The palladium-catalyzed cross-coupling reactions are efficient methods for carbon–carbon bond formation [1-7]. The biaryl derivatives generated in Suzuki cross-coupling reactions have been widely used in many natural products, pharmaceuticals and advanced materials; so, a large number of effective catalytic systems have been developed [8-11]. The standard Suzuki reaction using palladium salts and phosphine ligands suffers from limitations that have so far precluded many industrial applications. In spite of wide applications of Pd-catalysts in coupling reaction, the catalyst recovery and contamination of products by toxic palladium is a main problem; the acceptable limits of palladium pollution in pharmaceuticals were set as ppm level [12, 13]. Moreover, phosphine ligands are toxic and sensitive to air and moisture [14, 15]; so, heterogeneous phosphine-free catalysts are highly valuable.
In this regard, development of effective and practical catalytic approaches using an environmental friendly, low cost and safe ligands has been a topic of great interest during recent years [16-21]. Biomolecules such as DNA are highly favorable; their applications in various biomaterials and biocatalysts [22-27], their chemical stability, biodegradability, commercial availability, and also their low-cost make them attractive materials in catalyst field. Stabilization of metal nanoparticles such as Ag, Au, Co,[30, 31] Cu, Pt and Pd[34, 35] in DNA cavities by coordination and a large number of effective catalytic systems have been developed. [36, 37] However, solubility of DNA promoted us to fix it on a nano solid support to generate a recyclable heterogeneous catalyst.
Furthermore, use of robust reusable catalyst for cross-coupling reaction prepared from various solid supports such as microporous polymers, activated carbon, clays, magnetic nanoparticles and carbon nanotubes (CNTs) [9, 38-40] could be a suitable method for overcoming the disadvantages of palladium salts pollution. In recent years, carbon nanotubes (CNTs) due to their unique thermal, mechanical and chemical properties have attracted significant interests. They have unique features such as large surface, intrinsic low mass and easy surface modifications which might be favourable candidates as catalysts or supports [41-42]. Considering the fascinating structure of CNTs, such as large capability of loading organic molecules, they can be used as an efficient support for immobilization of DNA and palladium nanoparticles making a unique efficient and recoverable catalyst. The aromatic nucleobases of DNA interact through π–π stacking with carbon surface [43, 44] and stabilize palladium nanoparticles. Several reports in production and structure investigation of DNA-modified carbon materials and their uses in drug delivery, biosensors and high-performance modern materials are available .
These observations motivated us to explore the potential of this catalyst for such cross-coupling reactions. Now, in continuation of our recent investigations on the application of heterogeneous catalytic systems in cross-coupling reactions [8, 46-48], we would like to report the application of Pd/DNA@MWCNTs in the Suzuki and Sonogashira coupling reactions (Scheme 1). Its catalytic applications are rare and, to the best of our knowledge, Suzuki and Sonogashira employing immobilized palladium on DNA-modified CNTs have not been reported previously.
One of the most valid metal catalyzed carbon–carbon cross-coupling reactions of aryl halides with a terminal acetylene is the Sonogashira reactionwhich is widely used in pharmaceuticals and advanced materials [49-56]. The original catalytic system for Sonogashira couplings include the use of a palladium catalyst and a co-catalyst of copper(I) salt. Many different synthetic methods based on copper-free palladium catalysts have been reported for this reaction . However, from sustainability point of view, because of the high cost and toxicity of palladium, using effective heterogonous palladium catalytic systems is much more interesting.
RESULTS AND DISCUSSION
The preparation of Pd/DNA@MWCNTs (Scheme 2) catalyst was performed as explained in experiment section.
Single-stranded salmon testes of DNA (ss-DNA) was loaded on MWCNTs via non-covalent and simple way by mixing them in an aqueous solution, DNA/MWCNTs was formed and then reacted with palladium to obtain Pd/DNA@MWCNTs. The produced catalyst was characterized by several instrumental methods; the results are given in supplemental data. The FT-IR spectrum of the final catalyst was depicted presentation of aromatic nucleobases and phosphate group of DNA (Fig. S1). It can also be monitored by UV−Vis spectroscopy (Fig. S2). The structural properties of the synthesized catalyst was analyzed by XRD (Fig. S3). The palladium content of Pd/DNA@MWCNTs was found to be 0.12 mmolg-1 of the catalyst as measured by ICP-OES analysis. The morphology of the catalyst surface was studied by field emission scanning electron microscopy (FE-SEM) (Fig. 1). A transmission electron microscopy (TEM) image of catalyst revealed nanometer dimensions of the catalyst (Fig. S4). In the outset, for screening experiments, the model reaction was performed using bromobenzene and phenylboronic acid as substrates (Table 1).
It was first carried out without any catalyst, and no product was formed (Table 1, entry 1). In the presence of Pd@MWCNTs (with 5 mol% Pd), as ligand-free systems, appeared to be less active, and produced only trace amounts of product after 4 h (Table 1, entries 2). However, surprisingly, 0.002 g of Pd/DNA@MWCNTs containing 0.024 mol% of Pd showed the highest activity, and afforded the product in 96% yield. The critical effect of ligand on reaction performance was indicated. The effect of bases on the model reaction was investigated. As shown in Table 1, NaHCO3, K2CO3, K3PO4, Na2CO3 and NaOH were tested and NaOH was found as the most effective agent (Table 1, entries 3-7).
Further investigations revealed that the reaction is also affected by the other parameters including the amount of catalyst, substrate and base ratio, solvent and temperature which upon them the optimal reaction conditions should be EtOH: H2O in 1:1 ratio, bromobenzene : phenylbroronic acid in 1:1.2, at 65 °C, and 60 min (Table 1, entries 8-18). Under the optimized conditions, the scope of the reaction regarding to the kind of aryl halides was probed. The results are summarized in Table 2. Various substituents of aryl iodides, aryl bromides and aryl chlorides are transformed into the corresponding products in high to excellent yields. However, no significant different was observed among aryl iodides and aryl bromides substrate. The results show that aryl halides with electron-withdrawing substituents in comparison to electron-donating groups give more yields. Under the optimized reaction conditions assigned; application of this catalyst was also studied in the Sonogashira reaction. Aryl halides with various living groups and substituents converted to their corresponding products in high to excellent yields (Table 3). All of the products are known and characterized by comparing their physical data with those reported in the literature.
Generally, the catalyst was compatible with a wide range of functional groups and exhibited good activity in cross-coupling reactions for the construction of C–C bonds to synthesize derivatives of biphenyl and diphenylethyne using low amounts of palladium and green solvent (ethanol and water) under mild reaction conditions.
Moreover, combination of advantages of heterogeneous catalysts, such as a reasonable catalytic activity, stability and reusability, make this catalyst sufficient for cross-coupling reactions on efficiency, environmental and economic grounds. The template reaction of Suzuki was selected for studying the leaching of catalyst. After 30 minutes, the catalyst was separated and the remaining solution was stirred for 1 h, without catalyst, and no increase in conversion was detected. Moreover, ICP analysis of the remaining solution indicates no Pd in the reaction mixture. These results clearly confirm that this catalyst is heterogeneous in nature and Pd is not leached out from the solid surface of the catalyst during the coupling reaction.
Catalyst reusing is important from economic, environmental and industrial points of view. So, the recyclability of catalyst was checked in model reaction of Suzuki. At the end of reaction, the catalyst was separated, washed with ethanol and acetone and reused. As reported in Table 4, the catalyst was reused seven times with no significant loss of activity. Great recyclability of CNTs supported heterogonous catalyst was also reported previously . All these results demonstrate that the Pd/DNA@MWCNTs give high catalytic activity in cross-coupling reactions with more environmental and economic benefits compared to the wide range of homogenous catalysts reported previously.
This work provides a green and economical method for efficient Suzuki and Sonogashira under mild and aerobic conditions by DNA-modified MWCNTs-based Pd hybrid catalyst. In addition, our catalytic system has significantly low amount of palladium loading and could be reused for seven consecutive cycles without any marked loss of its activity.
General procedure for catalyst preparation
The catalyst (Pd/DNA@MWCNTs) was synthesized through the method which is described: 0.3 g of the as-received MWCNTs was dispersed in 25 mL of piranha (mixture of sulphuric acid 96 wt% and hydrogen peroxide 30 wt% in ratio 70:30) in a 100 mL round bottom flask equipped with a condenser, and dispersion was kept for 5 h.
Next, the dispersion was diluted in water and filtered. Then, the resulting solid was washed up to neutral pH and dried in vacuum at 40°C overnight. The DNA-functionalized MWCNTs were synthesized using Qu’s strategy . The ss-DNA was heated at 95°C for 1 h to obtain the single-stranded DNA. The CO2H-MWCNTs dispersion was mixed with single-stranded DNA (10 ml, 2 mg mL−1), NaBH4 was added (8 μL, 75 wt %; NaBH4/ MWCNTs-O) and the mixture refluxed at 100°C for 1 h. Then, the solution was centrifuged and washed several times with water and dried.
General procedure for Suzuki reaction
In a round-bottomed flask equipped with a mechanical stirring, aryl halide (1.0 mmol), phenylboronic acid (1.2 mmol), NaOH (4.0 equiv.) and 0.002 mg of catalyst (0.024 mol % of Pd) in 3.0 mL H2O : EtOH were stirred for 1 h under air atmosphere at 65. The progress of the reaction was monitored by TLC and GC. After completion of the reaction, the mixture was diluted with dichloromethane and water. The organic layer was washed, dried, concentrated and isolated by chromatography to afford the corresponding products. The products were characterized by comparing their properties, such as m.p, IR, 1H, and 13C NMR spectra with those reported in literature.
General procedure for Sonogashira reaction
In a round-bottom flask equipped with a mechanical stirrer, phenyl acetylene (1.2 mmol), aryl halide (1.0 mmol), catalyst (0.002 mg, 0.024 mol%), and NaOH (4.0 eq.) in H2O:EtOH (3 mL) were stirred under an air atmosphere at 65. The progress of the reaction was monitored by TLC and GC. After the end of the reaction, the mixture was diluted with dichloromethane and water. The organic layer was washed with brine and concentrated under reduced pressure. The product was isolated by column chromatography to give the corresponding products. The products were characterized by comparing their properties, such as m.p, IR, 1H, and 13C NMR spectra with those reported in the literature.
Financial support from the Isfahan University of Technology (IUT), Iran is appreciated. Additional financial support from the Center of Excellence in Sensor and Green Chemistry Research (IUT) is gratefully acknowledged.
CONFLICTS OF INTEREST
The authors declare that they have no conflict of interest.