catalysts

Article Highly Crystallized Pd/Cu Nanoparticles on Activated Carbon: An Efficient Heterogeneous Catalyst for Sonogashira Cross-

Zhen Wei 1, Zunyuan Xie 1,*, Lingxiang Gao 1, Yanyan Wang 1 , Huaming Sun 1, Yajun Jian 1, Guofang Zhang 1, Liwen Xu 1, Jianming Yang 2, Weiqiang Zhang 1,* and Ziwei Gao 1,* 1 Key Laboratory of Applied Surface and Colloid Chemistry MOE, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi’an 710062, China; [email protected] (Z.W.); [email protected] (L.G.); [email protected] (Y.W.); [email protected] (H.S.); [email protected] (Y.J.); [email protected] (G.Z.); [email protected] (L.X.); [email protected] (J.Y.) 2 Xi0an Modern Chemistry Research Institute, Xi’an 710065, China * Correspondence: [email protected] (Z.X.); [email protected] (W.Z.); [email protected] (Z.G.)

 Received: 29 December 2019; Accepted: 27 January 2020; Published: 5 February 2020 

Abstract: In the quest for efficient and recyclable heterogeneous catalysts for Sonogashira coupling reactions, a PEG-OMe (Methoxy Polyene Glycol) - mediated method was developed to immobilize Pd/Cu bimetallic nanoparticles on activated carbon (AC). Catalytic experiments showed that Pd/Cu@AC prepared in a PEG-OMe 500 had the highest activity. The morphology and composition of the catalyst were determined, and the identified crystallized and heterometallic nanoparticles of Pd/Cu were essential for an efficient catalytic cycle. The Pd/Cu@AC catalyst was successfully used in Sonogashira reactions (21 examples) including with aryl bromides as the coupling partner in EtOH at 80–100 ◦C. The catalyst was recycled at least nine times.

Keywords: bimetallic catalyst; activated carbon; solvothermal reduction; Sonogashira coupling reaction

1. Introduction The Csp–Csp2 cross-coupling reaction, also known as a Sonogashira reaction, has gained much attention because are important precursors of various pharmaceuticals, natural products, and organic materials [1–3]. Despite many attempts to develop a transition-metal-catalyzed Sonogashira coupling reaction using a single metal, such as Cu [4,5], Fe [6,7], Ni [8,9], and Au [10–14], most of today’s transition-metal-catalyzed cross-coupling chemistry still relies on a bimetallic catalyst system of Pd and Cu. In the putative catalytic cycle of a Sonogashira reaction, Pd and Cu are responsible for the of a C–X bond and the of an activated triple bond, respectively [15,16]. The Pd/Cu bimetallic catalyst system has excellent properties, probably because of the electron-donating and -accepting characteristics of Cu and Pd, respectively [17,18]. The “Cu effect” represents an adjustment or modification of the catalytic ability in Pd-catalyzed Sonogashira coupling reactions [19–21]. Recently, several Pd/Cu bimetallic nanoparticles (NPs) were loaded on commercially available insoluble organic or inorganic supports as heterogeneous catalysts, and were successfully used in cross-coupling reactions and other chemical reactions [22–39]. Supported bimetallic NP catalysts with minimal or no leaching are necessary for both environmental protection and cost reduction. In other words, it is essential to develop solid-supported Pd/Cu bimetallic NP heterogeneous catalysts using easily available raw materials and simple procedures and with a high catalytic efficiency.

Catalysts 2020, 10, 192; doi:10.3390/catal10020192 www.mdpi.com/journal/catalysts Catalysts 2020, 10, 192 2 of 10

The chemical reductant and solvent of a catalyst system are essential factors to tune the morphology and catalytic activity of heterogeneous Pd catalysts. For a bimetallic Pd/Cu catalyst system, a strong reductant such as sodium borohydride (NaBH4) [34] is used to generate highly uniform Pd/Cu composites. Diverse milder reductants are also used to reduce metal salts, such as DMF [26,28], toluene [36], ethanol [27–30], and morpholine [35]. The solvent of a catalyst system interacts with the reactants, intermediates, and final products, thus significantly affecting the reaction results. The compatible properties of polyols, water, DMF, oleylamine (OAm), and benzene with common reactants make it possible to use them as solvents and structure modulators to synthesize metal NPs. Interestingly, such as DMF, OAm, and polyols can serve as both reductant and solvent [40–42]. Polymeric oxygenated solvents such as dioxane and ethylene glycol (EG) with oxygen and hydroxyl groups can reduce Pd/Cu precursors under thermal conditions [9m]. We hypothesized that the polymeric oxygenated solvent PEG-OMe can be used as both reductant and solvent to fabricate uniform Pd/Cu bimetallic catalysts. To the best of our knowledge, PEG-OMe-mediated fabrication of bimetallic Pd/Cu NPs impregnated on activated carbon (AC) and their heterogeneous catalytic activity in cross-coupling reactions have not been reported. Carbonaceous material such as AC is commercially available, inexpensive, has a large surface area, is stable, and separates easily, and therefore could be an excellent support. Here, we report the synthesis and characterization of a new class of heterogeneous Pd/Cu bimetallic NPs supported on AC. This catalyst showed efficient catalytic activity in Sonogashira cross-coupling reactions under mild reaction conditions, and had high recyclability.

2. Results and Discussion The thermal solvolysis of transition-metal salts in reductive solvents led to the formation of the corresponding NPs. To finely control the composition of Pd/Cu NPs, organic solvents bearing multi-dentated oxygen donors were used to fabricate Pd/Cu@AC catalysts. As shown in Figure1a, the XRD patterns of Pd and Cu were identified by comparing them with that of amorphous AC. Angles of 2θ at 40.1◦, 46.59◦, and 68.11◦ were assigned to Pd (111), (200), and (220) planes, respectively (JCPDS#5-681), and 2θ angles of 43.34◦, 50.46◦, and 73.99◦ correspond to Cu (111), (200), and (220) planes, respectively (JCPDS#4-836) (Figure1b). The reductive solvents significantly a ffected the crystallization of deposited metallic NPs. In ethanol (Cat 1), only Pd0 deposited on the AC support. With the increase in the length of PEG chains such as PEG 300, PEG-OMe 350, and PEG-OMe 500, the loading of Cu0 increased accordingly. Interestingly, the crystallization of supported metallic NPs was also dependent on the PEGylated solvents. The results indicate that the coordination effect of metal ions with PEGylated solvents induced the aggregation and assembly of Pd0 and Cu0, perhaps because the coordination ability of the O atoms of the solvent helped to capture the metal ions. Cat 5 prepared in PEG-OMe 500 showed the highest crystallization of Pd/Cu NPs, with sharper and more intensive peaks than others. The STEM-EDS mapping images (Figure2) of Pd and Cu show that Pd and Cu homogeneously dispersed on the surface of AC support, respectively. The high-resolution TEM (HRTEM) images of Pd/Cu@AC show that the metallic NPs aggregated on the Cu network after the ultrasonic dispersion of the catalyst (Figure3A). The particle-size distribution analysis (Figure3B) indicates that the average diameter of these particles was ~9.3 nm. Three types of lattice with a void image (Figure3C) correspond to the pure Pd (111) (0.2265 nm), Pd (200) (0.1945 nm), and Cu (111) (0.2088 nm) planes. These results indicate the coexistence of Pd and Cu NPs on the surface of AC, and slight variations of d-spacing might result from the heterometallic interaction between Pd and Cu. Catalysts 2020, 10, x FOR PEER REVIEW 3 of 11 Catalysts 2020, 10, x FOR PEER REVIEW 3 of 11 XPS measurements for the surface composition of Pd/Cu@AC revealed the valence state of metal NPs.XPS Figure measurements 4 shows the for XPS the spectrasurface compositionof Pd 3d and of Cu Pd/Cu@AC 2p in Pd/Cu@AC. revealed Thethe valencesplitting state pattern of metal of Pd NPs.3d showedFigure 4 two shows triple the peaksXPS spectra around of 332 Pd to3d 348and eVCu, corresponding2p in Pd/Cu@AC. to theThe Pdsplitting 3d5/2 patternand Pd of3d3/2, Pd 3drespectively. showed two The triple two peaks lower around binding 332 energies to 348 ateV 335, corresponding.4 and 340.7 eVto thewere Pd related 3d5/2 toand metallic Pd 3d3/2, Pd0, respectively.whereas the The other two two lower sets of binding peaks atenergies 336.06 eV,at 335341.36.4 and eV, 340.7and at eV 337.36 were eV, related 342.89 to eV, metallic were related Pd0, whereasto two typesthe other of Pd two oxidant sets of [43]. peaks In at Figure 336.06 3B, eV, the 34 1.36binding eV, andenergy at 337.36 of Cu eV,2p3/2 342.89 peak eV, was were observed related at to932.08 two types eV, and of Pd the oxidant Cu 2p1/2 [43]. peak In Figurecentered 3B, at the 952.01 binding eV was energy attributed of Cu 2p3/2 to Cu0 peak or Cu+. was Theobserved shoulder at 932.08observed eV, andon Cu the 2p Cu peak 2p1/2 can peak be assignedcentered toat CuO.952.01 However, eV was attributed probably to because Cu0 or of Cu+. a small The amountshoulder of observedCatalystsCuO, the2020 on satellite, Cu10, 1922p peakspeak canof CuO be assigned at 940–945 to CuO.eV were However, not observed probably [44]. because of a small amount3 ofof 10 CuO, the satellite peaks of CuO at 940–945 eV were not observed [44].

(a) (b) (a) (b)

Figure 1. ((aa)) XRD XRD patterns patterns of of activated activated carbon carbon (AC) (AC) and and Pd/Cu@AC Pd/Cu@AC catalysts catalysts prepared prepared using different different Figure 1. (a) XRD patterns of activated carbon (AC) and Pd/Cu@AC catalysts prepared using different solvents: (Cat 1)1) EtOH,EtOH, (Cat(Cat 2)2) ethyleneethylene glycol glycol (EG), (EG), (Cat (Cat 3) 3) PEG PEG 300, 300, (Cat (Cat 4) 4) PEG-OMe PEG-OMe 350, 350, and and (Cat (Cat 5) solvents: (Cat 1) EtOH, (Cat 2) ethylene glycol (EG), (Cat 3) PEG 300, (Cat 4) PEG-OMe 350, and (Cat PEG-OMe5) PEG-OMe 500. 500. (*) (*) Di Diffractionffraction of of Pd Pd in in Pd Pd/Cu@AC/Cu@AC and and ((N◆)) di diffractionffraction of of Cu Cu in in PdPd/Cu@AC;/Cu@AC; ((bb)) XRDXRD 5) PEG-OMe 500. (*) Diffraction of Pd in Pd/Cu@AC and (◆) diffraction of Cu in Pd/Cu@AC; (b) XRD patterns of AC and Cat 55 PEG-OMePEG-OMe 500.500. patterns of AC and Cat 5 PEG-OMe 500.

Figure 2. (A) STEM images and STEM-EDS mapping images of (B) Pd/Cu, (C) Pd, and (D) Cu of the

Catalystsas-prepared 2020, 10, Pdx FOR/Cu@AC. PEER REVIEW 4 of 11 Figure 2. (A) STEM images and STEM-EDS mapping images of (B) Pd/Cu, (C) Pd, and (D) Cu of the 2 Figureas-prepared . (A) STEMPd/Cu@AC. images and STEM-EDS mapping images of (B) Pd/Cu, (C) Pd, and (D) Cu of the as-prepared Pd/Cu@AC.

Figure 3. (A) TEM image of Pd/Cu@AC; (B) particle-size distribution evaluated from (A); Figure 3. (A) TEM image of Pd/Cu@AC; (B) particle-size distribution evaluated from (A); (C) high- (C) high-resolution TEM (HRTEM) image of a part of (B). resolution TEM (HRTEM) image of a part of (B).

Figure 4. Core–shell XPS spectra of (A) Pd 3d and (B) Cu 2p.

The activity of Pd/Cu@AC catalysts was evaluated for Sonogashira coupling. Initially, 4- iodotoluene and were selected for the model reaction to test the activity of Cat 1– Cat 5. As shown in Table 1, Cat 1 prepared using EtOH provided an 87% yield, whereas Cat 2 provided less yield (80%) even though an XRD peak for Cu was clearly observed in Figure 1. This indicates that Pd had a major influence on the bimetallic catalysts of Sonogashira cross-coupling reactions. Furthermore, the activity of catalysts produced by polymeric solvents was better than other catalysts. The activities of solvothermally prepared monometallic catalysts, Pd@AC and Cu@AC (both produced in PEG-OMe 500), were also evaluated. They afforded products in 50% and 61% yields, respectively, much less than Pd/Cu@AC (up to 98% yield). The controlled experiments with mixtures of Pd@Ac and Cu@Ac as catalysts afforded a 67% yield, showing the superior activity of heterometallic catalysts. These results clearly indicate that the cooperative of Pd and Cu was essential to achieve a significant improvement in catalytic Csp2–Csp coupling reactions. The best result was obtained in the presence of Cat 5, 2 equiv of K2CO3, and 5 mol% of PPh3 in EtOH and N2 atmosphere at 80 °C for 12 h. Therefore, PEG-OMe 500 is an ideal solvent for the preparation of active Pd/Cu@AC catalysts, providing the highest crystallization of both Pd and Cu.

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XPS measurements for the surface composition of Pd/Cu@AC revealed the valence state of metal NPs. Figure4 shows the XPS spectra of Pd 3d and Cu 2p in Pd /Cu@AC. The splitting pattern of Pd 3d showed two triple peaks around 332 to 348 eV, corresponding to the Pd 3d5/2 and Pd 3d3/2, respectively. The two lower binding energies at 335.4 and 340.7 eV were related to metallic Pd0, whereas the other two sets of peaks at 336.06 eV, 341.36 eV, and at 337.36 eV, 342.89 eV, were related to two types of Pd oxidant [43]. In Figure3B, the binding energy of Cu 2p3 /2 peak was observed at 932.08 eV, and the Cu 2p1/2 peak centered at 952.01 eV was attributed to Cu0 or Cu+. The shoulder observed on Cu 2p peak can beFigure assigned 3. (A to) TEM CuO. image However, of Pd/Cu@AC; probably (B) because particle-size of a distribution small amount evaluated of CuO, from the (A satellite); (C) high- peaks of CuOresolution at 940–945 TEM eVwere (HRTEM) not observed image of a [ 44part]. of (B).

Figure 4. Core–shell XPS spectra of (A) Pd 3d and (B) Cu 2p. Figure 4. Core–shell XPS spectra of (A) Pd 3d and (B) Cu 2p. The activity of Pd/Cu@AC catalysts was evaluated for Sonogashira coupling. Initially, 4-iodotoluene and phenylacetyleneThe activity of werePd/Cu@AC selected catalysts for the model was reactionevaluated to testfor theSonogashira activity of coupling. Cat 1–Cat 5.Initially, As shown 4- iodotoluenein Table1, Cat and 1 preparedphenylacetylene using EtOH were selected provided for an the 87% model yield, reaction whereas to Cattest 2the provided activity lessof Cat yield 1– Cat(80%) 5. evenAs shown though in an Table XRD peak1, Cat for 1 Cuprepared was clearly using observed EtOH provided in Figure 1an. This 87% indicates yield, whereas that Pd hadCat a2 providedmajor influence less yield on the(80%) bimetallic even though catalysts an ofXRD Sonogashira peak for Cu cross-coupling was clearly reactions.observed in Furthermore, Figure 1. This the indicatesactivity of that catalysts Pd had produced a major by influence polymeric on solvents the bimetallic was better catalysts than otherof Sonogashira catalysts. Thecross-coupling activities of reactions.solvothermally Furthermore, prepared the monometallic activity of catalysts catalysts, produced Pd@AC by and polymeric Cu@AC solvents (both produced was better in than PEG-OMe other catalysts.500), were The also activities evaluated. of solvothermally They afforded productsprepared in monometallic 50% and 61% catalysts, yields, respectively, Pd@AC and much Cu@AC less (boththan Pdproduced/Cu@AC in (up PEG-OMe to 98% yield). 500), Thewere controlled also eval experimentsuated. They withafforded mixtures products of Pd@Ac in 50% and and Cu@Ac 61% yields,as catalysts respectively, afforded much a 67% less yield, than showing Pd/Cu@AC the (u superiorp to 98% activity yield). of The heterometallic controlled experiments catalysts. These with mixturesresults clearly of Pd@Ac indicate and that Cu@Ac the cooperative as catalysts catalysis afforded of Pda 67% and yield, Cu was showing essential the to superior achieve a activity significant of heterometallicimprovement incatalysts. catalytic These Csp2–Csp results coupling clearly reactions.indicate that The the best cooperative result was catalysis obtained of in Pd the and presence Cu was of essential to achieve a significant improvement in catalytic Csp2–Csp coupling reactions. The best Cat 5, 2 equiv of K2CO3, and 5 mol% of PPh3 in EtOH and N2 atmosphere at 80 ◦C for 12 h. Therefore, resultPEG-OMe was obtained 500 is an in ideal the presence solvent for of theCat preparation5, 2 equiv ofof K2 activeCO3, and Pd/ Cu@AC5 mol% of catalysts, PPh3 in EtOH providing and N2 the atmospherehighest crystallization at 80 °C for of 12 both h. Therefore, Pd and Cu. PEG-OMe 500 is an ideal solvent for the preparation of active Pd/Cu@ACTo investigate catalysts, the providing scope and the limitations highest crystallization of Pd/Cu@AC catalyst,of both Pd the and Sonogashira Cu. coupling reactions of various aryl iodides/bromides and phenyl/aliphatic catalyzed by Cat 5 were studied under the optimized reaction conditions, and the results are shown in Table2.

CatalystsCatalysts 2020, 202010, x, FOR10, x PEERFOR PEER REVIEW REVIEW 5 of 115 of 11 CatalystsCatalysts 2020, 102020, x ,FOR 10, x PEER FOR PEERREVIEW REVIEW 5 of 115 of 11 CatalystsCatalysts 2020,, 202010,, xx,, FORFOR10,, xx PEERPEERFORFOR PEERPEER REVIEWREVIEW REVIEWREVIEW 5 of 115 of 11 Catalysts 2020, 10, x FOR PEER REVIEW 5 of 11 TableTable 1. Pd/Cu@AC 1. Pd/Cu@AC catalyzed catalyzed cross-coupling cross-coupling of 4-iodotoluene of 4-iodotoluene and phenylacetylene. and phenylacetylene. TableTable 1. Pd/Cu@AC 1. Pd/Cu@AC catalyzed catalyzed cross-coupling cross-coupling of 4-iodotoluene of 4-iodotoluene and phenylacetylene.and phenylacetylene. TableTableTable 1. 1. P Pd/Cu@ACd/Cu@AC 1. Pd/Cu@AC catalyzed catalyzed catalyzed cross-coupling cross-coupling cross-coupling of of 4-iodotoluene 4-iodotoluene of 4-iodotoluene and and phenylacetylene.and phenylacetylene. phenylacetylene. EntryEntry CatalystsCatalysts IsolatedIsolated Yield Yield [%] [%] EntryEntry CatalystsCatalysts IsolatedIsolated Yield Yield [%] [%] EntryEntry1 1 CatalystsCatalystsCat 1Cat 1 IsolatedIsolated87 Yield Yield 87 [%] [%] 1 1 Cat 1Cat 1 87 87 211 12 Cat Cat 21Cat 1 12 808787 8780 2 2 Cat 2Cat 2 80 80 322 23 Cat Cat 32Cat 2 23 838080 8083 3 3 Cat 3Cat 3 83 83 433 34 Cat Cat 43Cat 3 34 898383 8389 4 4 Cat 4Cat 4 89 89 544 45 Cat Cat 54Cat 4 45 988989 8998 5 5 Cat 5Cat 5 98 98 655 56 Pd@AC CatCatPd@AC 5Cat 5 5 509898 98 50 6 6 Pd@ACPd@AC 50 50 766 67 Cu@AC Pd@ACPd@ACCu@ACPd@AC 6150 50 5061 7 7 Cu@ACCu@AC 61 61 877 78 Pd@AC+Cu@ACPd@AC+Cu@AC Cu@ACCu@ACCu@AC 6761 61 6167 8 8 Pd@AC+Cu@ACPd@AC+Cu@AC 67 67 1 1 8 8 Pd@AC+CPd@AC+Cu@ACu@AC 67 67 1Condition:1Condition: 4-iodotoluene 4-iodotoluene (0.58 mmol), (0.5Pd@AC+Cu@AC mmol), phenylacetylene phenylacetylene (0.6 mmol), (0.6 mmol), catalysts 67 catalysts (Pd, 3(Pd, mol%), 3 mol%), K2CO K3 2(1.0CO 3 (1.0 1Condition:11Condition: 4-iodotoluene 4-iodotoluene (0.5 mmol), (0.5 mmol), phenylacetylene phenylacetylene (0.6 mmol), (0.6 mmol), catalysts catalysts (Pd, 3(Pd, mol%), 3 mol%), K2CO K3 2(1.0CO 3 (1.0 1Condition:Condition: 4-iodotoluene 4-iodotoluene (0.5 mmol), (0.5 mmol), phenylacetylene phenylacetylene (0.6 mmol), (0.6 mmol), catalysts catalysts (Pd, 3(Pd, mol%), 3 mol%), K2CO K32 2(1.0(1.0CO3 3 (1.0(1.0 mmol),1Condition:mmol), EtOH EtOH4-iodotoluene (5 mL), (5 mL),PPh3 PPh (5.0(0.5 3 mol%), mmol),(5.0 mol%), 12phenylacetylene h, 1280 h,°C, 80 N °C,2 atmosphere. N (0.62 atmosphere. mmol), catalysts (Pd, 3 mol%), K2CO3 (1.0 mmol),mmol), EtOH EtOH (5 mL), (5 mL),PPh3 PPh(5.0 3mol%), (5.0 mol%), 12 h, 1280 h,°C, 80 N °C,2 atmosphere. N2 atmosphere. mmol),mmol), EtOH EtOH (5 mL), (5 mL),PPh3 PPh (5.0(5.03 3 mol%), mol%), (5.0(5.0 mol%),mol%), 1212 h,h, 12 128080 h, h,°C,°C, 8080 NN °C,°C,2 atmosphere. NN22 atmosphere. mmol), EtOH (5 mL), PPh3 (5.0 mol%), 12 h, 80 °C, N2 atmosphere. To investigateTo investigate the scopethe scope and andlimitations limitations of Pd/Cu@AC of Pd/Cu@AC catalyst, catalyst, the Sonogashirathe Sonogashira coupling coupling To investigateTo investigate the scopethe scope and andlimitations limitations of Pd/Cu@AC of Pd/Cu@AC catalyst, catalyst, the Sonogashirathe Sonogashira coupling coupling reactionsreactionsToTo investigate Toinvestigateof variousinvestigate of various arylthethe scopearyltheiodides/bromidesscope scopeiodides/bromides andand and limitationslimitations limitations and andphenyl/aliphatic ofof Pd/Cu@AC phenyl/aliphaticPd/Cu@ACof Pd/Cu@AC catalyst,acetylenescatalyst, catalyst, acetylenes thethe catalyzed SonogashiratheSonogashira catalyzed Sonogashira by Cat by couplingcoupling 5Cat werecoupling 5 were reactionsreactionsreactionsreactions ofof variousvarious ofof variousvarious arylaryl arylaryliodides/bromidesiodides/bromides iodides/bromidesiodides/bromides andand andphenyl/aliphaticandphenyl/aliphatic phenyl/aliphaticphenyl/aliphatic acetylenesacetylenes acetylenesacetylenes catalyzedcatalyzed catalyzedcatalyzed byby CatCat byby 55CatCat werewere 55 werewere studiedreactionsreactionsreactionsstudied under of of variousunder various of the various optimized the aryl aryl optimized aryliodides/bromides iodides/bromides reactioniodides/bromides reaction conditions, conditions, and and andphenyl/aliphatic phenyl/aliphatic and phenyl/aliphatic theand results the results areacetylenes acetylenes shown areacetylenes shown incatalyzed catalyzed Table incatalyzed Table 2. by by 2.Cat Catby 5Cat 5 were were 5 were studiedstudiedstudiedstudied underunder underunder thethe optimized optimized thethe optimizedoptimized reactionreaction reactionreaction conditions,conditions, conditions,conditions, andand andtheandthe results results thethe resultsresults areare shown shown areare shownshown inin TableTable inin TableTable 2.2. 2.2. studiedstudiedstudied under under under the the optimized theoptimized optimized reaction reaction reaction conditions, conditions, conditions, and and theand the results theresults results are are shown areshown shown in in Table Table in Table 2. 2. 2. The Thecross-couplings cross-couplings of aliphaticof aliphatic or arylor arylalkynes alkynes with with aryl aryliodides iodides afforded afforded products products in in The Thecross-couplings cross-couplings of aliphaticof aliphatic or arylor arylalkynes alkynes with with aryl aryliodides iodides afforded afforded products products in in reasonablereasonableThe cross-couplingsyields yields (Table (Table 2, entriesof 2, aliphatic entries 1–14). 1–14). orBoth aryl Both the alkyneselectron-rich the electron-rich with andaryl -deficientand iodides -deficient arylafforded aryliodides iodidesproducts afforded afforded in reasonableCatalystsreasonablereasonable2020 yields, 10, 192yieldsyields (Table (Table(Table 2, entries 2,2, entriesentries 1–14). 1–14).1–14). Both BothBoth the electron-richthethe electron-rich and and-deficient -deficient aryl aryliodides iodides afforded afforded5 of 10 productsreasonableproducts in yieldsmoderate-to-excellent in moderate-to-excellent (Table 2, entries yields1–14). yields Both(Table (Table the 2, electron-richentries 2, entries 1–6). 1–6). andThe -deficient Thearyl aryliodides aryliodides bearingiodides bearing affordedelectro- electro- productsproducts in moderate-to-excellent in moderate-to-excellent yields yields (Table (Table 2, entries 2, entries 1–6). 1–6). The Thearyl aryliodides iodides bearing bearing electro- electro- donatingproductsdonating groups in moderate-to-excellentgroups such such as –Ome as –Ome (methoxy), (methoxy),yields -Me(Table -Me(methyl) 2, (methyl) entries and –COMeand1–6). –COMe The (O=CCH aryl (O=CCH iodides3) afforded3) afforded bearing satisfactory satisfactoryelectro- donatingdonating groups groups such such as –Ome as –Ome (methoxy), (methoxy), -Me (methyl)-Me (methyl) and –COMeand –COMe (O=CCH (O=CCH3) afforded3) afforded satisfactory satisfactory donatingdonating groups groups such such as –Ome as –Ome (methoxy), (methoxy), -Me -Me(methyl) (methyl) and and–COMe –COMe (O=CCH (O=CCH3) afforded33) afforded satisfactory satisfactory yieldsdonatingyields (Table groups(TableTable 2, entries such 1.2,Pd entries as/Cu@AC 1–4).–Ome 1–4). The catalyzed(methoxy), Thehighest cross-couplinghighest -Me yiel (methyl) dsyiel wereds of 4-iodotoluenewereand provided –COMe provided by and(O=CCH 1-iodonaphthalene phenylacetylene.by 1-iodonaphthalene3) afforded satisfactory and and2- 2- yieldsyields (Table (Table 2, entries 2, entries 1–4). 1–4). The Thehighest highest yiel dsyiel wereds were provided provided by 1-iodonaphthaleneby 1-iodonaphthalene and and2- 2- iodothiophene,yieldsiodothiophene, (Table 2,with entries with 92% 92%and1–4). and99% The 99%yields, highest yields, respecti yiel respectidsvely. werevely. On provided theOn otherthe other byhand, 1-iodonaphthalene hand, phenylalkynes phenylalkynes bearing and bearing 2- iodothiophene,iodothiophene,iodothiophene,iodothiophene, withwith withwith 92%92% Entry92% 92%andand andand99%99% 99% 99%yields,yields, yields,yields, Catalysts respectirespecti respectirespectively.vely. On Isolated theOn otherthe Yield other hand, [%] hand, phenylalkynes phenylalkynes bearing bearing electron-donating/withdrawingiodothiophene,electron-donating/withdrawing with 92% and 99%groups yields,groups provided respecti provided goodvely. good Onresults theresults other(Table (Table hand, 2, entries 2,phenylalkynes entries 9–14). 9–14). Aliphatic bearing Aliphatic electron-donating/withdrawingelectron-donating/withdrawing1 groups groups provided Cat provided 1 good good results results (Table 87 (Table 2, entries 2, entries 9–14). 9–14). Aliphatic Aliphatic acetyleneselectron-donating/withdrawingacetylenes were were also alsosuccessfully successfully groups coupled coupled provided to 4-iodoanisole, to 4-iodoanisole,good results with with(Table yields yields 2,higher entries higher than 9–14). than60%. Aliphatic60%. The The1- 1- acetylenesacetylenes were were also alsosuccessfully successfully2 coupled coupled Cat to 24-iodoanisole, to 4-iodoanisole, with with 80yields yields higher higher than than 60%. 60%. The The1- 1- HexyneacetylenesHexyne provided wereprovided alsoa 96% asuccessfully 96%yield; yield; the 1- thecoupled 1-heptyne toand 4-iodoanisole, 1-octyneand 1- provided withprovided yields84–66% 84–66% higher yields yields than (Table (Table60%. 2, entries The 2, entries 1- HexyneHexyne provided provided a 96% a 96%yield;3 yield; the 1-heptynethe 1-heptyne Cat and 3 and1-octyne 1-octyne provided provided 83 84–66% 84–66% yields yields (Table (Table 2, entries 2, entries 15–17).Hexyne15–17). provided a 96% yield;4 the 1-heptyne Cat 4and 1-octyne provided 89 84–66% yields (Table 2, entries 15–17).15–17). 15–17). 5 Cat 5 98 The above-mentionedThe above-mentioned procedure procedure was wasineffective ineffective for less-active for less-active aryl arylbromides. bromides. Considering Considering the the The Theabove-mentioned above-mentioned procedure6 procedure was Pd@AC wasineffective ineffective for less-active forr less-activeless-active 50 aryl arylarylbromides. bromides.bromides. Considering ConsideringConsidering the thethe effecteffect ofThe ligands, above-mentionedof ligands, six six phosphine7 procedure ligands ligands were was Cu@AC were ineffectiveselected selected (Table fo (Tabler less-active S1). Notably, S1). 61 Notably, aryl Cat bromides. 5 Cat successfully 5 successfully Considering catalyzed catalyzed the effecteffect of ligands, of ligands, six phosphine six phosphine ligands ligands were were selected selected (Table (Table S1). Notably,S1). Notably, Cat 5Cat successfully 5 successfully catalyzed° catalyzed° theeffect cross-couplingthe of cross-coupling ligands, six of phosphinearyl of bromidesaryl8 bromides ligands and Pd@AC were phenyland + phenylselectedCu@AC acetylene (Table using S1). using X-Phos Notably, 67 X-Phos as Catthe as 5ligand thesuccessfully ligand at 100 at °°catalyzed100C for °°C 24 for 24 thethe cross-couplingcross-couplingthethe cross-couplingcross-coupling ofof arylaryl ofof arylarylbromidesbromides bromidesbromides andand andphenylandphenyl phenylphenyl acetylene acetylene using using X-Phos X-Phos as the as ligand the ligand at 100 at °100C for °C 24 for 24 h,the affording h,cross-coupling1 Condition:affording moderate-to-excellent 4-iodotoluene moderate-to-excellent of aryl (0.5bromides mmol), yields phenylacetylene and yields phenyl(Table (Table 2, acetylene (0.6 entries mmol),2, entries 18–21). catalystsusing 18–21). X-Phos (Pd, 3 mol%), as the K COligand(1.0 mmol),at 100 EtOH°C for 24 h, affordingh, affording moderate-to-excellent moderate-to-excellent yields yields (Table (Table 2, entries 2, entries 18–21). 18–21). 2 3 h,h, affording affordingh,(5 affording mL), PPhmoderate-to-excellent moderate-to-excellent3 (5.0 moderate-to-excellent mol%), 12 h, 80 ◦C, yields Nyields2 atmosphere. yields (Table (Table (Table 2, 2, entries entries 2, entries 18–21). 18–21). 18–21). TableTable 2. Sonogashira 2. Sonogashira cross-coupling cross-coupling of aryl of halidesaryl halides and terminal and terminal alkynes alkynes catalyzed catalyzed by Pd/Cu@AC. by Pd/Cu@AC. TableTable 2. Sonogashira 2. Sonogashira cross-coupling cross-coupling of aryl of halidesaryl halides and terminaland terminal alkynes alkynes catalyzed catalyzed by Pd/Cu@AC. by Pd/Cu@AC. TableTableTable 2. 2.2. Sonogashira Sonogashira 2. Sonogashira cross-coupling cross-coupling cross-coupling of of aryl arylaryl of halidesaryl halideshalides halides an andandd terminalan terminalterminald terminal alkynes alkynesalkynes alkynes catalyzed catalyzedcatalyzed catalyzed by byby Pd/Cu@AC. PdPd/Cu@AC. by/Cu@AC. Pd/Cu@AC.

c c c c EntryEntry Ar-X Ar-X R R Yield Yield [%]cc [%]cc Entry Entry Ar-X Ar-X R R Yield Yield [%]cc [%]cc EntryEntry Ar-X Ar-X R R Yield Yield [%] c[%] c c Entry Entry Entry Entry Ar-X Ar-X Ar-X Ar-X R R R R Yield Yield Yield Yield [%][%]c c [%] [%] c EntryEntryEntryEntry Ar-X Ar-X Ar-X Ar-X R R R R Yield Yield Yield Yield [%] [%] [%] [%]c Entry Entry Entry Ar-X Ar-X Ar-X Ar-X RR R R Yield Yield Yield [%] Yield [%] [%] [%]c

1 1 C6H5C 6H5 97 97 12 12 3-ClC3-ClC6H4 6H4 77 77 1 1 C66H55C 66H55 9797 9797 1212 1212 3-ClC3-ClC66H44 66H44 7777 7777 1 11 C6HC5C6H6H5 5 97129797 12 12 3-ClC 3-ClC63-ClCH6H4 4 6H4 7777 77 1 C6H5 97 12 3-ClC6H4 77

2 2 C6H5C 6H5 96 96 13 13 4-ClC4-ClC6H4 6H4 84 84 2 2 C6H5C 6H5 9696 96 1313 13 4-ClC4-ClC6H4 6H4 8484 84 2 22 C6HC5C6H66H555 9613969696 13 1313 4-ClC 4-ClC64-ClCH6H4 4 66H44 8484 8484 2 C6H5 96 13 4-ClC6H4 84

3 3 C6H5C 6H5 90 90 14 14 4-BrC4-BrC6H4 6H4 65 65 3 33 C6HC5C 6 H6H5 5 9090 90 9090 1414 14 1414 4-BrC4-BrC64-BrCH6H4 4 6H 4 656565 6565 3 3 C6H5C66H55 901490 14 4-BrC4-BrC6H4 66H44 65 65 3 C6H5 90 14 4-BrC6H4 65

4 4 C6H5C 6H5 90 90 15 15 n-C6Hn-C13 6H13 66 66 4 44 C6HC5C 6H6H5 5 90 9090 15 15 15 n-Cn-C6H6H13n-C13 6H13 6666 66 4 4 C6H5C 66H55 990015 9090 15 1515 n-C6Hn-C13 66H1313 6666 6666 4 C6H5 90 15 n-C6H13 66

I I Catalysts 2020, 10,I x FORI PEER REVIEW 6 of 11 CatalystsCatalystsCatalysts 2020, 2020202010, x,, FOR1010,,I I xx PEERFORFORII PEER PEERREVIEW REVIEWREVIEW 6 of 1166 ofof 1111 Catalysts5 Catalysts55 2020,, 202010,, xx, , FOR FOR10,, xxI PEER PEERFORFOR PEER PEERREVIEWREVIEWC6H REVIEWREVIEWC5C H 6H5 96 9696 16 16 16 n-Cn-CH5Hn-C11 5H11 84684 of 116 84 of 11 5 5Catalysts 2020, 10, x FOR PEERC6H REVIEW5C 6 6H5 5 96 96 16 16 n-C5 5H11n-C11 5H11 84 684 of 11 5 5 F3C F3C C6H5C 6H5 96 96 16 16 n-C5Hn-C11 5H11 84 84 5 5 F3C F3C C6H5C6H5 961696 16 n-C5Hn-C11 5H11 8484 F3C F3C 5 F3C F3C C6H5 96 16 n-C5H11 84 F3C F3C 6 F3C C6H5 91 17 n-C4H9 96 6 66 C66H55C C 66HH55 9191 9191 1717 1717 n-C44Hnn-C9-C9 44HH99 9696 9696 6 66 C6HC5C H6H5 919117 9191 17 17 17 n-Cn-CH4Hn-C9 4H9 969696 96 6 5 4 9

b 7 C6H5 92 18 C6H5 94 bb bb 7 77 C66H55C C 66HH55 9292 9292 1818b b 1818b C66H55C C 66HH55 9494 9494 7 77 C6HC5C 6H6H5 5 929218 92 92 1818 18 CC6H6H5 5C 6H5 949494 94

Br Br Br b Brr Brr 8 C6H5 99 19 Br Br C6H5 65 bb bb 8 88 C66H55C C 66HH55 9999 9999 1919b b 1919b C66H55C C 66HH55 6565 6565 8 88 C6HC5C 6H6H5 5 999919 99 99 1919 19 Me CC6H6H5 5C 6H5 656565 65 Me MeMe Me Me 4- b 9 4- 4-4- 95 b 20bb C6H5 46 9 99 4-C2H4-5C6H4 95 9595 20bb 20 20b C6H5CC 6HH5 46 4646 9 99 4-C2H5C6H4 95 9595 2020b 20b CC6H6H5 5C 66H55 464646 46 9 C22H55CC2626HH5454C C 66HH44 95 20 6 5C6H5 46 C2H5C26H54C 6H4

b 10 3-MeC6H4 64 21 C6H5 51 bbb bb 10 101010 3-MeC3-MeC3-MeC3-MeC66H44 H66HH44 6464 64 6464 212121b 2121b CCH66H55C C 66HH55 515151 5151 10 10 3-MeC3-MeC6H46 6H4 4 64 64 21 21 C6 6H5 5C 6H5 5151 51 6 4 6 5

≡ Conditions:Conditions: Ar-X Ar-X (0.5 (0.5 mmol), mmol), RC≡ RCCH≡≡ (0.6CH mmol),(0.6 mmol), Cat Conditions:Conditions:Conditions: Ar-X Ar-XAr-X (0.5 mmol),(0.5(0.5 mmol),mmol), RC≡≡ CHRCRC ≡(0.6CHCH mmol),(0.6(0.6 mmol),mmol), Cat CatCat Conditions:CatConditions: 5 (535 (53 mg,Ar-X mg, Pd Ar-X (0.5Pd 3 mol%),3 mmol), (0.5mol%), mmol), K 2RC COK2CO3 CHRC(23 equiv), (2(0.6CH equiv), mmol), (0.6 PPh mmol),PPh3 Cat3 (5 Cat 1111 4-MeC4-MeCH6H4 9797 5 (5355 mg, (53(53 Pdmg,mg, 3 PdPdmol%), 33 mol%),mol%), K2CO KK32 CO(2CO equiv),3 (2(2 equiv),equiv), PPh3 PPh PPh(5 3 (5(5 6 4 5 (535 mg, (53 Pdmg, 3 Pdmol%), 3 mol%), K2CO K32 2(2CO equiv),33 (2 equiv), PPh3 PPh(5 33 (5b 11 1111 4-MeC4-MeC4-MeC66H44 66HH44 9797 9797 (5 mol%),mol%),5 (53 EtOH EtOH mg, (5 Pd (5 mL), 3mL), mol%), 80 80◦2C, °C, 12K32 COh,12 N 3h, 2(2 atmosphere.N equiv),2 atmosphere.3 PPhb 3 (5 bb X- 11 11 4-MeC4-MeC6H4 6H4 97 97 mol%),mol%),mol%), EtOH EtOHEtOH (5 mL), (5(5 mL), mL),80 °C, 8080 12 °C,°C, h, 1212 N 2 h,h, atmosphere. NN2 atmosphere.atmosphere. b X- b X-X- mol%),b mol%), EtOH EtOH (5 mL), (5 mL),80 °C, 80 12 °C, h, c12 N2 h, atmosphere.c N22 atmosphere. b X- b X- mol%),X-Phosmol%), EtOHPhos (5 EtOH mol%), (5(5 mL),mol%), (5 100 mL),80 ◦100°C,C, 80 2412°C, °C, h. h, 24 c 12 NIsolated h.2 h, atmosphere. c NIsolated2 atmosphere. yields. yields. X- X- Phos Phos(5 mol%), (5 mol%), 100 °C,100 24 °C, h. 24 c Isolated h. cc Isolated yields. yields. PhosPhos (5 mol%), (5 mol%), 100 °C,100 24 °C, h. 24 c Isolated h. c IsolatedIsolated yields. yields.yields.

TheReusability cross-couplings of catalysts of aliphatic is essential or aryl alkynes for developing with aryl iodidesheterogeneous afforded catalysts. products In in reasonablethis regard, a ReusabilityReusabilityReusability of catalysts ofof catalystscatalysts is essential isis essentialessential for developingforfor developingdeveloping heterogeneous heterogeneousheterogeneous catalysts. catalysts.catalysts. In this InIn thisregard,this regard,regard, a aa yieldsrecyclingReusability (TableReusability2 test, entriesof was catalysts of 1–14).performed catalysts is Both essential isfor the essential the electron-rich for Pd/Cu@AC developingfor developing and cata -deficientheterogeneouslyst. heterogeneous The aryl catalyst iodides catalysts. was catalysts. a easilyff ordedIn this separatedIn products thisregard, regard, bya in the a recyclingrecyclingrecycling test wastesttest waswasperformed performedperformed for the forfor Pd/Cu@ACthethe Pd/Cu@ACPd/Cu@AC cata lyst.lyst.catacata lyst.lyst.TheThe ThecatalystThecatalyst catalystcatalyst waswas waswaseasilyeasily easilyeasily separatedseparated separatedseparated byby thethe byby thethe recyclingcentrifugationrecycling test wastest wasperformedof the performed reaction for themixt for Pd/Cu@ACtheure. Pd/Cu@AC The isolated cata lyst.cata yields lyst.The were catalystThe measuredcatalyst was waseasily for easilynine separated cycles. separated byAfter the by eight the centrifugationcentrifugationcentrifugation of the ofof reaction thethe reactionreaction mixt mixture.mixt ure.Theure. isolatedTheThe isolatedisolated yields yieldsyields were werewere measured measuredmeasured for nine forfor nineninecycles. cycles.cycles. After AfterAfter eight eighteight centrifugationcycles,centrifugation the of catalyst the of reaction the maintained reaction mixt ure.mixt 99% Theure. yields. isolatedThe isolated In yields the yields 9th were catalytic were measured measured experiment, for nine for ninecycles. the cycles.recycled After After eight catalyst eight cycles,cycles,cycles, the catalystthethe catalystcatalyst maintained maintainedmaintained 99% 99%99%yields. yields.yields. In th InIne 9thththee catalytic9th9th catalyticcatalytic experiment, experiment,experiment, the recycledthethe recycledrecycled catalyst catalystcatalyst cycles,providedcycles, the catalystthe 87% catalyst yield. maintained maintainedThese results 99% 99%yields. clearly yields. In indicate th Ine 9thth thee catalytic9th sustainability catalytic experiment, experiment, of the bimetallicthe recycledthe recycled catalyst. catalyst catalystThe Pd providedprovidedprovided 87% 87%87%yield. yield.yield. These TheseThese results resultsresults clearly clearlyclearly indicate indicateindicate the sustainability thethe sustainabilitysustainability of the ofof bimetallic thethe bimetallicbimetallic catalyst. catalyst.catalyst. The PdTheThe PdPd providedandprovided Cu 87% concentrations 87%yield. yield. These These results in the results clearlysolution clearly indicate were indicate analyzed the sustainability the sustainability during each of the cycleof bimetallic the by bimetallic ICP-MS catalyst. catalyst. (Figure The PdThe5). The Pd and andCuand concentrations CuCu concentrationsconcentrations in the inin solution thethe solutionsolution were werewere analyzed analyzedanalyzed during duringduring each each eachcycle cyclecycle by ICP-MS byby ICP-MSICP-MS (Figure (Figure(Figure 5). The 5).5). TheThe and catalystCuand concentrations Cu leachedconcentrations 0.5–1.3 in the inppm solutionthe of solution Pd were for eachwere analyzed cycle, analyzed duringwhile during the each Cu eachcycle leaching cycle by ICP-MS wasby ICP-MS faster. (Figure During (Figure 5). Thethe 5). firstThe catalystcatalystcatalyst leached leachedleached 0.5–1.3 0.5–1.30.5–1.3 ppm ppmppm of Pd ofof for PdPd each forfor each eachcycle, cycle,cycle, while whilewhile the Cu thethe leaching CuCu leachingleaching was wasfaster.was faster.faster. During DuringDuring the first thethe firstfirst catalystexperiment,catalyst leached leached 0.5–1.3the Cu0.5–1.3 ppm concentration ppm of Pd of for Pd eachwas for each30cycle, ppm, cycle, while and while the sharply Cu the leaching Cu decreased leaching was to wasfaster. <8 faster.ppm During in During the the next first the three first experiment,experiment,experiment, the Cu thethe concentration CuCu concentrationconcentration was waswas30 ppm, 3030 ppm,ppm, and andsharplyand sharplysharply decreased decreaseddecreased to <8 toto ppm <8<8 ppmppm in the inin next thethe nextnextthree threethree experiment,cycles.experiment, Afterthe Cuthe 9th concentration Cu recycle concentration experiment, was was30 ppm, the30 ppm, SEMand sharplyandimage sharply ofdecreased recycled decreased to Pd/Cu@AC <8 to ppm <8 ppm in wasthe in nexttheobtained nextthree three and cycles.cycles.cycles. After AfterAfter 9th recycle9th9th recyclerecycle experiment, experiment,experiment, the SEMthethe SEMSEM image imim ageofage recycled ofof recycledrecycled Pd/Cu@AC Pd/Cu@ACPd/Cu@AC was waswasobtained obtainedobtained and andand cycles.comparedcycles. After After 9th with recycle9th fresh recycle catalyst.experiment, experiment, An obviousthe SEMthe aggregatSEM image im ionofage recycled wasof recycledshown, Pd/Cu@AC andPd/Cu@AC it probably was wasobtained led obtained to the and yield- and comparedcomparedcompared with with withfresh freshfresh catalyst. catalyst.catalyst. An obvious AnAn obviousobvious aggregat aggregataggregationion waswasionion wasshown,wasshown, shown,shown, andand andititand probablyprobably itit probablyprobably ledled toto ledled thethe toto yield- yield- thethe yield-yield- compareddecreasingcompared with withinfresh the fresh catalyst.9th recyclecatalyst. An and obvious An subsequent obvious aggregat aggregat inactivation.ion wasion wasshown, shown, and itand probably it probably led to led the to yield- the yield- decreasingdecreasing in the in 9th the recycle 9th recycle and subsequentand subsequent inactivation. inactivation. decreasingdecreasing in the in 9th the recycle 9th recycle and subsequentand subsequent inactivation. inactivation. The control experiments using 0.5 ppm Pd and 1 ppm Cu afforded less than 41% yields. The TheThecontrol controlcontrol experiments experimentsexperiments using usingusing 0.5 ppm0.50.5 ppmppm Pd andPdPd andand1 ppm 11 ppmppm Cu affordedCuCu affordedafforded less lesslessthan than than41% 41%41%yields. yields.yields. However,The Thecontrol control the experiments Pd andexperiments Cu concentrations using using 0.5 ppm0.5 didppm Pd not andPd clea and1rly ppm change1 ppm Cu affordedinCu the afforded 9th lessrecycle lessthan with than41% yield 41%yields. decline, yields. However,However,However, the Pd thethe and PdPd andCuand concentrations CuCu concentrationsconcentrations did not diddid clea notnot rly cleaclea changerlyrly changechange in the inin 9th thethe recycle 9th9th recyclerecycle with with withyield yieldyield decline, decline,decline, However,rulingHowever, the out Pd the and possibilityPd Cu and concentrations Cu thatconcentrations the leached did not didPd cleaandnotrly cleaCu change wererly change the in catalyticthe in 9th the recycle 9thspecies. recycle with These with yield results yield decline, showeddecline, rulingrulingruling out the outout possibility thethe possibilitypossibility that thatthethat leached thethe leachedleached Pd and PdPd Cuandand were CuCu werewere the catalytic thethe catalyticcatalytic species. species.species. These TheseThese results resultsresults showed showedshowed rulingthatruling out the the out supported possibility the possibility bimetallic that thethat leached Pd/Cuthe leached NPsPd and wePd reCu and responsible were Cu were the catalytic the for catalytic the species.catalytic species. These activity. These results results showed showed that thethat supported the supported bimetallic bimetallic Pd/Cu Pd/Cu NPs NPswere we responsiblere responsible for the for catalytic the catalytic activity. activity. that thatthethat supported thethe supportedsupported bimetallic bimetallicbimetallic Pd/Cu Pd/CuPd/Cu NPs NPsNPswere wewe responsiblerere responsibleresponsible for the forfor catalytic thethe catalyticcatalytic activity. activity.activity.

Catalysts 2020, 10, 192 6 of 10 moderate-to-excellent yields (Table2, entries 1–6). The aryl iodides bearing electro-donating groups such as –Ome (methoxy), -Me (methyl) and –COMe (O=CCH3) afforded satisfactory yields (Table2, entries 1–4). The highest yields were provided by 1-iodonaphthalene and 2-iodothiophene, with 92% and 99% yields, respectively. On the other hand, phenylalkynes bearing electron-donating/withdrawing groups provided good results (Table2, entries 9–14). Aliphatic acetylenes were also successfully coupled to 4-iodoanisole, with yields higher than 60%. The 1- provided a 96% yield; the 1-heptyne and 1-octyne provided 84–66% yields (Table2, entries 15–17). The above-mentioned procedure was ineffective for less-active aryl bromides. Considering the effect of ligands, six phosphine ligands were selected (Table S1). Notably, Cat 5 successfully catalyzed the cross-coupling of aryl bromides and phenyl acetylene using X-Phos as the ligand at 100 ◦C for 24 h, affording moderate-to-excellent yields (Table2, entries 18–21). Reusability of catalysts is essential for developing heterogeneous catalysts. In this regard, a recycling test was performed for the Pd/Cu@AC catalyst. The catalyst was easily separated by the centrifugation of the reaction mixture. The isolated yields were measured for nine cycles. After eight cycles, the catalyst maintained 99% yields. In the 9th catalytic experiment, the recycled catalyst provided 87% yield. These results clearly indicate the sustainability of the bimetallic catalyst. The Pd and Cu concentrations in the solution were analyzed during each cycle by ICP-MS (Figure5). The catalyst leached 0.5–1.3 ppm of Pd for each cycle, while the Cu leaching was faster. During the first experiment, the Cu concentration was 30 ppm, and sharply decreased to <8 ppm in the next three cycles. After 9th recycle experiment, the SEM image of recycled Pd/Cu@AC was obtained and compared with fresh catalyst.Catalysts 2020 An, 10 obvious, x FOR PEER aggregation REVIEW was shown, and it probably led to the yield-decreasing in the7 of 9th 11 recycle and subsequent inactivation.

Figure 5. Recycling experiments using Pd/Cu@AC in the cross-coupling reaction between 4-iodotoluene andFigure phenylacetylene, 5. Recycling andexperiments the ICP-MS using results Pd/Cu@AC of Pd/Cu leaching in thein cross-coupling the solution of 1–9reaction cycles. between The yields 4- wereiodotoluene determined and byphenylacetylene, 1H-NMR. and the ICP-MS results of Pd/Cu leaching in the solution of 1–9 cycles. The yields were determined by 1H-NMR. The control experiments using 0.5 ppm Pd and 1 ppm Cu afforded less than 41% yields. However, the3. Materials Pd and Cu and concentrations Methods did not clearly change in the 9th recycle with yield decline, ruling out the possibility that the leached Pd and Cu were the catalytic species. These results showed that the supported3.1. Preparation bimetallic of Catalysts Pd/Cu NPs were responsible for the catalytic activity.

Bimetallic Pd/Cu@AC catalysts were prepared as follows: typically, Pd(II) acetate (Pd(OAc)2: 63.3 mg, 0.28 mmol), Cu(II) nitrate trihydrate (Cu(NO3)2•3H2O: 68.1 mg, 0.28 mmol), and AC (1 g) were dispersed in 30 mL of different solvents: EtOH (Cat 1), EG (Cat 2), PEG 300 (Cat 3), PEG-OMe 350 (Cat 4), and PEG-OMe 500 (Cat 5). Then, the mixture was heated in a Teflon-lined stainless-steel autoclave at 170 °C for 24 h. The catalyst was separated by decantation, washed with EtOH (30 mL, 5 times), and dried at 50 °C in an electrothermostatic blast oven.

3.2. General Procedure for Sonogashira Reactions

In a Schlenk tube, K2CO3 (1.0 mmol, 2 equiv), catalyst (3 mol% Pd), and ligand (5 mol% PPh3 or X-Phos) were added under N2 atmosphere. EtOH (5 mL) was transferred using a cannula. After adding the terminal (0.6 mmol, 1.2 equiv) and aryl halide (0.5 mmol, 1 equiv), the resulting mixture was stirred under N2 atmosphere at 80 °C for 12 h, or at 100 °C for 24 h. The products were isolated via flash chromatography with a selected eluent, such as Hexane: dichloromethane. For instance, after the reaction finished, the solid silica-gel was added into reaction mixture. The solvent was removed under vacuum. The solid residue was loaded on the column filled with a silica gel of 200 mesh. A fraction of the product band was collected. The pure product was contained after the eluent was removed. The pure product was characterized by 1HNMR and 13NMR [26].

3.3. Recycling Experiments After each catalytic reaction, the catalyst was separated by centrifugation and filtration, washed with H2O (3 mL) and EtOH (9 mL, 3 times), and dried at 50 °C for further recycling experiments. The catalytic experiments using the recycled catalysts were carried out under the same conditions as those of general procedure for the Sonogashira reactions.

Catalysts 2020, 10, 192 7 of 10

3. Materials and Methods

3.1. Preparation of Catalysts

Bimetallic Pd/Cu@AC catalysts were prepared as follows: typically, Pd(II) acetate (Pd(OAc)2: 63.3 mg, 0.28 mmol), Cu(II) nitrate trihydrate (Cu(NO ) 3H O: 68.1 mg, 0.28 mmol), and AC (1 g) 3 2• 2 were dispersed in 30 mL of different solvents: EtOH (Cat 1), EG (Cat 2), PEG 300 (Cat 3), PEG-OMe 350 (Cat 4), and PEG-OMe 500 (Cat 5). Then, the mixture was heated in a Teflon-lined stainless-steel autoclave at 170 ◦C for 24 h. The catalyst was separated by decantation, washed with EtOH (30 mL, 5 times), and dried at 50 ◦C in an electrothermostatic blast oven.

3.2. General Procedure for Sonogashira Reactions

In a Schlenk tube, K2CO3 (1.0 mmol, 2 equiv), catalyst (3 mol% Pd), and ligand (5 mol% PPh3 or X-Phos) were added under N2 atmosphere. EtOH (5 mL) was transferred using a cannula. After adding the terminal alkyne (0.6 mmol, 1.2 equiv) and aryl halide (0.5 mmol, 1 equiv), the resulting mixture was stirred under N2 atmosphere at 80 ◦C for 12 h, or at 100 ◦C for 24 h. The products were isolated via flash chromatography with a selected eluent, such as Hexane: dichloromethane. For instance, after the reaction finished, the solid silica-gel was added into reaction mixture. The solvent was removed under vacuum. The solid residue was loaded on the column filled with a silica gel of 200 mesh. A fraction of the product band was collected. The pure product was contained after the eluent was removed. The pure product was characterized by 1HNMR and 13NMR [26].

3.3. Recycling Experiments After each catalytic reaction, the catalyst was separated by centrifugation and filtration, washed with H2O (3 mL) and EtOH (9 mL, 3 times), and dried at 50 ◦C for further recycling experiments. The catalytic experiments using the recycled catalysts were carried out under the same conditions as those of general procedure for the Sonogashira reactions.

4. Conclusions A facile PEG-OMe-mediated solvothermal method was developed to fabricate highly crystallized Pd/Cu NP catalysts. Pd/Cu@AC (Cat 5) was prepared by supporting Pd/Cu based bimetallic NPs on AC using PEG-OMe 500. Cat 5 showed the best activity and recyclability in Sonogashira cross-coupling reactions. The catalyst was compatible with diverse aryl iodides and bromides, with moderate-excellent yields, and could be recycled at least nine times. The recyclability was consistent with the low-ppm leaching of supported metallic compositions. The AC-supported catalysts have several advantages, such as their recyclability, easy operation, and environmental friendliness, over conventional Pd catalysts. The Pd/Cu@AC catalysts may find applications in various other C-C coupling reactions.

Supplementary Materials: The following are available online at http://www.mdpi.com/2073-4344/10/2/192/s1, Figure S1: The XRD patterns of the activated carbon (AC) and Pd/Cu@AC Cat 5; Table S1: The reaction results between 4-Bromoanisole and phenylacetylene; NMR spectra data for the Sonogashira-cross coupling products. Author Contributions: Conceptualization, Z.X., W.Z., and Z.G.; methodology, Z.W. and Z.X.; validation, Z.W., Y.W., J.Y., and H.S.; formal analysis, G.Z., W.Z., and L.X.; investigation, Z.W.; writing—original draft preparation, Z.W.; writing—review and editing, Z.X., L.G., and Y.J.; supervision, L.X., W.Z., and Z.G.; project administration, W.Z. All authors have read and agreed to the published version of the manuscript. Funding: This research was supported by grants from National Natural Science Foundation of China (21771122, 21602129, 21571121), the 111 Project (B14041), Key Research and Development Project of Shaanxi Science and Technology Department (2017SF-064, 2017GY-124), Fundamental Research Funds for the Central Universities under Grant (GK201903026), and Projects of Xi0an Modern Institute of Chemistry (204-J-2018-315-4/6, 204-J-2019-0387-3/6-6). Conflicts of Interest: The authors declare no conflicts of interest. Catalysts 2020, 10, 192 8 of 10

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