Metal nanoparticles have gained considerable interest in academic and industrial fields [1] as they possess unique properties in electronics, optics, and organic synthesis. Metal nanoparticles have attracted a wealth of research as catalysts in chemical reactions and are now an important field in nanoscience and nanotechnology [2, 3].
Palladium nanoparticles (PdNPs) have proved to be a ubiquitous catalyst for many organic reactions, such as the Suzuki-Miyuara reaction [4], Heck reaction [5, 6], Hiyama reaction [7], Stille reaction [8], Hydrogenation reaction [9, 10], etc. The Suzuki-Miyuara reaction is one of the most powerful C-C coupling reactions of aryl halides with boronic acids [11]. The biaryl products from the Suzuki reaction are widely employed in industrial organic syntheses, in the production of natural, synthetic, and bioactive products. Additionally, biaryl compounds are further used in the synthesis of pharmaceutical intermediates, pesticides, and covalent organic frameworks [12, 13]. Although palladium is well established as a cross- coupling catalyst [14], PdNPs have great potential to replace conventional palladium catalysts because of their larger surface area and their ability to be recycled and reused. Formation of stable metal nanoparticles requires various stabilizers and supporting materials to prevent aggregation, resulting principally because of the high surface energy of the NPs [3, 15]. NPs supported on nanoporous materials are synthesized by complex and time-consuming methods that yield catalyst particles residing within the s upport internal surface. The result of which can lead to molecular diffusion limitations and reduce accessibility of the NPs to the reactants thereby lowering catalytic activity [16]. Furthermore, supported nanoparticles are more susceptible to leaching, whereby turn over numbers gradually decline affecting the lifetime of the catalyst [3]. Therefore, to circumvent the limitation of supporting nanomaterials, various stabilizers, such as amines, phosphines, thiols, surfactants, etc., are used for the synthesis of stable metal nanoparticles to limit agglomeration [1, 17, 18].
Recently, supramolecules, such as calixarenes [19], porphyrins [20], and cyclodextrins [21], have been exploited for their stabilizing properties towards PdNPs. Among them, calixresorcinarenes are gaining considerable attention because of their inherent hollow cavities and web-type structures [22], providing a stable nanoparticle environment. Calixresorcinarenes are large cyclic tetramers [23] possessing a cup-like hollow cavity surrounded by hydrophilic groups [24], and are easily synthesized by the condensation of resorcinols with any alkyl or aryl aldehyde. To our knowledge only Shen’s group [25] has used resorcinarene to synthesize PdNPs hitherto.
In this article we report the synthesis of the hydrazide derivative of resorcinarene and its use as a reducing agent as well as a stabilizing agent for the formation of tetra-methoxy resorcinarene tetra-hydrazine (TMRTH)-PdNPs. The TMRTH-PdNPs are stable under ambient conditions. Furthermore, the nanoparticles are recoverable and reusable and display high catalytic activity for the Suzuki reaction. Additionally, the TMRTH- PdNPs exhibit antimicrobial activity, suggesting their possible application in biological areas.
All chemicals of the highest purity available were purchased from commercial sources and used as received. Palladium acetate, 4-formyl boronic acid, phenylboronic acid, bromobenzene, and other aryl halides were purchased from Sigma-Aldrich. Water used in the experiment was prepared from Millipore water (resistivity, 18 MO cm, at 25 °C; Millipore Systems). TLC fluorescence active plates (F-2009) were procured from Merck.
The outline of the general procedure for the synthesis of TMR was reported elsewhere [26]. In the modified detailed procedure, 3-methoxyphenol (5.64 g, 0.045 mol) and propanal (2.63 g, 0.045 mol) were dissolved in dry dichloromethane (250 mL) in an ice bath under a N2 atmosphere. BF3·Et2O (12.77 g, 0.090 mol) was added dropwise to the solution over a 1-h period while maintaining the temperature below 20 °C throughout the addition. After 3 h of stirring, deionized water (100 mL) was added to the reaction mixture to quench the reaction. The organic layer was separated, collected, and dried over Na2SO4, and the solvent evaporated under vacuum yielding dark red oil, which was dissolved in a minimum quantity of hot ethanol to obtain orange crystals on cooling. Recrystallization was performed in ethanol to obtain 1.1 g (42%) of the TMR macrocycle as an off-white powder.
1H NMR (400 MHz, DMSO): δ = 0.85 (12H, t, -CH3), 1.75 (8H, t, -CH2), 3.61 (12H, s, -OCH3), 6.27 (4H, s, Ar-CH-), 6.79 (4H, s, Ar-CH-), 8.63 (4H, s, Ar-OH); 13C NMR (400 MHz, DMSO): δ = 12.62, 28.69, 35.21, 55.34, 98.93, 122.27, 122.91, 125.79, 153.06, 154.94; 13C DEPT (400 MHz, DMSO): δ = 28.70; ESI-Mass: 657.8 (M+1)+ ;FT-IR: 3527.65 cm-1 (Ar-OH); M.P. > 300 °C.
In a 500 mL three-neck round bottom flask equipped with a mechanical stirrer and reflux condenser, TMR (5.0 g, 0.007 mol), anhydrous potassium carbonate (10.51 g, 0.076 mol), and potassium iodide (0.11 g, 0.007 mol) were added to dry acetone (150 mL). The resulting mixture was refluxed under a N2 atmosphere for 0.5 h. Thereafter ethyl bromoacetate (25.45 g, 0.152 mol) was added and the reaction mixture further refluxed for 48 h. Acetone was removed under vacuum to obtain the residue, which was extracted in CHCl3 after neutralization. A compound containing a yellow organic layer was separated and dried under vacuum to obtain the yellow solid compound, which was further recrystallized in ethanol to yield the pure white solid compound, TMRTA, with 70% yield.
1H NMR (400 MHz, DMSO): δ = 0.86 (12 H, t, -CH3), 1.22 (12H, t, -CH3), 1.80 (8H, q, -CH2), 3.54 (12H, s, -OCH3), 3.96 (4H, s, Ar-CH-), 4.17 (16H, m, -CH2), 6.23 (4H, s, Ar-CH-), 6.57 (4H, s, Ar-CH-); 13C NMR (400 MHz, DMSO): δ = 12.59, 14.25, 27.52, 37.08, 55.56, 60.93, 68.37, 99.52, 126.27, 127.37, 128.11, 155.05, 155.71, 169.63; 13C DEPT (400 MHz, DMSO): δ = 60.93, 68.36, 27.63; ESI-Mass: 1024.2 (M+Na)+; FT-IR: 1736.59 cm-1 (-C=O); M.P. = 158 °C.
A mixture of the compounds TMRTA (5.0 g, 0.005 mol) and hydrazine hydrate (6.1 g, 0.097 mol) in 30 mL of ethanol was refluxed for 48 h before cooling to room temperature. The precipitated white solid was washed with absolute alcohol to obtain the pure compound, TMRTH with 75% yield (Scheme 1).
1H NMR (400 MHz, DMSO): δ = 8.51 (4H, s, -NH-), 6.96 (4H, s, Ar-CH-), 6.47 (4H, s, Ar-CH-), 4.39 (8H, s, -CH2-), 4.40 (4H, m, -CH-), 4.43 (4H, m, -NH-), 3.69 (12H, s, -O-CH3-), 1.84 (8H, t, -CH2-), 0.75 (12H, s, -CH3); 13C NMR (400 MHz, DMSO): δ = 166.99, 155.00, 153.56, 125.98, 125.29, 124.78, 97.44, 67.32, 56.09, 35.11, 28.14, 12.33; 13C DEPT (400 MHz, DMSO): δ = 67.32, 28.14; ESI-Mass: 945.6 (M+1)+; FT-IR (cm-1): 3412.9 (-NH2) 1685 (-CONH); M.P. > 250 °C.
Optimum conditions to prepare the TMRTH-PdNPs are as follows. Palladium acetate (PdAc, 0.011 g) was dissolved in 50 mL of distilled water and heated to 60 °C. Water soluble TMRTH (0.011 g) was added and the mixture was maintained at 60 °C for 5 h. The complete reduction of the palladium salt solution and formation of PdNPs were confirmed by the color change from brown to colloidal black (Scheme 2) and UV-Vis spectroscopy. As TMRTH is water-soluble, the concentration of TMRTH in TMRTH-PdNPs is 5.90 mg and the Pd loading in TMRTH-PdNPs is 2.66 mg. The obtained yield of the recyclable nanocatalyst, TMRTH-PdNps, collected by centrifugation is 8.56 mg. Thus, the method described above for the preparation of PdNPs is a simple one-pot process and requires only two reagents, TMRTH and PdAc. Furthermore, the process is undertaken in the presence of an environmentally friendly solvent, water.
A VEEGO VMP-DS melting point apparatus (Mumbai, India) was used to measure the melting points (uncorrected) in a single capillary tube. Centrifugation of the colloidal solutions was performed using a Remi C-24BL laboratory centrifuge. 1H NMR, 13C NMR, and 13C DEPT spectra were obtained on a Bruker AV-(III)-400 MHz spectrometer using a BBFO probe. Mass spectra were recorded on a Micromass Q-TOF micro mass spectrometer with a capillary voltage of 3000 V and a source temperature of 120 °C. Absorption spectra were recorded using a Jasco V-570 UV-Vis recording spectrophotometer (Easton, US) in the range of 200-800 nm. Transmission electron microscopy (TEM) micrographs were recorded on a JEOL JEM 2100 microscope using an accelerated voltage of 200 kV. Powder X-ray diffraction (XRD) was recorded on a PANalytical Empyrean powder diffractometer using Cu Kα. FT-IR spectra were measured on Jasco 4100 DR 80 spectrometer in the range of 4000-400 cm−1. Zeta potential and particle size were measured using a MalvernZetasizer ZEN3600 without dilution.
Resorcinarene hydrazide [22, 27, 28] derivatives are well known to function as a reducing agent as well as a stabilizing agent for the preparation of Au, Ag, and Au-Ag alloy nanoparticles. Herein, we believe for the first time the facile TMRTH- mediated synthesis of PdNPs using aqueous solutions of Pd(OAc)2 and TMRTH without the use of any external reducing agent. The synthesized TMRTH-PdNPs have been characterized by UV-Vis, TEM, energy-dispersive X-ray spectroscopy (EDX) and powder XRD.
UV-Vis spectroscopy was used to monitor the formation of the as-prepared TMRTH-PdNPs. Because, unlike other metal nanoparticles, PdNPs do not show any pronounced surface plasmon resonance, the disappearance of the band at 400 nm ascribed to palladium acetate (Fig. 1) can be correlated to the distinct color change from brown to black (Fig. 2) with successive addition of hydrazide and is considered to be the successful formation of TMRTH-PdNPs [29].
Zeta-potential is a tool to predict the long-term stability of nanoparticles [30]. The stability of the PdNPs as determined by zeta potential has been reported of having values of −16.4 (Fig. 3), which indicates moderate stability [31] of the synthesized PdNPs.
Strong signals from Pd are evident with weaker signals assigned to C and Cu for spot profiling by EDX analysis over a densely populated region on the surface of the film (Fig. 4(a)). TEM analysis reveals the size of the TMRTH-PdNPs to be 5 ± 2 nm with roughly spherical morphology (Fig. 4(b) and (c)).
The TMRTH-PdNPs were isolated in the solid form to study their catalytic activity. Powder XRD was also measured to confirm the formation of NPs. The XRD pattern shows peak reflections at 2θ = 40.22°, 46.63°, 68.38°, 82.27°, and 86.45°, correlating to d-spacing values of 0.2236, 0.1947, 0.1371, 0.1171, and 0.1125 nm, respectively (Fig. 5). The d-spacing values correspond to the (111), (200), (220), (311), and (222) crystallographic planes of an fcc lattice, respectively, indicating fcc TMRTH-PdNPs [32, 33, 34] in the present study.
Metal nanoparticles with x nm attract considerable attention [1] because of their relative high catalytic activity and selectivity [35]. Therefore the 5 ± 2 nm TMRTH-PdNPs can be expected to catalyze the Suzuki reaction. Precise control of the reaction condition, such as solvent and base selection, temperature, catalyst concentration, and reactant species are critical factors in the nanocatalyst performance [36]. Table 1 summarizes the various reaction conditions optimized for a model Suzuki reaction between 4-bromophenol and 4-formylphenyl boronic acid catalyzed by homogeneous PdNPs.
Solvents have a marked effect on the C-C coupling reaction, therefore, the effect of various solvents on the yield of the model reaction was studied by using a 1:1 mixture of water and organic solvent in the presence of 0.006 mmol PdNPs under ambient conditions. Acetone, DMF, ethanol, and 1,4-dioxane (Table 1, entries 1 and 5-7) proved to be better co-solvents than toluene, dichloromethane, and tetrahydrofuran (Table 1, entries 2-4) for this reaction.
Na2CO3 was selected as a base (Table 1, entry 7) over alternative bases, such as triethylamine, K2CO3, NaHCO3, KOH, and CH3COONa (Table 1, entries 8-12), for the model Suzuki reaction as improved conversion.
The product yield as a function of temperature was also studied. It was found that increasing the temperature had no effect on improved yield (Table 1, entries 18-20). Therefore, the optimum temperature of 40 °C was selected for the model reaction. Additionally, product yield was determined as a function of catalyst loading. TMRTH-PdNPs (0.006 mmol) was found to be optimum. It was observed that lowering the catalyst loading reduced yield even after extended periods of time, however, increasing the loading beyond the optimum value does not affect the yield of reaction (Table 1, entries 7, 13, and 14).
Furthermore, the optimized reaction conditions for TMRTH- PdNPs have also been compared with conventional Pd catalysts, such as palladium acetate and tetrakis (triphenyl phosphine)-Pd(0) (Table 1, entries 21 and 22), and the TMRTH- PdNPs display superior conversion over that of the conventional catalysts in terms of yield in addition to reaction time. Thus, the optimized reaction conditions of the model reaction (solvent = 1,4-dioxane-water (1:1), base = Na2CO3, temperature = 40 °C, TMRTH-PdNPs loading = 0.006 mmol) were used in all Suzuki cross-coupling reactions on varying aryl halides. All the aryl halides gave the desired cross-coupled products with good to excellent yields (Table 2).
To summarize, the synthesized TMRTH-PdNPs were free of usual limitations generally imposed on palladium catalyst systems, such as the requirement of an inert atmosphere [37, 38] and external additives [39].
Aryl halide (1 equiv.), arylboronic acid (1.2 equiv.), Na2CO3 (1.5 equiv.), and TMRTH-PdNps (0.006 mmol) were charged in a round-bottomed flask equipped with a stirrer in 10 mL mixture of 1,4-dioxane-water (1:1). The flask was placed in an oil-bath and the mixture was stirred at 40 °C for 10 min. Products were extracted with 3 ×10 mL of ethyl acetate and washed with 3 ×10 mL of water before drying over Na2SO4.The organic layer was evaporated under vacuum using a rotary evaporator to obtain the solid product. Thereafter, the solid was dried and weighed to record the yield. The products have been characterized by 1H NMR and electrospray ionization mass spectrometry.
Recyclability of the TMRTH-PdNPs was investigated for the model Suzuki reaction under optimized reaction conditions (as per Table 1). The reaction mixture was centrifuged for 15 min at 3000 rpm. The TMRTH-PdNPs were separated by centrifugation and washed with 1,4-dioxane and water to remove any adsorbed organic reagents. The catalyst was dried overnight at 50 °C prior to being reused. Without any further activation, the catalyst was used for five cycles with negligible compromise in the efficiency of the TMRTH-PdNPs (Fig. 6). Therefore, TMRTH- PdNPs can be recycled efficiently in the Suzuki- Miyaura reaction over five cycles maintaining 94% yield in 15 min at 40 °C.
To overcome the global problem of multi-drug resistant pathogens, nanoparticle research is providing new applications to establish continuity in the development of new antimicrobial agents [40, 41, 42]. In addition to the significant and wide use of PdNPs as catalysts, the PdNPs have also shown promise as antimicrobial agents [43, 44]. The size of the nanoparticles is a key factor in how effective they are as antimicrobial agents [45].
The evaluation of anti-bacterial activity of TMRTH-PdNPs against various microorganisms, such as E. Coli, P. Aeruginosa, S. Aureus, and S. Pygoenus and anti-fungal activity against numerous microorganisms, such as C. Albicans, A. Niger, and A. Clavatus was performed according to the micro-dilution procedure described by the National Committee for Clinical and Laboratory Standard [46, 47, 48]. The minimum inhibitory concentration of TMRTH-PdNPs was determined. The anti- bacterial activity (Fig. 7) was compared with standard drugs, such as Chloramphenicol and Ampicillin, while the anti-fungal activity (Fig. 8) was compared with standard drugs, such as Nystatin and Greseofulvin. It was observed that TMRTH-PdNPs show good antibacterial activity against gram-positive bacteria, over that of gram-negative bacteria as compared with palladium acetate and TMRTH.
We prepared a novel derivative of resorcinarene, TMRTH, which acts as a reducing agent as well as a stabilizing agent for the formation of water dispersible and stable TMRTH-PdNPs. The synthesized nanoparticles were characterized by TEM, EDX, and powder XRD. The nanoparticle catalysts require shorter reaction time and reduced catalyst loading to yield good conversion. The TMRTH-PdNPs possess good stability and are well dispersed in water. The nanocatalysts can be recycled over five cycles and therefore show promise excellent catalysts for the Suzuki-Miyuara cross-coupling reaction in comparison with conventional palladium catalysts. Additionally, the antibacterial activity against gram-positive bacteria suggests possible use in biological applications. Further investigations are on-going to apply these nanocatalysts in alternative applications and organic reactions.
The authors gratefully acknowledge the financial assistance provided by UGC (University Grant Commission) and DRDO (Defence Research Development Organisation), New Delhi. The authors also acknowledge Central Salt & Marine Chemicals Research Institute (Bhavnagar), Sophisticated Analytical In- strument Facility (Panjab University), and Gujarat Forensic Sciences University (Gandhinagar) for providing instrumental facilities and Gujarat University Library for e-journals.
2016, Vol. 37 Issue (2): 250-257
PDF (1122 KB)
2016, Vol. 37 Issue (2): 250-257
PDF (1122 KB)