Recyclable graphene-supported palladium nanocomposites for Suzuki coupling reaction

1 Introduction

Graphene is the sp² hybridized carbon allotrope, having good thermal, electrical and mechanical properties [1–6]. The specific surface area of graphene has attracted great interest of chemical researchers for the development of a new kind of composite materials, especially as a host to carry metal nanoparticles (MNPs) like palladium (Pd), gold, platinum, titanium, tin, zinc, etc. [1–9]. Various groups reported graphene based metal nanocomposites to catalyze different organic transformations like oxidation, Friedel craft addition, dehydrogenation, hydration, Pechmann condensation, Aza-Michael addition, Knoevenagel condensation, esterification, hydrogenation, coupling reaction, etc. in a facile, recyclable and sustainable manner [2, 4, 6, 10–13].

In catalysis, Pd metal offers the most favorable combinations of activity and selectivity throughout the reaction. Pd catalyzed C-C bond forming coupling reactions have contributed a remarkable impact of synthetic organic chemistry [14, 15]. Various approaches have been made to make Pd catalysts more reactive and recyclable for coupling reactions by using different types of organic/inorganic bases, ligands, solvent systems, different organic/inorganic supports (polymers, ionic liquids, montmorillonite clay, silica, zeolite, etc.) to anchor the Pd catalysts as well as substrates [16–23].

It is well documented that immobilization/stabilization of MNPs on a carbon substance is the most favorable condition for improving their catalytic activity [1–10]. The presence of functional groups and the high specific surface area of chemically modified graphenes offer the high capability of loading MNPs on to it, through hydrophobic and electrostatic interactions [1–6]. These graphene based MNPs also offer stability against air and moisture, as well as easy handling during the reaction. In various reports, Pd nanoparticles were immobilized with graphene oxide (GO) or reduced GO (rGO) and further tested as catalysts for different coupling reactions such as the Heck and Suzuki reactions [1–5, 10].

The Suzuki cross-coupling reaction of aryl or vinyl boronic acid with aryl or vinyl halides is one of the important reactions in the area of the chemical science [10, 24–32]. Initially GO immobilized as well as intercalated Pd nanoparticles were investigated for the Suzuki-Miyura coupling reaction in aqueous solution and surprisingly the catalytic system was found to be highly active in terms of yield and selectivity [1, 2, 10, 12, 28–33]. In another parallel report, Pd-graphene (Pd/G) hybrids were synthesized by reducing Pd(OAc)₂ using sodium dodecyl sulfate (SDS). These Pd/G catalysts were further tested in aqueous as well as aerobic conditions, to increase the reaction rate of the Suzuki reaction [10]. He and Gao [33] also synthesized Au/GO nanocomposites for Suzuki-Miyaura coupling and yielded the corresponding reaction products in high yield [33].

Pd/GO and Pd/rGO were active with respect to other commercially available Pd catalysts (e.g. Pd on charcoal), but collectively, Pd/GO and Pd/rGO had various drawbacks, like high catalyst loading, catalyst leaching (via agglomeration of Pd metals into the clusters) during the recycling test, limited substrate scope, requirement of polar solvents, etc. [1–5, 10, 12, 27–37].

Various reports and reviews have been published on exploring the application of ionic liquids as a reaction medium for different organic transformations [18–20]. Recently, 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene bis(trifluoromethylsulfonyl)imide [MTBD][bmsi] ionic liquid immobilized graphene-supported Pt nanoparticles were tested to study the oxygen reduction reaction. Surprisingly, [MTBD][bmsi] immobilized graphene-supported Pt nanoparticles were found to be highly active for electro-catalytic reaction in terms of yield and selectivity [34].

In this work, we synthesized the Pd/rGO composites, and tested them as catalysts for the phosphine ligand-free Suzuki reaction 1-butyl-3-methylimidazolium [bmim] NTf₂ in the ionic liquid reaction medium. We used [bmim] NTf₂ ionic liquid as the reaction medium due to its air and moisture stability, easy availability and higher utility in several organic reactions with respect to other reported ionic liquids. The reaction conditions were studied and optimized.

2 Materials and methods

All of the chemicals were purchased from Sigma Aldrich (St. Louis, MO, USA), Acros (Geel, Belgium) or Fluka (St. Louis, MO, USA). The Pd-graphene hybrids were characterized by high-resolution transmission electron microscopy (Philips Tecnai G2 F20, FEI imaging software) and energy dispersive X-ray spectroscopy (EDX) (Philips Tecnai G2 F20, FEI imaging software). Nuclear magnetic resonance (NMR) (JEOL USA Delta™ NMR Data Processing Software) spectra were recorded on a standard Bruker 300WB spectrometer with an Avance console at 300 MHz and 75 MHz for ¹H and ¹³C NMR, respectively. Mass spectra (EI) were obtained at 70 eV with a Shimadzu GCMQP 100 EX spectrometer. The residue was purified by flash chromatography with hexane/ethyl acetate.

3 Results and discussion

The morphology of Pd/rGO and GO were examined by scanning electron microscopy (SEM) analysis (Figure 1A and B). SEM images of Pd/rGO and GO samples were captured using a JEOL-JSN7500F operated at 5 kV. In the captured SEM image, GO flakes have comparatively large surfaces and the morphology resembles a thin curtain or wrinkled sheet. These factors confirmed a good exfoliation pattern of graphite during the oxidation process. SEM images of Pd/rGO confirmed the presence of well dispersed and agglomeration free Pd nanoparticles.

Figure 1:

Scanning electron microscopy (SEM) analysis of graphene oxide (GO) and Pd/reduced GO (rGO); (A) SEM image of GO; (B) SEM image of Pd/rGO.

Size distribution of Pd nanoparticles was further analyzed by transmission electron microscopy and the mean sizes of Pd nanoparticles dispersed on the graphene sheets were recorded (4 nm, ±2) (Supplemental Figure 1A and B). The presence of Pd nanoparticles on graphene is confirmed by EDX (Supplemental Figure 2). The oxygen and sulfur signal appears due to the presence of residual dodecanoate and sulfonate groups. Copper peaks were found in EDX data due to the presence of copper grid.

The X-ray diffraction (XRD) patterns were documented by Bruker axs D8 Advance, Germany. Figure 2 represents the XRD pattern of pristine graphite, GO and Pd/rGO. XRD data confirmed the formation of GO as well as the formation of Pd/rGO. The pristine graphite powder gave its sharp characteristic peak at 26.1°, with the corresponding d spacing of 0.339 m. As we synthesized the GO followed by the oxidation of graphite powder in acidic medium, because of that we found hydroxyl, carboxyl and epoxy groups on graphite sheets. A broad peak at 26.3–24.8° showed the signs of exfoliation in GO, which correspond to C (002). We observed interlayer spacing of 0.688 nm C (002) mainly because of intercalated species between the layers. After the reduction process, the diffraction peak (11.6°) corresponding to GO disappeared and a broad significant diffraction peak appeared at 25.9°. The broadening of the characteristic XRD peak of Pd/rGO mainly happened because of small sheet size and random arrangement of Pd/rGO stacked sheets. A sharp diffraction peak near 42.4° confirmed the presence of agglomeration free and well dispersed Pd nanoparticles (JCPDS card no. 87-641, d=2.28, 1.97).

Figure 2:

X-ray diffraction (XRD) analysis of graphene oxide (GO), pristine graphite and Pd/reduced GO (rGO).

The catalyst effect of Pd/rGO on the Suzuki cross-coupling reaction (Scheme 1) between phenyl boronic acid and 4-bromo anisole was studied under different reaction parameters, like reaction time, catalyst loading, solvent systems, etc. (Table 1, Entry 1–16 and Scheme 1). The results from Table 1 suggest that the bases have dramatic effects on the yield of cross-coupling products in the ligand free Suzuki reaction. Among the bases, potassium carbonate gave the best result (Table 1, Entry 5). In addition, a profound solvent effect on the reaction was observed and [bmim]NTf₂ was found to be more effective over other organic solvents for the Pd/rGO catalyzed Suzuki reaction. We also tested well reported Pd catalysts such as PdCl₂, Pd acetate and Pd on activated charcoal (Pd/C) (10% w/w Pd) against Pd/rGO catalysts in the reaction condition. Surprisingly, lower yields were observed in all of the cases with respect to Pd/rGO catalyst (Table 1, Entry 22–24). Such results support that GO works as a useful support in catalysis since the structural defects allow surface functionalization and improving the interaction of anchored MNPs with reactants [27, 28].

Scheme 1:

Suzuki model reaction for catalyst optimization.

As summarized in Table 1 (Entry 1–33), [bmim] NTf₂ mediated Pd/rGO was found to be highly active in terms of yield and selectivity for the Suzuki reaction. After the reaction, the product was easily recovered by simple extraction with diethyl ether, followed by decantation of the upper organic layer. No aqueous work-up was required during the reaction.

For the recycling of Pd/rGO/[bmim]NTf₂ catalytic system, no significant loss in yield was found up to eight runs (Scheme 2 and Figure 3), although the catalyst activity dropped mainly because of agglomeration of Pd nanoparticles. It was confirmed by a transmission electron microscopy image of Pd/rGo after catalysis (Supplemental Figure 1B).

Scheme 2:

Catalyst recycling protocol.

Figure 3:

Recycling results of Pd/reduced graphene oxide (rGO)/[bmim]NTf₂ for Suzuki reaction.

Under the optimized reaction conditions (Pd/rGO as a catalyst, K₂CO₃ as a base and [bmim] NTf₂ as a solvent), a series of aryl/hetero aryl halides with aryl boronic acid were tested, and the results are summarized in Table 2, Scheme 3, Entry 1–18. All of the substrates enjoyed the proposed protocol, and were easily isolated. The Pd/rGO was found to be efficient in catalyzing the coupling of different ranges of aryl/ hetero aryl halides with a series of aryl boronic acids, in excellent yield, regardless of their activating or deactivating substituents and the reactions could be finished in 1 h [32–35]. Electron rich as well as electron-deficient, aryl/hetero aryl halides coupled efficiently with aryl boronic acids (Table 2, Scheme 3, Entry 1–18). Aryl boronic acids with electron-withdrawing substituted groups, which are less nucleophilic and hence, transmetallate more slowly than electron-neutral analogues, are prone to homocoupling and protodeboronation side reactions. The identity of the coupling products was confirmed by ¹H and ¹³C NMR, MS spectra 28–32.

Table 2

Pr/reduced graphene oxide (rGO) catalyzed Suzuki cross coupling reaction of aryl halides with aryl boronic acids in [bmim]NTf₂.

^aThe reaction was carried out with Pd/reduced graphene oxide (rGO) (0.100 g), aryl/hetero aryl halide (0.50 mmol), aryl boronic acid (1 mmol), K₂CO₃ (1.5 mmol), [bmim]NTf₂ (2 ml) at 100°C for 1 h.

^bIsolated yields after column chromatography.

Scheme 3:

Application of Pd/reduced graphene oxide (rGO) catalyst for Suzuki cross-coupling reaction in [bmim]NTf₂.

Indazole, the indole bioisoster, is a highly applicable intermediate and found in various biologically active compounds such as lonidamine and Akt1 inhibitor [38, 39]. Due to a series of applications in terms of biological activity, the syntheses of indazole derivatives as well as the structural modification of the indazole ring system have been recently reviewed by the scientific community [39–42]. We applied the Pd/rGO catalysts for the synthesis of novel indazole derivatives followed by the Suzuki reaction. We applied the optimized Pd/rGO catalyzed Suzuki reaction condition to couple 5-bromo-1-ethyl-1H-indazole with N-Boc-2- pyrroleboronic acid in [bmim]NTf₂ reaction medium and surprisingly, our Pd/rGO catalyst system offered the corresponding reaction product 2-(1-ethyl-1H-indazol-5-yl)-pyrrole-1-carboxylic acid tert-butyl ester in good yield (88%) (Table 3, Entry 1). We also synthesized four different indazole derivatives with N-Boc-2-pyrroleboronic acid and the corresponding results are summarized in Table 3, Entry 2–5.

Table 3

Catalytic application of Pd/reduced graphene oxide (rGO) for novel synthesis.

^aIsolated yield after column chromatography.

4 Conclusion

In conclusion, we successfully synthesized Pd/rGO by reducing Pd nitrate in the presence of SDS. The [bmim]NTf₂ mediated Pd/rGO was found to be highly active as a catalyst for the Suzuki reaction and recycled up to eight times without any significant lost in terms of the product yield. The Pd/rGO catalyst can be used for novel pyrrolyl indazole synthesis, yielding five useful indazole derivatives with comparatively good yield in comparison with other reported procedures [42].

Supplemental material: All the analytical data are available in the online Supplemental material.