Chiral positional isomers of covalent organic frameworks, their preparation methods and applications

Abstract

This invention discloses chiral positional isomers of covalent organic frameworks (COFs), their preparation methods, and applications. These chiral positional isomers are one-dimensional COFs with precise chiral site arrangements: 4-L-DTP-BFPPQ COF and 5-L-DTP-BFPPQ COF. This invention constructs two one-dimensional chiral positional isomers with the same chemical composition but different chiral microenvironments by controlling the connection positions (4-position and 5-position) of the chiral centers contained in the organic building blocks. Furthermore, a one-dimensional chiral COF with high crystallinity was successfully constructed via a Schiff base reaction.

Description

Technical Field

[0001] This invention belongs to the field of organic materials, specifically relating to chiral positional isomers of covalent organic frameworks, their preparation methods, and applications. Background Technology

[0002] In recent years, significant progress has been made in the study of two-dimensional and three-dimensional chiral covalent organic frameworks (COFs), with chirality primarily derived from the introduction of chiral side chains, chiral building blocks, or post-modification strategies. However, these strategies have inherent limitations: complex dimensional topologies may lead to random distribution of chiral centers within the channels, making it difficult to guarantee the uniformity and precise controllability of the chiral microenvironment; simultaneously, interlayer stacking structures may bury active chiral sites, reducing their accessibility. These factors make it more difficult to delve into the mechanisms between chiral generation, transmission, and functional expression. Therefore, there is an urgent need to develop novel chiral COF systems with simpler structures and more precise controllable chiral site arrangements. One-dimensional COFs, as an emerging and underestimated dimension in the COF family, are characterized by strictly limited covalent extension in one dimension, typically forming ordered layered or fibrous assemblies through non-covalent interactions such as π-π stacking. This structure offers unique opportunities for chiral research: on the one hand, the one-dimensional linear structure minimizes structural complexity, allowing for precise design and high-level preservation of the arrangement of chiral building blocks on the chain (such as position, spacing, and orientation); on the other hand, the resulting ordered assemblies still provide stable porous channels, ensuring the free diffusion of substrate molecules. It is noteworthy that positional isomerism, a core concept in organic chemistry used to regulate molecular properties, has not yet received sufficient attention in the field of chiral materials. Introducing chiral positional isomerism into the COF framework—that is, keeping the chemical composition unchanged and only changing the relative substitution position of the chiral center on the rigid framework—potentially enables fine-tuning of the pore microenvironment, thereby allowing for a systematic study of the amplification effect of microstructural changes on macroscopic chiral functions. Summary of the Invention

[0003] Based on this, this invention combines the well-defined structure of one-dimensional COFs with the precise control of chiral positional isomerism to construct a series of novel one-dimensional chiral positional isomers of COFs and explore the influence of the spatial arrangement of chiral catalytic sites on the performance of asymmetric catalysis. This invention proposes and synthesizes a pair of one-dimensional COF positional isomers with precise chiral site arrangements. By designing V-shaped chiral building blocks, two types of one-dimensional chiral COFs with different structures were successfully synthesized. This invention achieves fine design of the chiral microenvironment by precisely controlling the substitution positions (4-position and 5-position) of the chiral centers contained in the constructed building blocks, thereby obtaining two positional isomers with the same chemical composition but different chiral spatial arrangements. Subsequently, one-dimensional chiral COFs with high crystallinity were constructed through Schiff base reactions. Systematic characterization confirmed that these isomers possess high crystallinity and permanent porosity. After testing, although both exhibited similar high catalytic activity in the asymmetric aldol condensation reaction, their enantioselectivity showed significant differences: 4-L-DTP-BFPPQ COF showed superior enantioselectivity (ee value 87%), which was significantly better than 5-L-DTP-BFPPQ COF.

[0004] The technical solution of this invention is as follows.

[0005] Chiral positional isomers of covalent organic frameworks, which are one-dimensional COFs positional isomers with precise chiral site arrangements, including at least one of the following structures:

[0006]

[0007] 4-L-DTP-BFPPQ COF 5-L-DTP-BFPPQ COF

[0008] Furthermore, the isomer has a relatively loose chain spacing; its structure is arranged in a typical AA stacking pattern, with a highly long-range ordered interlayer arrangement.

[0009] Furthermore, thermogravimetric analysis of the isomers showed that there was almost no weight loss at 311–325°C.

[0010] Furthermore, the 4-L-DTP-BFPPQ COF exhibits a petal-like morphology; the 5-L-DTP-BFPPQ COF exhibits a needle-like morphology.

[0011] Furthermore, the specific surface area of ​​the isomer is 48 m² / g to 266 m² / g; it has mesoporous characteristics.

[0012] A method for preparing chiral positional isomers of covalent organic frameworks (COFs) achieves fine design of chiral microenvironments by precisely controlling the substitution positions (4-position and 5-position) of the chiral centers contained in the organic building blocks. This results in two positional isomers with the same chemical composition but different chiral spatial arrangements, which are then used to construct one-dimensional chiral COFs with high crystallinity via Schiff base reaction.

[0013] Specifically, the steps include the following:

[0014] (1) Monomer synthesis:

[0015] N-Boc-L-proline and dibromoaniline were dissolved in CH2Cl2 solution, and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride was added. The mixture was stirred at room temperature for 20-28 h. After the reaction was completed, water was added and the mixture was extracted with dichloromethane. The combined organic phases were washed with water, dried over Na2SO4, and then concentrated under vacuum. The mixture was purified by column chromatography to obtain an oily liquid.

[0016] The oily liquid, 4-methoxycarbonylphenylboronic acid, K2CO3, and Pd(PPh3)4 were added to a pressure-resistant bottle; then, under an argon atmosphere, a deoxygenated 1,4-dioxane / water = 4 / 1 (v / v) mixed solvent was added to the pressure-resistant bottle; the reaction mixture was stirred at 95-100 °C for 20-26 h, then water was added and extracted with dichloromethane; the combined organic phases were washed with water, dried over Na2SO4, concentrated under vacuum, and purified by silica gel column chromatography to obtain 4-L-DTP-Boc or 5-L-DTP-Boc;

[0017] (2) Synthesis of 4-L-DTP-BFPPQ COF and 5-L-DTP-BFPPQ COF:

[0018] 4-L-DTP-Boc or 5-L-DTP-Boc, BFPPQ, o-dichlorobenzene, n-butanol, and an aqueous solution were added to a microwave tube. After degassing through three freeze-evacuation-thawing cycles, the tube was sealed under vacuum and heated at 80-110°C for 2.5-3.5 days. The precipitate was separated by filtration, washed successively with THF and methanol, and vacuum dried overnight to obtain an orange-yellow solid chiral 4-L-DTP-BFPPQ-Boc COF or 5-L-DTP-BFPPQ-Boc COF; the solid was then washed and vacuum dried.

[0019] The synthesized 4-L-DTP-BFPPQ-Boc COF or 5-L-DTP-BFPPQ-Boc COF and HCl / 1,4-dioxane were added to a glass bottle for Boc removal treatment; the resulting suspension was stirred at room temperature for 1.5-2 h; the mixture was filtered, and THF, MeOH containing 2% Et3N, H2O and MeOH were added sequentially; the obtained 4-L-DTP-BFPPQ COF or 5-L-DTP-BFPPQ COF was purified, and then dried under vacuum at 80-110 ℃ to obtain a brownish-yellow powder, namely 4-L-DTP-BFPPQ COF or 5-L-DTP-BFPPQ COF.

[0020] In the above method, in step (1), the dibromoaniline is 2,4-dibromoaniline or 3,5-dibromoaniline;

[0021] In the purification steps of column chromatography and silica gel column chromatography, ethyl acetate / petroleum ether at a ratio of 1:8 is used as the eluent.

[0022] In the above method, in step (2), the aqueous solution is an aqueous solution of acetic acid or an aqueous solution of trifluoroacetic acid.

[0023] This invention provides a covalent organic framework chiral positional isomer as a catalyst for asymmetric aldol condensation reactions. Furthermore, due to its well-defined and tunable chiral microenvironment, permanent porosity, and high accessibility to chiral sites, it can also be applied to chiral recognition, chiral separation, and chiral chromatographic stationary phases to achieve highly selective recognition and separation of chiral compounds.

[0024] Compared with the prior art, the advantages of the present invention are:

[0025] This invention provides a novel class of one-dimensional chiral porous materials, expanding the structural types of chiral covalent organic frameworks (COFs). It also establishes a clear structure-activity relationship between "positional isomerism—microenvironmental differences—asymmetric properties" in chiral COFs, providing new research ideas for the rational design of high-performance chiral porous materials. By precisely controlling the substitution positions of chiral centers on the building block framework, this invention achieves precise control over the chiral microenvironment of the pores and the interchain stacking pattern while maintaining a basically consistent chemical composition, thereby effectively improving the accessibility of chiral sites and asymmetric catalytic performance. Compared to traditional two-dimensional or three-dimensional chiral COFs, the one-dimensional chiral COFs constructed in this invention have advantages such as well-defined structures, regular arrangement of chiral sites, and sufficient exposure of active sites, while also possessing high crystallinity, good thermal stability, and permanent porosity. Among them, 4-L-DTP-BFPPQ COF exhibits excellent catalytic activity and high enantioselectivity in asymmetric aldol condensation reactions, indicating that the positional isomerism strategy can effectively control the chiral microenvironment and improve catalytic performance. This invention provides a new technical route for the application of one-dimensional chiral COFs in asymmetric catalysis, chiral recognition, and chiral separation. Attached Figure Description

[0026] Figure 1 This is a schematic diagram of the synthesis of 4-L-DTP-BFPPQ COF and 5-L-DTP-BFPPQ COF.

[0027] Figure 2 Characterization diagrams of 4-L-DTP-BFPPQ COF and 5-L-DTP-BFPPQ COF. (a) shows the AA packing structure of 4-L-DTP-BFPPQ COF; (b) shows the PXRD pattern (blue curve) of 4-L-DTP-BFPPQ COF, the PXRD pattern (black curve) obtained from experimental and AA packing structure refinement, and the difference curve (green curve) between experimental and refined values ​​of 4-L-DTP-BFPPQ COF; (c) shows the PXRD pattern (red curve) of 5-L-DTP-BFPPQ COF, the PXRD pattern (black curve) obtained from experimental and AA packing structure refinement, and the difference curve (green curve) between experimental and refined values ​​of 5-L-DTP-BFPPQ COF; (d) shows the AA packing structure of 5-L-DTP-BFPPQ COF; (e) shows the AB packing structure of 4-L-DTP-BFPPQ COF; (f) shows the AB packing structure of 5-L-DTP-BFPPQ COF; the orange bars represent the Bragg positions.

[0028] Figure 3Infrared spectra of 4-L-DTP-BFPPQ COF and 5-L-DTP-BFPPQ COF are shown. (a) is the infrared spectrum of 4-L-DTP-BFPPQ COF; (b) is the infrared spectrum of 5-L-DTP-BFPPQ COF. 13 (c) C10 NMR spectrum; (d) Infrared spectrum of 4-L-DTP-BFPPQ COF; (e) Infrared spectrum of 5-L-DTP-BFPPQ COF. 13 C10 NMR spectrum.

[0029] Figure 4 TGA curves for 4-L-DTP-BFPPQ-Boc COF and 4-L-DTP-BFPPQ COF;

[0030] Figure 5 The nitrogen adsorption-desorption curve of 4-L-DTP-BFPPQ COF at 77 K is shown.

[0031] Figure 6 SEM image of 4-L-DTP-BFPPQ COF.

[0032] Figure 7 TGA curves for 5-L-DTP-BFPPQ-Boc COF and 5-L-DTP-BFPPQ COF.

[0033] Figure 8 The nitrogen adsorption-desorption curve of 5-L-DTP-BFPPQ COF at 77 K is shown.

[0034] Figure 9 SEM image of 5-L-DTP-BFPPQ COF. Detailed Implementation

[0035] In this embodiment, 4,4',4'',4'''-(pyrene-1,3,6,8-tetramethyl)tetraphenylamine (BFPPQ) was purchased from Bidex Pharmaceuticals. The analytical column TZ1 (250 × 4.6 mm, 5 μm) was kindly provided by Guangdong Longsha Biotechnology Co., Ltd. (Guangzhou, China), and this column was packed with silica gel coated with amylose tris(3,5-dimethylphenylcarbamate). All other materials were commercially available reagent-grade products and used directly without further purification. Powder X-ray diffraction (PXRD) patterns were acquired using a Rigaku Ultima IV X-ray powder diffractometer (Rigaku Corporation, Tokyo, Japan) with copper target Kα radiation (λ = 1.5406 Å). Liquid chromatography-mass spectrometry (LC-MS) determinations were performed using an Agilent 1260-6460 system (Agilent Technologies, Santa Clara, USA) or a Shimadzu LCMS-2020 system (Shimadzu Corporation, Kyoto, Japan). Proton and carbon nuclear magnetic resonance spectroscopy ( 1 H NMR and 13 C10 NMR was acquired on a Bruker Avance NEO 600 MHz NMR spectrometer (Bruker GmbH, Karlsruhe, Germany) at room temperature with tetramethylsilane as an internal standard. 13 C-cross polarized magic angle rotation (CP-MAS) spectra were acquired on a Bruker AVANCE III 400WB MHz spectrometer (Bruker GmbH, Karlsruhe, Germany), with a magic angle rotation rate of 10 kHz. Fourier transform infrared (FT-IR) spectra were measured using a PerkinElmer Spectrum Two infrared spectrometer (PerkinElmer, Waltham, USA), with a measurement range of 4000–400 cm⁻¹. −1 Potassium bromide pellet method was used. Thermogravimetric analysis (TGA) was performed using a Netzsch TG 209F3 thermogravimetric analyzer (Netzsch GmbH, Germany) under a nitrogen atmosphere with a heating rate of 10 °C / min. Nitrogen adsorption-desorption isotherms were measured at 77 K using a Micromeritics ASAP 2460 surface area and porosity analyzer (Micromeritics Atlanta, USA). Scanning electron microscopy (SEM) images were acquired using a Carl Zeiss Gemini 500 field emission scanning electron microscope (Carl Zeiss AG, Oberkohend, Germany). Enantiomer excess (ee) was determined using a Shimadzu LC-20ADXR high-performance liquid chromatography system (Shimadzu Corporation, Kyoto, Japan) with a TZ1 analytical column.

[0036] Example 1

[0037] Synthesis of 4-L-DTP-Boc monomer

[0038]

[0039] 4-L-DTP-Boc: N-Boc-L-proline (6.00 g, 27.89 mmol) and 2,4-dibromoaniline (5 g, 20 mmol) were dissolved in CH2Cl2 (100 mL), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 6 g, 31.4 mmol) was added. The mixture was stirred at room temperature for 24 h. After the reaction was complete, water was added and the mixture was extracted with dichloromethane. The combined organic phases were washed with water, dried over Na2SO4, and then concentrated under vacuum. The product was purified by column chromatography using ethyl acetate / petroleum ether in a 1:8 ratio as eluent to give compound 4 as an oily liquid. 1 H NMR (400 MHz, Chloroform-d6), δ = 8.30 (d, J = 8.8 Hz, 1H), 7.66 (d, J = 2.3 Hz, 1H), 7.41 (d, J = 8.9 Hz, 1H), 4.41 (d, J = 55.1 Hz, 1H), 3.47 (d, J = 46.5 Hz, 2H), 2.51-2.11 (m, 2H), 1.98 -1.91 (m, 2H), 1.46 (s, 9H). Compound 4 (4.5 g, 10 mmol), 4-methoxycarbonylphenylboronic acid (4.5 g, 30 mmol), K₂CO₃ (4.5 g, 12 mmol), and Pd(PPh₃)₄ (1 g, 0.34 mmol) were added to a pressure-resistant flask. Then, under an argon atmosphere, a deoxygenated 1,4-dioxane / water = 4 / 1 (v / v) mixed solvent was added to the flask. The reaction mixture was stirred at 100°C for 24 h, then water was added and extracted with dichloromethane. The combined organic phases were washed with water, dried over Na₂SO₄, and then concentrated under vacuum. Purification was performed by silica gel column chromatography using ethyl acetate / petroleum ether in a 1:8 ratio as eluent to give 4-L-DTP-Boc as white crystals (yield: 71%). 1H NMR (400 MHz, DMSO-d6), δ = 10.09 (s, 1H), 10.06 (s, 1H), 8.00 (d, J = 4.5 Hz, 6H), 7.86(t, J = 8.4 Hz, 1H), 7.79-7.65 (m, 4H), 4.16 (d, J = 8.3 Hz, 1H), 3.26 (dd, J= 12.1, 5.2 Hz, 2H), 2.12-2.00 (m, 1H), 1.73 (d, J = 25.5 Hz, 3H), 1.35 (d, J= 7.1 Hz, 9H).

[0040] Example 2

[0041] Synthesis of 5-L-DTP-Boc monomer

[0042]

[0043] 5-L-DTP-Boc: N-Boc-L-proline (6.00 g, 27.89 mmol) and 3,5-dibromoaniline (5 g, 20 mmol) were dissolved in CH2Cl2 (100 mL), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 6 g, 31.4 mmol) was added. The mixture was stirred at room temperature for 24 h. After the reaction was complete, water was added and the mixture was extracted with dichloromethane. The combined organic phases were washed with water, dried over Na2SO4, and then concentrated under vacuum. The product was purified by column chromatography using ethyl acetate / petroleum ether in a 1:4 ratio as eluent to give compound 5 as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6), δ = 10.28 (d, J = 3.6 Hz, 1H), 7.88 (dd, J = 5.4, 1.8 Hz, 2H), 7.50 (t, J =1.8 Hz, 1H), 4.19 (ddd, J = 23.0, 8.4, 3.7 Hz, 1H), 3.47-3.35 (m, 2H), 3.32(d, J = 6.3 Hz, 1H), 2.20 (dddd, J = 18.1, 13.9, 9.1, 4.2 Hz, 1H), 1.98-1.74(m, 3H), 1.40 (s, 3H), 1.28 (s, 6H). Compound 5 (4.5 g, 10 mmol), 4-methoxycarbonylphenylboronic acid (4.5 g, 10 mmol), K₂CO₃ (4.5 g, 12 mmol), and Pd(PPh₃)₄ (1 g, 0.34 mmol) were added to a pressure-resistant flask. Then, under an argon atmosphere, a deoxygenated 1,4-dioxane / water = 4 / 1 (v / v) mixed solvent was added to the flask. The reaction mixture was stirred at 100°C for 24 h, then water was added and extracted with dichloromethane. The combined organic phases were washed with water, dried over Na₂SO₄, and then concentrated under vacuum. Purification was performed by silica gel column chromatography using ethyl acetate / petroleum ether in a 1:8 ratio as eluent to give 5-L-DTP-Boc as pale yellow crystals (yield: 74%). 1 H NMR (400 MHz, DMSO-d6), δ = 10.31(d, J = 3.1 Hz, 1H), 10.09 (s, 2H), 8.10 (dd, J = 7.1, 1.6 Hz, 2H), 8.08-8.03(m, 4H), 7.99 (d, J = 8.3 Hz, 4H), 7.81 (dt, J = 6.0, 1.7 Hz, 1H), 4.30 (ddd,J = 28.2, 8.4, 3.8 Hz, 1H), 3.47 (ddd, J = 11.9, 9.4, 4.5 Hz, 1H), 3.42-3.37(m, 1H), 2.26 (ttd, J = 11.2, 8.5, 7.9, 4.2 Hz, 1H), 2.01-1.81 (m, 3H), 1.42(s, 3H), 1.31 (s, 6H).

[0044] Example 3

[0045] The synthesis of 4-L-DTP-BFPPQ COF and 5-L-DTP-BFPPQ COF, such as Figure 1 As shown.

[0046] 4-L-DTP-BFPPQ COF: 4-L-DTP-Boc (17.5 mg, 0.035 mmol), BFPPQ (8.5 mg, 0.015 mmol), o-dichlorobenzene (0.2 mL), n-butanol (0.8 mL), and aqueous acetic acid solution (0.1 mL, 3 M) were added to a microwave tube. After three freeze-degassing cycles, the tube was sealed under vacuum and heated at 80 °C for 3 days. The precipitate was separated by filtration, washed successively with THF and methanol, and then dried under vacuum at 100 °C overnight to obtain an orange-yellow solid chiral 4-L-DTP-BFPPQ-Boc COF (yield: 82%). For further purification, the tube was washed with THF using a Soxhlet extraction for 24 h and dried under vacuum at 80 °C. The synthesized 4-L-DTP-BFPPQ-Boc COF (30 mg) and 1.0 mL of 4 M HCl / 1,4-dioxane were added to a 10 mL glass bottle for Boc removal. The resulting suspension was stirred at room temperature for 1.5 h. The mixture was filtered, and THF (1 × 6 mL), MeOH (containing 2% Et3N) (2 × 6 mL), H2O (1 × 6 mL), and MeOH (1 × 6 mL) were added sequentially. The obtained 4-L-DTP-BFPPQ COF was purified by Soxhlet extraction in THF for 24 h, and then dried under vacuum at 80 °C to obtain a brownish-yellow powder.

[0047] 5-L-DTP-BFPPQ COF: 5-L-DTP-Boc (17.5 mg, 0.035 mmol), BFPPQ (8.5 mg, 0.015 mmol), pure o-dichlorobenzene (1.0 mL), and trifluoroacetic acid aqueous solution (0.1 mL, 6 M) were added to a microwave tube. After three freeze-evacuation-thawing cycles for degassing, the tube was sealed under vacuum and heated at 110 °C for 3 days. The precipitate was separated by filtration, washed successively with THF and methanol, and then dried under vacuum at 100 °C overnight to obtain a brownish-yellow solid chiral 5-L-DTP-BFPPQ-Boc COF (yield 75%). For further purification, the tube was washed with THF using a Soxhlet extraction for 24 h and dried under vacuum at 80 °C. The synthesized 5-L-DTP-BFPPQ-Boc COF (30 mg) and 1.0 mL of 4 M HCl / 1,4-dioxane were further added to a 10 mL glass bottle for Boc removal. The resulting suspension was stirred at room temperature for 1.5 h. The mixture was filtered, and THF (1 × 6 mL), MeOH (containing 2% Et3N) (2 × 6 mL), H2O (1 × 6 mL), and MeOH (1 × 6 mL) were added sequentially. The obtained 5-L-DTP-BFPPQ COF was purified by Soxhlet extraction in THF for 24 h, and then dried under vacuum at 80 °C to obtain an orange-yellow powder.

[0048] Example 4

[0049] 4-L-DTP-BFPPQ COF and 5-L-DTP-BFPPQ COF catalyze asymmetric aldol condensation:

[0050] At room temperature, 0.1 mmol of aldehyde, 0.03 mmol of 4-nitrobenzoic acid, 1.0 mL of water, and 0.3 mL of cyclohexanone were added to a 10 mL vial containing a chiral COF catalyst (0.03 mmol based on the chiral center). The mixture was stirred and reacted at room temperature for 1 day. After the reaction (monitored by thin-layer chromatography) was complete, the chiral COF catalyst was separated by centrifugation and thoroughly washed three times with dichloromethane. The combined organic phases were concentrated under reduced pressure to obtain the crude product, which was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 3 / 1) to obtain the corresponding aldol condensation product. The enantiomeric excess (ee) was determined by high-performance liquid chromatography using a TZ1 analytical column, and the yield was the separation yield.

[0051] Example 5

[0052] In this embodiment, the structures of the synthesized 4-L-DTP-BFPPQ COF and 5-L-DTP-BFPPQ COF were characterized.

[0053] The crystallinity of the two synthesized chiral COFs was analyzed by powder X-ray diffraction (PXRD). Figure 2 As shown, the PXRD peak positions of 4-L-DTP-BFPPQ-Boc COF and 5-L-DTP-BFPPQ-Boc COF are highly similar, indicating that the two chiral COFs have similar crystal structures. In the experimental PXRD curve of 4-L-DTP-BFPPQ-Boc COF, a strong peak at approximately 4.14° and smaller peaks at approximately 6.41°, 10.58°, and 23.26° can be observed, corresponding to diffraction planes at (100, 110, 200, and 001), respectively. For 5-L-DTP-BFPPQ-Boc... For COFs, the PXRD peaks at 3.96°, 6.02°, 10.20°, and 24.00° correspond to the diffraction of the crystal planes (100, 110, 210, and 001), respectively. The slight difference in the position of the characteristic diffraction peaks corresponding to the 100 and 001 crystal planes of these two chiral COFs may be due to the positional isomerism of the chiral monomers, which affects the overall stacking and interchain interactions of the COFs. At the same time, it can be observed that the π-π stacking interaction of 5-L-DTP-BFPPQ COF is strong, while that of 4-L-DTP-BFPPQ COF is weak, indicating that 4-L-DTP-BFPPQ COF has a relatively loose interchain spacing. Furthermore, the PXRD patterns of both chiral COFs after Boc removal treatment showed high similarity to those of the COFs before Boc removal. This strongly suggests that the crystalline framework structure of 4-L-DTP-BFPPQ COF and 5-L-DTP-BFPPQ COF obtained after Boc removal treatment was completely preserved without collapse or irreversible structural transformation. Subsequent Pawley refinement of 4-L-DTP-BFPPQ COF and 5-L-DTP-BFPPQ COF using Materials Studio software further improved the PXRD results of 4-L-DTP-BFPPQ COF, showing even better agreement with the simulated AA stacking structure (R0). wp = 2.18%, R p = 1.71%), indicating that 4-L-DTP-BFPPQ COF is arranged in a typical AA packing mode with highly long-range ordered interlayer arrangement. The main diffraction positions (e.g., 3.96°, 6.02°) of the experimental PXRD pattern of 5-L-DTP-BFPPQ COF can be largely reproduced by the simulated curve, indicating that the simulated pattern of the AA packing mode is basically consistent. The experimental PXRD pattern and the simulated AA packing model show high consistency in the positions of the main diffraction peaks, and the Pawley refinement yields a small difference factor (R0). wp = 3.93%, Rp = 2.87%), indicating that 5-L-DTP-BFPPQ COF is closer to the AA stacking mode.

[0054] Fourier transform infrared (FT-IR) spectroscopy was used to analyze the changes in these two chiral COFs before and after the removal of the Boc protecting group. The 4-L-DTP-BFPPQ-Boc COF and 5-L-DTP-BFPPQ-Boc COF before deprotection showed similar FT-IR peaks, and also exhibited similar characteristics after deprotection. Compared to the monomers, the FT-IR spectra of these chiral COFs showed amino vibrations (3200-3500 cm⁻¹). -1 ) and aldehyde vibration (1694 cm) -1 The significant attenuation at ~1620 cm⁻¹, and at ~1620 cm⁻¹ -1 The presence of characteristic C=N stretching vibrations indicates the successful construction of imine bonds. Figure 3 (a) and Figure 3 (c) in the middle. Solid state. 13 C-cross polarization magic angle rotation (CP / MAS) NMR analysis provides more detailed structural information. 13 CCP / MAS NMR spectroscopy showed that chiral 4-L-DTP-BFPPQ COF ( Figure 3 (b) and chiral 5-L-DTP-BFPPQ COF ( Figure 3 The (d) group in the COFs exhibits a signal peak of imine carbon at 160 ppm, further confirming the formation of C=N bonds in both COFs. The characteristic peaks observed in the 4-L-DTP-BFPPQ COF and 5-L-DTP-BFPPQ COF at 173, 62, 47, 31, 26 ppm and 171, 61, 47, 31, 25 ppm, respectively, can be clearly attributed to the corresponding carbon atoms in the chiral L-proline fragment. This confirms the successful synthesis of the two chiral COF materials.

[0055] Thermogravimetric analysis (TGA) showed that the two chiral COFs obtained under nitrogen atmosphere exhibited high thermal stability. At temperatures close to 311°C, the 4-L-DTP-BFPPQ COF showed almost no weight loss, while the 5-L-DTP-BFPPQ COF remained stable up to 325°C. Figure 4 and 7 Notably, significant weight loss was observed in the TGA curves of both chiral types within the range of 190°C to 250°C, confirming the successful removal of the Boc protecting group in 4-L-DTP-BFPPQ COF and 5-L-DTP-BFPPQ COF.

[0056] Scanning electron microscopy (SEM) images show that 4-L-DTP-BFPPQ COF exhibits a petal-like morphology. Figure 6 ), 5-L-DTP-BFPPQ COF exhibits a needle-like morphology ( Figure 9 The specific surface areas of 4-L-DTP-BFPPQ COF and 5-L-DTP-BFPPQ COF were characterized by nitrogen adsorption-desorption experiments at 77 K. The specific surface areas of 4-L-DTP-BFPPQ COF and 5-L-DTP-BFPPQ COF were 48 m² / g and 266 m² / g, respectively. Compared with the chiral COFs before Boc removal, the specific surface areas increased, mainly due to the removal of the Boc group and the resulting increase in pore size, which also indirectly confirms the successful removal of the Boc group. Furthermore, both one-dimensional chiral COFs exhibited typical type IV isotherms, indicating mesoporous characteristics.

[0057] Example 6

[0058] Experimental study on the asymmetric aldol condensation properties of 4-L-DTP-BFPPQ COF and 5-L-DTP-BFPPQ COF:

[0059] PXRD and nitrogen adsorption analysis confirmed that both chiral COFs formed highly crystalline porous structures. The core structural difference lies in the location of the chiral L-proline in the 4-L-DTP-BFPPQ COF, which is attached to the 4-position of the DTP unit, while in the 5-L-DTP-BFPPQ COF, the chiral proline group is attached to the meta-position, a more distal site. Therefore, by controlling the substitution position of the chiral center on the aromatic ring skeleton (position 4 vs. position 5), the regulatory effect of positional isomerism on the chiral microenvironment and asymmetric catalytic performance can be systematically studied. To investigate the influence of the spatial arrangement of chiral catalytic sites on asymmetric catalytic performance, this application selected the asymmetric aldol condensation reaction as a model for evaluation.

[0060] Table 1. Asymmetric aldol condensation reaction catalyzed by chiral 5-L-DTP-BFPPQ COF (solvent optimization)

[0061]

[0062] a Reaction conditions: aldehyde (0.10 mmol), ketone (0.3 mL), 5-L-DTP-BFPPQ COF (0.03 mmol), p-nitrobenzoic acid (0.03 mmol) and solvent (1 mL), reacted at room temperature for 1 day; b Separation yield; c Determined by chiral high-performance liquid chromatography; dDetermined by chiral high-performance liquid chromatography; e Solvent / H2O (1 mL / 0.1 mL).

[0063] First, 5-L-DTP-BFPPQ COF was selected for asymmetric catalysis experiments. In the process of optimizing the catalytic reaction conditions, the solvent system had a significant impact on the reaction yield and enantioselectivity. Therefore, solvent screening was first conducted. When pure organic solvents were selected as the reaction conditions and p-nitrobenzoic acid was selected as the additive, it was found that almost no reaction occurred in the following pure organic solvents. Based on the previous research, a mixed solvent of water and organic solvent was used as the reaction solvent. The experiment showed that the presence of water helps to improve the reaction performance. When the ratio of organic solvent to water was 1:10, the reaction was basically complete within one day, with a yield of 90-98%, but the enantioselectivity was only 60-66% (Table 1). Compared with the above mixed solvents, it was found that the catalytic effect was significantly improved under the reaction conditions of H2O and DMF. Therefore, based on this, the total solvent volume was kept at 1 mL, and the solvent ratio of DMF and H2O was further adjusted. As can be seen from Table 1, the reaction performance continuously improved with the increase of the proportion of water. When the reaction solvent was pure water, 5-L-DTP-BFPPQ COF achieved the best catalytic performance, with a yield of 96% and an ee value of 78% within one day.

[0064] Table 2. Asymmetric aldol condensation reaction catalyzed by chiral 5-L-DTP-BFPPQ COF (solvent ratio)

[0065]

[0066] a Reaction conditions: aldehyde (0.10 mmol), ketone (0.3 mL), 5-L-DTP-BFPPQ COF (0.03 mmol), p-nitrobenzoic acid (0.03 mmol) and solvent (1 mL), reacted at room temperature for 1 day; b Separation yield; c Determined by chiral high-performance liquid chromatography; d Determined by chiral high-performance liquid chromatography; e DMF / H2O (0.9 mL / 0.1 mL); f DMF / H2O (0.7 mL / 0.3 mL); g DMF / H2O (0.5 mL / 0.5 mL); h DMF / H2O (0.3 mL / 0.7 mL); I DMF / H2O (0.1 mL / 0.9 mL).

[0067] Although the activity and enantioselectivity of the asymmetric aldol condensation reaction were significantly improved under optimal solvent conditions using pure water, there was still room for further improvement in its ee value. Therefore, this example further investigated the effects of different acidic additives on the reaction (Table 3). Several common additives, including oxalic acid, benzoic acid, 2,5-dihydroxybenzoic acid, p-toluenesulfonic acid, trifluoroacetic acid, acetic acid, glycolic acid, and p-nitrobenzoic acid, were initially screened to evaluate their effects on the reaction. A few additives inhibited the reaction, resulting in a significant decrease in conversion rate, while the ee values ​​of most additives were between 59-69%. Notably, p-nitrobenzoic acid (item 8 in Table 3) showed the best catalytic performance, achieving a yield of 96% and an enantioselectivity of 78% within one day. Through optimization of solvent type, solvent ratio, and additives, the optimal reaction conditions were determined in this reaction model using pure water as the reaction solvent and p-nitrobenzoic acid as the additive.

[0068] Table 3 Optimization of aldol reaction conditions (additives)

[0069]

[0070] a Reaction conditions: aldehyde (0.10 mmol), ketone (0.3 mL), 5-L-DTP-BFPPQ COF (0.03 mmol) and water (1 mL), reacted at room temperature for 1 day; b Separation yield; c Determined by chiral high-performance liquid chromatography; d Determined by chiral high-performance liquid chromatography.

[0071] Building upon this, we further compared the catalytic performance of 4-L-DTP-BFPPQ COF and 5-L-DTP-BFPPQ COF under optimal conditions. The results showed that 4-L-DTP-BFPPQ COF exhibited superior catalytic performance, achieving a yield of 97% and an enantioselectivity of 87%. Based on structural characterization and literature reports, we attributed this to the difference in pore microenvironment and one-dimensional chain packing density caused by the different substitution positions of the chiral centers. In one-dimensional chiral COFs, the catalytic reaction mainly occurs near the inter-chain channels and the exposed chiral active sites on the outer side of the framework. PXRD analysis revealed that the π-π packing of 5-L-DTP-BFPPQ COF was significantly stronger than that of 4-L-DTP-BFPPQ COF, indicating that 5-L-DTP-BFPPQ COF has a smaller inter-chain spacing and a more compact packing structure compared to 4-L-DTP-BFPPQ COF. This overly dense packing can lead to two adverse consequences: firstly, some chiral proline catalytic sites may be embedded in the interlayer, making it difficult for them to contact the substrate; secondly, dense packing may cause narrowing of the pores, hindering the diffusion of reactants to the active site, thereby reducing the effective utilization rate of the active site. In contrast, the relatively loosely packed 4-L-DTP-BFPPQ COF has a more dispersed interchain spacing, which is conducive to substrate molecules entering the interchain gaps and making more sufficient contact with the catalytic site, thus improving the accessibility of the chiral site. In addition, although 4-L-DTP-BFPPQ COF and 5-L-DTP-BFPPQ COF have the same chemical composition and AA packing pattern, the monomer linked at the 4-position experiences less steric hindrance in the backbone, which is conducive to rapid diffusion and effective collision of the substrate; while the monomer linked at the 5-position has greater steric hindrance, which may reduce the probability of collision between the reactant and the catalytic site, further exacerbating the difference in catalytic performance.

[0072] Table 4. Asymmetric aldol condensation reactions catalyzed by 4-L-DTP-BFPPQ COF and 5-L-DTP-BFPPQ COF

[0073]

[0074] a Reaction conditions: aldehyde (0.10 mmol), cyclohexanone (0.3 mL), COF (0.03 mmol), additive (0.03 mmol), and DMF / H2O (1 mL), reacted at room temperature for 1 day; b Separation yield; c Determined by chiral high-performance liquid chromatography; d Determined by chiral high-performance liquid chromatography.

[0075] In summary, the reason why the one-dimensional COF with proline linked at the ortho position exhibits higher enantioselectivity is that it creates a reactor with weaker π-π stacking and less steric hindrance, thereby achieving better enantioselectivity in asymmetric catalysis.

Claims

1. A covalent organic framework chiral positional isomer, characterized in that, These covalent organic framework chiral positional isomers are one-dimensional COFs positional isomers with precise chiral site arrangements, including at least one of the following structures: 4-L-DTP-BFPPQ COF 5-L-DTP-BFPPQ COF.

2. The chiral positional isomer of the covalent organic framework according to claim 1, characterized in that, The isomer has a relatively loose chain spacing; Its structure is arranged in a typical AA stacking pattern, with a highly ordered interlayer arrangement.

3. The chiral positional isomer of the covalent organic framework according to claim 1, characterized in that, Thermogravimetric analysis of the isomers showed that there was almost no weight loss at 311–325°C.

4. The chiral positional isomer of the covalent organic framework according to claim 1, characterized in that, 4-L-DTP-BFPPQCOF exhibits a petal-like morphology; the 5-L-DTP-BFPPQCOF exhibits a needle-like morphology.

5. The chiral positional isomer of the covalent organic framework according to claim 1, characterized in that, The specific surface area of ​​the isomer is 48 m² / g to 266 m² / g; it has mesoporous properties.

6. A method for preparing the chiral positional isomers of the covalent organic framework according to any one of claims 1 to 5, characterized in that, By precisely controlling the substitution positions (4-position and 5-position) of the chiral centers contained in the organic building blocks, the chiral microenvironment was finely designed, thereby obtaining two positional isomers with the same chemical composition but different chiral spatial arrangements. One-dimensional chiral COFs with high crystallinity were constructed through Schiff base reaction.

7. The method for preparing the chiral positional isomers of the covalent organic framework according to claim 6, characterized in that, Includes the following steps: (1) Monomer synthesis: N-Boc-L-proline and dibromoaniline were dissolved in CH2Cl2 solution, and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride was added. The mixture was stirred at room temperature for 20-28 h. After the reaction was completed, water was added and the mixture was extracted with dichloromethane. The combined organic phases were washed with water, dried over Na2SO4, and then concentrated under vacuum. The mixture was purified by column chromatography to obtain an oily liquid. The oily liquid, 4-methoxycarbonylphenylboronic acid, K2CO3, and Pd(PPh3)4 were added to a pressure-resistant bottle; then, under an argon atmosphere, a deoxygenated 1,4-dioxane / water = 4 / 1 (v / v) mixed solvent was added to the pressure-resistant bottle; the reaction mixture was stirred at 95-100 °C for 20-26 h, then water was added and extracted with dichloromethane; the combined organic phases were washed with water, dried over Na2SO4, concentrated under vacuum, and purified by silica gel column chromatography to obtain 4-L-DTP-Boc or 5-L-DTP-Boc; (2) Synthesis of 4-L-DTP-BFPPQ COF and 5-L-DTP-BFPPQ COF: 4-L-DTP-Boc or 5-L-DTP-Boc, BFPPQ, o-dichlorobenzene, n-butanol, and an aqueous solution were added to a microwave tube. After degassing through three freeze-evacuation-thawing cycles, the tube was sealed under vacuum and heated at 80-110°C for 2.5-3.5 days. The precipitate was separated by filtration, washed successively with THF and methanol, and vacuum dried overnight to obtain an orange-yellow solid chiral 4-L-DTP-BFPPQ-Boc COF or 5-L-DTP-BFPPQ-Boc COF; the solid was then washed and vacuum dried. The synthesized 4-L-DTP-BFPPQ-Boc COF or 5-L-DTP-BFPPQ-Boc COF and HCl / 1,4-dioxane were added to a glass bottle for Boc removal treatment; the resulting suspension was stirred at room temperature for 1.5-2 h; the mixture was filtered, and THF, MeOH containing 2% Et3N, H2O and MeOH were added sequentially; the obtained 4-L-DTP-BFPPQ COF or 5-L-DTP-BFPPQ COF was purified and then dried under vacuum at 80-110 ℃ to obtain a brownish-yellow powder, namely 4-L-DTP-BFPPQ COF or 5-L-DTP-BFPPQ COF.

8. The method for preparing the chiral positional isomers of the covalent organic framework according to claim 7, characterized in that, In step (1), the dibromoaniline is 2,4-dibromoaniline or 3,5-dibromoaniline; In the purification steps of column chromatography and silica gel column chromatography, ethyl acetate / petroleum ether at a ratio of 1:8 is used as the eluent.

9. The method for preparing the chiral positional isomers of the covalent organic framework according to claim 7, characterized in that, In step (2), the aqueous solution is an aqueous solution of acetic acid or an aqueous solution of trifluoroacetic acid.

10. The covalent organic framework chiral positional isomers according to any one of claims 1 to 5 are used as catalysts in the fields of asymmetric aldol condensation reactions, chiral recognition, chiral separation, and chiral chromatographic stationary phases.

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