Wencheng Lang,
Qin Yang,
Xueping Song,
Mengyun Yin and
Limei Zhou*
Chemical Synthesis and Pollution Control Key Laboratory of Sichuan Province, China West Normal University, Nanchong 637002, Sichuan, China. E-mail: cwnuzhoulimei@163.com
First published on 28th February 2017
Copper nanoparticles immobilized on montmorillonite (MMT) by biquaternary ammonium salts (N1,N6-dibenzyl-N1,N1,N6,N6-tetramethylheptane-1,6-diaminium bromide, Q) were prepared by cation-exchange and impregnation–reduction and designated Cu-Q-MMT. The material was extensively characterized by various characterization techniques such as FTIR, XRD, XPS, SEM, TEM, and N2 adsorption–desorption. The Cu-Q-MMT could be used as a highly active heterogeneous catalyst for cascade sequence to indole-2-carboxylic esters from ortho-bromobenzaldehydes with ethyl acetamidoacetate. Even for inactive chlorobenzaldehydes, a good yield could be obtained. In addition, the catalyst can be reused six times without any significant loss of activity. The high activity and stability of the Cu-Q-MMT catalyst is mainly attributed to the excellent synergistic effects of biquaternary ammonium salts, Cu nanoparticles and the nanospace structure of MMT.
The indole motifs are important substructure in numerous synthetic alkaloids.14–18 Their extensive use in the field of biology and pharmaceutics has motivated researchers to promote new synthetic strategies.19–22 Although studies on the synthesis of indole derivatives have achieved a lot, the preparation of some specific substituted patterns remains difficult such as 2-substituted-indole derivatives.23,24 As far as we all know, many indole-2-carboxylic esters and its derivatives are used as powerful precursors for antimicrobial, anticonvulsant and anticancer drugs.25–28 Usually, the synthesis of indole-2-carboxylic esters contains a build of C–N bond. Recently, Cu is reported as a cheap catalyst for the synthesis of indole-2-carboxylic esters. In 2009, Cai group described copper salts catalyzed one-pot synthesis of indole-2-carboxylic esters from ortho-halobenzaldehyde.29 Following, several groups has reported some similar methods with copper catalyzed this kind of reaction.30–32 However, all of the reported methods in the literature to obtain the desired product are homogeneous catalysis systems which have some drawbacks: the separation of the catalyst from the reaction mixture, lack of adequate catalyst recycling methods and the residue of relatively high metal as contamination for the products. The latter problems are intolerable in the context of biological applications. To solve these problems, we immobilized Cu nanoparticles on montmorillonite by Gemini quaternary ammonium salts (Cu-Q-MMT) (Fig. 1) and used it as heterogeneous catalyst for cascade sequence to indole-2-carboxylic esters.
Q-MMT and Cu-Q-MMT materials were prepared by a method similar to our previous reported method7 (seen in ESI, S6†).
The X-ray diffraction patterns supplied very useful information on the inter layer spacing of the layered material, which provides the information regarding the interlayer distance of montmorillonite. The success of the intercalation was mainly verified by measuring the increase in the basal (001) d-spacing.35 Fig. 3 described the X-ray diffraction patterns of MMT, Q-MMT, Cu-Q-MMT and the recycled catalyst. The curve (a) represents the XRD pattern of MMT. It can be seen that the (001) diffraction peak is at 2θ = 7°. The characteristic basal spacing d is 1.26 nm as calculated from Bragg's law. This reflection shifted to 5.45° in the Q-MMT (curve (b)), meaning an increase in the basal spacing from 1.26 nm to 1.62 nm. The enlarged d-spacing values indicated the intercalation of Q within silicate layers. When the Q-MMT was further modified with copper, this peak shifted to different angles 5.97° with the basal d-spacing decreasing to 1.48 nm (curve (c)). This decrease can be explained by that parts of the unstable Q between the layers of montmorillonite were washed or replaced by Cu2+ in the process of impregnation–reduction. The curve (d) is the XRD pattern of the recycled catalyst. From the spectrum we cannot get its basal d-spacing values which indicated the (001) diffraction peak shift to the left (2θ < 3°). The reason may be that the interlayer structure of MMT has been destroyed under basic reaction conditions.
The effective method of study the montmorillonite dispersed state in water is scanning electron microscope (SEM) and the most common method of analysis element composition is energy dispersive X-ray spectrometer (EDS).36 The SEM patterns of MMT, Q-MMT and Cu-Q-MMT are shown in the Fig. 4. The surface morphology of all samples indicated layered structure of montmorillonite. Obviously, the native MMT could disperse well in water (Fig. 4a). It is visible from the Fig. 4b that the modified Q-MMT dispersed worse in water and finally agglomerated. This phenomenon revealed that the surface of silicate platelets changed from hydrophilic one into hydrophobic one, which is caused by the interaction of alkyl chains and benzene rings. After modification of copper nanoparticles, the hydrophobic abate and agglomeration degree of Cu-Q-MMT dropped (Fig. 4c). It is confirmed by the SEM results that biquaternary ammonium salts Q has been successfully modified into the layers of montmorillonite. The EDS analysis also revealed the copper loaded into the montmorillonite (Fig. 4d).
The TEM micrographs of Cu-Q-MMT and the recycled catalyst are displayed in Fig. 5. As shown in Fig. 5, the morphology of copper nanoparticles is close to lamellar structure. After recycled six times, the particle size of copper nanoparticles became smaller. And a part of copper nanoparticles was lost in the recycle experiments. The amount of Cu loaded in virgin Cu-Q-MMT and recycled Cu-Q-MMT were 11.8% and 10.2%, respectively.
The XPS analysis of virgin catalyst and recycled catalyst were shown in Fig. 6. It was clear that copper was in the Cu2+ and Cu0 components. Cu 2p3/2 peak at 932.4 eV could be assigned to Cu0, whereas the peak at 934.6 eV and 934.5 eV could be assigned to Cu2+ (Fig. 6a and b), which probably results from oxidation of the Cu0 nanoparticles upon exposure to air.37
To study the thermal stability of the organoclay and the environments of the inserting molecules, thermogravimetric analysis was performed. The TGA curves of MMT, Q-MMT and Cu-Q-MMT were shown in Fig. 7. It is reported that the decomposition of montmorillonite occurs in two steps: desorption of water from the interlayer space occurs between 25–200 °C and dehydroxylation of the layer crystal lattice structure occurs between 500–800 °C.38 The decomposition of Q-MMT and Cu-Q-MMT has obvious differences from MMT. Studies showed the decomposition of the organoclay often takes place in three steps: desorption of water from the interlayer space, decomposition of organic cation, and dehydroxylation of the layer crystal lattice structure. In this work the decomposition of organic cation steps occurs between 200–500 °C, which also implied that the catalyst Cu-Q-MMT was relatively stable below 200 °C. From all the spectra above, it can be concluded that Cu-Q-MMT has been successfully modified by Q and Cu nanoparticles.
The nitrogen adsorption–desorption isotherms of MMT, Q-MMT, Cu-Q-MMT and the recycle catalyst are given in Fig. 8. The isotherm on montmorillonite is of type IV characteristics according to the classification of Brunauer group, thereby indicating the mesoporous structures of all the samples. Combined with the result of XRD, it can be concluded that Cu-Q-MMT catalyst has nano space structure.
Fig. 8 The nitrogen adsorption–desorption isotherms of MMT (a), Q-MMT (b), Cu-Q-MMT (c) and the recycle catalyst (d). |
The reaction of orthobromobenzaldehyde with ethyl acetamidoacetate was chosen as model for optimizing the reaction conditions (seen in ESI, S8–10†). And the optimal conditions were DMSO as solvent, Cs2CO3 as base, at 80 °C, under N2 atmosphere. With the optimal conditions in hand, the catalytic performances of several catalysts were compared (Table 1).
Entry | Catalyst | Conditions | Yield |
---|---|---|---|
a Condition A: Cs2CO3, DMSO, 12 h, 80 °C, N2; B: 15 mmol% Cu, Cs2CO3, DMSO, 12 h, 80 °C, N2; C: 20 mmol% Cu, Cs2CO3, DMSO, 16 h, 80 °C; D: 20 mmol% Cu, Cs2CO3, 2-Me-THF, 16 h, 80 °C. | |||
1 | MMT | A | 18% |
2 | Q-MMT | A | 19% |
3 | Cu-MMT | B | 75% |
4 | Cu-MMT(run 1) | B | 45% |
5 | Cu-MMT(run 2) | B | 28% |
7 | Cu-Q-MMT | B | 85% |
8 | Cu-Q-MMT(run 1) | B | 82% |
9 | Cu-Q-MMT(run 2) | B | 82% |
10 | Cu-Q-MMT(run 3) | B | 82% |
11 | Cu-Q-MMT(run 4) | B | 81% |
12 | Cu-Q-MMT(run 5) | B | 83% |
13 | Cu-Q-MMT(run 6) | B | 80% |
14 | Cu-Q-MMT(run 7) | B | 72% |
15 | CuI31 | C | 50% |
16 | CuI30 | D | 59% |
Firstly, it can be concluded that Cu is important for the reaction of orthobromobenzaldehyde and ethyl acetamidoacetate to indole-2-carboxylic esters because the yield is up to 75% after the loading of Cu on the MMT (catalyst Cu-MMT). Cu catalysts are often used in the C–N cross-coupling reaction.37 So the C–N cross-coupling is the key step for forming the indole-2-carboxylic esters. And with the amount of Cu and reaction temperature increasing, the yield of indole-2-carboxylic esters increased (seen in ESI, S9†). Although the Cu-MMT gave good yield, the activity declined obviously in the recycle experiments (entry 4 and 5), which also indicated its poor stability. To improve the stability of the catalyst, the MMT was modified by biquaternary ammonium salts Q before the loading of Cu. Encouragingly, the catalyst Cu-Q-MMT could catalyze this reaction with a higher yield (85%) than Cu-MMT (75%). A possible explanation is that biquaternary ammonium salts on the MMT increase the hydrophobicity of MMT surface, benefit the adsorption of product of aldol reaction on the MMT surface, and the coordination of Cu on the MMT surface with product of aldol reaction, thereby enhancing the catalytic activity. Most importantly, the catalyst Cu-Q-MMT could reuse for 6 times without significant loss of activity. The results suggested that biquaternary ammonium salts Q modified on the MMT favor to improve the stability of catalyst as we expected. Besides, the catalyst Cu-Q-MMT showed more significant advantages: lower amount of Cu, shorter reaction time and higher activity, comparing to the reported homogeneous catalysts CuI (entry 15 and 16). The high activity and stability of Cu-Q-MMT catalyst is mainly attributed to the excellent synergistic effects of biquaternary ammonium salts, Cu nanoparticles and the nano space structure of MMT. The nano space structure of catalyst is beneficial to improve the activity, selectivity and stability of catalyst.39–41
The generality and scope of the reaction catalyzed by Cu-Q-MMT were also explored. The results are summarized in Table 2. And the products were characterized by 1H NMR, 13C NMR and HRMS (seen in ESI, S11–27†). Various benzaldehydes were compatible under the reaction conditions. Electronic effect and steric hindrance had a little impact on the outcome of the reaction. It is clear that the reactivity of the orthohalobenzaldehyde followed the trend of bromobenzaldehyde > chlorobenzaldehyde. So, 4-chloroindole-2-carboxylic ester was obtained as main product when 2-bromo-6-chlorobenzaldehyde was substrate (entry 7). In 2009, Cai group reported the cascade process of chlorobenzaldehyde with ethyl isocyanoacetate to indole-2-carboxylic ester at the yield of 20%.29 Since then, there is little report on the one-pot synthesis of indole-2-carboxylic esters from chlorobenzaldehyde because of its low reactivity. In our experiment, catalyzed by Cu-Q-MMT, 2-chlorobenzaldehydes and 2,4-dichlorobenzaldehyde coupled with ethyl acetamidoacetate to the aimed indole-2-carboxylic esters gave encouraging separation yields of 68% and 75%, respectively (entry 8 and 9).
Footnote |
† Electronic supplementary information (ESI) available. See DOI: 10.1039/c6ra25861a |
This journal is © The Royal Society of Chemistry 2017 |