Roxane dendritic macromolecular compound and synthesis method thereof

Abstract

The synthetic method comprises the following steps: under the protection of an inert atmosphere, carrying out nucleophilic substitution reaction on a compound A, potassium carbonate and deuterated bromoethane in acetonitrile to obtain a compound B; adding the compound B, the compound C, cuprous iodide and bis (triethyl phosphine) platinum iodide into chloroform and diisopropylamine, and carrying out a coupling reaction to obtain a compound D; tetra (4-ethynylbenzene) methane is taken as a core and is subjected to coupling reaction with a compound D and a compound E respectively to obtain DG1 and G1. And on the basis, deuterated rotaxane dendritic macromolecules D2G2, DG2, D1G2, D3G3, D2G3, D1G3 and DG3 with deuterated structures and completely non-deuterated rotaxane dendritic macromolecules G2 and G3 are introduced into different layers of a compound D and a compound E through repeated and alternately iterative deprotection-coupling reaction respectively, so that deuterated rotaxane dendritic macromolecules D2G2, DG2, D1G2, D3G3, D2G3, D1G3 and DG3 are introduced into different layers. The synthetic process is simple, the yield is high, and high-algebraic full-non-deuterated rotaxane dendrimer compounds and selective deuterated rotaxane dendrimer compounds can be successfully prepared.

Description

Technical Field

[0001] The present invention belongs to the technical field of mechanically interlocked molecules, relates to rotaxane dendrimers, and particularly relates to a rotaxane dendrimer compound and a synthesis method thereof. Background Art

[0002] Mechanically interlocked molecules (MIMs) such as rotaxanes, catenanes, and molecular knots have received extensive attention from supramolecular chemists due to their unique structures and broad application prospects in fields such as molecular machines. In recent years, by mimicking the precise arrangement of nanomechanical units in biological systems, introducing multiple mechanically interlocked molecules into specific supramolecular skeletons, and then constructing novel dynamic supramolecular systems has become a frontier and hot topic in supramolecular chemistry research. As a new type of mechanically interlocked molecule, rotaxane dendrimers contain multiple precisely arranged rotaxane units in their backbone structures, so they have both the controllable motion characteristics of rotaxanes and the specific topological structure characteristics of dendrimers, and are expected to exhibit great potential applications in fields such as artificial molecular machines and bionic intelligent materials, which has attracted great attention from chemists in recent years.

[0003] After nearly three decades of development, a series of rotaxane dendrimers with structural diversity have been precisely synthesized. However, due to their unique three-dimensional multi-level structure and other characteristics, it has become extremely difficult to study the kinetic processes of rotaxane dendrimers under stimulus-responsive conditions. Traditional characterization methods such as nuclear magnetic resonance, ultraviolet fluorescence, and electrochemistry cannot provide relatively intuitive molecular conformation information, making it extremely difficult to study their motion processes.

[0004] Compared with conventional characterization methods, small-angle neutron scattering (SANS) technology has extremely high sensitivity for organic systems containing a large number of hydrogen atoms. It can study the size and shape of particles in solution through contrast variation technology (deuteration), and achieve labeling and selective observation of specific regions in the structure. Therefore, based on novel deuterated rotaxane dendrimers and combined with SANS characterization technology, the fine structural changes of rotaxane dendrimers under anion stimulus-responsive conditions can be systematically studied, thereby obtaining the motion characteristics and related kinetic parameters of the rotaxane units in the backbone under stimulus-responsive conditions. However, there are currently no relevant reports on deuterated dendrimers, especially rotaxane dendrimers with deuteration treatment of a large number of hydrogen atoms on the rotaxane units, due to the high challenge of their synthesis process. Summary of the Invention

[0005] Aiming at the above deficiencies existing in the prior art, the purpose of the present invention is to provide a rotaxane dendrimer compound and a synthesis method thereof. The synthesis process of the present invention is simple and has a high yield, and can successfully synthesize high-generation fully non-deuterated rotaxane dendrimers and selectively deuterated rotaxane dendrimer compounds.

[0006] The technical solution of the present invention is realized as follows:

[0007] A method for synthesizing a rotaxane dendrimer compound, comprising the following steps:

[0008] S1: Under the protection of an inert atmosphere, compound A, potassium carbonate, and deuterated bromoethane are subjected to a nucleophilic substitution reaction in acetonitrile to obtain compound B; the structural formulas of compound A and compound B are as follows:

[0009]

[0010] S2: Under the protection of an inert atmosphere, compound B, compound C, copper(I) iodide, and platinum(II) bis(triethylphosphine) iodide are added to chloroform and diisopropylamine for a coupling reaction to obtain compound D; the structural formulas of compound C and compound D are as follows:

[0011]

[0012] S3: Using tetra(4-ethynylphenyl)methane as the core, a coupling reaction with compound D gives the first-generation deuterated rotaxane dendrimer compound DG1; the structural formula of compound DG1 is as Figure 1 shown.

[0013] S4: Using tetra(4-ethynylphenyl)methane as the core, a coupling reaction with compound E gives the first-generation non-deuterated rotaxane dendrimer compound G1, and the structural formula of compound G1 is as Figure 2 shown; the structural formula of compound E is as follows:

[0014]

[0015] S5: Compound G1 is respectively reacted with compound D and compound E using repeated alternating deprotection-coupling reactions to obtain the second-generation deuterated rotaxane dendrimer compound D2G2 (the structural formula of which is as Figure 4 shown) and the second-generation non-deuterated rotaxane dendrimer compound G2 (the structural formula of which is as Figure 6 shown); compound DG1 is respectively reacted with compound D and compound E using repeated alternating deprotection-coupling reactions to obtain the second-generation deuterated rotaxane dendrimer compound DG2 with two layers (the structural formula of which is as Figure 5 shown) and the second-generation deuterated rotaxane dendrimer compound D1G2 with the first layer ((the structural formula of which is as Figure 3 shown);

[0016] S6: Compound G2 is respectively reacted with compound D and compound E using repeated alternating deprotection-coupling reactions to obtain the third-generation deuterated rotaxane dendrimer compound D3G3 with three layers (the structural formula of which is as Figure 9as shown) and the third-generation non-deuterated rotaxane dendrimer compound G3 (whose structural formula is as Figure 11 shown); The compound D2G2 and the compound E are reacted by a repeated alternating deprotection-coupling reaction to obtain the second-layer deuterated third-generation rotaxane dendrimer compound D2G3 (whose structural formula is as Figure 8 shown); The compound D1G2 and the compound E are reacted by a repeated alternating deprotection-coupling reaction to obtain the first-layer deuterated third-generation rotaxane dendrimer compound D1G3 (whose structural formula is as Figure 7 shown); The compound DG2 and the compound D are reacted by a repeated alternating deprotection-coupling reaction to obtain the three-layer deuterated third-generation rotaxane dendrimer compound DG3 (whose structural formula is as Figure 10 shown).

[0017] Further, in step S1, the molar ratio of compound A to deuterated bromoethane is 1:10 to 100, preferably 1:11.

[0018] Further, in step S2, the molar ratio of compound C to compound B is 1:2 to 20, preferably 1:6.

[0019] Further, in step S3, the molar ratio of tetra(4-ethynylphenyl)methane to compound D is 1:1 to 8, preferably 1:4.4; Copper iodide is also added, and the molar ratio of compound D to copper iodide is 1:0.01 to 1, preferably 1:0.1; In step S4, the molar ratio of tetra(4-ethynylphenyl)methane to compound E is 1:1 to 8, preferably 1:4.4; Copper iodide is also added, and the molar ratio of compound E to copper iodide is 1:0.01 to 1, preferably 1:0.1.

[0020] Further, in step S5, when synthesizing compound D2G2, the molar ratio of the deprotected compound G1 to compound D is 1:1 to 16, preferably 1:8.8; Copper iodide is also added, and the molar ratio of compound D to copper iodide is 1:0.01 to 1, preferably 1:0.1; When synthesizing compound G2, the molar ratio of the deprotected compound G1 to compound E is 1:1 to 16, preferably 1:8.8; Copper iodide is also added, and the molar ratio of compound E to copper iodide is 1:0.01 to 1, preferably 1:0.1; When synthesizing compound DG2, the molar ratio of the deprotected compound DG1 to compound D is 1:1 to 16, preferably 1:8.8; Copper iodide is also added, and the molar ratio of compound D to copper iodide is 1:0.01 to 1, preferably 1:0.1; When synthesizing compound D1G2, the molar ratio of the deprotected compound DG1 to compound E is 1:1 to 16, preferably 1:8.8; Copper iodide is also added, and the molar ratio of compound E to copper iodide is 1:0.01 to 1, preferably 1:0.1.

[0021] Further, in step S6, when synthesizing compound D3G3, the molar ratio of deprotected compound G2 to compound D is 1:1 to 32, preferably 1:17.6; cuprous iodide is also added, and the molar ratio of compound D to cuprous iodide is 1:0.01 to 1, preferably 1:0.1; when synthesizing compound G3, the molar ratio of deprotected compound G2 to compound E is 1:1 to 32, preferably 1:17.6; cuprous iodide is also added, and the molar ratio of compound E to cuprous iodide is 1:0.01 to 1, preferably 1:0.1; when synthesizing compound D2G3, the molar ratio of deprotected compound D2G2 to compound E is 1:1 to 32, preferably 1:17.6; cuprous iodide is also added, and the molar ratio of compound E to cuprous iodide is 1:0.01 to 1, preferably 1:0.1; when synthesizing compound D1G3, the molar ratio of deprotected compound D1G2 to compound E is 1:1 to 32, preferably 1:17.6; cuprous iodide is also added, and the molar ratio of compound E to cuprous iodide is 1:0.01 to 1, preferably 1:0.1; when synthesizing compound DG3, the molar ratio of deprotected compound DG2 to compound D is 1:1 to 32, preferably 1:17.6; cuprous iodide is also added, and the molar ratio of compound D to cuprous iodide is 1:0.01 to 1, preferably 1:0.1.

[0022] Further, in step S1, the temperature of the nucleophilic substitution reaction is 35 to 90 °C, preferably 80 °C; the reaction time is 4 to 24 h, preferably 18 h.

[0023] Further, in steps S2, S3, S4, S5 and S6, the temperature of the coupling reaction is -30 to 35 °C, preferably 25 °C; the reaction time is 2 to 24 h, preferably 12 h.

[0024] The present invention also provides a series of rotaxane dendrimers, including the first-generation rotaxane dendrimer compounds DG1 and G1 synthesized by using the synthesis method of a deuterated rotaxane dendrimer described above; the second-generation rotaxane dendrimer compounds D2G2, G2, DG2 and D1G2; the third-generation rotaxane dendrimer compounds G3, D3G3, D2G3, D1G3 and DG3.

[0025] Compared with the prior art, the present invention has the following beneficial effects:

[0026] 1. The synthesis process of the present invention is simple, efficient, with mild and easily controllable reaction conditions. Moreover, there are no small molecule and oligomer by-products generated, and the target rotaxane dendrimer compound is the only product, reducing subsequent complex purification steps. This not only improves the synthesis efficiency but also effectively reduces the synthesis cost. Meanwhile, the present invention successfully prepares high-generation and monodisperse rotaxane dendrimer compounds, solving the synthesis problem of high-generation rotaxane dendrimer compounds and providing the possibility for industrial production.

[0027] 2. The present invention realizes the precise design and regulation of the molecular structure by introducing deuterated structures into different layers of the rotaxane dendrimer. The deuterated rotaxane units are precisely distributed in specific layers of the dendritic molecular skeleton, enabling the molecule to exhibit unique physicochemical properties between different layers. This precise control of the structure provides the possibility for subsequent comparative studies of the molecular conformations between different layers through advanced characterization techniques such as small-angle neutron scattering (SANS), contributing to a deeper understanding of the structure-function relationship of rotaxane dendrimers.

[0028] 3. The rotaxane dendrimer compounds synthesized by the present invention have broad application prospects in the fields of artificial molecular machines, bionic intelligent materials, drug delivery systems, etc. The unique structures and properties of these compounds endow them with great potential in molecular recognition, information storage, energy conversion, etc. Meanwhile, combined with the small-angle neutron scattering characterization technique, the present invention can systematically study the fine structural changes of deuterated rotaxane dendrimers under stimuli, revealing the motion characteristics of the rotaxane units in the skeleton and related kinetic parameters. This in-depth study of the molecular motion mechanism not only helps to understand the basic properties of rotaxane dendrimers but also provides a scientific basis for the development of new functional materials based on these molecules, possessing important scientific value and application prospects. Description of the Drawings

[0029] Figure 1 - Structural formula of compound DG1.

[0030] Figure 2 - Structural formula of compound G1.

[0031] Figure 3 - Structural formula of compound D1G2.

[0032] Figure 4 - Structural formula of compound D2G2.

[0033] Figure 5 - Structural formula of compound DG2.

[0034] Figure 6 - Structural formula of compound G2.

[0035] Figure 7- Structural formula of compound D1G3.

[0036] Figure 8 - Structural formula of compound D2G3.

[0037] Figure 9 - Structural formula of compound D3G3.

[0038] Figure 10 - Structural formula of compound DG3.

[0039] Figure 11 - Structural formula of compound G3.

[0040] Figure 12 - 1H NMR and 13C NMR spectra of compound B.

[0041] Figure 13 - 1H NMR and 13C NMR spectra of compound D.

[0042] Figure 14 - 1H NMR spectra of compounds DG1, G1, D1G2, D2G2, DG2 and G2 in Example 1.

[0043] Figure 15 - 13C NMR spectra of compounds DG1, G1, D1G2, D2G2, DG2 and G2 in Example 1.

[0044] Figure 16 - 1H NMR spectra of compounds D1G3, D2G3, D3G3, DG3 and G3 in Example 1.

[0045] Figure 17 - 13C NMR spectra of compounds D1G3, D2G3, D3G3, DG3 and G3 in Example 1.

[0046] Figure 18 - 1H NMR spectrum of compound G3 under the stimulation of TBAA anions in Example 1.

[0047] Figure 19 - SANS diagram of compound G3 under the stimulation of TBAA anions in Example 1. Detailed implementation mode

[0048] The present invention will be further described in detail below with reference to the accompanying drawings and specific implementation modes.

[0049] Example 1

[0050] (1) Synthesis of compound A, compound C and compound E

[0051] Compound A was synthesized with reference to T. Ogoshi, T. Aoki, K. Kitajima, S. Fujinami, T.-A. Yamagishi, Y. Nakamoto, Facile, Rapid, and High-Yield Synthesis of Pillar[5]Arene from Commercially Available Reagents and Its X-Ray Crystal Structure. J. Org. Chem. 2011, 76, 328 - 331. The synthetic route is as follows:

[0052]

[0053] Compound C and compound E were synthesized with reference to X.-Q. Wang, W. Wang, W.-J. Li, L.-J. Chen, R. Yao, G.-Q. Yin, Y.-X. Wang, Y. Zhang, J. Huang, H. Tan, Y. Yu, X. Li, L. Xu, H.-B. Yang, Dual stimuli-responsive rotaxane dendrimers with reversible dimension modulation, Nat. Commun. 2018, 9, 3190. The synthetic route is as follows:

[0054]

[0055] (2) Synthesis of compound B

[0056] Compound A (500 mg, 0.82 mmol) and potassium carbonate (4.53 g, 32.76 mmol) were added to 10 mL of acetonitrile under a nitrogen atmosphere, and the system was stirred at room temperature for 30 min. Subsequently, deuterated bromoethane (0.67 mL, 9.02 mmol) was added, and the system was heated to 80 °C and stirred for 18 h. After the reaction was completed, the reaction solution was cooled to room temperature, and then the reaction mixture was filtered and the filtrate was concentrated in vacuo. The crude product was purified by flash column chromatography (eluent: n-hexane:dichloromethane = 10:1, v / v) to obtain white solid compound B with a yield of 85%.

[0057] The reaction route is as follows:

[0058]

[0059] (3) Synthesis of compound D

[0060] Compound C (150 mg, 0.20 mmol), compound B (1.13 g, 1.20 mmol) and Pt(PEt3)2I2 (548 mg, 0.80 mmol) were placed in a reaction flask. Then the reaction flask was evacuated and filled with N2 three times. Then 15 mL of a mixed solvent of anhydrous and oxygen-free CHCl3 and i-Pr2NH (v / v, 2:1) was added using a syringe. The resulting solution was stirred at -10 °C for 2 hours, and then CuI (4 mg) was added under an inert atmosphere, heated to room temperature, and stirred overnight. The solution was concentrated and separated by column chromatography (n-hexane:dichloromethane = 2:1, v / v). White solid compound D was obtained with a yield of 82%.

[0061] The synthetic route of compound D is as follows:

[0062]

[0063] (4) Synthesis of the first-generation rotaxane dendrimer compounds DG1 and G1

[0064] 4.1 Tetrakis(4-ethynylphenyl)methane (15 mg, 0.036 mmol) and compound D (357 mg, 0.16 mmol) were placed in a two-necked flask. After displacing nitrogen three times, a degassed mixed solution of dichloromethane and diethylamine was added. Subsequently, a catalytic amount of copper(I) iodide (3 mg) was added under a nitrogen atmosphere, and the mixture was stirred at room temperature overnight. After the reaction was completed, the solvent was dried under vacuum, and the product was separated by preparative gel permeation chromatography to obtain the first-generation deuterated rotaxane dendrimer compound DG1 with a yield of 85%. The structural formula of compound DG1 is as Figure 1 shown.

[0065] Then the first-generation deuterated rotaxane dendrimer compound DG1 (100 mg, 0.011 mmol) containing a triisopropylsilyl protecting group was dissolved in tetrahydrofuran. A solution of tetrabutylammonium fluoride (56 mg, 0.18 mmol) in tetrahydrofuran was slowly added under an ice bath condition. Subsequently, the system was removed from the ice bath and slowly restored to room temperature and then continuously stirred for one hour. After the reaction was completed, 5 mL of deionized water was added to the system to quench the reaction. Subsequently, the aqueous layer was extracted with dichloromethane (5 × 50 mL). The combined organic layers were washed with water (5 × 50 mL) in turn, the solvent was rotary evaporated, and the crude product was separated by preparative gel permeation chromatography to obtain the first-generation deuterated rotaxane dendrimer compound without the protecting group with a yield of 98%.

[0066] 4.2 Place tetrakis(4-ethynylphenyl)methane (15 mg, 0.036 mmol) and compound E (348 mg, 0.16 mmol) in a two-necked flask. After displacing nitrogen three times, add a degassed mixed solution of dichloromethane and diethylamine. Subsequently, add a catalytic amount of copper(I) iodide (3 mg) under a nitrogen atmosphere and stir at room temperature overnight. After the reaction is completed, dry the solvent under vacuum and separate by preparative gel permeation chromatography to obtain the first-generation non-deuterated rotaxane dendrimer compound G1 with a yield of 89%. The structural formula of compound G1 is as shown in Figure 2 shown.

[0067] Then dissolve the first-generation non-deuterated rotaxane dendrimer compound G1 (100 mg, 0.012 mmol) containing a triisopropylsilyl protecting group in tetrahydrofuran. Slowly add a solution of tetrabutylammonium fluoride (58 mg, 0.18 mmol) in tetrahydrofuran under an ice bath. Subsequently, remove the ice bath from the system and slowly warm it to room temperature and continue stirring for one hour. After the reaction is completed, add 5 mL of deionized water to the system to quench the reaction. Then extract the aqueous layer with dichloromethane (5×50 mL). Combine the organic layers and wash them successively with water (5×50 mL), rotary evaporate the solvent, and separate the crude product by preparative gel permeation chromatography to obtain the first-generation non-deuterated rotaxane dendrimer compound without the protecting group with a yield of 97%.

[0068] (5) Synthesize the second-generation rotaxane dendrimer compounds DG2, D2G2, D1G2, and G2.

[0069] 5.1 Weigh the obtained first-generation deuterated rotaxane dendrimer compound without the protecting group (51 mg, 0.0067 mmol) and compound E (129 mg, 0.059 mmol) in a two-necked flask of appropriate size. After displacing nitrogen three times, add a degassed mixed solution of dichloromethane and diethylamine. Subsequently, add a catalytic amount of copper(I) iodide (1.1 mg) under a nitrogen atmosphere and stir at room temperature overnight. After the reaction is completed, dry the solvent under vacuum and separate by preparative gel permeation chromatography to obtain the first-layer deuterated second-generation rotaxane dendrimer compound D1G2 with a yield of 90%. The structural formula of compound D1G2 is as shown in Figure 3 shown.

[0070] Subsequently, the first-generation deuterated second-generation rotaxane dendrimer compound D1G2 (87.6 mg, 0.0036 mmol) was dissolved in tetrahydrofuran. A solution of tetrabutylammonium fluoride (36.5 mg, 0.12 mmol) in tetrahydrofuran was slowly added under an ice bath condition. Subsequently, the system was removed from the ice bath and slowly restored to room temperature, followed by continuous stirring for one hour. After the reaction was completed, 5 mL of deionized water was added to the system to quench the reaction. Subsequently, the aqueous layer was extracted with dichloromethane (5 × 50 mL). The combined organic layers were successively washed with water (5 × 50 mL), and the solvent was rotary evaporated. The crude product was separated by preparative gel permeation chromatography to obtain the first-generation deuterated second-generation rotaxane dendrimer compound with the protecting group removed, and the yield was 93%.

[0071] 5.2 The obtained first-generation non-deuterated rotaxane dendrimer compound with the protecting group removed (75 mg, 0.01 mmol) and compound D (194.6 mg, 0.088 mmol) were weighed in a suitable round-bottom flask with a side arm. After displacing nitrogen three times, a degassed mixed solution of dichloromethane and diethylamine was added. Subsequently, a catalytic amount of copper(I) iodide (1.7 mg) was added under a nitrogen atmosphere, and the mixture was stirred at room temperature overnight. After the reaction was completed, the solvent was dried under vacuum, and the product was separated by preparative gel permeation chromatography to obtain the second-generation deuterated second-generation rotaxane dendrimer compound D2G2, and the yield was 86%. The structural formula of compound D2G2 is as Figure 4 shown.

[0072] Subsequently, the second-generation deuterated second-generation rotaxane dendrimer compound D2G2 (110 mg, 0.0045 mmol) was dissolved in tetrahydrofuran. A solution of tetrabutylammonium fluoride (45.4 mg, 0.14 mmol) in tetrahydrofuran was slowly added under an ice bath condition. Subsequently, the system was removed from the ice bath and slowly restored to room temperature, followed by continuous stirring for one hour. After the reaction was completed, 5 mL of deionized water was added to the system to quench the reaction. Subsequently, the aqueous layer was extracted with dichloromethane (5 × 50 mL). The combined organic layers were successively washed with water (5 × 50 mL), and the solvent was rotary evaporated. The crude product was separated by preparative gel permeation chromatography to obtain the second-generation deuterated second-generation rotaxane dendrimer compound with the protecting group removed, and the yield was 90%.

[0073] 5.3 Weigh the obtained deprotected first-generation deuterated rotaxane dendrimer compound (81 mg, 0.011 mmol) and compound D (210 mg, 0.093 mmol) in a branched-neck flask of appropriate size. After displacing nitrogen three times, add a degassed mixed solution of dichloromethane and diethylamine. Subsequently, add a catalytic amount of copper(I) iodide (1.8 mg) under a nitrogen atmosphere and stir at room temperature overnight. After the reaction is completed, dry the solvent under vacuum and separate by preparative gel permeation chromatography to obtain the two-layer deuterated second-generation rotaxane dendrimer compound DG2 with a yield of 87%. The structural formula of compound DG2 is as shown in Figure 5 shown.

[0074] Then dissolve the two-layer deuterated second-generation rotaxane dendrimer compound DG2 (112 mg, 0.0046 mmol) in tetrahydrofuran. Slowly add a tetrahydrofuran solution of tetrabutylammonium fluoride (46 mg, 0.15 mmol) under an ice bath condition. Subsequently, remove the system from the ice bath, slowly warm it to room temperature, and continue stirring for one hour. After the reaction is completed, add 5 mL of deionized water to the system to quench the reaction. Then extract the aqueous layer with dichloromethane (5×50 mL). The combined organic layers are washed with water (5×50 mL) in sequence, and the solvent is rotary evaporated. The crude product is separated by preparative gel permeation chromatography to obtain the deprotected two-layer deuterated second-generation rotaxane dendrimer compound with a yield of 88%.

[0075] 5.4 Weigh the obtained deprotected first-generation non-deuterated rotaxane dendrimer compound (90 mg, 0.012 mmol) and compound E (233.5 mg, 0.11 mmol) in a branched-neck flask of appropriate size. After displacing nitrogen three times, add a degassed mixed solution of dichloromethane and diethylamine. Subsequently, add a catalytic amount of copper(I) iodide (2 mg) under a nitrogen atmosphere and stir at room temperature overnight. After the reaction is completed, dry the solvent under vacuum and separate by preparative gel permeation chromatography to obtain the second-generation non-deuterated rotaxane dendrimer compound G2 with a yield of 91%. The structural formula of compound G2 is as shown in Figure 6 shown.

[0076] Then dissolve the second-generation non-deuterated rotaxane dendrimer compound G2 (241 mg, 0.01 mmol) in tetrahydrofuran. Slowly add a tetrahydrofuran solution of tetrabutylammonium fluoride (101 mg, 0.32 mmol) under an ice bath condition. Subsequently, remove the system from the ice bath, slowly warm it to room temperature, and continue stirring for one hour. After the reaction is completed, add 5 mL of deionized water to the system to quench the reaction. Then extract the aqueous layer with dichloromethane (5×50 mL). The combined organic layers are washed with water (5×50 mL) in sequence, and the solvent is rotary evaporated. The crude product is separated by preparative gel permeation chromatography to obtain the deprotected second-generation non-deuterated rotaxane dendrimer compound with a yield of 86%.

[0077] (6) The third-generation rotaxane dendrimer compounds D1G3, D2G3, D3G3, DG3, G3.

[0078] 6.1 Weigh the obtained deprotected first-layer deuterated second-generation rotaxane dendrimer compound (34 mg, 0.0016 mmol) and compound E (60 mg, 0.027 mmol) in a branched flask of appropriate size. After displacing nitrogen three times, add a degassed mixed solution of dichloromethane and diethylamine. Subsequently, add a catalytic amount of copper(I) iodide (0.5 mg) under a nitrogen atmosphere and stir at room temperature overnight. After the reaction is completed, dry the solvent under vacuum and separate by preparative gel permeation chromatography to obtain the first-layer deuterated third-generation rotaxane dendrimer compound D1G3 with a yield of 91%. The structural formula of compound D1G3 is as Figure 7 shown.

[0079] 6.2 Weigh the obtained deprotected second-layer deuterated second-generation rotaxane dendrimer compound (56 mg, 0.0026 mmol) and compound E (99 mg, 0.045 mmol) in a branched flask of appropriate size. After displacing nitrogen three times, add a degassed mixed solution of dichloromethane and diethylamine. Subsequently, add a catalytic amount of copper(I) iodide (0.9 mg) under a nitrogen atmosphere and stir at room temperature overnight. After the reaction is completed, dry the solvent under vacuum and separate by preparative gel permeation chromatography to obtain the second-layer deuterated third-generation rotaxane dendrimer compound D2G3 with a yield of 85%. The structural formula of compound D2G3 is as Figure 8 shown.

[0080] 6.3 Weigh the obtained deprotected second-generation non-deuterated rotaxane dendrimer compound (57 mg, 0.0026 mmol) and compound D (104 mg, 0.046 mmol) in a branched flask of appropriate size. After displacing nitrogen three times, add a degassed mixed solution of dichloromethane and diethylamine. Subsequently, add a catalytic amount of copper(I) iodide (0.9 mg) under a nitrogen atmosphere and stir at room temperature overnight. After the reaction is completed, dry the solvent under vacuum and separate by preparative gel permeation chromatography to obtain the third-layer deuterated third-generation rotaxane dendrimer compound D3G3 with a yield of 87%. The structural formula of compound D3G3 is as Figure 9 shown.

[0081] 6.4 The obtained deprotected two-layer deuterated second-generation rotaxane dendrimer compound (57 mg, 0.0026 mmol) and compound D (102 mg, 0.045 mmol) were weighed in a branched-neck flask of appropriate size. After replacing nitrogen three times, a degassed mixed solution of dichloromethane and diethylamine was added. Subsequently, a catalytic amount of copper(I) iodide (0.9 mg) was added under a nitrogen atmosphere, and the mixture was stirred at room temperature overnight. After the reaction was completed, the solvent was dried under vacuum, and the three-layer deuterated third-generation rotaxane dendrimer compound DG3 was obtained by preparative gel permeation chromatography with a yield of 97%. The structural formula of compound DG3 is as shown in Figure 10 shown.

[0082] 6.5 The obtained deprotected non-deuterated second-generation rotaxane dendrimer compound (140 mg, 0.0065 mmol) and compound E (252 mg, 0.12 mmol) were weighed in a branched-neck flask of appropriate size. After replacing nitrogen three times, a degassed mixed solution of dichloromethane and diethylamine was added. Subsequently, a catalytic amount of copper(I) iodide (2.2 mg) was added under a nitrogen atmosphere, and the mixture was stirred at room temperature overnight. After the reaction was completed, the solvent was dried under vacuum, and the third-generation non-deuterated rotaxane dendrimer compound G3 was obtained by preparative gel permeation chromatography with a yield of 83%. The structural formula of compound G3 is as shown in Figure 11 shown.

[0083] 1. The proton nuclear magnetic resonance spectra and carbon nuclear magnetic resonance spectra of compound B and compound D synthesized in this example are as shown in Figure 12 and Figure 13 shown, respectively. The proton nuclear magnetic resonance spectra and phosphorus nuclear magnetic resonance spectra of the compounds DG1, G1, D1G2, D2G2, DG2, G2, D1G3, D2G3, D3G3, DG3 and G3 prepared in this example are as shown in Figure 14 , Figure 15 , Figure 16 and Figure 17 shown. It can be seen from the figures that the compounds DG1, G1, D1G2, D2G2, DG2, G2, D1G3, D2G3, D3G3, DG3 and G3 were successfully synthesized.

[0084] 2. For proton nuclear magnetic resonance titration using deuterated tetrahydrofuran as the medium, first, compound G3 (11 mg) was dissolved in 500 μL of deuterated tetrahydrofuran, and then different equivalents of tetrabutylammonium acetate salt (TBAA) were gradually added to the solution of compound G3. The proton nuclear magnetic resonance spectra are as shown in Figure 18As shown, it can be seen from the figure that there are differences in the chemical shift changes of the nuclear magnetic resonance hydrogen spectrum caused by the movement of macrocycles with different numbers of layers after the stimulation of tetrabutylammonium acetate. Combining with the small-angle neutron scattering technique to further verify the structure of the selectively deuterated rotaxane dendrimer, and it can be concluded from the data that the stimulation of tetrabutylammonium acetate will preferentially act on the outermost layer. As the amount of tetrabutylammonium acetate stimulation increases, it further enters the inner layer of the dendrimer backbone (as shown in Figure 19 ). Therefore, based on the deuterated rotaxane dendrimer and combined with the SANS characterization technique, the fine structural changes under anion stimulation can be systematically studied, so as to obtain the movement characteristics of the rotaxane units in the backbone under stimulation response.

[0085] Example 2

[0086] This example is the same as Example 1, except that when synthesizing compound B, compound A in this example is (0.9 mmol); when synthesizing compound D, compound Pt(PEt3)2I2 in this example is (0.70 mmol); when synthesizing compound DG1, cuprous iodide in this example is (2.5 mg); when synthesizing compound G1, cuprous iodide in this example is (2.6 mg); when synthesizing compound D1G2, cuprous iodide in this example is (0.9 mg); when synthesizing compound D2G2, cuprous iodide in this example is (1.5 mg); when synthesizing compound DG2, cuprous iodide in this example is (1.4 mg); when synthesizing compound G2, cuprous iodide in this example is (2.3 mg); when synthesizing compound D1G3, cuprous iodide in this example is (0.45 mg); when synthesizing compound D2G3, cuprous iodide in this example is (0.8 mg); when synthesizing compound D3G3, cuprous iodide in this example is (0.8 mg); when synthesizing compound DG3, cuprous iodide in this example is (0.85 mg); when synthesizing compound G3, cuprous iodide in this example is (0.8 mg).

[0087] The yields of compounds B, D, DG1, G1, D1G2, D2G2, DG2, G2, D1G3, D2G3, D3G3, DG3 and G3 in this example are 50.3%, 70.6%, 72.4%, 73.0%, 69.1%, 75.3%, 66.2%, 59.8%, 62.0%, 63.1%, 59.6%, 65.7%, 60.9% respectively.

[0088] Example 3

[0089] This example is the same as Example 1, except that when synthesizing Compound B, the deuterated bromoethane in this example is (0.6 mL); when synthesizing Compound D, Compound C in this example is (0.15 mmol); when synthesizing Compound DG1, the compound tetrakis(4-ethynylphenyl)methane in this example is (0.030 mmol); when synthesizing Compound G1, the compound tetrakis(4-ethynylphenyl)methane in this example is (0.030 mmol); when synthesizing Compound D1G2, Compound E in this example is (0.050 mmol); when synthesizing Compound D2G2, Compound D in this example is (0.080 mmol); when synthesizing Compound DG2, Compound D in this example is (0.080 mmol); when synthesizing Compound G2, Compound E in this example is (0.095 mmol); when synthesizing Compound D1G3, Compound E in this example is (0.020 mmol); when synthesizing Compound D2G3, Compound E in this example is (0.040 mmol); when synthesizing Compound D3G3, Compound D in this example is (0.041 mmol); when synthesizing Compound DG3, Compound D in this example is (0.038 mmol); when synthesizing Compound G3, Compound E in this example is (0.039 mmol).

[0090] The yields of Compounds B, D, DG1, G1, D1G2, D2G2, DG2, G2, D1G3, D2G3, D3G3, DG3 and G3 in this example are 56.3%, 46.5%, 58.3%, 55.6%, 60.1%, 58.5%, 49.6%, 43.7%, 55.6%, 49.3%, 47.5%, 50.2% and 46.1% respectively.

[0091] Comparative Example 1

[0092] This example is the same as Example 1, except that when synthesizing Compound B, Compound A in this example is (2.0 mmol); when synthesizing Compound D, Compound C in this example is (0.40 mmol); when synthesizing Compound DG1, tetrakis(4-ethynylphenyl)methane in this example is (0.070 mmol); when synthesizing Compound G1, tetrakis(4-ethynylphenyl)methane in this example is (0.070 mmol); when synthesizing Compound D1G2, Compound E in this example is (0.030 mmol); when synthesizing Compound D2G2, Compound D in this example is (0.040 mmol); when synthesizing Compound DG2, Compound D in this example is (0.050 mmol); when synthesizing Compound G2, Compound E in this example is (0.060 mmol); when synthesizing Compound D1G3, Compound E in this example is (0.015 mmol); when synthesizing Compound D2G3, Compound E in this example is (0.02 mmol); when synthesizing Compound D3G3, Compound D in this example is (0.030 mmol); when synthesizing Compound DG3, Compound D in this example is (0.026 mmol); when synthesizing Compound G3, Compound E in this example is (0.025 mmol).

[0093] The yields of Compounds B, D, DG1, G1, D1G2, D2G2, DG2, G2, D1G3, D2G3, D3G3, DG3 and G3 in this example are 26.3%, 46.5%, 20.3%, 22.4%, 33.1%, 26.5%, 28.3%, 25.6%, 16.5%, 18.6%, 12.9%, 16.3% and 16.7% respectively.

[0094] Comparative Example 2

[0095] This example is the same as Example 1, except that when synthesizing compound B, compound A in this example is (2.0 mmol); when synthesizing compound D, compound Pt(PEt3)2I2 in this example is (5.0 mmol); when synthesizing compound DG1, cuprous iodide in this example is (4.0 mg); when synthesizing compound G1, cuprous iodide in this example is (4.5 mg); when synthesizing compound D1G2, cuprous iodide in this example is (2.5 mg); when synthesizing compound D2G2, cuprous iodide in this example is (3.5 mg); when synthesizing compound DG2, cuprous iodide in this example is (3.6 mg); when synthesizing compound G2, cuprous iodide in this example is (4.5 mg); when synthesizing compound D1G3, cuprous iodide in this example is (1.9 mg); when synthesizing compound D2G3, cuprous iodide in this example is (2.0 mg); when synthesizing compound D3G3, cuprous iodide in this example is (2.2 mg); when synthesizing compound DG3, cuprous iodide in this example is (2.5 mg); when synthesizing compound G3, cuprous iodide in this example is (2.0 mg).

[0096] In this example, the yields of compounds B, D, DG1, G1, D1G2, D2G2, DG2, G2, D1G3, D2G3, D3G3, DG3 and G3 are 20.3%, 29.6%, 46.5%, 34.5%, 52.0%, 41.6%, 39.6%, 46.0%, 38.5%, 33.6%, 29.8%, 27.5% and 30.1% respectively.

[0097] Finally, it should be noted that the above embodiments of the present invention are only examples for illustrating the present invention, and are not intended to limit the implementation manners of the present invention. For those of ordinary skill in the art, other different forms of changes and modifications can be made on the basis of the above description. It is impossible to list all the implementation manners here. Any obvious changes or modifications derived from the technical solutions of the present invention are still within the protection scope of the present invention.

Claims

1. A method for synthesizing a rotaxane dendrimer compound, characterized in that, It includes the following steps: S1: Under the protection of an inert atmosphere, compound A, potassium carbonate, and deuterated bromoethane undergo a nucleophilic substitution reaction in acetonitrile to obtain compound B; the structural formulas of compound A and compound B are as follows: S2: Under the protection of an inert atmosphere, compound B, compound C, copper iodide, and platinum diiodide bis(triethylphosphine) are added to chloroform and diisopropylamine for a coupling reaction to obtain compound D; the structural formulas of compound C and compound D are as follows: S3: Using tetra(4-ethynylphenyl)methane as the core, it undergoes a coupling reaction with compound D to obtain the first-generation deuterated rotaxane dendrimer compound DG1; the structural formula of compound DG1 is as follows: S4: Using tetra(4-ethynylphenyl)methane as the core, it undergoes a coupling reaction with compound E to obtain the first-generation non-deuterated rotaxane dendrimer compound G1, and the structural formulas of compound E and compound G1 are as follows: S5: Compound G1 is respectively reacted with compound D and compound E using repeated alternating deprotection-coupling reactions to obtain the second-generation deuterated rotaxane dendrimer compound D2G2 and the second-generation non-deuterated rotaxane dendrimer compound G2; Compound DG1 is respectively reacted with compound D and compound E using repeated alternating deprotection-coupling reactions to obtain the second-generation deuterated rotaxane dendrimer compound DG2 with two layers of deuterium and the second-generation deuterated rotaxane dendrimer compound D1G2 with the first layer of deuterium. The structural formulas of compound DG2, D2G2, D1G2, and compound G2 are as follows: S6: Compound G2 is respectively reacted with compound D and compound E using repeated alternating deprotection-coupling reactions to obtain the third-generation deuterated rotaxane dendrimer compound D3G3 with three layers of deuterium and the third-generation non-deuterated rotaxane dendrimer compound G3; compound D2G2 is reacted with compound E using repeated alternating deprotection-coupling reactions to obtain the second-generation deuterated rotaxane dendrimer compound D2G3 with two layers of deuterium; compound D1G2 is reacted with compound E using repeated alternating deprotection-coupling reactions to obtain the second-generation deuterated rotaxane dendrimer compound D1G3 with the first layer of deuterium; Compound DG2 is reacted with compound D using repeated alternating deprotection-coupling reactions to obtain the third-generation deuterated rotaxane dendrimer compound DG3 with three layers of deuterium. The structural formulas of compound G3, D3G3, D2G3, D1G3, and DG3 are as follows:

2. The synthesis method of a rotaxane dendrimer compound according to claim 1, characterized in that, In step S1, the molar ratio of compound A to deuterated bromoethane is 1:10 to 100, preferably 1:

11.

3. The synthesis method of a rotaxane dendrimer according to claim 1, characterized in that, In step S2, the molar ratio of compound C to compound B is 1:2 to 20, preferably 1:

6.

4. The synthesis method of a rotaxane dendrimer compound according to claim 1, characterized in that, In step S3, the molar ratio of tetra(4-ethynylphenyl)methane to compound D is 1: to 8, preferably 1:4.4; in step S4, the molar ratio of tetra(4-ethynylphenyl)methane to compound E is 1:1 to 8, preferably 1:4.

4.

5. The synthesis method of a rotaxane dendritic macromolecular compound according to claim 1, characterized in that, In step S5, when synthesizing compound D2G2, the molar ratio of deprotected compound G1 to compound D is 1:1 to 16, preferably 1:8.8; when synthesizing compound G2, the molar ratio of deprotected compound G1 to compound E is 1:1 to 16, preferably 1:8.8; when synthesizing compound DG2, the molar ratio of deprotected compound DG1 to compound D is 1:1 to 16, preferably 1:8.8; when synthesizing compound D1G2, the molar ratio of deprotected compound DG1 to compound E is 1:1 to 16, preferably 1:8.

8.

6. The synthesis method of a rotaxane dendritic macromolecular compound according to claim 1, characterized in that, In step S6, when synthesizing compound D3G3, the molar ratio of deprotected compound G2 to compound D is 1:1 to 32, preferably 1:17.6; when synthesizing compound G3, the molar ratio of deprotected compound G2 to compound E is 1:1 to 32, preferably 1:17.6; when synthesizing compound D2G3, the molar ratio of deprotected compound D2G2 to compound E is 1:1 to 32, preferably 1:17.6; when synthesizing compound D1G3, the molar ratio of deprotected compound D1G2 to compound E is 1:1 to 32, preferably 1:17.6; when synthesizing compound DG3, the molar ratio of deprotected compound DG2 to compound D is 1:1 to 32, preferably 1:17.

6.

7. A method for synthesizing a rotaxane dendritic macromolecular compound according to claim 1, characterized in that, In steps S3, S4, S5 and S6, when carrying out the coupling reaction, 0.01 to 1 equivalent of copper(I) iodide is added at each site, preferably 0.

1.

8. The synthesis method of a rotaxane dendritic macromolecular compound according to claim 1, characterized in that, In step S1, the temperature of the nucleophilic substitution reaction is 35 to 90 °C, preferably 80 °C; the reaction time is 4 to 24 h, preferably 18 h.

9. The synthesis method of a rotaxane dendrimer according to claim 1, characterized in that, In steps S2, S3, S4, S5 and S6, the temperature of the coupling reaction is -30 to 35 °C, preferably 25 °C; the reaction time is 2 to 24 h, preferably 12 h.

10. A rotaxane dendrimer compound, characterized in that, The first-generation rotaxane dendrimer compounds DG1 and G1; the second-generation rotaxane dendrimer compounds D2G2, G2, DG2 and D1G2; the third-generation rotaxane dendrimer compounds G3, D3G3, D2G3, D1G3 and DG3 synthesized by using the synthesis method of a deuterated rotaxane dendrimer compound according to any one of claims 1 to 9.

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