Ag, Au and ZrO2@reduced graphene oxide nanocomposites; Pd free catalysis of suzuki-miyaura coupling reactions

Suzuki coupling is a widely used, well-studied and versatile method in synthetic chemistry for development of C–C bonds where palladium-based catalysts have been used extensively in the reaction to date. We report a Suzuki-cross-coupling reaction for C–C bonds formation between aryl halides and phenylboronic acid by using Metal/metal oxide@Reduced graphene oxide nanocomposites being efficient, simple and cost-effective. In this work, plant mediated synthesis of silver, gold and zirconia nanoparticles doped Reduced Graphene Oxide nanocomposites is reported where 30 mg of each of the catalysts resulted in C-C bond formation achieving percentage yield comparable to palladium-based catalyst used as standard in series of reactions, attaining highest yield with silver based catalyst. The catalysts demonstrated high catalytic activity over three cycles of recycling with no loss. Bromoaryl and phenylboronic acid are coupled together by the increased surface area of the reduced graphene oxide substrate, which also exhibits enhanced reactivity toward other chemical reactions. XRD, FTIR and UV–vis analyses were used to describe the synthesized catalyst. Using the devised technique, various substituted aryl halides have been used successfully with modest to high yields of the desired biphenyls.


Introduction
In all types of chemical reactions, formation and breaking of chemical bonds takes place. Cross coupling, one of the auspicious methods for single bond formation between two carbon atoms, even if it is a difficult process, has been researched in recent decades [1]. Heck, Negishi and Suzuki's invention of Pd catalyzed C-C bond formation has greatly influenced synthetic processes and has found numerous uses in targeted synthesis. Due to the relatively benign reaction conditions, they are widely used in synthetic applications. Numerous natural products and other compounds with complex chemical structures that are physiologically active have been synthesized using these three cross-coupling reactions. They are also utilized in the pharmaceutical and fine chemical industries. Among cross coupling reactions, Suzuki coupling is most significant class of C-C bond making reactions, the transition metal-based coupling reactions that have changed and advanced the years to provide trust able good result. In Suzuki reactions two partners i.e., boronic acid and organohalide are coupled in presence of palladium [2,3]. Reactions involving C-C bond formation using Pd as catalyst have been extensively investigated [4] and effects of various organic and inorganic bases, ligands and solvent systems have been explored to make catalysis more responsive and eco-friendly for coupling reactions [5]. However, use of Pd catalysts is associated with low efficiency in separation limit, metal leaching and inferior selectivity and owing to Any further distribution of this work must maintain attribution to the author(s) and the title of the work, journal citation and DOI. these limitations lots of efforts have been made to modify Pd based catalysts [6,7]. In Suzuki coupling, in addition to palladium other metals like rhodium, nickel and platinum has also been used [8].
Graphene is gaining great interest for researchers due to its particular surface, good thermal, electrical and mechanical properties [9], particularly as a host for metal nanoparticles including palladium, titanium, zinc platinum, gold, tin, etc Graphene-based materials are capable candidates due to their distinctive properties like their large particular surface area, exceptional physical, mechanical and chemical properties, chemical versatility, tenability and combining ability with their solutions. Various attempts were made to introduce Pd nanoparticles on graphene support [10,11]. In a related research, Pd-graphene hybrids were prepared and evaluated in both aqueous and aerobic settings to speed up the coupling [12]. Wang et al, (2013), prepared the heterocyclic carbinepalladium complex (NHC-Pd 2+ ) on the surface of graphene oxide (GO) as a successful catalyst for Suzuki Miyaura coupling reactions. Pd/GO and Pd/RGO were shown to be more active than other commercially available Pd catalysts such as Pd on charcoal [13,14]. Similarly, Pd-Carbon nanotube exhibited significant catalytic activity for discussed reactions [15]. However, higher energy requirements as well as being expensive, Palladium catalysts leave room for further research to develop more sustainable catalysts for the Suzuki coupling reaction [16].
Multiple efforts have been carried out in quest of more sustainable catalysts e.g., Au/GO nanocomposites for Suzuki-Miyaura coupling have been synthesized yielding high corresponding reaction products [17]. In another report, copper (II) Schiff base Cu-NH 2 -GO) composite embedded onto graphene oxide was examined in Suzuki Miyuara coupling reactions where composite showed high performance, high conversion, safer reuse and easy recovery [18]. Catalytic activity of silver nanoparticles was also evaluated and concluded that it could be boosted by properly monitoring the size and shape of the silver nanoparticles [19]. In a subsequent attempt, good efficiency of silver nanoparticles doped TiO 2 nanoparticles as catalyst has been demonstrated in the coupling of bromoaryl with phenylboronic acid [20]. Some other metals based catalysts have also been explored for Suzuki-Miyaura coupling e.g., Nickel catalyzed couplings under base free conditions, by using various aromatic and heteroaromatic aldehydes was investigated where catalytic C-C bond formation proceeds smoothly which provides useful synthetic strategy [21,22]. In quest of searching Pd free catalysts, GO immobilized copper was also synthesized and its catalytic potential for coupling was evaluated [23].
The present study describes the use of various metals loaded on reduced graphene oxide and their comparison thereof to find the best possible Pd free solution for C-C coupling. The aq. concentration of flowers from the medicinal plant Aerva javanica, a member of the genus Aerva and family Amaranthaceae was used to create all of the nanocomposites [24]. It is well known that A. javanica is rich in flavonoids [25], polyphenolics, and sugars [26] serving as reducing as well as stabilizing agents for nanocomposite fabrication. In the current investigation, the plant successfully assisted in the reduction of metal and graphene oxide in one step. This methodology is most suitable and practical for the production of required biphenyls under benign operational conditions since it allows for higher product yields.

Preparation of reduced graphene oxide (RGO)
Flowers of Aerva javanica were collected from Pakistan's desert area (Cholistan). The flowers were dried in the shade; 10 g of dried flowers were steeped in 100 ml of deionized water and heated for one hour not exceeding 45°C. After cooling at room temperature, the concentrate was filtered and centrifuged to get rid of any suspended particles and stored at 4°C for future use.
For synthesis of graphite oxide from graphite, modified Hummers Method was used. In three neck flask 2 g of graphite, 1.75 g NaNO 3 and 150 ml H 2 SO 4 were added and mixed for 2 h in ice water. 9 g of KMnO 4 was gradually added to this reaction mixture with constant stirring. Reaction mixture was left for 5 days at room temperature subsequently followed by addition of 200 ml H 2 SO 4 and further mixing for 2 h. Then 6 g hydrogen peroxide aqueous solution was added to reaction mixture and was further mixed for 2 h. Resulting product was washed afterwards with 3% H 2 SO 4 and 0.5% H 2 O 2 . After washing, the dispersion was centrifuged in deionized water for an hour at a speed of 4000 rpm. After several more washes with de-ionized water, brown-black graphite oxide dispersion was finally produced. To prepare graphene oxide from graphite oxide, initially graphite oxide was distributed in distilled water and then the mixture was sonicated for 30 min to get graphene oxide sheets. Aqueous plant extract was then added to it (density = 0.1 g ml −1 ), and the entire dispersion was left to stir at 98°C for a day. The end result was a dark powdered reduced graphene oxide. To get rid of extra plant concentrate, it was rinsed repeatedly with distilled water. After being re-dispersed in water using sonication, the mixture was centrifuged for 30 min at 4000 rpm to separate the desired product. A graphical representation of experimental procedure is shown in figure 1.

Synthesis of metal/metal oxide @reduced graphene oxide nano composite (MRGO)
The reported methodology was used to prepare nanocomposite [24]. In a general procedure 170 mg RGO, 0.5 mM of Palladium (II) chloride, Zirconium (IV) chloride, Gold (IV) chloride, and Silver nitrate were used for preparation of nano composites i.e., Pd@RGO, ZrO 2 @ RGO, Au@RGO and Ag@RGO respectively. RGO dispersion in water was made through sonication, afterwards this reduced graphene oxide suspension and aqueous extract of A. javanica was added along with 0.5 mM of respective metal salt followed by stirring of mixture at 90°C for 24 h. The resulting black powdered product underwent washing, 12000 rpm centrifugation and 80°C drying.

Evaluation of catalytic activity of the nanocomposite catalysts for coupling reactions
In round bottom flask, ethyl alcohol (15 ml), alkyl halide (2 mmol), phenyl boronic acids (2 mmol) and sodium carbonate (2 mmol) were added and reaction mixture was constantly stirred with heating. After an hour, when temperature of reaction mixture reached to 90°C, catalyst (30-60 mg) was added and then stirred for almost 18 h while observing reaction by thin layer chromatography. After 18 h, rotary evaporator was used to remove solvent from reaction mixture and chloroform extraction was performed for reaction concentrate where aqueous and organic layers were separated with the help of separating funnel. By using sodium sulphate organic layer was dried, after evaporation impure product was refined by column chromatography. Centrifugal separation of catalyst was performed, which was then cleaned, dried and used again.

Results and discussion
3.1. Characterization of synthesized Ag@RGO, Au@RGO, ZrO 2 @RGO nanocomposites In FTIR spectra of Ag@RGO nanocomposite, presented in figure 2, the peaks at 1537 cm −1 and 1030 cm −1 have been assigned to C=C and C-O spreading vibrations respectively. A peak at 1334 cm −1 is due to C-O vibrations of carboxylic group [27]. In FTIR spectrum of ZrO 2 @RGO, a broad peak at 3227 cm −1 is dedicated to the stretching vibration of O-H due to adsorbed water molecules, while a peak at 1634cm −1 is recognized as the bending vibration of water molecules. In the area below 600 cm −1 , specific peaks at 503, and 496 cm −1 are due to Zr-O stretching vibrations [28]. In ATR spectrophotometric measurements of Au@RGO, the bands at 1044 cm −1 , 1363 cm −1 are dedicated to the C-O of alkoxy and carboxylic group respectively, whereas, peak at 1618 cm −1 is assigned to C=C (aromatic ring) vibrations. The wide band at 3209 cm −1 attributed to O-H stretching on the surface of RGO [29].
The UV absorption spectra of RGO displayed band at 238 nm. ZrO 2 @RGO nanocomposites showed an absorption peak at 230 nm and a peak at around 268 nm, indicating that the network in ZrO 2 @RGO nanocomposites has been partially restored [28]. The UV absorption spectra of Ag@RGO, absorption bands at 429 nm correlate to SPR band of Ag while band for RGO appeared at and 255 nm, independently demonstrating Ag nanoparticle deposition on the exterior of RGO sheets. Au@RGO revealed an absorption peak at 252nm for RGO and 513 nm for Au nanoparticles, demonstrating the formation of gold particles on the surface of RGO. At 269 nm, ZrO 2 @RGO showed a distinctive SPR band ( figure 3).
XRD pattern of GO along with prepared catalysts is shown in figure 4, peak at 2θ = 9.1°is showing presence of graphene oxide while a broad shoulder at 2θ = 22.1°due to reduced GO. In Ag@RGO crystal structure of composite shows the main peaks at 2θ values of 25.8°linking to the RGO and 38.19°, 44.37°, 64.56°and 77.47°d egree consistent to the (111), (200), (220) and (311) planes consistently, which shows that structure of AgNPs is face centered cubic when compared to JCPDS file no: 04-0783. Due to presence of organic compounds present in plant extract which was used for the synthesis of nanocomposites, few unpredicted peaks appeared at 32.27 and 46.14, in green synthesis of nano particle presence of such unknown crystal structures have formerly been described [30].Crystalline size of particle was predicted 14 nm by using Debye-Scherer's formula. XRD pattern of Au@RGO showed crests at 2θ values of nearly 38.16°, 44.41°, 64.54°, and 77.51°, which were fixed to the

Application of prepared catalysts in suzuki miyaura (SM) coupling reaction
By utilizing sodium carbonate as a base, coupling reaction was done at 90°C in ethanol, where analysis was started by evaluating Pd based catalyst in series of reactions of different derivatives of halobenzene and phenylboronic acid to check the efficiency of prepared catalysts in SM coupling reactions. A general reaction procedure is given in figure 5 while reaction products along with experimental yield and reaction conditions are summarized in table 1.
As stated, primary investigations were started with bromobenzaldehyde and phenylboronic acid as coupling partner in presence of PdCl 2 as a catalyst (0.2 mM) which, after systematically evaluating the reaction parameters (figure 5), afforded biphenyl in 85% yield in presence of ethanol as a solvent. Efforts under comparatively lower temperature contributed moderate yield, while higher yield i.e., 91% was attained by using K 2 CO 3 as base. In quest of finding more catalysts for coupling reactions, a number of prepared catalysts were evaluated for their catalytic potential in C-C bond formation. Fortunately, among prepared catalysts, Ag@RGO, Au@RGO and ZrO 2 @RGO were found successful as catalyst in preparation of biphenyl. The coupling occurred with satisfactory results comparable to Pd@RGO catalyst (45%-55% yield) under optimized experimental conditions in model reaction carried out with bromobenzaldehyde (2 mM) and phenylboronic acid (2 mM) as coupling partner in presence of Pd@RGO catalyst (25 mg) and Na 2 CO 3 base. Among the three catalysts, catalytic potential of silver-based catalyst was found to be higher than Zirconia based catalyst which was subsequently found better  than gold-based catalyst yielding 41%, 37% and 32% respectively. Lower yields of RGO based Pd catalyst may be associated with decreased wt % of Pd in nanocomposite as compared to PdCl 2 .
Under optimized conditions, another series of reactions was carried out with reactants 4-bromobenzaldehyde and phenyl boronic acids with Pd@RGO, Ag@RGO, ZrO 2 @RGO and Au@RGO catalysts yielding [1,1'-biphenyl]-4-carbaldehyde in 44, 39, 35 and 26% yield respectively indicating comparable catalytic potential of Pd and Ag based catalytic system. In another set of reactions carried out with 4-chloroaniline and phenyl boronic acids, keeping all reaction conditions same with Pd@RGO, Ag@RGO, ZrO 2 @RGO and Au@RGO catalysts yielded [1,1'-biphenyl]-4-amine in satisfactory yields. It was observed that electron withdrawing group on phenyl boronic acid facilitated the reaction while increasing the percentage yield i.e., [1,1'-biphenyl]-4,4'-dicarbaldehyde was attained in high yields in reactions carried out by using 4-bromobenzaldehyde and 4-formyl phenylboronic acid as reactants under same experimental conditions. Encouraged by the results, the scope of the reaction was studied for numerous aryl halides and various boranes as coupling partners and it was observed that by using our catalytic system, boosting yields of biaryls were achieved with various combinations of substituted coupling partners. Recyclability test of Ag@RGO nanocomposites catalysts was done to check the ability of catalysts for further use which was unchanged up to three consecutive uses.
PdCl 2 is used as catalyst for C-C bond formation in these coupling reactions. Pd fits to transition metals which have d-10 system; we assumed that alternative metals of same cluster and neighboring groups in transition metals may additionally be utilized in C-C bond formation. Unfortunately, with metal salts we could not get encouraging results, as silver nitrate with similar reaction settings; improvement of reaction conditions would possibly provide positive results. Amazingly encouraging yields of biphenyl was obtained by using silver nanocomposite with reduced graphene oxide. Throughout the catalysts screening, obviously PdCl 2 gave glorious yield in all C-C bond formation making biphenyl, derivatives in outstanding yields followed by Pd@RGO that performed well with the yield in the range of (40%-55%), this catalyst has formerly been stated in Suzuki couplings [31]. It is pertinent to mention here that the difference in yield by using PdCl 2 and Pd@RGO catalysts is associated to % weight of Pd in both catalysts 60% in palladium chloride 40% in Pd@RGO. Among different prepared catalysts we obtained positive results with three metal composites i.e., Ag@RGO, Au@RGO and Zr@RGO yielded biphenyls. However, yields achieved for Au@RGO were lesser but consequences were inspiring for further two catalysts i.e., Ag@RGO and ZrO 2 @RGO. A comparative description of reaction yields of different biphenyls by using various prepared catalysts is shown in figure 6. Some other nanocomposites of RGO like, Yb 2 O 3 @RGO, Cr@RGO and Bi 2 O 3 @RGO were also checked in coupling reactions but these catalysts were found inactive. As shown in table 1, different types of aryl bromides and aryl boronic acids were transformed into the consistent products. It had been ascertained that aryl bromides bearing different substituents e.g., amino, acetyl group and formyl on the arene rings were all well-matched with the reaction conditions, affording the consistent biphenyls. Higher yields were earned with formyl substitution in any of starting material. Structures of manufactured biphenyls were established by melting points and comparison of spectroscopic analysis with literature.

Catalyst recyclability
By choosing the coupling of phenylboronic acid with bromobenzene, the reusability of the Ag@RGO catalytic system was studied. Centrifugation was used to remove the catalyst from the reaction mixture. The residue was then cleaned with ethyl alcohol and dried in an extremely hot air oven so that it could be employed in another catalytic cycle. Even after three successive cycles, a substantial reduction in the catalytic activity of the recycled catalyst was not seen.

Conclusion
In summary, Pd free catalytic systems were fabricated via environmentally benign procedure. Ag@RGO, Au@RGO and ZrO 2 @RGO were found active catalysts for C-C coupling among a number of catalysts. Biphenyls have successfully been synthesized by using RGO based catalysts, where Ag@RGO was found to be an effective catalyst among other prepared catalysts that could be recycled three times without suffering any reduction in product yield.