Hajar Mahmoudia,
Abbas Ali Jafari*a,
Soroosh Saeedia and
Habib Firouzabadi*b
aDepartment of Chemistry, College of Sciences, Yazd University, 89195-741 Yazd, Iran. E-mail: jafari@yazd.ac.ir
bLate Professor Moshfegh Laboratory, Chemistry Department, Shiraz University, Shiraz 71454, Iran. E-mail: firouzabadi@chem.susc.ac.ir
First published on 2nd December 2014
A modified sulfonic acid functionalized magnetic nanoparticle composite (Fe3O4@γFe2O3–SO3H) is prepared by the use of ultrasonic irradiation. By this modification, the size of the nano-particles was reduced and the magnetization of the material was highly improved. This improvement drastically affected the efficiency and magnetic separation of the material as a catalyst. This new modified nanomagnetic compound was used as a highly efficient and recyclable catalyst for functionalization of indole derivatives via Michael addition and Friedel–Crafts alkylation reactions in entirely environmentally friendly media at room temperature. This modified magnetic material can be easily applied for large-scale operations producing the desired products in excellent yields in highly pure states.
The Michael addition reaction and bisindolyl methane synthesis are important C–C bond forming reactions, which have found wide synthetic applications in material sciences, agrochemicals, and pharmaceuticals.10–12 Several homogeneous acid and base catalysts are used to effect these reactions. In the presence of strong bases or acids, side reactions such as multiple condensations, polymerizations, and rearrangements are common to occur.13–17 Furthermore; many of these procedures have some drawbacks consisting of corrosive and expensive reagents, low yield of products, difficult handling, and long reaction times. To overcome the mentioned difficulties, chemists investigated a wide range of strategies. One of the logical solution for the above mentioned problems is to use heterogeneous catalysts carrying nano-materials (NMs).18–20
Nano scale particles reveal novel properties which are not found in their macroscopic counterparts. These properties contribute to the efficiency and capability of nano-catalysts in the reactions.21–28 However; the major problems in using the nano-catalysts are their isolation and recovery from the reaction mixture. One of the smart ways for the isolation and separation of catalysts can be accomplished by their support on the surface of magnetic nanoparticles (MNPs). By this achievement, the catalyst can be isolated by an external magnet from the reaction mixture by minimum contamination of the products. In addition, by adopting this strategy, easy recycling of the catalyst without using the time consuming filtration step can be achieved.29–32 Undoubtedly, the utilization of MNPs in catalysts separation constitutes the economically and technologically important application that has stimulated vast research efforts in this area.33–36 However, it is noteworthy to state that, the naked metallic nanoparticles with the high surface area to volume ratio are highly chemically active and are easily oxidized in air, resulting generally in loss of magnetism and disperser of MNPs.37 Hence, for this reason, it is important to develop a protection strategy for stabilizing the naked MNPs against degradation during or after the synthesis. This strategy consists of coating the naked magnetic nanoparticles with polymers or an inorganic layer such as gold, silica or carbon.38–43 There is also notable to declare that, the coating protocol may provide useful sites for further functionalization of the material. For instance, the strong acids, known as damaging materials in industry and environment, can be supported on MNPs. Sulfonic acid-functionalized magnetic nanoparticles (SAMN) is known as the recoverable solid strong acid.44–46 The SAMN is of great interest in both academic and industrial communities due to its economically importance and environmentally benign features. Nevertheless, up to now, only a few strategies for the preparation of SAMN have been reported in the literature. Along of our interest for applying SAMN as a catalyst in important synthetic reactions,47 now we report a modification for the preparation of the SAMN by using ultrasound irradiation instead of vigorous mechanical steering.47 By this modification a promising advancement in magnetic separation of the material, smaller size of the nano-particles and as a result higher catalytic activity has been observed. This modified SAMN has been used as an effective catalyst for the high yielding eco-friendly processes for the preparation of Michael adducts and also for the preparation of 3-substituted indolyl derivatives via Friedel–Crafts alkylation reaction of indole.
The new SAMN was characterized by XRF, TEM, and VSM and the amounts of sulfonic acid functional group on magnetic nanoparticles with maghemite coating supports was determined by the neutralization titration method to be in the range of 4–4.5 mmol g−1.
X-ray fluorescence analysis (Table 1) confirms the presence of sulfonic acid on the catalyst surface. The XRF analysis proves that the use of ultrasonic irradiation, instead of vigorous stirring in sulfonation process of MNPs, reduces the conversion of Fe3O4 to γFe2O3. The amount of γFe2O3 on the outer layer of Fe3O4 is less than that of our previously reported procedure47 (Fig. 1).
Compound | Concentrationb (%W/W) | Concentrationc (%W/W) |
---|---|---|
a Loss on ignition (1000 °C, 2 h).b Ultrasonic irradiation.c Vigorous stirring. | ||
Fe2O3 | 23.50 | 42.65 |
Fe3O4 | 20.05 | 0 |
SO3 | 19.06 | 20.26 |
Cl | 2.01 | 1.66 |
V2O5 | 0.060 | 0.073 |
Al2O3 | 0.031 | 0.041 |
MnO | 0.027 | 0.034 |
CaO | 0.019 | 0.029 |
CuO | 0.010 | 0.020 |
ZnO | 0.009 | 0.009 |
LOIa | 35.28 | 35.48 |
Total | 100.05 | 100.26 |
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Fig. 1 XRF analysis of SAMN (a) by vigorous steering47 (b) under ultrasonic irradiation. |
The results of transmission electron microscopy (TEM) analysis of the SAMN demonstrate uniform-sized particles with spherical morphology with an average size range of 5–10 nm (Fig. 2). This also shows the effect of ultrasonic irradiation upon the size of the particles with respect to vigorous stirring (10–15 nm).47
The magnetization curves of the Fe3O4 and modified SAMN were further recorded at room temperature (Fig. 3). The saturation magnetization value of the modified SAMN is 90 emu g−1 (Fig. 3b). The number is smaller than that of uncoated magnetic nanoparticles which is 93 emu g−1 (Fig. 3a) and becomes nearly 1.63 times greater than that of our previous report for the preparation of Fe3O4@γFe2O3–SO3H47 which is 55 emu g−1 (Fig. 3c) and nearly 3.2 times greater than γFe2O3–SO3H46 that is 28 emu g−1 (Fig. 3d).
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Fig. 3 Magnetization loops of (a) Fe3O4, (b) modified SAMN (c) previously reported SAMN47 (d) γFe2O3–SO3H.46 All the data are recorded at room temperature. |
The magnetization curve of the modified SAMN assures that the use of ultrasonic irradiation produces an agile SAMN which accumulates in a blink by an external magnetic field from water (Fig. 4).
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Fig. 4 (a) Dispersed modified SAMN in water (b) fast separation of the modified SAMN with a magnet bar from water. |
This modified material has been successfully applied as a catalyst for Michael addition and Friedel–Crafts reactions. In order to optimize the reaction conditions with respect to temperature, time, and the molar ratio of the substrates, the reaction of indole with methyl vinyl ketone as a model reaction was studied. The reaction was proceeded sluggishly and after a prolonged reaction time (5 h), the corresponding Michael adduct was produced in only 20% yield in the absence of the catalyst. Then, similar reaction was performed in the presence of different mol% of the modified SAMN. We observed a drastic rate enhancement under solvent free conditions and also in different solvents. Promising results were obtained at room temperature when solvent free condition or solvents such as EtOH, CH3CN, n-hexane, CH2Cl2 and acetone were used (Table 2).
Entry | Cat. (mol%) | Solvent | Temp. (°C) | Time (min) | Conversion (%) |
---|---|---|---|---|---|
1 | — | — | 25 | 300 | 20 |
2 | Fe3O4 (0.07 g) | — | 25 | 300 | 100 |
3 | Fe3O4@γFe2O3–SO3H (5) | — | 25 | 30 | 100 |
4 | Fe3O4@γFe2O3–SO3H (7) | — | 25 | 20 | 100 |
5 | Fe3O4@γFe2O3–SO3H (10) | — | 25 | 10 | 100 |
6 | Fe3O4@γFe2O3–SO3H (15) | — | 25 | 5 | 100 |
7 | Fe3O4@γFe2O3–SO3H (10) | EtOH | 25 | 180 | 100 |
8 | Fe3O4@γFe2O3–SO3H (10) | H2O | 25 | 300 | 30 |
9 | Fe3O4@γFe2O3–SO3H (10) | H2O | 100 | 300 | 70 |
10 | Fe3O4@γFe2O3–SO3H (10) | PEG | 25 | 300 | 20 |
11 | Fe3O4@γFe2O3–SO3H (10) | n-Hexane | 25 | 150 | 100 |
12 | Fe3O4@γFe2O3–SO3H (10) | CH3CN | 25 | 120 | 100 |
13 | Fe3O4@γFe2O3–SO3H (10) | CH2Cl2 | 25 | 120 | 100 |
14 | Fe3O4@γFe2O3–SO3H (10) | Acetone | 25 | 240 | 100 |
In order to show the general applicability of the method, the reaction of various indoles with α,β-unsaturated carbonyl compounds under solvent free conditions was studied. The results of this study are tabulated in Table 3.
Entry | Product | Time (min) | Yield (%) |
---|---|---|---|
a Reaction conditions: indole (1 mmol), α,β-unsaturated carbonyl compound (1.1 mmol) and modified SAMN (0.1 mmol, 0.03 g) were mixed and mechanically stirred at room temperature. | |||
1 | ![]() |
10 | 95 |
2 | ![]() |
60 | 90 |
3 | ![]() |
180 | 93 |
4 | ![]() |
240 | 90 |
5 | ![]() |
10 | 97 |
6 | ![]() |
5 | 95 |
7 | ![]() |
120 | 97 |
8 | ![]() |
60 | 98 |
In continuation of our studies, Friedel–Crafts alkylation reaction of indole with an aldehyde was also investigated in the presence of the modified catalyst. At first, the reaction of benzaldehyde with indole was studied as a model reaction to optimize the reaction conditions. In the absence of the catalyst, 3,3′-(phenylmethylene)bis(1H-indole) was produced in only 30% yield after a long reaction time (24 h). In the presence of the modified catalyst, the reaction was progressed well at room temperature and the desired bisindolyl methane was produced rapidly (15 min) in a quantitative yield in solvents such as EtOH, CH3CN, CH2Cl2 and petroleum ether at different reaction times (Table 4).
Entry | Cat. (mol%) | Solvent | Tem. (°C) | Time (h) | Conversion (%) |
---|---|---|---|---|---|
1 | — | EtOH | 25 | 24 | 30 |
2 | Fe3O4 | EtOH | 25 | 5 | 100 |
3 | Fe3O4@γFe2O3–SO3H (5) | EtOH | 25 | 1 | 100 |
4 | Fe3O4@γFe2O3–SO3H (7) | EtOH | 25 | 0.5 | 100 |
5 | Fe3O4@γFe2O3–SO3H (10) | EtOH | 25 | 0.33 | 100 |
6 | Fe3O4@γFe2O3–SO3H (15) | EtOH | 25 | 0.25 | 100 |
7 | Fe3O4@γFe2O3–SO3H (10) | H2O | 25 | 24 | 50 |
8 | Fe3O4@γFe2O3–SO3H (10) | H2O | 100 | 5 | 60 |
9 | Fe3O4@γFe2O3–SO3H (10) | PEG | 25 | 24 | 30 |
10 | Fe3O4@γFe2O3–SO3H (10) | CH3CN | 25 | 2.5 | 100 |
11 | Fe3O4@γFe2O3–SO3H (10) | CH2Cl2 | 25 | 6 | 100 |
12 | Fe3O4@γFe2O3–SO3H (10) | Petroleum ether | 25 | 8 | 100 |
However, in order to show the advancement of the catalytic activity of the ultrasonically assisted preparation of SAMN with our previously reported SAMN,47 the reaction of benzaldehyde with indole was studied (Scheme 2). As it is evident from the results, the catalytic activity of the modified SAMN is considerably 18 times greater than the non-modified one.
To demonstrate the general widespread application of the method, the addition of structurally different indoles to aldehydes in EtOH at room temperature was studied. The results of this study are listed in Table 5.
Entry | Product | Time (min) | Yield (%) |
---|---|---|---|
a Reaction conditions: indole (2 mmol), aldehyde (1 mmol) and modified SAMN (0.1 mmol, 0.03 g) and ethanol (1 mL) were mechanically stirred at room temperature. | |||
1 | ![]() |
20 | 95 |
2 | ![]() |
30 | 91 |
3 | ![]() |
10 | 95 |
4 | ![]() |
20 | 94 |
5 | ![]() |
20 | 90 |
6 | ![]() |
15 | 93 |
7 | ![]() |
5 | 93 |
8 | ![]() |
60 | 98 |
The high purity of the products with respect to the iron contamination has been approved by manganometry titration analysis.
Considering the importance of using catalysts for the large scale operation and their further applications in industry, we have studied the use of the catalyst in large scale Michael addition and Friedel–Crafts alkylation reactions with success under solvent free condition and in EtOH respectively (Scheme 3 and 4).
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Scheme 3 Michael addition of indole to methyl vinyl ketone in large scale catalyzed by modified SAMN catalyst. |
Efficient recycling of the catalyst is important from environmental and economic point of views. Therefore, recycling of this catalyst was studied for the reaction of indole with methyl vinyl ketone (Fig. 5). After completion of each run, the catalyst was separated by an external magnetic bar and then was reused for another batch of the reaction. This process has been repeated for 5 consecutive runs without observable decrease in catalytic activity of the catalyst (Fig. 5). This observation shows that the morphology and also the size of the particles of the catalyst should not be changed during different runs. In order to approve this statement, TEM image of the catalyst after the first run of recycling (Fig. 6) was compared with the TEM image of the catalyst before reaction (Fig. 2) It shows that the size (10–15 nm) and the morphology (spherical) of the catalyst has been preserved during the reaction.
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Fig. 5 Recycling of the modified catalyst for 5 consecutive runs for Michael addition reaction of indole with methyl vinyl ketone. |
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Fig. 6 TEM image of the catalyst after the 1st run of recycling shows that the size (10–15 nm) and the morphology (spherical) of the catalyst nano particles are preserved. |
Footnote |
† Electronic supplementary information (ESI) available. See DOI: 10.1039/c4ra11605d |
This journal is © The Royal Society of Chemistry 2015 |