This is the accepted version of the article: Martín-Illán J.Á., Rodríguez-San-Miguel D., Rodríguez-San-Miguel D., Franco C., Imaz I., Maspoch D., Maspoch D., Puigmartí-Luis J., Zamora F., Zamora F., Zamora F., Zamora F.. Green synthesis of imine-based covalent organic frameworks in water. Chemical Communications, (2020). 56. : 6704 - . 10.1039/d0cc02033h. Available at: https://dx.doi.org/10.1039/d0cc02033h Green Synthesis of Imine-based Covalent Organic Frameworks in Water Jesús Á. Martín-Illán,a David Rodríguez-San-Miguel,a,b Carlos Franco,b Inhar Imaz,c Daniel Maspoch,c,d Josep Puigmartí-Luis,b* and Félix Zamoraa,e,f,g* Dynamic covalent bonds have been advantageously used to direct However, more recently, because of the enhanced chemical the synthesis of crystalline porous covalent organic frameworks robustness, COFs produced by Schiff-base chemistry (e.g. imine- (COFs). Unlike the standard synthetic protocols that involve harsh based COFs) have been largely developed.21 conditions, this work provides a high-yield “one-pot” green synthesis of imine-based COFs in water. Additionally, this aqueous Currently, the most typical synthetic protocol to produce synthesis can be performed under microwave conditions, imine-based COFs requires using acid catalysts, solvothermal considerably reducing the reaction time. conditions (temperatures as high as 120-150 0C), long reaction times (48-72 hours) and high boiling point and hazardous organic solvents, such as mesitylene, 1,4-dioxane, N,N- dimethylformamide (DMF), N,N-dimethylacetamide (DMA), Covalent organic frameworks (COFs) are organic crystalline and o-dichlorobenzene (DCB), among others.21 polymers showing permanent porosity.1,2 Modular chemistry concepts are behind the synthesis of these materials, producing programmed, extended and ordered structures, which properties can be fine-tuned based on the selection of molecular building blocks.3 Thus, the combination of the building blocks determines not only the COF architecture but also their physico-chemical properties. Indeed, COFs present interesting properties going from gas storage and separation4–6 to applications in optoelectronics,7 drug delivery,8,9 molecular separation,10,11 sensing,12,13 water decontamination14 and catalysis.15–17 A key factor to successfully control COF crystallinity is the use of reversible covalent bonds to connect the molecular building blocks while allowing error correction.2,18,19 Hence, the most typical reactions used to a. Departamento de Química Inorgánica, Universidad Autónoma de Madrid, 28049 Madrid, Spain. Tel: 34 91 4973962; E-mail: felix.zamora@uam.es. b. Department of Chemistry and Applied Biosciences, Institute for Chemical and Bioengineering, ETH Zurich, Vladimir Prelog Weg 1, 8093 Zurich, Switzerland. c. Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and BIST Campus UAB, Bellaterra, 08193 Barcelona, Spain. Scheme 1. Synthetic scheme of a) TAPB-BTCA-COF and TZ-BTCA-COF; and b) HZ-BTCA- d. ICREA, Pg. Lluís Companys 23, 08010 Barcelona, Spain. COF. e. Instituto Madrileño de Estudios Avanzados en Nanociencia (IMDEA-Nanociencia), Cantoblanco, Madrid E-28049, Spain. f. Institute for Advanced Research in Chemical Sciences (IAdChem). Universidad Autónoma de Madrid. 28049 Madrid, Spain. g. Condensed Matter Physics Center (IFIMAC). Universidad Autónoma de Madrid. 28049 Madrid, Spain. † Electronic Supplementary Information (ESI) available: Additional experimental data and theoretical calculations. See DOI: 10.1039/x0xx00000x produce COFs are based on condensation reactions between two different monomers. Initially, a large variety of boron- based COFs synthesized by the condensation reaction of two boronic acids or boronic acids with catechols were described.1,20 Fig. 1 a) Experimental (blue) and simulated (purple) PXRD patterns of TAPB-BTCA-COF. b) N2 adsorption–desorption isotherm of TAPB-BTCA-COF. Adsorption branch in black, desorption branch in red. c) Bar graph representing the yields of TAPB-BTCA-COF obtained at different pH values. At pH 2 no product was obtained. In view of the great potential applications of these new indicating the completion of the reaction. 13C CP-MAS solid- porous materials, it will be highly desired to develop more state NMR spectrum also confirmed the formation of imine sustainable procedures to prepare high-quality COFs, i.e. with a bonds showing the characteristic signal at 155 ppm that high porosity and crystallinity. Thus far, only a few reports have corresponds to the imine carbon (Table S1 and Fig. S2, ESI†). Fig. focused on green synthetic protocols for the production of 1a shows the PXRD pattern of TAPB-BTCA-COF, which matches COFs.22–25 For example, Banerjee et al. and Zhao et al. have with the simulated pattern in AA eclipsed stacking model.28 The recently reported the synthesis of keto-enamine-based COFs intense first peak was attributed to the strongly reflecting (100) using a hydrothermal method.26,27 However, these processes plane. The thermogravimetric analysis (TGA) of TAPB-BTCA-COF have been limited to this specific type of COFs. In fact, both in N2 atmosphere demonstrated its thermal stability up to 500 authors explored the ability of their procedures to generate 0C (Fig. S3, ESI†). Note here that all these data are in good imine-linked COFs and concluded that the lack of hydroxyl agreement with previously reported values for TAPB-BTCA-COF groups in the aldehyde building block precluded the synthesis synthesized under standard solvothermal conditions and using of COFs. This highlights the fact that the chemistry of imine and hazardous organic solvents.29 Additionally, the microporosity of keto-enamine-linked COFs is significantly different, and that TAPB-BTCA-COF was confirmed by N2 adsorption analysis at 77 new synthetic protocols are needed to synthesize imine-linked K (Fig. 1b and Table S7, ESI†), from which a BET surface area COFs in more environmentally friendly conditions. (SABET) of 806 m2 g-1 was calculated (Fig. S4, ESI†). To the best of our knowledge, this SABET value of TAPB-BTCA-COF is one of the Herein we report a simple protocol for preparing imine- highest reported, even when compared to TAPB-BTCA-COF based COFs using water as solvent and a limited amount of synthesized using tetrahydrofuran:mesitylene mixtures in acetic acid as catalyst at relatively low temperatures. The so- solvothermal conditions.30 The collected isotherm is a type IV formed COFs are obtained in high yield showing good isotherm according to IUPAC classification, presenting a crystallinity and porosity. Additionally, we also demonstrate hysteresis loop. This behaviour can be attributed to the that the same protocol can be carried out under microwave presence of some mesoporosity resulting from the nanocrystal irradiation, significantly reducing the reaction time from some assembly (Fig. S5, ESI†) and/or to some structural swelling; as days down to hours. sometimes observed in this type of materials. 31,32 We started with the aqueous synthesis of the imine-based In order to further understand the factors that affect the TAPB-BTCA-COF made of 1,3,5-benzenetricarbaldehyde (BTCA) generation of imine-based COFs under these mild conditions, and 1,3,5-tris-(4-aminophenyl)benzene (TAPB) (Scheme 1a). we evaluated the influence of pH in the synthesis of TAPB- TAPB-BTCA-COF was synthesized by mixing two aqueous BTCA-COF. To this end, we reproduced its synthesis in water at solutions, one containing BTCA and the other containing TAPB several pH values from 2 to 4 by adjusting the amount of acetic and acetic acid. The resulting mixture (pH 2.4) was then heated acid (ESI for experimental details). Fig. 1c indicates the clear at 80 0C for 5 days (ESI for experimental details). Fourier dependence that the imine-condensation reaction has with pH, transform infrared spectroscopy (FT-IR), 13C CP-MAS solid-state where a maximum yield was obtained at pH value 2.4 (see also NMR and powder X-ray diffraction (PXRD) of the resulting solid Table S3). Even though the reaction yield decreased by 30 %, we corroborated the formation of TAPB-BTCA-COF. FT-IR spectrum also observed that the TAPB-BTCA-COF powder obtained at pH showed the presence of imine bonds through the appearance 3 showed a good value of SABET above 750 m2 g-1 (Fig. S6 and of the characteristic C=N stretching at 1624 cm-1 (Fig. S1, ESI†). Table S7, ESI†). Surprisingly, the SABET was dramatically Moreover, the characteristic vibrations of the amino and decreased at pH 3.5, where values around 150 m2 g-1 were carbonyl groups of the precursors were not appreciated, found. Remarkably, in all the conditions screened, the 1). To this end, we employed similar conditions to the ones synthesized COF powders showed clear TAPB-BTCA-COF described above where the pH was adjusted to obtain the diffraction peaks (Fig. S7, ESI†). maximum yield in both COFs synthesis (ESI for experimental details). Note here that a small amount of DMSO (0.3 % in vol.) We attribute the changes of the reaction yield at different was used to facilitate the solubilization of TZ in water during the pHs to the degree of protonation of TAPB in the aqueous synthesis of TZ-BTCA-COF (for further details see ESI).33 medium. While BTCA was soluble in the complete pH range Remarkably, FT-IR spectra (Figs S12 and S13, ESI†), 13C CP-MAS studied, the solubility of TAPB was pH dependent (Table S5). solid-state NMR spectra (Tables S5 and S6 and Figs S14 and S15, Note that TAPB is a weak triprotic base with a large aromatic ESI†) and TGA (Figs S16 and S17, ESI†) of HZ-BTCA-COF and TZ- skeleton. Accordingly, even though the neutral amine has an BTCA-COF matched with the previously reported data for both extremely low solubility in water, its charged ammonium COFs synthesized under conventional solvothermal cations are the predominant species in highly acidic solutions conditions.5,34 Moreover, the PXRD patterns of both synthesized and are readily dissolved in water. Thus, at pH 4, a TAPB COFs matched with the corresponding simulated patterns in AA concentration of only 31 μM was available to react with BTCA eclipsed stacking models (Fig. 2a).5,34 In fact, the SABET values (Table S5), and therefore, the formation of TAPB-BTCA-COF was measured were 1366 m2 g-1 for HZ-BTCA-COF (Figs. S18 and S19) almost precluded at this pH. At pH < 3.5, the solubility of TAPB and 1533 m2 g-1 for TZ-BTCA COF (Figs. S20 and S21). These increased gradually, also increasing the yield of the reaction values are comparable to those previously reported for both until complete solubilisation was achieved at an optimal pH of COFs obtained by solvothermal synthesis in mesitylene:dioxane 2.4 (Table S3), with a maximum yield of 97 %. However, mixtures.5,34 lowering the pH beyond this point resulted in a complete inhibition of the reaction, with no solid precipitating from the reaction mixture, which remained clear and colourless after 5 days at 80 0C. This is in agreement with the work of Banerjee et al,26 who observed that it is not possible to obtain imine-based COFs in aqueous solutions with a high concentration of acetic acid even using hydrothermal conditions. The lack of reaction at this low pH value can be easily rationalized considering again the basic nature of TAPB and the mechanism of the imine formation. We found out that the pKa value for the first acid- base equilibrium of the TAPB system (that is, from the fully protonated triammonium ion to the doubly protonated molecule) is close to 3.5 (Fig. S8). This implies that, at pH 2, only 3 % of the TAPB molecules will have one non-protonated amine that can act as a nucleophile. This is of great importance, since Fig. 2 a) PXRD patterns of HZ-BTCA-COF obtained in water (blue) and simulated (purple). and of TZ-BTCA-COF obtained in water (red) and simulated (orange). b) PXRD patterns the crucial step for the formation of an imine bond from an of TAPB-BTCA-COF obtained in water close to ambient conditions (RT TAPB-BTCA-COF, aldehyde and an amine is the nucleophilic attack of the nitrogen green), under hydrothermal MW conditions (MW TAPB-BTCA-COF; black) and simulated of the amino group to the carbon of the carbonyl group. (purple). Therefore, at pH 2, even though TAPB is completely dissolved in the reaction mixture, it cannot react with BTCA because its Finally, to further reduce the energy costs and shorten the reactivity is greatly decreased due to the protonation of the reaction times, we prepared TAPB-BTCA-COF in water close to amino groups. Hence, these results show that, in order to room temperature conditions (RT TAPB-BTCA-COF) and under synthesise imine-based COFs in water, it is necessary to find the hydrothermal microwave radiation (MW TAPB-BTCA-COF). For pH range in which both amine and aldehyde building blocks are the first case, RT TAPB-BTCA-COF could be prepared (90 % completely dissolved but also reactively active to trigger the yield) by heating an aqueous solution (pH 2.4) of TAPB and condensation reaction. On the other hand, the change of BTCA in the presence of acetic acid and at 35 oC for 5 days. surface area is likely related to the presence of undissolved Interestingly, this COF showed a crystallinity (Fig. 2b) and SABET monomers, as also suggested by Zhao et al. for keto-enamine of 803 m2 g-1 (Table S7 and Figs. S23 and S24, ESI†) similar to the COFs.27 In order to further support this hypothesis, we prepared same material synthesized at 80 oC. TAPB-BTCA-COF at pH 2.4 doubling the concentration of monomers (ESI for experimental details). Under these Also, microwave radiation was proven useful for the conditions, the yellow solid obtained showed a large decrease aqueous synthesis of imine-based COFs. Here, we heated an in crystallinity (Fig. S10) and a loss of porosity (Fig. S11). aqueous mixture (pH 2.4) containing both precursors and acetic acid at 80 0C in a 200 W microwave oven (ESI for experimental Having successfully produced TAPB-BTCA-COF in water, we details). MW TAPB-BTCA-COF was obtained in 5 hours with an extended our aqueous method to the synthesis of HZ-BTCA-COF equivalent yield (85 %) to the reaction carried out for 5 days and TZ-BTCA-COF, where HZ and TZ stand for hydrazine and using conventional heating. The FT-IR spectrum (Fig. S25) and 2,4,6-tris(4-aminophenyl)-1,3,5-triazine, respectively (Scheme PXRD pattern (Fig. 2b) of MW TAPB-BTCA-COF were similar to those previously obtained for TAPB-BTCA-COF. Moreover, MW 9 Q. Fang, J. Wang, S. Gu, R. B. Kaspar, Z. Zhuang, J. Zheng, H. TAPB-BTCA-COF showed a SABET of 566 m2g-1 (Table S7 and Figs. Guo, S. Qiu and Y. Yan, J. Am. Chem. Soc., 2015, 137, 8352– 8355. S26 and S27, ESI†). This value is slightly smaller than the 10 J. Shen, R. Zhang, Y. Su, B. Shi, X. You, W. Guo, Y. Ma, J. Yuan, previous TAPB-BTCA-COF synthesized in water, but it is in the F. Wang and Z. Jiang, J. Mater. Chem. A, 2019, 7, 18063– range of that synthesized in organic solvents, 28,35 including 18071. mesitylene:dioxane mixtures.29,30 11 H. Yang, L. Yang, H. Wang, Z. Xu, Y. Zhao, Y. Luo, N. Nasir, Y. Song, H. Wu, F. Pan and Z. Jiang, Nat. Commun., 2019, 10, This work provides a simple one-step green method to 2101. synthesize imine-based COFs in water with good quality in 12 P. Albacete, A. López-Moreno, S. Mena-Hernando, A. E. Platero-Prats, E. M. Pérez and F. Zamora, Chem. Commun., terms of crystallinity and porosity; in high yields; and avoiding 2019, 55, 1382–1385. the use of harmful organic solvents and high temperatures. The 13 L. Ascherl, E. W. Evans, M. Hennemann, D. Di Nuzzo, A. G. versatility of this method has been corroborated preparing Hufnagel, M. Beetz, R. H. Friend, T. Clark, T. Bein and F. three structurally and chemically different imine-based COFs. Auras, Nat. Commun., 2018, 9, 3802. We also showed that imine-based COFs can also be produced in 14 L. Merí-Bofí, S. Royuela, F. Zamora, M. L. Ruiz-González, J. L. Segura, R. Muñoz-Olivas and M. J. Mancheño, J. Mater. water decreasing the reaction temperature down to 35 0C, or by Chem. A, 2017, 5, 17973–17981. using microwave heating with a significant reduction of the 15 Y. Han, M. Zhang, Y.-Q. Zhang and Z.-H. Zhang, Green Chem., reaction time, from several days down to 5 hours. The results 2018, 20, 4891–4900. obtained pave the way for large-scale synthesis of imine-based 16 P.-F. Wei, M.-Z. Qi, Z.-P. Wang, S.-Y. Ding, W. Yu, Q. Liu, L.-K. COFs in water presenting a more sustainable method that Wang, H.-Z. Wang, W.-K. An and W. Wang, J. Am. Chem. Soc., 2018, 140, 4623–4631. avoids the use of organic solvents, otherwise required for COF 17 S. M. J. Rogge, A. Bavykina, J. Hajek, H. Garcia, A. I. Olivos- synthesis. Suarez, A. Sepúlveda-Escribano, A. Vimont, G. Clet, P. Bazin, F. Kapteijn, M. Daturi, E. V. Ramos-Fernandez, F. X. Llabrés i Xamena, V. Van Speybroeck and J. Gascon, Chem. Soc. Rev., Conflicts of interest 2017, 46, 3134–3184. 18 Y. Jin, Y. Hu and W. Zhang, Nat. Rev. Chem., 2017, 1, 0056. There are no conflicts to declare. 19 C. S. Diercks and O. M. Yaghi, Science, 2017, 355, eaal1585. 20 E. L. Spitler and W. R. Dichtel, Nat. Chem., 2010, 2, 672–677. 21 J. L. Segura, M. J. Mancheño and F. Zamora, Chem. Soc. Rev., Acknowledgements 2016, 45, 5635–5671. 22 X. Li, Y. Qi, G. Yue, Q. Wu, Y. Li, M. Zhang, X. Guo, X. Li, L. Ma This work was supported by the EU (ERC-2015-STG and S. Li, Green Chem., 2019, 21, 649–657. microCrysFact 677020 and ERC-Co 615954), Swiss National 23 F. Zhang, J. Zhang, B. Zhang, X. Tan, D. Shao, J. Shi, D. Tan, L. Science Foundation (Project no. 200021_160174 and Liu, J. Feng, B. Han, G. Yang, L. Zheng and J. Zhang, 200021_181988), ETH Zürich, Catalan AGAUR (project 2017 SGR ChemSusChem, 2018, 11, 3576–3580. 24 S. Karak, S. Kandambeth, B. P. Biswal, H. S. Sasmal, S. Kumar, 238), and MICINN (MAT2016-77608-C3-1P and RTI2018- P. Pachfule and R. Banerjee, J. Am. Chem. Soc., 2017, 139, 095622-B-I00). It was also funded by the CERCA 1856–1862. Program/Generalitat de Catalunya. ICN2 is supported by Severo 25 W. Dai, F. Shao, J. Szczerbiński, R. McCaffrey, R. Zenobi, Y. Ochoa program from MINECO (SEV-2017-0706). Jin, A. D. Schlüter and W. Zhang, Angew. Chem. Int. Ed., 2016, 55, 213–217. 26 J. Thote, H. Barike Aiyappa, R. Rahul Kumar, S. Kandambeth, B. P. Biswal, D. Balaji Shinde, N. 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