MIL-101(Cr)-SO3Ag: An efficient catalyst for solvent-free A3 coupling reactions

Accepted Manuscript Title: MIL-101(Cr)-SO3 Ag: an efficient catalyst for solvent-free A3 coupling reactions Author: Weng-Jie Sun Fu-Gui Xi Wu-Liang Pan En-Qing Gao PII: DOI: Reference:

S1381-1169(16)30558-1 http://dx.doi.org/doi:10.1016/j.molcata.2016.12.008 MOLCAA 10147

To appear in:

Journal of Molecular Catalysis A: Chemical

Received date: Revised date: Accepted date:

18-9-2016 5-12-2016 6-12-2016

Please cite this article as: Weng-Jie Sun, Fu-Gui Xi, Wu-Liang Pan, En-Qing Gao, MIL101(Cr)-SO3Ag: an efficient catalyst for solvent-free A3 coupling reactions, Journal of Molecular Catalysis A: Chemical http://dx.doi.org/10.1016/j.molcata.2016.12.008 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Cover Page MIL-101(Cr)-SO3Ag: an efficient catalyst for solvent-free A3 coupling reactions Weng-Jie Sun, Fu-Gui Xi, Wu-Liang Pan and En-Qing Gao* Shanghai Key Laboratory of Green Chemistry and Chemical Processes, College of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China

Corresponding author: En-Qing Gao Shanghai Key Laboratory of Green Chemistry and Chemical Processes, College of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China Fax: +86-21-62233404 E-mail: [email protected]

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Graphical abstract

Highlights

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The synthesis of propargylamines through A3 (alkyne-aldehyde-amine) coupling was studied

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MIL-101(Cr)-SO3Ag is a reusable catalyst for facile synthesis of propargylamines.

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The yield of propargylamines was > 90% under mild conditions

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The catalytic reaction starting with benzaldehyde leads to chalcone.

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The reaction mechanism was investigated

Abstract: An Ag(I)-functionalized MOF, MIL-101-SO3Ag, was synthesized and demonstrated to be an efficient and environmentally friendly catalyst for the syntheses of propargylamines through A3 coupling of aldehydes, terminal alkynes and amines. A quite small amount of the catalyst can efficiently catalyze the reactions of aliphatic aldehydes, alkynes, and amines under solvent-free conditions to give propargylamines in excellent yields (> 90%). The TOF can be as high as 6600 h-1. The catalytic efficiency is higher than other catalysts available in the literature. The catalyst could be easily recycled without a significant loss of its catalytic activity. In addition, we found that the catalyst also promotes the secondary reaction in which 1

the propargylamines formed from aromatic aldehydes undergo propargyl-to-allenyl isomerization and subsequent hydrolysis to give chalcones.

Keywords: Metal-organic frameworks; Silver(I) catalysts; A3 coupling; Heterogeneous catalysis

1. Introduction In recent years, multicomponent reactions (MCRs) have attracted much attention as it could synthesize diverse complex organic compounds from simple organic moieties via a one-pot process. Generally, these reactions are highly atom-economic, time-saving, and energy-efficient. A famous MCR is the Mannich-type three-component coupling reactions of alkynes, aldehydes, and amines (A3 coupling) through C–C and C-N coupling [1, 2]. The reaction represents an established, convenient, and efficient method for the synthesis of propargylamines, which are important key components of various natural products [3-5] and versatile precursors for the synthesis of various pharmacological compounds such as quinolones [6], indolizines [7], oxazoles [8], pyrroles [9] and imidazole [10]. Many metal compounds have been reported to be homogeneous catalysts for A3 reactions, including Au(I)/Au(III) [11, 12], Cu(I)/Cu(II) [13, 14], Mg(II) [15], In(III) [16], Zn(II) [17] and Fe(III) [18] species. Heterogeneous catalysts such as metallic/metal-oxide nanoparticles [19, 20] and polymer supported metal complexes [21] have been developed. Since Li and his co-workers reported the AgI-catalyzed A3 reactions in 2003 [22], silver has received increasing attention for its high activity in promoting the three-component coupling reaction. Many Ag(I) complexes such as those with N-heterocyclic carbenes (NHCs) [23] and pyridine-containing ligands [24] have been invented as homogeneous catalysts. Beyond that, efficient heterogeneous Ag catalysts have also been reported, some recent examples being silver oxide nanoparticles [25], PS-supported NHC–Ag(I) [26], and zeolite supported silver nanoparticles [27]. Metal-organic frameworks (MOFs) are porous hybrid materials constructed from metal ions or clusters and organic linkers. Thanks to their highly designable frameworks, great 2

structural versatility, high surface areas, tunable pore sizes and tailorable functionalities [28, 29], MOFs have been extensively studied as appealing platforms for the design of functional materials for various applications such as gas storage, catalysis and sensing [30-32]. In particular, for catalytic applications, MOFs have been demonstrated as versatile carriers for immobilization of various catalytic species. Some MOFs with inherent or postsynthetically immobilized Cu or Au sites have been tested for A3 coupling [33-35], and to our knowledge, the study of MOF-supported Ag(I) catalysts for A3 coupling is still lacking. MIL-101(Cr) is a suitable candidate due to its good thermal stability and excellent chemical stability [36]. Various catalytic sites have been installed into MIL-101(Cr) through the use of pre-functionalized ligands or by post-synthetic modification at the metal center, the organic linker or the pore space [37-39]. The sulfonate-functionalized MOF, MIL-101(Cr)-SO3H [40, 41], provides a platform for post-synthetic modification via metal coordination. Several metal ions have been loaded on MIL-101(Cr)-SO3H to enhance the catalytic activity of MOFs [42, 43]. Very recently, the Ag(I)-functionalized MOF (MIL-101(Cr)-SO3Ag) has been studied for olefin–paraffin separation , desulfurization, and iodide removal [44-47]. We expected that the material could be a promising Ag(I) catalyst. In this paper, we report its use as the catalyst for A3 coupling. As will be shown, the catalyst is highly efficient with a turnover frequency up to 6600 h-1, and it shows easy recovery and excellent recycling stability.

2. Experimental 2.1 Synthesis Synthesis of MIL-101(Cr)-SO3H. MIL-101(Cr)-SO3H was prepared according to a literature method [40] with some modification. Sulfoterephthalic acid (3.35 g, 12.5 mmol), CrO3 (1.25 g, 12.5 mmol) and concentrated aqueous hydrochloric acid (0.8 ml, 25 mmol) were dissolved in water (50 mL) and then transferred to a Teflon-lined stainless steel autoclave. The solution was heated at 453 K for six days under the hydrothermal conditions. The reaction product was harvested by centrifugation and washed three times with deionized water (400 mL) and methanol (100 mL) followed by drying in air at room temperature. The green powder was purified in DMF at 120 °C for 24 h followed by in a mixed solution of methanol and H2O at 120 °C for 24 h. 3

Synthesis of MIL-101(Cr)-SO3Ag. MIL-101(Cr)-SO3Ag was prepared according to the reported method by Ma [47] with some modification. MIL-101(Cr)-SO3H (200 mg, 0.209 mol) and AgBF4 [200 (1.03), 400 (2.05) or 800 (4.11) mg (mol)] were added to the 30 ml CH3CN/H2O (1:1) solution. The mixture was stirred under room temperature for 12 h, and then the solid was collected by filtration followed by washing with CH 3CN and water each for three times. The solid was dried at 110 ºC for 4 h. ICP analysis, Cr:Ag molar ratio (Ag modification percentage of sulfate groups): 2.3:1 (21 mol%), 2.1:1 (22 mol%) and 1.7:1 (29 mol%) for the AgBF4 dose of 200, 400 and 800 mg respectively. Obviously, the preparation of the sample with 21 mol% modification has the highest efficiency in Ag utilization, so the sample was chosen for further characterization and catalytic use. 2.2 Characterization The X-ray powder diffraction patterns of the samples were measured using a Rigaku Ultima IV X-ray Diffractometer with Cu Kα radiation (λ = 1.54 Å) at a scanning rate of 10 ˚C/min, with accelerating voltage and current of 35 kV and 25 mA, respectively. SEM study was carried out with a S-4800 HITACHI scanning electron microscope. Elemental analyses were determined on an Elementar Vario ELIII analyzer. FT-IR spectra were recorded in the range 5004000 cm1 using KBr pellets on a Nicolet NEXUS 670 spectrophotometer. The leached metal amount was detected by inductively coupled plasma atomic emission spectroscopy (ICP-AES) using a IRIS Intrepid II XSP spectrometer. Gas chromatography (GC) was conducted using a Linghua GC 9890E instrument equipped with an FID detector and an SE-54 capillary column (30 m0.25 mm0.25 m). The temperature program for GC analysis was set as follows: the temperature was held at 40 ˚C for 1 min, then raised to 260 ˚C at 30 ˚C/min and held for 5 min. Inlet and detector temperatures were 280 ˚C. The analysis was carried out directly after sampling to avoid any additional conversion. 2.3 Catalytic test To a 25 mL flask containing dried MIL-101(Cr)-SO3Ag catalyst (20 mg, containing 0.012 mmol Ag) and paraformaldehyde (312mg, 10.4mmol) was added under stirring a mixture of phenylacetylene (0.88 ml, 8 mmol) and piperidine (0.79 ml, 8 mmol). The mixture was stirred at 100 ºC for 2 h. The slurry was centrifuged and washed with dichloromethane (10 ml) for three times. Then the catalyst was dried overnight to recycle. The yield was confirmed by 1H 4

NMR of the crude reaction mixture dissolved in CDCl3. 2.4 Spectroscopic data for some products 1-(3-Phenylprop-2-yn-1-yl)piperidine: 1H NMR (400 MHz, CDCl3): δ = 1.32-1.40 (m, 2H), 1.52-1.60 (m, 4H), 2.48 (s, 4H), 3.39 (s, 2H), 7.17-7.22 (m, 3H), 7.32-7.35 (m, 2H). N-(1,3-Diphenyl-2-propynyl)piperidine: 1H NMR (400 MHz, CDCl3): δ = 1.29-1.37 (m, 2H), 1.42-1.56 (m, 4H), 2.46 (t, 4H), 4.69 (s, 1H), 7.15-7.27 (m, 5H), 7.37-7.44(m, 3H), 7.54 (d, 2H). (E)-chalcone: 1H NMR (400 MHz, CDCl3): δ = 7.33-7.38 (m, 3H), 7.41-7.50 (m, 3H), 7.50-7.55 (m, 1H), 7.56-7.61 (m, 2H), 7.75 (d, J=15.7 Hz, 1H), 7.93-7.99 (m, 2H); 13C NMR (100 MHz, CDCl3): δ = 122.1, 128.5, 128.5, 128.6, 129.0, 132.8, 134.9, 138.2, 144.9, 190.6. 3. Results and discussion 3.1 Synthesis and characterization of the catalysts MIL-101(Cr)-SO3Ag was synthesized by a simple method as shown in Scheme 1. First, the sulfonic-functionalized MOF (MIL-101(Cr)-SO3H) was prepared by a hydrothermal procedure [40]. Then the MOF was subjected to post-synthetic modification through the coordination of Ag(I) to the sulfonate group. An excess of AgBF4 with respect to the sulfonic group was used. According to ICP analytic results, the modification ratio of sulfonic groups increased from 21 to 29 % when the starting amount of AgBF4 was varied from 200 to 800 mg (about 5 to 20 equivalents). That is, increasing the amount of AgBF4 did not lead to proportional increase in the loading amount of Ag(I). For better utilization of the silver source, we chose the 200 mg procedure and used the corresponding product with 21% modification for subsequent characterization and catalytic study.

MIL-101(Cr)-SO3Ag shows a similar PXRD profile to that of MIL-101(Cr)-SO3H (Fig. 1), which indicated that the crystal structure did not undergo any significant change after the modification. According to the SEM image (Fig. 1, top), the particles of the material show an average size of about 2 μm, with irregular morphology. The nitrogen adsorption isotherm of MIL-101(Cr)-SO3Ag taken at 77K is presented in Fig. S1. We could see that the MOF remains highly porous after Ag(I) modification. The Brunauer−Emmett−Teller (BET) specific surface area is 1497 m2/g, the pore volume is 0.90 cm3/g and the adsorption average pore 5

width counted by BET data is 2.40 nm. The BET surface area is somewhat larger than that reported for similar materials which may be because our material has a lower modification percentage of Ag(I) (21 % versus 51 %). The area is smaller than MIL-101-SO3H (1856 m2/g ) [47] owing to the partial occupancy of the pore space by Ag(I). The thermal stability of the catalyst is an important characteristic of a catalyst. According to TGA (Fig. S2), the weight loss up to 300 ºC should be the release of absorbed and coordinated water. The rapid weight loss observed above this temperature may be due to the thermal decomposition of the –SO3H group followed by the complete breakdown of the structure. The results are in accordance with the previous reports [48] and shows that the catalyst is stable up to 300 ºC.

The FTIR spectra of MIL-101(Cr)-SO3H and MIL-101(Cr)-SO3Ag (Fig. S3) show strong absorption at 1180, 1080 and 1025 cm-1, which can be attributed to the O=S=O symmetric stretching mode, the in-plane skeletal vibration of the benzene ring with a sulfonic substituent, and the S-O stretching vibration, respectively [48]. The influence of Ag(I) modification on IR spectra is undetectable. The result clearly proves that the sulfonic group is not damaged during the modification reaction. In addition, there are no broad bands around 1030 cm-1, which shows that BF4- has been completely washed away.

3.2 Catalytic properties Our initial investigation was focused on the solvent effect on the A3 coupling over MIL-101(Cr)-SO3Ag (0.15 mol%, referring to the amount of Ag(I) relative to the alkyne substrates). We chose phenylacetylene, paraformaldehyde and piperidine as the model substrates for they are the simplest components in this reaction. Toluene, DMF and 1,4-dioxane, which have been widely used as solvents for A3 coupling, were tested for comparison. The results are summarized in Table 1, entries 1-3. It is evident that these solvents are all excellent for the reaction. The reaction in DMF or 1,4-dioxane proceeded smoothly at 100C to afford the expected propargylamine with almost complete conversion within 2 h, while the use of toluene led to a somewhat decreased yield. We also performed the reaction under solvent-free conditions. It turned out that the “neat” reaction can give excellent 6

yield comparable to that in DMF or 1,4-dioxane (Table 1, entry 4). Considering the obvious advantages from both environmental and economic viewpoints, we choose to study the three-component coupling reactions under solvent-free conditions.

The catalytic activity of the Ag(I) catalyst was confirmed by comparison with control experiments. In absence of any catalyst or in the presence of the MIL-101(Cr)-SO3H precursor (Table 1, entries 10 and 11), the model reaction gave very low yield (~ 10%) under the otherwise identical conditions. The results clearly confirm the necessity of Ag(I) sites for the MOF to catalyze the reaction.

The influence of the catalyst dosage was investigated. When the quantity of MIL-101(Cr)-SO3Ag was reduced, the yield slightly decreased (Table 1, entries 4-7). Even at quite a low catalyst amount of 0.02 mol%, the yield after 2 h can still reach 88%. The kinetic data were obtained for reactions in presence of different dosage of the catalyst (Fig. 2). As can be seen, the rate of the reaction increases with the dosage. The reaction could complete within 30 minutes by increasing the catalyst amount to 0.3 mol%. The turnover frequency (TOF) was calculated using the data at 5 min (Table 1, entries 12-14). The value increases with decreasing dosage of catalyst, and it is as high as 6600 h-1 with 0.06 mol% catalyst. The data indicate very high activity of the catalyst for A3 coupling. The catalyst is compared with some previous ones with comparable data (Table 2), we could clearly see that MIL-101-SO3Ag system has a satisfactory result with very little amount of catalyst and quite great reaction rate. The temperature factor was also under consideration. At the temperature of 80 oC, the yield of the propargylamine after 2 h is even lower than that after 0.5 h at 100 oC (Table 1, entries 8, 9), which suggests that the reaction is significantly influenced by temperature.

3.3 Reusability test of MIL-101(Cr)-SO3Ag catalyst The reusability of MIL-101(Cr)-SO3Ag was examined by recycling the catalyst for five 7

consecutive reaction runs of phenylacetylene, paraformaldehyde and piperidine on a larger scale under the typical neat conditions. For each run, the heterogeneous mixture after reacting for 2 h was centrifuged to separate the solid catalyst from the reaction mixture. The catalyst was thoroughly washed twice with dichloromethane, dried in air overnight, and then used for another reaction cycle. As shown in Fig. 3, the yield of the propargylamine product remains at a high level  94%) in the recycling tests, which shows that the catalyst could be reused without significant degradation in catalytic performance. PXRD and FTIR measurements were performed to probe the change of MOF after reaction (Figs. S3 and S4). The PXRD pattern of the recovered MIL-101(Cr)-SO3Ag catalyst is very similar to that of the fresh catalyst, proving the chemical stability of the framework under the solvent-free catalytic conditions. The FTIR spectrum of the used catalyst displays weak absorptions at 2856, 2937 and 3193 cm-1, which are absent in the fresh catalyst. The same bands were also observed after a sample of the unused catalyst was stirred in piperidine, so they are attributable to the (C-H) and (N-H) vibration modes of piperidine adsorbed in the MOF. Piperidine could not be removed even by heating at 110 ºC for 4 h, but there was no sign that it would reduce the catalytic activity of MIL-101(Cr)-SO3Ag. The tight absorption of piperidine may be due to the acid-base interactions with the unmetalated SO3H groups in the catalyst. Therefore, the SO3H groups in the catalysts are neutralized in the first run and remain unprotonated in subsequent runs, exerting little influence on the catalytic reaction. 3.4 Scope of the catalytic reaction and formation of chalcones A variety of substrates for A3 coupling have been examined to expand the scope of the catalytic system under the typical solvent-free conditions at 100 C with 0.3 mol% catalyst. The results are collected in Table 3. The reactions produce the corresponding propargylamines in modest to good yields (42-98%) within 0.5 h, and excellent yields ( 92%) can be achieved after prolonged time (4-10 h), except for the reaction of benzaldehyde. The catalytic data are compared as follows to gain further information. Different terminal alkynes besides phenylacetylene were allowed to react with paraformaldehyde and piperidine. All aromatic alkynes with a para substituent on the phenyl ring react slower than phenylacetylene, whether the substituent is electron-donating or electron-withdrawing. The reactivity in the present catalytic system decreases in the following 8

order: phenylacetylene > p-chlorophenylacetylene > p-methylphenylacetylene > p-tert-butylphenylacetylene. Although electronic effects cannot be excluded if comparing the p-Cl and p-Me substrates, it seems that the geometrical factor predominates because the decrease in reactivity is consistent with the increase in size of the substituents: H < Cl < CH 3 < tert-C4H9 (Table 3, entries 5, 6). The geometrical effects are typical of porous catalysts, where the pore sets size or shape limitations on the substrate, the intermediate state and/or the product. Cyclohexylacetylene is less reactive than aromatic alkynes except for the bulky p-tert-butylphenylacetylene. This can be attributed to the lower acidity of the aliphatic terminal alkyne than aromatic ones (Table 3, entries 8).

To vary the amine substrate, morpholine and diethylamine were examined for the A3 coupling with phenylacetylene and paraformaldehyde. It turned out that these two amines are less reactive than piperidine. Nevertheless, the corresponding propargylamines can be yielded in 92% yield if prolonging the reaction time to 4 h. Various aldehyde substrates were tested for the reaction with phenylacetylene and piperidine. Overall, the reaction rates decline if paraformaldehyde was replaced by other aliphatic aldehydes (Table 3, entries 1, 2), and the straight-chain butylaldehyde is less reactive than the branched counterpart and cyclic aldehydes.

When benzaldehyde was tested, the reaction gave the corresponding propargylamine in 85 % after 4 h. The relatively low reactivity of aromatic aldehydes compared to aliphatic ones is as expected. Unexpectedly, we found that the yield did not increase but decrease when further prolonging the reaction time, indicating transformation of the propargylamine. Indeed, NMR analysis of the reaction mixtures indicated the formation of new species, and the content of the species continuously increased as the propargylamine content decreased during the prolonged reaction (Fig. 4). According to 1H and 13C NMR analysis on an isolated solid, the final product was proposed to be chalcone in the exclusive E configuration, showing the typical coupling parameter for trans-vinylic protons (3JH-H = 15.7 Hz). We propose that chalcone should not be a primary product from the reaction of the A3 substrates but a secondary product arising from propargylamine. This is based on the following considerations. 9

(i) In the early stage (at least 0.5 h) of the reaction using benzaldehyde, no chalcone but only propargylamine was detected; (ii) while prolonging the reaction, the amount of chalcone increases in parallel to the decrease in propargylamine; (iii) the propargylamine product should not be reverted to the starting materials for lack of C-C activation pathways under the reaction conditions. To further confirm that chalcone is formed from propargylamine, the pure propargylamine derived from benzaldehyde, N-(1,3-Diphenyl-2-propynyl)piperidine, was allowed to react with water over MIL-101(Cr)-SO3Ag under the same conditions for the A3 reaction. In the presence of piperdine, the conversion of the propargylamine to chalcone was indeed observed (Scheme 2, A). When no piperdine was used in the reaction, no hydrolysis of the propargylamine was detected (Scheme 2, B), suggesting that piperdine plays an important role in the hydrolysis. Furthermore, chalcone cannot be obtained directly from benzaldehyde and phenylacetylene (Scheme 2, C).

Phenylacetylene derivatives were tested to see the electronic effects of substituents on the formation of chalcones. As shown in Fig. S5, the electron-donating methoxyl substituent on the benzene ring has no significant influence on the conversion of the phenylacetylene, while the electron-withdrawing trifluoromethyl substituent decreases the conversion, consistent with the results for the A3 coupling with supported gold(III) catalysts [51]. On the other hand, the yield of the corresponding chalcone decreased with the methoxyl substituent (12% after 18 h) but significantly increased with the trifluoromethyl substituent (81% after 18 h), compared with the case without substituent (26% after 18 h). Actually, in the case of trifluoromethyl, propargylamine disappeared after 18 h, with chalcone as the only product. The results indicate that the electron-withdrawing substituent is beneficial for the conversion from propargylamine to chalcone. The electron-donating methoxyl substituent has the opposite effect. The formation of chalcones from the traditional staring materials of A3 coupling has only recently been discovered. In 2013, Alonso et al. discovered the CuNP-catalyzed formation of chalcones from N-heterocyclic aldehydes (such as 2-pyridinecarbaldehyde), terminal alkynes 10

and secondary amines (CuNP = copper nanoparticles) [52, 53]. Au(I)-catalyzed reactions using -ketoaldehydes have also been reported shortly later[54]. Very recently the reactions have been extended to benzaldehyde derivatives by using Cu(II) catalysts [55]. Our study with MIL-101(Cr)-SO3Ag represents the first Ag-catalyzed formation of chalcones from typical A3 staring materials. As previously reported for the Au and Cu catalysts, no enone products were detected in our Ag-catalyzed A3 reactions using aliphatic aldehydes. 3.5 Proposed reaction mechanism Based on our experimental results and referring to the earlier reports on Au and Cu catalyzed processes [52, 55, 56], a tentative mechanism proposed as shown in Scheme 3. The upper cycle (I) is for the catalytic formation of propargylamines through A3 coupling. The π-complexation between the alkyne triple bond and Ag(I) on MOF activates the terminal C-H bond with enhanced acidity to facilitate the formation of silver acetylide. The latter is then added to the iminium intermediate formed from the aldehyde and amine substrates, affording the desired propargylamine and regenerating the catalyst. The down cycle (II) presents the transformation from propargylamines to chalcones. The transformation involves the base-mediated propargyl-to-allenyl isomerization and subsequent hydrolysis of the allenylamine intermediate to the final chalcone product. Piperidine plays an important role in the reaction. It serves as the base that deprotonates the tertiary propargyl C-H group and thus initiates the isomerization. Then the resulting piperidinium cation serves as an acid to protonate the allenic anion to give a neutral allenylamine. The Ag(I) center in the catalyst could play a double role in promoting the isomerization. It can form a π-complex with the alkyne bond, which activates the propargyl C-H bond and thus facilitates deprotonation. It can also form a -complex with the allenic anion, which helps to stabilize the allenide anion to the benefit of isomerization. A key factor determining the isometrization could be the acidity of the tertiary C-H group. For propargylamine derived from an aromatic aldehyde (R = Ar), the tertiary C-H group is simultaneously bonded by an aromatic ring (benzylic) and an alkyne group (propargylic), so it has a fairly strong acidity to allow for deprotonation by piperidine. This is well consistent with the observation that the electron-donating and electron-withdrawing substituents in the phenylacetylene substrate have positive and negative effects, respectively, on the formation of chalcones (see above). For propargylamines in which 11

the group is not benzylic, the acidity is not enough to allow for deprotonation. This explains the absence of enone products in the reactions starting from aliphatic aldehydes.

4. Conclusions In summary, we have demonstrated that MIL-101-SO3Ag can serve as an efficient and environmentally friendly catalyst for the syntheses of propargylamines through A3 coupling. A quite small amount of the catalyst can efficiently catalyze the reactions of aliphatic aldehydes, alkynes, and amines, with a TOF up to 6600 h-1. The catalyst could be easily recycled without a significant loss of its catalytic activity. In addition, we found that the catalyst also promotes the secondary reaction in which the propargylamines formed from aromatic aldehydes undergo propargyl-to-allenyl isomerization and subsequent hydrolysis to give chalcones. Further research to gain better understanding of this reaction is ongoing in our laboratory.

Acknowledgements This work is supported by the National Science Foundation of China (NSFC nos. 21471057 and 21173083).. Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.molcata.xxxx.

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Captions for Schemes and Figures

Fig. 1. PXRD patterns (bottom) of MIL-101(Cr)-SO3H and MIL-101(Cr)-SO3Ag and the SEM image (top) of MIL-101(Cr)-SO3Ag.

Fig. 2. Influence of the catalyst amount for A3-coupling reaction.

Fig. 3. The reusability of MIL-101(Cr)-SO3Ag. Fig. 4. Variation of the yields of chalcone and propergylamine in the phenylacetylene-benzaldehyde-piperidine reaction.

Scheme 1. Synthesis of MIL-101(Cr)-SO3Ag.

Scheme 2. Tests of possible routes to chalcone

Scheme 3. Proposed catalytic mechanism for the formation of propargylamines and chalcones.

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Fig. 1. PXRD patterns (bottom) of MIL-101(Cr)-SO3H and MIL-101(Cr)-SO3Ag and the SEM image (top) of MIL-101(Cr)-SO3Ag

Fig. 2. Influence of the catalyst amount for A3-coupling reaction

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Fig. 3. The reusability of MIL-101(Cr)-SO3Ag. (Reaction conditions: phenylacetylene (8.0 mmol), paraformaldehyde (10.4 mmol), piperidine (8.0 mmol), reused catalyst MIL-101(Cr)-SO3Ag (40 mg), 2h)

Fig. 4. Variation of the yields of chalcone and propergylamine in the phenylacetylene-benzaldehyde-piperidine reaction.

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COOH SO3H

H2O/HCl COOH

AgBF4

CrO3

CH3CN/H2O SO3Ag

SO3H

Scheme 1. Synthesis of MIL-101(Cr)-SO3Ag

Scheme 2. Tests of possible routes to chalcone

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HO O

N

R

H2 O

R HN H R

N

SO3Ag Ph

SO3Ag

Ph

Cycle I

H

Ph Ph N

SO3Ag Ph

N

R

• Ar H2 O

propargylamine

R = Ar H N

H

H2 N

H N

Cycle II

N

Ar

Ar

H

N •

SO3Ag

SO3Ag

O

Ph

Ph Ph

Ar chalcone

H N

H2 N

Scheme 3. Proposed catalytic mechanism for the formation of propargylamines and chalcones.

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Table 1. Catalytic data for the A3 coupling of phenylacetylene, paraformaldehyde and piperidine Entry

Solvent

Catalyst amount (mol%) a

Temp (ºC)

Time (h)

Yield(%) (TOF (h-1)) b

1 toluene 0.15 100 2 80 2 1,4-dioxane 0.15 100 2 97 3 DMF 0.15 100 2 97 4 0.15 100 2 97 5 0.06 100 2 96 6 0.03 100 2 93 7 0.02 100 2 88 8 0.3 100 0.5 97 9 0.3 80 2 86 10 100 2 12 c 11 0.15 100 2 <10 12 0.3 100 5 min 72(2880) 13 0.15 100 5 min 62(4956) 14 0.06 100 5 min 33(6600) a b 1 mol% were calculated via Ag(I). Yields were calculated via H NMR of the crude reaction mixture; TOF was calculated only for the reactions proceeding for 5 min. c The catalyst was MIL-101(Cr)-SO3H.

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Table 2. Comparison of different A3-coupling catalysts Catalyst

Solvent

Amount (mol%)

Temp (ºC)

Time (h)

Yield (%)

InCl3[16]

toluene

10

120

20

80

Hg2Cl2 [49]

acetonitrile

5

70

4

89

NHC-Ag [50]

dichloromethane

2

40

6

91

PS-NHC-Ag [26]

-

2

25

24

97

ZSM-5/Ag [27]

glycol

2

75

0.5

96

MIL-101-SO3Ag

-

0.3

100

0.5

97

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Table 3. Catalytic data for the A3 coupling of various substrates R3

R2 CHO

MIL-101(Cr)-Ag

HN R1

R2 R1

o

N

100 C

R3

R3

R4

Entry

R1

R2

Amine

Time (h)

Yield (%)

1

Ph

Propyl

Piperidine

0.5 / 8

48 / 93

2

Ph

Isopropyl

Piperidine

0.5 / 4

56 / 97

3

Ph

Cyclohexyl

Piperidine

0.5 / 4

74 / 95

4

Ph

Cyclopentyl

Piperidine

4

98

5

4-MeC6H4

H

Piperidine

0.5 / 4

74 / 95

6

4-ClC6H4

H

Piperidine

0.5 / 4

80 / 98

H

Piperidine

0.5 / 10

42 / 94

7

4-t-BuC6H4

8

Cyclopentyl

H

Piperidine

0.5 / 8

42 / 96

9

Ph

H

Morpholine

0.5 / 4

45 / 92

10

Ph

H

Diethylamine

0.5 / 4

63 / 92

Reaction conditions: alkyne (8.0 mmol), aldehyde (10.4 mmol), amine (8.0 mmol), catalyst(20 mg), 100 ºC. Yields were calculated via 1H NMR of the crude reaction mixture.

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