABMP and 1.15g (6.61mmol) PMDETA were dissolved in 15ml of DMF, the solution was stirred at room temperature and passed through argon for 30min, during which time ultrasound was added 3 times, and then 0.5g was added under the protection of argon (3.31mmol N3)21N3-β-CD and 0.47g (3.31mmol) CuBr were flushed with argon for 20 minutes, the reaction bottle was sealed and reacted at 35°C for 50 minutes. After the reaction is finished, dilute with dichloromethane, wash with a mixed solution containing ammonium chloride and sodium chloride for 3 to 5 times, then continue to wash with water for 3 times with an aqueous solution containing sodium chloride, and add tetrahydrofuran to aid dissolution before each washing , the amount of tetrahydrofuran is THF/dichloromethane volume less than 0.25. The resulting organic solution was dried over anhydrous sodium sulfate, filtered and the solvent was removed under reduced pressure. The obtained product was dissolved in tetrahydrofuran, precipitated in n-hexane and purified three times. The resulting white solid product β-CD-b1-Br ₄₂ was vacuum-dried at room temperature to constant weight. The molar ratio of 21N ₃ -β-CD, ABMP, CuBr, N,N,N',N,'N"-pentamethyldiethylenetriamine (PMDETA) is 1:1.2:1:2; The ratio of DMF to 21N ₃ -β-CD is 30 (mL): 1 (g), and the yield is 70%.

Step 4: 1 g (3.94 mmol Br) of β-CD-b1-Br ₄₂ was dissolved in 10 ml of DMF, and then 0.31 g (4.73 mmol) of NaN ₃ was added. The reaction mixture was ventilated with argon gas at room temperature for 20 minutes, the reaction bottle was sealed, and the reaction was placed at 70° C. to 80° C. for 13 hours. After the reaction is over, after the system is cooled to room temperature, dichloromethane is added to dilute, and then washed three times with an aqueous solution containing sodium chloride, and tetrahydrofuran is added before each washing to aid dissolution. The resulting organic phase was dried over anhydrous sodium sulfate, filtered and the solvent was removed under reduced pressure. The obtained product was dissolved in tetrahydrofuran, precipitated in n-hexane and purified three times. The resulting white solid product β-CD-b1-(N ₃ ) ₄₂ was dried under vacuum at room temperature to constant weight. The molar ratio of β-CD-b1-Br ₄₂ to sodium azide is 1:50.4; the ratio of DMF to β-CD-b1-Br ₄₂ is 10 (mL): 1 (g). The yield was 76%.

Step 5: 0.99g (2.78mmol) ABMP and 0.8g (4.63mmol) PMDETA were dissolved in 15ml of DMF, and the reaction solution was passed through argon for 30min at room temperature, during which time ultrasound was added 3 times, and then 0.5g was added under the protection of argon (2.32mmolN ₃ )β-CD-b1-(N ₃ ) ₄₂ and 0.33g (2.32mmol)CuBr were passed through argon for 20min, the reaction bottle was sealed, and the reaction was carried out at 27°C for 1.3h. After the reaction is finished, dilute with dichloromethane, wash with water 5 times with a mixed solution containing ammonium chloride and sodium chloride, then continue to wash with water for 2 times with an aqueous solution containing sodium chloride, add tetrahydrofuran to aid dissolution before each wash, tetrahydrofuran The dosage is less than 0.25 volume of tetrahydrofuran/dichloromethane. The resulting organic solution was dried over anhydrous sodium sulfate, filtered and the solvent was removed under reduced pressure. The obtained product was dissolved in tetrahydrofuran, precipitated in n-hexane and purified 2 to 3 times. The second-generation dendrimer β-CD-b2-Br ₈₄ was obtained as a white solid, which was vacuum-dried at room temperature to constant weight. The molar ratio of β-CD-b1-(N ₃ ) ₄₂ , ABMP, CuBr, N,N,N',N,'N"-pentamethyldiethylenetriamine (PMDETA) is 1:1.2 : 1: 2; the ratio of DMF to β-CD-b1-(N ₃ ) ₄₂ is 30 (mL): 1 (g). Yield: 68%.

Example 5:

Step 1: Add 9.4g (74mmol) 2-chloropropionyl chloride and 1.0g (18.5mmol OH) β-CD to 20mL of N-methylpyrrolidone solvent, and react at a temperature of 25°C for 48h; the reaction is complete After that, ethyl acetate was added and washed three times with aqueous solution containing sodium chloride. The organic layer was collected, and after drying by adding anhydrous sodium sulfate, anhydrous sodium sulfate and color were removed with a neutral alumina column. Then tetrahydrofuran was added, and the precipitate was purified three times in n-hexane to obtain the white solid product 21N ₃ -β-CD. The product was dried to constant weight under vacuum at room temperature. The molar ratio of sodium azide to 21Cl-β-CD is 42:1; the ratio of DMF to 21Cl-β-CD is 3 (ml): 1 (gram). The yield was 72.8%.

Step 2: Dissolve 1g (8.92mmol) of 5-hexynoic acid in 40mL of toluene, then add 16.35g (62.4mmol) of dibromoneopentyl glycol and 0.068g (0.54mmol) of p-TSA, then the mixture is placed in Dean- Reflux in an oil bath at 123°C for 8 hours under StarK device conditions. After the reaction, the reaction system was cooled to room temperature, the solid was removed by filtration, and the solvent was removed under reduced pressure. The obtained crude product was purified with a silica gel column, using a mixed solvent of dichloromethane/diethyl ether (volume ratio 10:1) as the eluent. The solvent was removed under reduced pressure to obtain a colorless liquid product, multifunctional monomer ABMP, which was vacuum-dried at room temperature to constant weight. The molar ratio of described 5-hexynoic acid, dibromoneopentyl glycol, p-toluenesulfonic acid is 1:7:0.04; The consumption ratio of toluene and 5-hexynoic acid is 40 (ml): 1 (gram) . The yield was 78%.

Step 3: Dissolve 1.41g (3.97mmol) ABMP and 1.15g (6.61mmol) PMDETA in 15ml of DMF, stir the solution at room temperature and pass argon for 30min, during which time ultrasonication is performed 3 times, and then add 0.5g under the protection of argon (3.31mmol N3)21N3-β-CD and 0.47g (3.31mmol) CuBr, continue flushing with argon for 20min, seal the reaction bottle, and react at 25°C-35°C for 40min-1h. After the reaction is finished, dilute with dichloromethane, wash with water 5 times with a mixed solution containing ammonium chloride and sodium chloride, then continue to wash with water for 2 times with an aqueous solution containing sodium chloride, add tetrahydrofuran to aid dissolution before each wash, tetrahydrofuran The dosage is less than 0.25 volume of tetrahydrofuran/dichloromethane. The resulting organic solution was dried over anhydrous sodium sulfate, filtered and the solvent was removed under reduced pressure. The obtained product was dissolved in tetrahydrofuran, precipitated in n-hexane and purified 2 to 3 times. The resulting white solid product β-CD-b1-Br ₄₂ was vacuum-dried at room temperature to constant weight. The molar ratio of 21N ₃ -β-CD, ABMP, CuBr, N,N,N',N,'N"-pentamethyldiethylenetriamine (PMDETA) is 1:1.2:1:2; The ratio of DMF to 21N ₃ -β-CD is 30 (mL): 1 (g), and the yield is 70%.

Step 4: 1 g (3.94 mmol Br) of β-CD-b1-Br ₄₂ was dissolved in 10 ml of DMF, and then 0.31 g (4.73 mmol) of NaN ₃ was added. The reaction mixture was ventilated with argon for 20 min at room temperature, the reaction bottle was sealed, and the reaction was placed at 80° C. for 14 h. After the reaction is over, after the system is cooled to room temperature, dichloromethane is added to dilute, and then washed three times with an aqueous solution containing sodium chloride, and tetrahydrofuran is added before each washing to aid dissolution. The resulting organic phase was dried over anhydrous sodium sulfate, filtered and the solvent was removed under reduced pressure. The obtained product was dissolved in tetrahydrofuran, precipitated in n-hexane and purified three times. The resulting white solid product β-CD-b1-(N ₃ ) ₄₂ was dried under vacuum at room temperature to constant weight. The molar ratio of β-CD-b1-Br ₄₂ to sodium azide is 1:50.4; the ratio of DMF to β-CD-b1-Br ₄₂ is 10 (mL): 1 (g). The yield was 76%.

Step 5: 0.99g (2.78mmol) ABMP and 0.8g (4.63mmol) PMDETA were dissolved in 15ml of DMF, and the reaction solution was passed through argon for 30min at room temperature, during which time ultrasound was added 3 times, and then 0.5g was added under the protection of argon (2.32mmolN ₃ )β-CD-b1-(N ₃ ) ₄₂ and 0.33g (2.32mmol)CuBr were passed through argon for 20min, the reaction bottle was sealed, and reacted at 35°C for 1h. After the reaction is finished, dilute with dichloromethane, wash with water 5 times with a mixed solution containing ammonium chloride and sodium chloride, then continue to wash with water for 2 times with an aqueous solution containing sodium chloride, add tetrahydrofuran to aid dissolution before each wash, tetrahydrofuran The dosage is less than 0.25 volume of tetrahydrofuran/dichloromethane. The resulting organic solution was dried over anhydrous sodium sulfate, filtered and the solvent was removed under reduced pressure. The obtained product was dissolved in tetrahydrofuran, precipitated in n-hexane and purified twice. The second-generation dendrimer β-CD-b2-Br ₈₄ was obtained as a white solid, which was vacuum-dried at room temperature to constant weight. The molar ratio of β-CD-b1-(N ₃ ) ₄₂ , ABMP, CuBr, N,N,N',N,'N"-pentamethyldiethylenetriamine (PMDETA) is 1:1.2 : 1: 2; the ratio of DMF to β-CD-b1-(N ₃ ) ₄₂ is 30 (mL): 1 (g). Yield: 68%.

From Figures 4 to 8 of the infrared spectrum, it can be seen that after the nucleophilic substitution reaction with sodium azide, the infrared vibration peak of the azide group appears in the infrared spectrum, and the infrared stretching vibration peak of the azide disappears after the click reaction, which proves that the click reaction proceeds completely. It can be seen from the infrared spectrogram Figure 9 that the stretching vibration peaks of the alkynyl group and the ester bond appear, which proves that ABMP has been synthesized. It can be seen from the NMR spectrum in Figure 15 that the multifunctional group monomer ABMP has been successfully synthesized. From the NMR spectra shown in Figures 10 to 14 and the gel permeation chromatography (GPC) of the major molecules of the dendrimer in Figure C, it can be seen that the resulting product is consistent with the designed expected product structure.

Claims (8)

1. A dendrimer with β-CD as the core, characterized in that: with β-CD as the core, 21 hydroxyl groups on the CD are all modified dendrimer β-CD containing multiple functional groups -b2-Br ₈₄ , the structure is as follows: The structural characteristics of the multifunctional monomer ABMP in the synthesis process are: 2. a method for preparing claim 1 with β-CD as the core dendrimer, characterized in that the steps are as follows: Step 1: react 21Cl-β-CD and sodium azide in N,N-dimethylformamide DMF as the solvent temperature, and react at 25°C-30°C for 48h-60h to obtain 21N ₃ -β-CD; The mol ratio of described sodium azide, 21Cl-β-CD is 42: 1, and the consumption ratio of DMF and 21Cl-β-CD is 3 milliliters: 1 gram; Step 2: Dissolve 5-hexynoic acid in toluene, then add dibromoneopentyl glycol and a catalytic amount of p-toluenesulfonic acid p-TSA, then place the reaction in a Dean-StarK apparatus at 120°C to 123 Reflux in an oil bath at °C for 8h to 10h to obtain the multifunctional monomer ABMP; the molar ratio of 5-hexynoic acid, dibromoneopentyl glycol, and p-toluenesulfonic acid p-TSA is 1:7: 0.04, the ratio of the amount of toluene to 5-hexynoic acid is 40 ml: 1 g; Step 3: Dissolve the multifunctional monomer ABMP and the ligand N,N,N',N,'N"-pentamethyldiethylenetriamine PMDETA in DMF, remove oxygen by air blowing, and then Add 21N ₃ -β-CD and CuBr under the protection of nitrogen, and continue to deoxygenate by blowing gas; then seal it under the protection of argon, and place it at 25°C-35°C for 40min-1h to obtain the first-generation branched product β-CD-b1-Br ₄₂ ; the molar ratio of 21N ₃ -β-CD, ABMP, CuBr, PMDETA is 1: 1.2: 1: 2, the amount ratio of DMF to 21N ₃ -β-CD is 30 ml: 1 gram; Step 4: Dissolve the first-generation branched product β-CD-b1-Br ₄₂ and sodium azide in DMF, deoxygenate by air blowing, then seal under the protection of argon, and place at 70°C to 80°C The reaction time is 12h to 14h; the molar ratio of β-CD-b1-Br ₄₂ and sodium azide is 1:50.4, and the ratio of DMF to β-CD-b1-Br ₄₂ is 10ml:1g; Step 5: Dissolve the multifunctional monomer ABMP and the ligand N,N,N',N,'N"-pentamethyldiethylenetriamine PMDETA in DMF, remove oxygen by air blowing, and then Add the β-CD-b1-(N ₃ ) ₄₂ and CuBr treated in step 4 under the protection of nitrogen, and continue to deoxygenate by gas blowing; then seal it under the protection of argon, and place it at 25 ° C ~ 35 ° C for 1 h ~ 1.5h to obtain the second-generation dendrimer β-CD-b2-Br ₈₄ ; the molar ratio of the β-CD-b1-(N ₃ ) ₄₂ , ABMP, CuBr, and PMDETA is 1:1.2:1:2, The dosage ratio of DMF and β-CD-b1-(N ₃ ) ₄₂ is 30ml: 1g. 3. The method according to claim 2, characterized in that: the 21Cl-β-CD in the step 1 is obtained by the synthetic reaction of 2-chloropropionyl chloride and β-CD. 4. The method according to claim 2, characterized in that: after the step 1 is reacted at 25°C to 30°C for 48h to 60h, after the reaction is completed, ethyl acetate is added and washed with an aqueous solution containing sodium chloride; Collect the organic layer, add anhydrous sodium sulfate to dry, remove anhydrous sodium sulfate and color with a neutral alumina column; then add an appropriate amount of tetrahydrofuran, precipitate in n-hexane and purify 2 to 3 times to obtain a white solid product 21N ₃ -β-CD. 5. The method according to claim 2, characterized in that: after the reflux 8h～10h reaction of said step 2 is finished, the reaction system is cooled to room temperature, the solid is removed by filtration, and the solvent is removed under reduced pressure; For purification, use a mixed solvent of dichloromethane and ether as the eluent; remove the solvent under reduced pressure to obtain a colorless liquid product, multifunctional monomer ABMP, and dry it in vacuum at room temperature to constant weight; the volume ratio of dichloromethane and ether is 10: 1. 6. The method according to claim 2, characterized in that: said step 3 is reacted at 25°C to 35°C for 40min to 1h after the reaction is completed, diluted with dichloromethane, and then ammonium chloride and sodium chloride The mixed solution was washed with water, and then continued to be washed with an aqueous solution containing sodium chloride, and tetrahydrofuran was added to aid dissolution before each washing, and the amount of tetrahydrofuran was such that the volume of tetrahydrofuran and dichloromethane was less than 0.25; Afterwards, the solvent was removed under reduced pressure; the obtained product was dissolved in tetrahydrofuran, precipitated in n-hexane for purification, and the white solid product β-CD-b1-Br ₄₂ was obtained. 7. The method according to claim 2, characterized in that: the step 4 is placed under the condition of 70°C to 80°C for 12h to 14h after the reaction is completed, after the system is cooled to room temperature, dichloromethane is added to dilute, and then Wash with an aqueous solution containing sodium chloride, and add tetrahydrofuran to aid dissolution before each washing. The volume ratio of tetrahydrofuran to dichloromethane is less than 0.25; the obtained organic phase is dried with anhydrous sodium sulfate, filtered, and the solvent is removed under reduced pressure to obtain the product Dissolved in tetrahydrofuran, precipitated in n-hexane and purified to obtain a white solid product β-CD-b1-(N ₃ ) ₄₂ , which was vacuum-dried at room temperature to constant weight. 8. The method according to claim 2, characterized in that: said step 5 is reacted at 25°C to 35°C for 1h to 1.5h after the reaction is completed, diluted with dichloromethane, and mixed with ammonium chloride and chloride The mixed solution of sodium was washed with water, and then continued to be washed with an aqueous solution containing sodium chloride, and tetrahydrofuran was added to aid dissolution before each washing, and the amount of tetrahydrofuran was such that the volume ratio of tetrahydrofuran to dichloromethane was less than 0.25; Afterwards, the solvent was removed under reduced pressure, and the obtained product was dissolved in tetrahydrofuran, precipitated in n-hexane and purified to obtain the second-generation dendrimer β-CD-b2-Br ₈₄ as a white solid, which was vacuum-dried at room temperature until constant Heavy.