Intermediate single crystal trapping of COF-300 via organic Lewis acid catalysis

Abstract

A sterically hindered organic Lewis acid catalyst, B(C₆F₅)₃, was utilized to regulate the reaction kinetics of COF-300 synthesis, enabling direct observation of the intermediate single-crystal growth stage. This approach establishes a novel experimental basis for mechanistic studies of COF crystallization and provides valuable insight into controlled crystal formation pathways.

---

Covalent organic frameworks (COFs) are crystalline porous materials formed through the covalent bonding extension of organic building blocks.^1,2 The vast reticular chemical design space imparts substantial versatility in the structures and functions of COFs.^3–8 A long-standing issue in COF chemistry is the understanding and control of the crystallization process. Traditional solvothermal synthesis is typically subjected to uncontrolled polymerization, where fast precipitation of polymers occurs, leading to the formation of powder COFs with small crystal domains.⁹ Single crystals are crucial for precise structural characterization, enabling deeper insights into structure–property correlations that are otherwise obscured by the limitations inherent to powder samples.^10–14 The breakthroughs in the controlled growth of COFs were achieved in 2018. Dichtel's team obtained large boronate ester-linked 2D COF single crystals by slowly adding monomers to preformed nanoparticle seed colloids.¹⁵ Ma and coworkers successfully synthesized single crystals of imine-linked 3D COFs using a modulated approach.¹⁰

Despite the significant progress in synthesizing single-crystalline COFs, further controlling the growth process and investigating the involved intermediate phases are challenging.^16,17 Lotsch and coworkers observed a solvated triple imine condensation product of 1,3,5-triformylbenzene intermediate during mechanochemical synthesis of LZU-1.¹⁸ Ma and coworkers synthesized an imine oligomer of COF-320 via a liquid–liquid interfacial crystallization method.¹⁹ Wang and colleagues prepared similar imine-linked oligomers using ionic liquids as a catalyst.²⁰ We reason that the steric hindrance of the catalyst may provide an additional way to regulate the polymerization degree in COF synthesis.²¹ In this work, we show that B(C₆F₅)₃ (BCF), a classical bulky organic Lewis acid, can promote the formation of both an oligomer intermediate and the final framework COF-300 under carefully controlled conditions (Scheme 1).^22,23

Scheme 1 Synthesis of COF-300 and SIM-300.

The condensation of tetrakis(4-aminophenyl)methane (TAM) and 1,4-benzenedialdehyde (BDA) in 2 mL 1,4-dioxane/mesitylene (1/3, v/v) with a catalytic amount of BCF at 60 °C for 72 h yields 7-fold interpenetrated hydrated COF-300 (Scheme 1, condition A).^11,24 The powder X-ray diffraction (PXRD) pattern (Fig. 1a) and the characteristic C=N stretching vibration at 1621 cm⁻¹ in the FT-IR spectrum match the reported data of COF-300 (Fig. 1b).²⁴ COF-300 produced by this method has a high Brunauer–Emmett–Teller (BET) surface area of 956 m² g⁻¹ (Fig. 1c) and is thermally stable up to 400 °C (Fig. S1).

Fig. 1 (a) Experimental and simulated PXRD patterns, (b) FT-IR spectra, and (c) N₂ sorption isotherms of COF-300 and SIM-300. (d) Solid-state ¹³C NMR spectra of SIM-300.

In contrast, when incubating the reaction mixture at 30 °C for 72 h after the initial reaction at 60 °C for 24 h, yellow single crystals of the intermediate oligomer SIM-300 were obtained (Scheme 1, condition B).²³ The PXRD pattern of SIM-300 is significantly different from that of COF-300, demonstrating its different phase structure (Fig. 1a). The FT-IR spectrum of SIM-300 exhibits a strong vibration band at 1698 cm⁻¹, corresponding to the unreacted aldehyde group, in addition to the C=N vibration band at 1621 cm⁻¹ (Fig. 1b). Solid-state ¹³C NMR spectroscopy confirms the presence of both aldehyde and imine groups in SIM-300, showing the corresponding signals at 192 and 157 ppm, respectively (Fig. 1d). The linker composition of SIM-300 determined by ¹H NMR spectroscopy after acid digestion matches the theoretical value of 1 : 4 (TAM to BDA, Fig. S2). The nitrogen sorption study shows that SIM-300 is nonporous with a low BET surface area of 48 m² g⁻¹ (Fig. 1c). The thermogravimetric analysis (TGA) revealed that SIM-300 is thermally stable up to 400 °C under a nitrogen atmosphere (Fig. S1).

The structure of SIM-300 is unambiguously resolved by single-crystal X-ray diffraction analysis (Fig. 2). SIM-300 crystallizes in the I4₁/a space group with unit-cell parameters of a = b = 25.771(2) Å, c = 7.6244(8) Å, and α = β = γ = 90°. The oligomer molecule adopts a quasi-tetrahedral conformation, featuring four terminal, unreacted aldehyde groups positioned at the ends of its four arms. The oxygen atom of the aldehyde group forms an intramolecular O⋯H–C hydrogen bond with an adjacent molecule in the unit cell (d_O⋯H = 2.611 Å, Fig. 2). These hydrogen-bond interactions contribute to the formation of a densely packed three-dimensional network. It should be noted that TAM and COF-300 crystallize in the same I4₁/a space group. The lattice parameters are a = b = 16.8018 Å, c = 7.1674 Å for TAM, and a = b = 26.2260(18) Å, c = 7.5743(10) Å for COF-300 (Fig. 3a).^10,25 The central carbons of TAM entities in the unit cells of the three crystals are located at the same positions due to the symmetry constraints of the I4₁/a space group. Therefore, the molecular packings of the three crystals are also highly similar. The attachment of four BDA molecules to TAM via an imine bond leads to the formation of SIM-300, resulting in a remarkable expansion of the a and b axes from 16.8018 to 25.771(2) Å (53.4%) and a slight elongation of the c axis from 7.1674 to 7.6244(8) Å (6.4%) due to increased molecular size (Fig. 3a). From SIM-300 to COF-300, a pair of oligomers related by (0, −0.5, 1.75) needs to expel one of the BDA fragments by breaking one C=N bond and then forming a new C=N bond between the released amine group and the aldehyde group of the other BDA fragment (Fig. 3b and Fig. S3). This reorganization step only slightly changes the cell axis lengths from SIM-300 to COF-300 (<2%, Fig. 3a). The most influential structural features are the orientation of TAM and the dihedral angles between the two phenyl groups stretching along the c direction of TAM. In the crystal structure of SIM-300, the angles are 97.0 and 116.0° for one set of oligomer molecules and 108.8 and 109.8° for the other set (Fig. S4), while in COF-300, the angles are 111.5° and 105.5° (Fig. S5).

Fig. 2 The single crystal structure of SIM-300 viewed from different directions.

Fig. 3 (a) The change of unit cell dimensions from TAM to SIM-300 and to COF-300. (b) Schematic illustration of the structural transformation from SIM-300 to COF-300.

The distinct reaction pathways were further ex situ investigated by scanning electron microscopy (SEM) and PXRD analyses (Fig. 4). For COF-300 growth under condition A, spherical aggregates consisting of elongated, rod-shaped crystallites were consistently observed throughout the reaction. As the reaction progressed, these aggregates became denser and the rod evolved with well-defined square-pyramidal ends (Fig. 4a and Fig. S6). This morphological evolution is characteristic of an Ostwald ripening process.^26,27 PXRD analysis revealed a SIM-300-to-COF-300 transformation process. At 24 hours, characteristic diffraction peaks corresponding to SIM-300 were observed along with unreacted TAM. At 48 hours, a mixed phase containing both SIM-300 and COF-300 was detected. Finally, after 72 hours, sharp and distinct diffraction peaks corresponding exclusively to COF-300 appeared (Fig. 4c). Under condition B, visible grain-like microcrystals of SIM-300 began to appear after incubation at 30 °C for 24 hours, with significant disassembly of the initial spherical aggregates. In the next 48–72 hours, these crystals further grew to ca. 100 µm in size (Fig. 4b). In the low temperature incubation stage, TAM was gradually consumed, and the diffraction intensity of SIM-300 became stronger with a smaller full width at half maximum, indicating increased crystal size (Fig. 4d). This process is a typical Ostwald ripening process. The less stable spherical aggregates gradually dissolved to release molecular building blocks, facilitating the continuous growth of larger, thermodynamically favored SIM-300 single crystals.

Fig. 4 SEM images of solid precipitates at different time intervals during the synthesis of COF-300 (a) and SIM-300 (b). The corresponding PXRD patterns during the synthesis of COF-300 (c) and SIM-300 (d). Black triangles, orange asterisks, and green circles indicate the diffraction peaks of SIM-300, TAM, and COF-300, respectively.

To investigate differences in catalytic activity between AcOH and BCF, model Schiff base condensation reactions between benzaldehyde and aniline were conducted. As shown in Fig. S7, the AcOH-catalyzed reaction rapidly approached equilibrium within 1 h (yield: 73%). In contrast, the BCF-catalyzed reaction achieved only a 57% yield after 1 h, which increased slightly to 70% after 3 h, indicating the lower catalytic activity of BCF. In addition to its weaker catalytic performance, the relatively large molecular size of BCF likely causes higher diffusion barriers to reactive sites compared to protons, thereby hindering further condensation or imine-exchange reactions, especially at lower temperatures. Consequently, BCF may become trapped within the initially formed dense SIM-300 network, restricting subsequent polymerization necessary for COF-300 formation. Under these conditions, SIM-300 crystals continue to grow via the Ostwald ripening process, ultimately yielding SIM-300 as a kinetically trapped product.

In summary, we have demonstrated that the organic Lewis acid BCF can regulate the condensation kinetics in the synthesis of COF-300, enabling direct observation of the oligomer intermediate in a single crystal form. SEM and PXRD monitoring of the reaction progress provides solid experimental evidence of a preassembly of the oligomer intermediate and a subsequent phase transformation during the formation of COF-300. This study complements the mechanistic understanding of COF growth proposed in recent intermediate tracing studies.^16,28,29 The approach presented herein offers an alternative strategy for the controlled synthesis of COFs and an opportunity for investigating the crystallization dynamics of COFs.

Conflicts of interest

The authors declare no competing financial interests.

Data availability

The data that support the findings of this study are available from the corresponding authors upon reasonable request.

Supplementary information (SI) is available. See DOI: https://doi.org/10.1039/d6cc02265k.

CCDC 2512929 contains the supplementary crystallographic data for this paper.³⁰

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grants 22401035, 22527801, 22025101, and 22222103), the Fundamental Research Funds for the Central Universities (DUT22LAB606), Liaoning Binhai Laboratory (LBLE-2023-02), International Cooperation Program of the International Office of Dalian University of Technology, and the Guangdong Basic and Applied Basic Research Foundation (2024A1515140058). J. H. is grateful for the startup fund from Great Bay University (YJKY230010) and the Guangdong Recruitment Program (2023QN10C724) for support.

References

1. A. P. Côté, A. I. Benin, N. W. Ockwig, M. O'Keeffe, A. J. Matzger and O. M. Yaghi, Science, 2005, 310, 1166–1170.
2. H. M. El-Kaderi, J. R. Hunt, J. L. Mendoza-Cortés, A. P. Côté, R. E. Taylor, M. O'Keeffe and O. M. Yaghi, Science, 2007, 316, 268–272.
3. H. Zheng, H. Li, J. Ji, F. Chen, Y. Wang, J. Suo, J. Song, D. Zhao, V. Valtchev, S. Qiu and Q. Fang, J. Am. Chem. Soc., 2025, 147, 39223–39231.
4. J. Zhang, C. Cheng, L. Guan, H.-L. Jiang and S. Jin, J. Am. Chem. Soc., 2023, 145, 21974–21982.
5. W. Zhang, L. Chen, S. Dai, C. Zhao, C. Ma, L. Wei, M. Zhu, S. Y. Chong, H. Yang, L. Liu, Y. Bai, M. Yu, Y. Xu, X.-W. Zhu, Q. Zhu, S. An, R. S. Sprick, M. A. Little, X. Wu, S. Jiang, Y. Wu, Y.-B. Zhang, H. Tian, W.-H. Zhu and A. I. Cooper, Nature, 2022, 604, 72–79.
6. H. S. Sasmal, A. Kumar Mahato, P. Majumder and R. Banerjee, J. Am. Chem. Soc., 2022, 144, 11482–11498.
7. X. Zhang, J. Hu, H. Liu, T. Sun, Z. Wang, Y. Zhao, Y.-B. Zhang, P. Huai, Y. Ma and S. Jiang, J. Am. Chem. Soc., 2025, 147, 1709–1720.
8. R. Liu, Z. Li, H. Zhao, L. Zhang, R. Lan, Q. Wang and H. Yang, Adv. Funct. Mater., 2024, 35, 2418627.
9. B. J. Smith, A. C. Overholts, N. Hwang and W. R. Dichtel, Chem. Commun., 2016, 52, 3690–3693.
10. T. Ma, E. A. Kapustin, S. X. Yin, L. Liang, Z. Zhou, J. Niu, L.-H. Li, Y. Wang, J. Su, J. Li, X. Wang, W. D. Wang, W. Wang, J. Sun and O. M. Yaghi, Science, 2018, 361, 48–52.
11. J. Han, J. Feng, J. Kang, J.-M. Chen, X.-Y. Du, S.-Y. Ding, L. Liang and W. Wang, Science, 2024, 383, 1014–1019.
12. B. Yu, R.-B. Lin, G. Xu, Z.-H. Fu, H. Wu, W. Zhou, S. Lu, Q.-W. Li, Y. Jin, J.-H. Li, Z. Zhang, H. Wang, Z. Yan, X. Liu, K. Wang, B. Chen and J. Jiang, Nat. Chem., 2024, 16, 114–121.
13. J. Zhang, Z. Wang, J. Suo, C. Tuo, F. Chen, J. Chang, H. Zheng, H. Li, D. Zhang, Q. Fang and S. Qiu, J. Am. Chem. Soc., 2024, 146, 35090–35097.
14. L. Yi, Y. Gao, S. Luo, T. Wang and H. Deng, J. Am. Chem. Soc., 2024, 146, 19643–19648.
15. A. M. Evans, L. R. Parent, N. C. Flanders, R. P. Bisbey, E. Vitaku, M. S. Kirschner, R. D. Schaller, L. X. Chen, N. C. Gianneschi and W. R. Dichtel, Science, 2018, 361, 52–57.
16. C. Kang, K. Yang, Z. Zhang, A. K. Usadi, D. C. Calabro, L. S. Baugh, Y. Wang, J. Jiang, X. Zou, Z. Huang and D. Zhao, Nat. Commun., 2022, 13, 1370.
17. W. Zhang, Y. Zhang, W. Ma, X. Han, W. Gong, Y. Liu and Y. Cui, Chemistry, 2025, 11, 2451–9294.
18. S. T. Emmerling, L. S. Germann, P. A. Julien, I. Moudrakovski, M. Etter, T. Friščić, R. E. Dinnebier and B. V. Lotsch, Chemistry, 2021, 7, 1639–1652.
19. L. Hou, C. Shan, Y. Song, S. Chen, L. Wojtas, S. Ma, Q. Sun and L. Zhang, Angew. Chem., Int. Ed., 2021, 60, 14664–14670.
20. Z. Zheng, Q. Lin, S. Peng, Y. Zhang, S. Xu, H. Zhang and H. Wang, Sci. China: Chem., 2025, 68, 3636–3646.
21. W. Zhao, Q. Zhu, X. Wu and D. Zhao, Chem. Soc. Rev., 2024, 53, 7531–7565.
22. F. J. Uribe-Romo, J. R. Hunt, H. Furukawa, C. Klöck, M. O’Keeffe and O. M. Yaghi, J. Am. Chem. Soc., 2009, 131, 4570–4571.
23. X. Shi, L. Yi and H. Deng, Sci. China: Chem., 2022, 65, 1315–1320.
24. T. Ma, J. Li, J. Niu, L. Zhang, A. S. Etman, C. Lin, D. Shi, P. Chen, L.-H. Li, X. Du, J. Sun and W. Wang, J. Am. Chem. Soc., 2018, 140, 6763–6766.
25. D. Laliberté, T. Maris, E. Demers, F. Helzy, M. Arseneault and J. D. Wuest, Cryst. Growth Des., 2005, 5, 1451–1456.
26. W. Ma, G. Li, C. Zhong, Y. Yang, Q. Sun, D. Ouyang, W. Tong, W. Tian, L. Zhang and Z. Lin, Chem. Commun., 2021, 57, 7362–7365.
27. H. Zhao, G. Liu, Y. Liu, L. Zhou, L. Ma, Y. He, X. Zheng, J. Gao and Y. Jiang, Nano Res., 2023, 16, 281–289.
28. J. Liu, X. Su, Y. Xu, W. Tang, T. Yang and J. Gong, Chem. Sci., 2025, 16, 15037–15044.
29. L. Bourda, S. Bhandary, S. Ito, C. R. Göb, P. Van Der Voort, K. Van Hecke and L. Meshi, IUCrJ, 2024, 11, 510–518.
30. CCDC 2512929: Experimental Crystal Structure Determination, 2026 DOI:10.5517/ccdc.csd.cc2qbx77.

---

Footnote

† Tian Wang, Ming-Yang Fu and Hao Wang contributed equally to this work.

---