Amino-functionalized Zr(IV) metal–organic framework as bifunctional acid–base catalyst for Knoevenagel condensation

Accepted Manuscript Title: Amino-functionalized Zr(IV) metal-organic framework as bifunctional acid-base catalyst for Knoevenagel condensation Author: Yang Yang Hong-Fei Yao Fu-Gui Xi En-Qing Gao PII: DOI: Reference:

S1381-1169(14)00140-X http://dx.doi.org/doi:10.1016/j.molcata.2014.04.002 MOLCAA 9064

To appear in:

Journal of Molecular Catalysis A: Chemical

Received date: Revised date: Accepted date:

6-12-2013 1-4-2014 3-4-2014

Please cite this article as: Y. Yang, H.-F. Yao, F.-G. Xi, E.-Q. Gao, Aminofunctionalized Zr(IV) metal-organic framework as bifunctional acid-base catalyst for Knoevenagel condensation, Journal of Molecular Catalysis A: Chemical (2014), http://dx.doi.org/10.1016/j.molcata.2014.04.002 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.

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*Graphical Abstract (for review)

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*Highlights (for review)

Highlights



UiO-66-NH2 catalyzes the reaction of aldehydes with cyanoacetate or



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malononitrile. The catalyst is heterogeneous, recyclable and shows size effects on substrates

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 It is proposed that the activity may arise from a dual acid–base character.

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Amino-functionalized Zr(IV) metal-organic framework as bifunctional

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acid-base catalyst for Knoevenagel condensation

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Yang Yang, Hong-Fei Yao, Fu-Gui Xi and En-Qing Gao*

Shanghai Key Laboratory of Green Chemistry and Chemical Processes, Department of

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Chemistry, East China Normal University

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Shanghai 200062, China

captions for Schemes and Figures: page 23

2 schemes: pages 26, 27

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6 figures: pages 28-34

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2 tables: pages 24, 25

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main text with abstract, keywords, references and embedded Tables and figures: pages 1-22

Corresponding author:

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En-Qing Gao

Shanghai Key Laboratory of Green Chemistry and Chemical Processes, Department of Chemistry, East China Normal University Shanghai 200062, China Fax: +86-21-62233404 E-mail: [email protected]

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Amino-functionalized Zr(IV) metal-organic framework as bifunctional acid-base catalyst for Knoevenagel condensation Yang Yang, Hong-Fei Yao, Fu-Gui Xi and En-Qing Gao*

East

China

Normal

University,

Shanghai

200062,

China.

E-mail:

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Chemistry,

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Shanghai Key Laboratory of Green Chemistry and Chemical Processes, Department of

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[email protected]

Abstract:

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The amino-functionalized metal-organic framework of Zr(IV) with 2-aminoterephthalate, UiO-66-NH2, was studied as a solid catalyst for Knoevenagel condensation. The material can

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efficiently catalyze the condensation reaction of benzaldehyde with ethyl cyanoacetate or malononitrile in highly polar solvents such as DMF, DMSO and ethanol. The catalytic system

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has also been tested for various aromatic aldehydes, the conversion easily reaching more than 90% under mild conditions. It was demonstrated that the catalytic process is heterogeneous

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and shows size effects, characteristic of a porous catalyst. The catalyst can be recycled without losing its framework integrity and catalytic activity. The catalytic activity has been compared with dimethyl 2-aminoterephthalate and the isostructural amino-free MOF (UiO-66). The superior performance of UiO-66-NH2 has been attributed to the site-isolated

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acid-base bifunctional character. It has been proposed that the Zr site in close proximity to the amino group activates aldehydes to promote the formation of aldimine intermediates from the aldehydes and the amino group.

Keywords: Metal-organic frameworks; Bifunctional acid-base catalysts; Knoevenagel condensation; Heterogeneous catalysis

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1.Introduction In recent years, metal–organic frameworks (MOFs) have attracted considerable attention due to their special characteristics such as hybrid compositions, diverse networks, tunable porosity and tailorable surfaces [1, 2]. Owing to these characteristics, MOFs are promising materials for various technological applications such as gas storage/capture [3-5], separation

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[6, 7], and heterogeneous catalysis [8-11]. Heterogeneous catalysis is superior to homogeneous catalysis for easier separation, reusability, minimized waste and cleaner

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products. Heterogeneous catalysts also offer the possibility of combining isolated acidic and

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basic sites for cooperative or tandem catalysis [12-15]. Furthermore, porous solid catalysts may provide confined space to influence reactivity and selectivity. The application of MOFs as porous heterogeneous catalysts alternative or complementary to microporous zeolites is

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especially interesting, since the pore size and chemical functionality of MOFs can be modulated within a wider range [2, 11, 16]. In principle, the active sites of MOF catalysts can

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be metal centers with unsaturated (or labile) coordination environments, catalytic functional groups attached to any components of the frameworks, or other catalytic species (molecules,

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metals, etc.) encapsulated in the pores, and the sites may be inherent in the frameworks or generated by post-synthetic methods [11, 17-22].

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The three-dimensional (3D) Zr(IV) MOFs of formula [Zr6O4(OH)4(L)6], such as UiO-66 [L = 1,4-benzenedicarboxylate (BDC)] and UiO-66-NH2 [L = 2-amine-1,4-benzenedicarboxylate (BDC-NH2)], are based on the octahedral [Zr6(µ3-O)4(µ3-OH)4(µ2-COO)12] cluster and featured by alternating octahedral and tetrahedral cages sharing triangular windows [23] (Fig.

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1). The MOFs contain potential Lewis-acid sites (Zr(IV) centers) upon activation and/or base sites (NH2 groups), and remarkably, they show exceptionally high thermal and chemical stability. However, for only a few reactions have these MOFs been studied as heterogeneous catalysts, including the cross-aldol condensation between benzaldehyde and heptanal [24], the cyclization of citronellal to isopulegol [25, 26], the cycloaddition of CO2 to styrene oxide [27], the acetalization of benzaldehyde with methanol [28], and photocatalytic reactions [29-34]. Electronic effects of linker substitution on Lewis acid catalysis have been studied [28]. It was found that the Lewis acidity and the catalytic activity increase in the order of UiO-66-NH2 < UiO-66 < UiO-66-NO2. It was also demonstrated that the introduction of amino groups into 2

Page 5 of 37

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linkers leads to an increase in basicity [25, 28].

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Fig. 1. Structure of UiO-66. (a) A [Zr6(µ3-O)4(µ3-OH)4(µ2-COO)12] cluster. (b) The porous

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systems in which octahedral and tetrahedral cages share triangular windows.

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Scheme 1. Knoevenagel condensation. In this paper, we report the catalytic study of UiO-66-NH2 for Knoevenagel condensation.

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The Knoevenagel condensation of a carbonyl group with the methylene group activated by two electron withdrawing groups (Scheme 1) is an important C-C bond coupling reaction and

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has been widely used in the synthesis of fine chemicals and pharmaceuticals. The condensation can be catalyzed by bases or Lewis acids, either homogeneous (such as amines [35, 36], ZnCl2 and Mg(ClO4)2 [37, 38]) or heterogeneous (such as hydrotalcite [39], silica-supported basic catalysts [40, 41]). Considering the demand for environmentally

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friendly heterogeneous catalysts and the intriguing features of MOFs, the exploration of MOF catalysts for the Knoevenagel condensation has become a topic of increasing interest in recent years [42-50]. The MOFs used are diverse in composition and structure, and most of them contain the amino group as Lewis base sites, such as the BDC-NH2-base metal-carboxylate frameworks IRMOF-3, MIL-101(Al)-NH2, MIL-53-NH2, and UMCM-1-NH2 [45, 46]. MIL-101(Cr) with post-synthetically introduced amino groups has also been studied for Knoevenagel condensation [51]. In this work, we demonstrate that UiO-66-NH2 is an efficient, size-selective, stable, and recyclable heterogeneous catalyst and that the superior catalytic performance to UiO-66 is attributable to the bifunctional acid-base character. 3

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2. Experimental 2.1 Synthesis All chemicals (A. R. grade, purity 98 wt% or higher) were obtained from commercial sources and used without further purification. UiO-66-NH2 and UiO-66 synthesized by following a solvothermal procedure reported in the literature [52, 53], using acetic acid as

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modulator. ZrCl4 (0.7 mmol, 0.164 g) and H2BDC-NH2 (0.7 mmol, 0.127 g) were dissolved in the mixture of N,N'-dimethylformamide (DMF, 8 ml), acetic acid (1.2 ml) and deionized

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water (0.05 ml) at room temperature. After stirring for about 5 minutes, the mixture was

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sealed in a 23 ml Teflon liner, heated in an oven at 120 ˚C for 48 hours, and then cooled to room temperature. A yellow solid powder was obtained by filtration, washed three times with DMF. The product was soaked and stirred in refluxing methanol for 24 h, filtered and dried at

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70 ˚C in an oven. The formula of the material thus obtained was estimated to be

4.4%; calculated: C 28.7, H 3.1, N 4.2%. 2.2 Characterization

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[Zr6O4(OH)4(BDC-NH2)6]14H2O according to elemental analysis. Found: C 29.2, H 3.8, N

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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

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˚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

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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 In a typical catalytic experiment, 0.144 g of the catalyst (corresponding to 0.45 mmol 4

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amino groups) was placed in a flask and heated at 150 ˚C for 4 hours. After three cycles of vacuum pumping and nitrogen injection, the solution of ethyl cyanoacetate or other active methylene compounds (10 mmol) in an appropriate solvent (5 mL) was added with stirring and heated to a given temperature. After temperature equilibrium, benzaldehyde (5 mmol) was added to initiate the reaction. The reaction mixture was stirred under a static nitrogen

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atmosphere, and small aliquots of the supernatant were withdrawn at different time intervals to monitor the reaction conversion by GC.

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3 . Results and discussion

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3.1 Characterization of the UiO-66-NH2 catalyst.

Fig. 2. PXRD patterns (a) and SEM picture (b) of UiO-66-NH2

UiO-66-NH2 was synthesized according to literature procedures. The XRD pattern of the 5

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as-synthesized sample (Fig. 2a) is in good agreement with the literature data and with the simulated pattern of pristine UiO-66 [24], evidencing good synthetic reproducibility and phase purity. The SEM morphology (Fig. 2b) shows that the particles are of nanometer size with a distribution in the range of 40-90 nm. After thermal activation at 150 ˚C, the reflections at large angles become less intensive, but the main characteristic peaks remain, indicating that

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the overall phase integrity is retained although the activation leads to some degree of disorder in the framework. Fig. 2a also shows the XRD patterns of the UiO-66-NH2 sample after one

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and three cycles of catalytic reactions. It is interesting to note that the reflections at large

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angles are recovered after the catalytic reaction, indicating that the disorder caused by thermal treatment is repaired. It can be deduced that the original crystalline phase of the material is retained without significant degradation in structural integrity after the catalytic reactions.

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3.2 Catalytic properties

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Table 1. UiO-66-NH2 catalyzed Knoevenagel condensation between benzaldehyde

and

T (˚C) 80 80 80 40 40 60 80 40 40 40 40 40

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Solvent EtOH

DMF

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Entry 1 2 3 4 5 6 7 8 9 10 11 12

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ethyl cyanoacetate: influence of catalytic dose, solvent, and temperature.

DMSO DCM EtOAc THF Toluene

Time (h) 2 2 2 0.5/2 0.5/2 0.5 0.5 0.5/2 2 2 2 2

Conv (%) 27 67 94 25/79 27/92 58 91 31/95 5 3 2 <1

Conditions: reactants: benzaldehyde (5 mmol), ethyl cyanoacetate (10 mmol); solvent: 5 ml; Cat: UiO-66-NH2, 0.144 g (corresponding to 0.45 mmol amino groups), except for entry 1 (no catalyst) and entry 2 (0.072 g, corresponding to 0.23 mmol amino groups). 6

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3.2.1 Influence of catalytic dose, solvent, and temperature The condensation reaction of benzaldehyde with ethyl cyanoacetate, which affords -cyanocinnamate, was performed as test reaction to study the effects of different reaction conditions, including the catalytic dose, the solvent, and the reaction temperature. The results obtained for the reactions performed in ethanol at 80 ˚C in the presence of

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different amount of catalysis are given in Table 1 (entries 1-3). While the blank reaction in the absence of any catalyst gave a benzaldehyde conversion of only 27% after 2 h, introducing

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UiO-66-NH2 and increasing the amount led to significant increase in the conversion. With

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0.144 g UiO-66-NH2 (corresponding to 9 mol% amino groups), the conversion reached 94% after 2 h. For comparison, the blank reaction needs 17 h to reach a conversion of >90% (complete conversion needs more than 21 h). These results clearly confirm that UiO-66-NH2

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is active in catalyzing the Knoevenagel reaction. No by-product was observed during the reaction, so the selectivity for -cyanocinnamate is 100%.

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Strong effects of solvent polarity have been observed for catalytic Knoevenagel reactions. To establish the solvent effects for UiO-66-NH2, we performed the reaction in different

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solvents (Table 1). It proved that the catalyst has the highest activity (> 90 % conversion within 2 h) in DMSO and DMF (entries 5, 8), which have the highest polarity (dielectric

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constants  = 48.9 for DMSO and 36.7 for DMF). Ethanol (protic,  = 24.3, is also a good medium for the reaction (entry 4). By contrast, nonprotic and less polar solvents, including DCM ( = 9.1), THF ( = 7.5), EtOAc ( = 6.02) and toluene ( = 2.4), are not good media (entries 9-12). The effects can be generally explained by the assumption that polar solvents

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help to stabilize the charged transition-state complex of the reaction [36]. Besides, the strong hydrogen-bonding acceptor ability of DMSO and DMF can facilitate proton transfer [45]. On the one hand, the solvent effects are similar to those observed for some basic organocatalysts [35, 36] and for the amine-functionalized MOF catalysts IRMOF-3 [45, 46] and NH2-MIL-101(Al) [48], although sometimes ethanol was found to be better than DMF and DMSO due to its amphiprotic character. On the other hand, the effects are in clear contrast with those observed for some amino-tagged silicas, for which toluene is better than polar solvents [40, 41]. For some other catalysts, the solvent effects are not necessarily related to the polarity or the amphiprotic nature. For example, the catalytic activity of ZIF-8, -9 and -10 7

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(ZIF = zeolite imidazolate framework) for Knoevenagel condensation in toluene was found to be intermediate between that in THF (higher) and that in DCM (lower) [49, 50]. For solid-supported base catalysts, it has been reported that the higher the hydrophilicity (or the surface polarity) of the support, the lower the effect of the solvent [41, 46], but the opposite trend has also been reported [40]. Therefore, there is no general trend for the effect of solvents

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on the Knoevenagel reaction. Nevertheless, the results for UiO-66-NH2, IRMOF-3 and NH2-MIL-101(Al) consistently indicate that amino-tagged MOFs perform better in highly

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polar solvents.

The temperature dependence of the catalytic performance of UiO-66-NH2 was checked by

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performing the Knoevenagel reaction in DMF at 40, 60 and 80 ˚C (Table 1, entries 5-7). As expected, the reaction rate increases quickly with the temperature, the conversion within 30

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min changing from 27 % at 40 ˚C to 91 % at 80 ˚C. The conversion at 40 ˚C can reach a high level (> 90 %) within 2 h.

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3.2.2 The influence of different substrates

Having established that UiO-66-NH2 is a good catalyst for the Knoevenagel condensation

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between benzaldehyde and ethyl cyanoacetate, we extend the study to various substrates, including different aromatic aldehydes and methylene compounds. The results are listed in

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Table 2.

Diethyl malonate and malononitrile have been compared with ethyl cyanoacetate (entries 1-3). Under the same catalytic conditions, diethyl malonate led to a trace conversion of benzaldehyde after 2 h, whereas malononitrile caused a conversion of 98% within 40 min.

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The different reactivity of the methylene compounds is consistent with their different acidity, which increases in the order of diethyl malonate (pKa = 16.4 [54]) < ethyl cyanoacetate (pKa = 13.1 [55]) < malononitrile (pKa = 11.1 [56]). Actually, no Ar-NH2-functionalized materials (including MOFs) have been found to be able to efficiently catalyze the Knoevenagel reaction between benzaldehyde and diethyl malonate, because the pKa is too high for the amine group or the in-situ formed imine group to induce deprotonation.

Table 2: UiO-66-NH2 catalyzed Knoevenagel condensation of different substrates.a 8

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Entry

Aldehyde

Methylene

time (min)

Conv (%)

120

92

2

120

<2

3

40

98

4

5

100

5

40

98

6

40

O N

1

cr

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8

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97

40

40

92

9

40

87

120

56 (21) b

120

15 (19) b

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7

11

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10

a

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Conditions: aldehyde (5 mmol), methylene compound (10 mmol), DMF (5 ml), Catalyst

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(0.144 g, corresponding to 0.45 mmol amino groups), 40 ˚C. b The conversion for the control test in the absence of any catalyst is given in parentheses for comparison.

Various aromatic aldehydes have been tested for catalytic Knoevenagel condensation with malononitrile. It was found that the activity of UiO-66-NH2 for 2-nitrobenzaldehyde is much higher than that for benzaldehyde, as the reaction for the former aldehyde can reach completion within only 5 min (entry 4 in Table 2). This reflects the great accelerating effect of the strong electron-withdrawing nitro group, as would be expected for a reaction involving nucleophilic attack at the carbonyl group. The catalyzed reactions of the three 9

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methyl-substituted benzaldehydes proceed readily to give  97% conversions after 40 min (entries 5-7). The conversions are similar to that for benzaldehyde, but the initial reaction rates of these substrates are different. As shown in Fig. 3, compared with the non-substituted benzaldehyde, the initial reaction rate of 2-methylbenzaldehyde is similar (or slightly faster), the reaction of the 3-isomer is obviously slower, and notably, the 4-isomer was more reactive,

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though methyl is an electron-donating group. The position effect of methyl substitution on the reactivity of benzaldehyde is similar to that observed for the Knoevenagel condensation

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catalyzed by ZIF-8 [49] and ZIF-9 [50], where the reactivity varies in the order of

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4-methylbenzaldehyde  2-methylbenzaldehyde > benzaldehyde > 3-methylbenzaldehyde.

Fig. 3. Time dependence of reaction conversion for the condensation of different monosubstituted bezaldehydes (5 mmol) with malononitrile (10 mmol) in DMF (5 ml, 40 ˚C)

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in the presence of 0.144 g catalyst (corresponding to 0.45 mmol amino groups).

The catalyst system is also efficient for the Knoevenagel reactions of larger aromatic aldehydes (1-naphthaldehyde and 9-anthraldehyde) with malononitrile, though the conversion is somewhat decreased when the aldehyde substrate becomes more bulky (comparing entries 3, 8 and 9 in Table 2). The decreased conversion may be a (weak) indicator of size effects. The effects are more appreciable for the reactions of different aldehydes with ethyl cyanoacetate (molecular dimensions ~3.4×7.3 Å2), which are bulkier than malononitrile (~2.8×4.3 Å2). As shown by entries 1 and 10, the conversion of 9-anthraldehyde (56%, ~5.9×9.2 Å) reacting with ethyl cyanoacetate is much lower than that of benzaldehyde (92%, 10

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~6.0×4.3 Å2). The results could reflect that the probability of two bulky substrates forming transition-state complexes is significantly reduced due to the limited space in the catalyst. To further confirm the size effects, 9-anthraldehyde was reacted with a still bulkier methylene substrate, tert-butyl cyanoacetate (~4.3×8.2 Å2). The independent control reactions of 9-anthraldehyde with ethyl and tert-butyl cyanoacetates in the absence of any catalyst give

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similar conversions (around 20% after 2 h, entries 10 and 11), indicating that the intrinsic reactivity of the two methylene substrates is comparable. In the presence of UiO-66-NH2, the

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reaction with ethyl cyanoacetate shows a much higher conversion (56%), indicating a

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catalytic process. By contrast, the use of UiO-66-NH2 for the reaction with tert-butyl cyanoacetate leads to a conversion (15%) comparable to (or even slightly lower than) that for the reaction without any catalyst, indicating that UiO-66-NH2 is not active for the two bulky

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substrates. Thus, it is very likely that the catalytic reaction over UiO-66-NH2 proceeds inside the pores. The pore system of perfect UiO-66 crystals consists of interconnected tetrahedral

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and octahedral cages with free diameters of about 8 and 11 Å, respectively. Notably, some recent studies have demonstrated that real UiO-66 and analogs contains an amount of defects

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due to missing linkers between Zr6 clusters [57-59]. The linker vacancies lead to expanded pores so that the real pore dimensions can be larger. The failure in catalyzing the reaction

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between 9-anthraldehyde and tert-butyl cyanoacetate could be because the pores are still too small for the two bulky substrates diffuse into the pores of the catalyst to access the active sites and to form the transition state required for the reaction. 3.2.3 Heterogeneity and reusability

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With a solid catalyst for liquid-phase reactions, an issue of great concern is whether the catalytic process is heterogeneous or homogeneous. In the latter case, the species leached into the liquid phase is partially or fully responsible for the observed catalytic activity. This is practically undesirable. The heterogeneous nature of our catalyst system for Knoevenagel reactions is implied in some results of the above catalytic experiments. For example, the dependence of benzaldehyde conversion on the amount of solid catalyst (Table 1) could be an implication. The solid shows no appreciable solvability. It means that if there were any dissolved species, it would be quite easy for the liquid phase to be saturated by the species. Once saturated, the amount of the species in a given volume of liquid would be independent 11

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of the dose of the solid. Then, if the dissolved species were responsible for the catalytic activity, the reaction conversion would be independent of the amount of the solid. Therefore, the dependence of conversion on solid dose may be taken as a (weak) indication of heterogeneous catalysis. A stronger evidence is the size selectivity for substrates (Table 2), which is difficult to achieve with homogeneous catalysts but characteristic of porous

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heterogeneous catalysts. In order to give a more direct confirmation, a control reaction was performed between benzaldehyde and ethyl cyanoacetate in DMF. After the reaction

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proceeded at 40 C for 2 h, the catalyst was removed by hot filtration. The filtrate was further

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heated at the same temperature and the composition was monitored at given time intervals. The results are compared in Fig. 4 with those obtained for the reaction under the same conditions but without the filtering procedure. Obviously, no appreciable reaction took place

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after removal of the catalyst, indicating that no active species were leached into the liquid phase and providing a direct evidence for the heterogeneity of the catalyst system. This is also

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ed

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confirmed by ICP-AES analysis, which suggests no detectable Zr in the liquid phase.

Fig. 4. Filtration test of the catalyst. Conditions: benzaldehyde (8 mmol), ethyl cyanoacetate (7 mmol), Cat. 0.10 g (corresponding to 0.31 mmol amino groups), solvent: DMF (5 ml), 40 ˚C. The conversion is based on ethyl cyanoacetate.

Another issue of great concern for solid catalysts is the recyclability. To check this for UiO-66-NH2, the catalyst was used for three cycles for the reaction between benzaldehyde and malononitrile. After each cycle, the solid was filtered out, soaked and stirred in methanol for 24 h, filtered out again and washed with methanol. The recovered solid was heated at 150 12

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˚C for 4 hours and then reused in the next cycle. The results of the three cycles are very similar. As shown in Fig. 5a, the conversion of benzaldehyde after 1 h remains at the high level of  97%, indicating that the catalyst could be reused without significant degradation in catalytic performance. The recyclability is consistent with the good chemical resistance of the structure against the reaction conditions, which has been demonstrated by XRD

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measurements (see Fig. 2a). The intactness of the catalyst is also confirmed by the fact the FT-IR spectra of the catalyst shows no appreciable difference after catalytic reactions (Fig.

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ce pt

ed

M

an

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cr

5b).

Fig. 5. (a) Catalyst recycling studies. Conditions: benzaldehyde (5 mmol), malononitrile (10 mmol), solvent: DMF (5 ml), Cat. 0.144 g, 40 ˚C, 1 h. (b) IR spectra of the fresh and used catalysts.

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3.2.4 Mechanism considerations

Fig. 6. (a) Knoevenagel condensation with different catalysts. Conditions: benzaldehyde (5 mmol), ethyl cyanoacetate(10 mmol), solvent: EtOH (5 ml), 80 ˚C, Cat. 0.45 mmol Zr or NH2, 2 h. (b) The reactions of benzaldehyde (1 mmol) with DMBDC-NH2 (1.2 mmol) in EtOH (6

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ml, 80 ˚C) in the absence/presence of UiO-66 (0.014 g).

To determine the role of the amine group in the catalyst, the amine-free MOF (UiO-66) prepared and activated by similar procedures was tested as catalyst for the reaction between benzaldehyde and ethyl cyanoacetate. As can be seen from Fig. 6a, under the same catalytic conditions, the amino-free MOF led to much lower conversion than UiO-66-NH2. Since the two MOFs are isostructural, the superior performance of UiO-66-NH2 indicates that the basic amine group is important in promoting the Knoevenagel reaction, as is normally expected for NH2-tagged catalysts. It has been demonstrated that the introduction of amino groups into the 14

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linkers of UiO-66 leads to an appreciable increase in basicity [28]. The organic analogue of UiO-66-NH2, dimethyl 2-amine-1,4-benzenedicarboxylate (DMBDC-NH2), was also tested under the same conditions. The homogeneous reaction showed a low conversion of 29 %, which is only slightly higher than the reaction without any catalysts and much lower than the heterogeneous reaction using UiO-66-NH2 (see Fig. 6a), though the amount of amino groups

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was set to be equal in two catalytic reactions. This could indicate that the catalytic activity of amine is enhanced in the MOF structure or that the reaction is promoted by other sites besides

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amine. The Knoevenagel reactions with aniline as homogenous catalyst have also been

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reported to give much lower conversion than those with IRMOF-3 as heterogeneous catalyst [45, 46]. The high activity of IRMOF-3 compared to aniline was attributed to the increased basicity of the aromatic amino group when incorporated within the MOF structure. It was

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proposed that the increase of basicity could be due to the intramolecular hydrogen bonding interaction between the amino group and an carboxylate oxygen (coordinated to Zn(II)) [45].

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However, this explanation fails for DMBDC-NH2, which could have similar hydrogen interactions but does not show significant catalytic activity. A DFT study [60] suggested that

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the basicity of the aromatic amine (Ar-NH2) and the aldimine derivative (Ar-N=CHC6H5) indeed increases in going from aniline to DMBDC-NH2 and that the increase is more

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significant in going further to the amine embedded in IRMOF-3. The increase has been related to the stabilization of the protonated aminium and iminium species, which are hydrogen bonded to a carboxylate oxygen to generate a 6-membered planar ring. The theoretical study also indicated that the aldimine intermediates are the most basic species in

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the reaction systems and should be the active species that deprotonate ethyl cyanoacetate. However, the DFT energetic study on the catalytic cycles of Knoevenagel condensation indicated that the increased catalytic activity of IRMOF-3 seems to be unrelated to its increased basicity but could be explained by its adsorption ability for the water by-product which would otherwise poisons the catalytic amino sites. It should be noted that the theoretical study was based on the hypothesis that the amine groups are the only catalytic sites in the MOF, not considering the possibility of the existence of other active sites. A recent reinvestigation of IRMOF-3 for Knoevenagel condensation suggested that the MOF behaves as an 'unexpected' bifunctional acid-base catalyst [15]. The 15

Page 18 of 37

'unintentional' acid sites come from a defective origin, either Zn–OH species formed upon partial hydrolysis of the framework or ZnO particles entrapped inside the cavities during the synthesis. As already mentioned, UiO-66 is much less active than UiO-66-NH2, but it is noteworthy that the NH2-free MOF still show significant catalytic activity (50% after 2 h, See Fig. 6a)

ip t

when compared with the blank non-catalytic reaction. This suggests that the Knoevenagel reaction could also be promoted by Zr(IV) centers (Lewis acid sites), so UiO-66-NH2 could

cr

be a bifunctional acid-base catalyst for Knoevenagel condensation. The bifunctional character

us

has recently been proposed to explain the high activity of the material for the cross-aldol condensation between heptanal and benzaldehyde [24]. The acid sites in UiO-66 and UiO-66-NH2 could be the open Zr(IV) sites generated by dehydration of the Zr6O4(OH)4

an

cluster to give Zr6O6. It has been shown that the dehydration begins at about 100 ˚C for UiO-66 and even below the temperature for UiO-66-NH2 [24]. Therefore, the activation

M

procedure (heating at 150 ˚C) that we applied before catalytic reactions could induce partial dehydration. Another origin of the Lewis acid site could be the presence of defects. Since the

ed

UiO-66 MOFs are much stable than MOF-5 and IRMOF-3, one would not expected that the Zr MOFs contains a large density of defects of similar origin to those in the Zn MOFs.

ce pt

However, recent studies have demonstrated the presence of linker vacancies (defects due to the missing of organic linkers between Zr6 clusters) even in well-crystallized UiO-66 materials [57-59]. The defects could generate open metal sites upon heating. Whatever the origin of the acid sites is, the presence of both acid and base sites could explain the superior

Ac

performance of UiO-66-NH2.

Comparisons among ZrO2, DMBDC-NH2 and their mixture may give some information about the acid-base cooperation. As shown in Fig. 6a, ZrO2 and DMBDC-NH2 show very low activity (the conversions are higher than the blank test by only 8% and negligibly 2%, respectively), while the mixture show enhanced activity (15% higher than the blank test), indicating the presence of some cooperation, although weak. The much higher activity of UiO-66-NH2 than UiO-66 may indicate much stronger cooperation in the porous framework. Probably, the framework arranges Zr and amino sites in close proximity on the inner surface so that the two sites can cooperate more efficiently. 16

Page 19 of 37

Knoevenagel condensation, as a modification of aldol condensation, may proceed via different mechanisms that depend on the nature of the catalyst used. A Lewis acid site usually interacts with the carbonyl oxygen of benzaldehyde, thus the C=O bond is further polarized to facilitate the nucleophilic attack at the carbon atom. Strong bases would cause direct deprotonation of the methylene group, generating the carbanion that attacks the carbonyl

ip t

carbon atom of benzaldehyde. For amino-based catalysts, it is generally accepted that the reaction proceeds via aldimine intermediates [45, 60]. Two nucleophilic addition-elimination

cr

processes are involved, as illustrated in Scheme 2a. The first is the formation of an aldimine

us

intermediate (and water) from aldehyde and the amine group at the catalyst surface. The aldimine intermediate is more basic than the original amine and also more reactive than the original aldehyde [36]. Thus, the methylene compound is activated (deprotonated) by

an

aldimine rather than by amine, and meanwhile the aldimine group is also activated by the proton transfer. Therefore, the second addition-elimination process is facilitated, which occurs

M

between methylene and aldimine (rather than aldehyde) groups to give the product and to regenerate the amine catalyst. Spectroscopic evidences for the formation of intermediate

ed

aldimine have been recently reported for amino-tagged silicas and IRMOF-3 [45, 61]. According to this mechanism, the formation of the aldimine intermediate is important.

ce pt

We have studied the formation by reacting benzaldehyde with DMBDC-NH2 under the conditions used for the Knoevenagel reaction. As can be seen from Fig. 6b, the formation of aldimine in the absence of any catalyst is much slower than in the presence of UiO-66. The results clearly suggest the catalytic role of the Zr MOF for aldimine formation. The promotion

Ac

is most likely due to the activation of carbonyl groups by Zr sites. Based on the above considerations, the cooperative acid-base bifunctional catalysis of UiO-66-NH2 can be speculated as follows (Scheme 2b). The Zr site serves to activate benzaldehyde so that the amino group in close proximity the Zr site can readily attack the carbonyl group to generate the aldimine intermediate, which serves not only as a base (the N atom) to extract proton from methylene but also as an acid (the C atom) to couple with methylene. This synergic process is a little different from that proposed for the cross-aldol condensation between heptanal and benzaldehyde [24], where the reaction was supposed to occur between benzaldehyde activated by Zr(IV) and the heptanal methylene group activated 17

Page 20 of 37

ed

M

an

us

cr

ip t

by amine.

Scheme 2. (a) Mechanism for amine-catalyzed Knoevenagel condensation. (b) Aldimine

4. Conclusions

ce pt

formation promoted by the Lewis acid site in close proximity to the amine group.

In this work, we reported the use of UiO-66-NH2 as solid catalyst for Knoevenagel

Ac

condensation. It has been demonstrated that the catalyst shows better performance in highly polar solvents such as DMF, DMSO and ethanol. It can efficiently catalyze the condensation reactions of aromatic aldehydes with cyanoacetate and malononitrile, the conversion easily reaching more than 90% under mild conditions within a short time (dependent on the substrates). The catalytic process is heterogeneous and shows size effects, characteristic of a porous catalyst with active sites inside the pores. The catalyst can be recycled without losing its framework integrity and catalytic activity. Compared with the homogeneous amino precursor (2-aminoterephthalate) and the isostructural amino-free MOF (UiO-66), the superior performance of UiO-66-NH2 has been attributed to the acid-base bifunctional 18

Page 21 of 37

character. It was proposed that the Zr site in close proximity to the amino group facilitates the formation of aldimine intermediates, which are the active species reacting with the methylene compounds. This study further demonstrates that MOFs can offer extraordinary opportunity of achieving site-isolated acid-base catalysts, which are desirable for more efficient and more facile organic synthesis. Working along this line, we are exploring such catalysts for

ip t

multi-component reactions. Acknowledgements

cr

This work is supported by the National Science Foundation of China (NSFC nos. 21173083

us

and 91022017) and the Research Fund for the Doctoral Program of Higher Education of

an

China.

References

M

[1] C. Wang, D. Liu, W. Lin, J. Am. Chem. Soc. 135 (2013) 13222-13234. [2] H. Furukawa, K. E. Cordova, M. O'Keeffe, O. M. Yaghi, Science 341 (2013)

ed

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ce pt

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Ac

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ip t

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cr

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us

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ed

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Ac

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ip t

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[34] C. G. Silva, I. Luz, i. X. F. X. Llabres, A. Corma, H. Garcia, Chem. Eur. J. 16 (2010)

cr

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[35] M. Climent, A. Corma, I. Dominguez, S. Iborra, M. Sabater, G. Sastre, J. Catal. 246 (2007) 136-146.

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ce pt

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ip t

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cr

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[53] S. J. Garibay, S. M. Cohen, Chem. Commun., 46 (2010) 7700-7702. [54] B. R. Gelin, M. Karplus, J. Am. Chem. Soc. 26 (1975) 6996-7006. [55] F. G. Bordwell, H. E. Fried, J. Org. Chem. 46 (1981) 4328-4331.

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M

Chem. Soc. 135 (2013) 10525.

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ed

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ce pt

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Ac

[61] R. Wirz, D. Ferri, A. Baiker, Langmuir 22 (2006) 3698-3706

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Captions for Schemes and Figures

Scheme 1. Knoevenagel condensation.

Scheme 2. (a) Mechanism for amine-catalyzed Knoevenagel condensation. (b) Aldimine

ip t

formation promoted by the Lewis acid site in close proximity to the amine group.

cr

Fig. 1. Structure of UiO-66. (a) A [Zr6(µ3-O)4(µ3-OH)4(µ2-COO)12] cluster. (b) The porous

us

systems in which octahedral and tetrahedral cages share triangular windows.

an

Fig. 2. PXRD patterns (a) and SEM picture (b) of UiO-66-NH2

Fig. 3. Time dependence of reaction conversion for the condensation of different

M

monosubstituted bezaldehydes (5 mmol) with malononitrile (10 mmol) in DMF (5 ml, 40 ˚C)

ed

in the presence of 0.144 g catalyst (corresponding to 0.45 mmol amino groups).

Fig. 4. Filtration test of the catalyst. Conditions: benzaldehyde (8 mmol), ethyl cyanoacetate

ce pt

(7 mmol), Cat. 0.10 g (corresponding to 0.31 mmol amino groups), solvent: DMF (5 ml), 40 ˚C. The conversion is based on ethyl cyanoacetate.

Fig. 5. (a) Catalyst recycling studies. Conditions: benzaldehyde (5 mmol), malononitrile (10

Ac

mmol), solvent: DMF (5 ml), Cat. 0.144 g, 40 ˚C, 1 h. (b) IR spectra of the fresh and used catalysts.

Fig. 6. (a) Knoevenagel condensation with different catalysts. Conditions: benzaldehyde (5 mmol), ethyl cyanoacetate(10 mmol), solvent: EtOH (5 ml), 80 ˚C, Cat. 0.45 mmol Zr or NH2, 2 h. (b) The reactions of benzaldehyde (1 mmol) with DMBDC-NH2 (1.2 mmol) in EtOH (6 ml, 80 ˚C) in the absence/presence of UiO-66 (0.014 g).

23

Page 26 of 37

Table 1. UiO-66-NH2 catalyzed Knoevenagel condensation between benzaldehyde

and

ethyl cyanoacetate: influence of catalytic dose, solvent, and temperature.

DMSO DCM EtOAc THF Toluene

ip t

Conv (%) 27 67 94 25/79 27/92 58 91 31/95 5 3 2 <1

cr

Time (h) 2 2 2 0.5/2 0.5/2 0.5 0.5 0.5/2 2 2 2 2

us

DMF

T (˚C) 80 80 80 40 40 60 80 40 40 40 40 40

an

Solvent EtOH

M

Entry 1 2 3 4 5 6 7 8 9 10 11 12

Conditions: reactants: benzaldehyde (5 mmol), ethyl cyanoacetate (10 mmol); solvent: 5 ml; Cat:

ed

UiO-66-NH2, 0.144 g (corresponding to 0.45 mmol amino groups), except for entry 1 (no catalyst) and

Ac

ce pt

entry 2 (0.072 g, corresponding to 0.23 mmol amino groups).

24

Page 27 of 37

time (min)

Conv (%)

120

92

2

120

<2

3

40

98

4

5

100

5

40

6

40

us

Table 2: UiO-66-NH2 catalyzed Knoevenagel condensation of different substrates.a Entry

Aldehyde

Methylene O N

1

cr

an

98

40

92

40

87

120

56 (21) b

120

15 (19) b

ce pt

9

Conditions: aldehyde (5 mmol), methylene compound (10 mmol), DMF (5 ml), Catalyst

Ac

a

97

40

ed

8

11

98

M

7

10

ip t

O

(0.144 g, corresponding to 0.45 mmol amino groups), 40 ˚C. b The conversion for the control test in the absence of any catalyst is given in parentheses for comparison.

25

Page 28 of 37

Ac

ce pt

ed

M

an

us

cr

ip t

Scheme 1

26

Page 29 of 37

Ac

ce pt

ed

M

an

us

cr

ip t

Scheme 2

27

Page 30 of 37

ce pt

ed

M

an

us

cr

ip t

for web

Ac

Fig. 1

28

Page 31 of 37

ce pt

ed

M

an

us

cr

ip t

for print

Ac

Fig. 1

29

Page 32 of 37

Ac

ce pt

ed

M

an

us

cr

ip t

Fig. 2

30

Page 33 of 37

Ac

ce pt

ed

M

an

us

cr

ip t

Fig. 3

31

Page 34 of 37

Ac

ce pt

ed

M

an

us

cr

ip t

Fig. 4.

32

Page 35 of 37

Ac

ce pt

ed

M

an

us

cr

ip t

Fig. 5

33

Page 36 of 37

Ac

ce pt

ed

M

an

us

cr

ip t

Fig. 6

34

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