Turkish Journal of Chemistry Turk J Chem (2015) 39: 1265 { 1278 http://journals.tubitak.gov.tr/chem/ ⃝c TU(cid:127)BI_TAK Research Article doi:10.3906/kim-1505-34 Synthesis, characterization, and microwave-assisted catalytic activity in Heck, Suzuki, Sonogashira, and Buchwald{Hartwig cross-coupling reactions of novel benzimidazole salts bearing N-phthalimidoethyl and benzyl moieties Hasan KU(cid:127)C(cid:24)U(cid:127)KBAY1;(cid:3), U(cid:127)lku(cid:127) YILMAZ1;2, Kemal YAVUZ1, Nesrin BUG(cid:21)DAY1 1Department of Chemistry, Faculty of Science and Arts, I_n(cid:127)onu(cid:127) University, Malatya, Turkey 2Battalgazi Vocational School, I_no(cid:127)nu(cid:127) University, Malatya, Turkey Received: 14.05.2015 (cid:15) Accepted/Published Online: 07.08.2015 (cid:15) Printed: 25.12.2015 Abstract:Five novel benzimidazole salts (1{5) having N-phthalimidoethyl and 4-substituted benzyl were synthesized andidenti(cid:12)edby 1HNMR, 13CNMR,andIRspectroscopicmethodsandmicroanalysis. Amixtureofthebenzimidazole salts(1{5),Pd(OAc) ,andK CO inDMF-H Ocatalyzed,inhighyield,theSuzuki{MiyauraandtheHeck{Mizoroki 2 2 3 2 cross-coupling reactions assisted by microwave irradiation in 5 min. The novel benzimidazole salts (1{5), Pd(OAc) , 2 Cs CO ,PEG,andCunanoparticlescatalyzed,inhighyield,theSonogashiracouplingreactionpromotedbymicrowave 2 3 irradiation in 10 min. The same benzimidazole salts (1{5), Pd(OAc) , Cs CO , and TBAB catalyzed, in moderate 2 2 3 or low yield, the Buchwald{Hartwig reaction assisted by microwave irradiation in 60 min. The efficiency of the catalyst systeminthesefourreactionswasdiscussedaswellastheelectron-releasingandwithdrawingsubstituenteffectsonthe benzimidazole ligands. Key words: Heck{Mizoroki coupling, Suzuki{Miyaura coupling, Sonogashira coupling, Buchwald{Hartwig coupling, benzimidazole derivatives, catalyzes, N-heterocyclic carbene, microwave 1. Introduction Metal-catalyzed C{C and C{heteroatom bond formations are some of the most attractive methods in synthetic organic chemistry. Applications of these types of reactions have been continuously increasing and they have become a standard synthesis method for synthetic chemists. Several transition metal complexes including Pd, Cu, Fe, Ni, and Zn are employed for these types of bond-forming reactions.1;2 Among all metals evaluated for such cross-coupling reactions, palladium has been a common metal due to its reactivity and selectivity, and tolerance of a wide range of functional groups on both coupling partners.3 The catalytic activities of metal atoms also strictly depend on coordinated ligands. In general, phosphine and N-heterocyclic carbenes are used as efficient ligands. However, N-heterocyclic carbene ligands seem to be more appropriate due to their air and moisture resistances, stabilities at high temperature, and their lower toxicity than phosphine-based ligands.4;5 Conventionally, organic reactions are carried out by thermal heating, which is a rather slow and inefficient method. In order to overcome this problem, microwave irradiation can be used instead of thermal heating. Furthermore,atthebeginningofthiscentury,greenchemistryattractedconsiderableinterestinthedevelopment of environmentally benign routes to numerous materials.6 Among these routes, microwave irradiation has (cid:3)Correspondence: [email protected] DedicatedtoProfDrMetinBalc(cid:16)ontheoccasionofhisretirement. 1265 KU(cid:127)C(cid:24)U(cid:127)KBAY et al./Turk J Chem become an effective tool in organic syntheses. Using metal catalysts in conjunction with microwaves may have signi(cid:12)cant advantages over classical heating methods since the inverted temperature gradient under microwave conditions may lead to increased lifetime of the catalyst, preventing wall effects.7;8 Despitetheextensiveliterature, eitheronconventionalheatingoronmicrowavepromotedcross-coupling reactions individually or together with the Suzuki and the Heck reactions,9(cid:0)36 there are limited examples that usetheMizoroki{Heck, theSuzuki{Miyaura, theSonogashira, andtheBuchwald{Hartwigreactionstogetherin one study, except for some review reports37(cid:0)41 and books.42;43 Herein,wedescribethesynthesisofnewbenzimidazoliumsalts(1{5)containing3-(2-(N-phthalimido)ethyl and 1-substituted benzyl moieties. The compounds were fully characterized by elemental analysis, and IR, 13C NMR, and 1H NMR spectroscopy. The microwave-assisted catalytic activity of N-heterocyclic carbene com- plexesofpalladiumwasdetermined,generatedinsitufromthenewbenzimidazoliumsaltsinthepresenceofan appropriate base. Owing to their wide applications in C{C and C{N bond formations in organic synthesis, N- heterocycliccarbenescontainingimidazoleorbenzimidazolemoietieshavebecomeanimportanttoolincoupling reactions. In contrast to the extensive study of imidazole containing N-heterocyclic carbene complexes,44(cid:0)49 benzimidazole containing carbene complexes have been studied less. The present study was planned in order to explore the effectiveness of in situ formed N-heterocyclic carbene complexes containing novel benzimidazole ligands in cross coupling reactions. The catalytic efficiency of the catalyst system in these four popular reac- tions, namely the Mizoroki{Heck, the Suzuki{Miyaura, the Sonogashira, and the Buchwald{Hartwig reaction, as well as electron-releasing and withdrawing substituent effects on the benzimidazole ligands was discussed. 2. Results and discussion NewbenzimidazoliumbromidesaltscontainingbenzylandN-phthalimidoethyl(1{5)weresynthesizedfromthe treatment of 1-benzylbenzimidazole with N-(2-bromoethyl)phthalimide in re(cid:13)uxing DMF with good yields of 68%{80%. The synthesis of the benzimidazolium salts 1{5 is summarized in the Scheme. The structures of the benzimidazoliumsalts(1{5)wereelucidatedbyIR, 1HNMR, 13CNMR,andmicroanalyses. Allspectraldata were in accordance with the assumed structures. The IR spectra of benzimidazolium salts 1{5 have C=N and C=Ostretchingbandsintherangeof1559{1563cm(cid:0)1 and1694{1716cm(cid:0)1,respectively. TheC=Nstretching frequencies of the benzimidazolium salts are slightly smaller than the normal (unconjugated) C=N stretching frequency value because of (cid:25)-electron delocalization on the imidazolium ring. The characteristic NCHN resonance in the 1H NMR spectra and NCHN resonance in the 13 C NMR spectra of benzimidazolium salts (1{5) were observed at around 9.97{10.04 ppm and 143.2{143.4 ppm, respec- tively. These values are in good agreement with the previously reported results.50(cid:0)53 Scheme. Synthetic pathways of the benzimidazolium salts (1{5). 1266 KU(cid:127)C(cid:24)U(cid:127)KBAY et al./Turk J Chem 2.1. The Heck{Mizoroki, Suzuki{Miyaura, Sonogashira, and Buchwald{Hartwig coupling reac- tions Palladium-catalyzed carbon{carbon coupling reactions, such as the Mizoroki{Heck in the early 1970s, the Suzuki{Miyaura in 1990, the Sonogashira in 1975, and the Buchwald{Hartwig carbon{nitrogen coupling re- action in 1995, are now recognized as essential in the tool box of every synthetic chemist.54 The resulting coupling products of these reactions are generally valuable materials like natural, biologically active, inge- niously designed organic materials with novel electronic, optical, or mechanical properties. Despite signi(cid:12)cant progress in palladium-catalyzed coupling reactions, considerable attention has been devoted to determining the mild reaction conditions and an environmentally benign, clean, economical, simple, and selective protocol for the formation of C{C and C{N bonds. In continuation of our work on C{C coupling reactions, we describe an environmentally benign highly efficient catalyst system having a benzimidazole scaffold that can be used as a precursor of N-heterocyclic carbene and make an appropriate comparison among the four famous palladium catalyzed coupling reactions. 2.1.1. The Heck{Mizoroki coupling reaction Palladium-catalyzed Heck{Mizoroki coupling has been recognized as one of the most powerful tools for the formation of C{C bonds and used in diverse areas such as the preparation of hydrocarbons, novel polymers, pharmaceuticals, organics, (cid:12)ne chemicals, agrochemicals, and dyes, and in new enantioselective syntheses of natural products in both academia and industry. In recent years, numerous papers have been published concerning improvements to the Heck{Mizoroki reaction, but it is still a hot topic for many research groups to explorethebestcatalyticsystemwithhighlyselective,active,cheaper,andenvironmentallyfriendlyprocedures. On the basis of this perspective, we aimed to (cid:12)nd a new and efficient catalyst system containing synthesized novelbenzimidazoleligandsthatwereprecursorsofN-heterocycliccarbeneswithstronger (cid:27)-donorcharacterand lowertoxicitycomparedwithphosphineligands. Pd-catalyzedC{Ccouplingreactionsaresensitivetowardsthe nature of the base, the solvent used for the reactions, time, and temperature as well as catalyst concentration. In order to (cid:12)nd the optimum reaction conditions for the Heck{Mizoroki coupling reaction, a series of test experiments was performed with 4-bromoanisole and styrene as model compounds. The test reactions were performed using different bases such as Cs CO , K CO , and DBU (1,8-diazabicyclo[5.4.0]undec-7-en) and 2 3 2 3 different solvents such as EtOH/H O and DMF/H O for 5 and 10 min at 80, 100, and 120 ◦C. 2 2 ItwasfoundthattheHeck{Mizorokicouplingreactioncatalyzedbybenzimidazoliumsalt(1),Pd(OAc) , 2 and base catalyst system gave the highest yield when using DMF/H O mixture as a solvent and Cs CO or 2 2 3 K CO asabaseat120 ◦C/300Wmicrowaveheatingfor5min. Aconsiderableincreasecouldnotbeobtained 2 3 incatalyticreactionyieldsbyprolongingthe timefrom5to10min. Weobservedagoodeffectonthecatalytic yield by increasing the temperature from 80 ◦C to 120 ◦C/300 W for 5 min. After these results, we chose K CO as a base, since it is cheaper than Cs CO and water/DMF as a solvent. To evaluate the effect of 2 3 2 3 Pd(OAc) concentrations, the reaction was carried out in the presence of 0.5 and 1 mol % Pd(OAc) under 2 2 optimized conditions and the isolated yields of the corresponding coupling products are shown in Table 1. ControlexperimentsshowedthattheHeck{Mizorokicouplingreactiondidnotoccurintheabsenceof 1. The results obtained under optimum conditions are given in Table 1. Under the optimized reaction conditions, three different aryl halides bearing electron-donating, electron-neutral, and electron-withdrawing groups were reacted with styrene, affording the coupled products in quite good yield. Electron-de(cid:12)cient aromatic halides (Table 1, entries 20{24) gave higher yields than the electron-rich ones. It can also be concluded that the 1267 KU(cid:127)C(cid:24)U(cid:127)KBAY et al./Turk J Chem electron releasing group on p-substituted benzyl attached to the nitrogen atom of the benzimidazolium salts slightly increased the catalytic activity (Table 1, entries 13, 18, and 23). In order to compare conventional and microwave heating systems, we also tested the catalytic yields using a conventional heating system in a preheated oil bath for 5 min at 120 ◦C but the desired coupling product could not be isolated (Table 1, entry 10). Table 1. The Heck{Mizoroki coupling reactions of aryl halides with styrene. Entry R Salt Yields (%)a 1 OCH 1 73b 3 2 OCH 1 74c 3 3 OCH 1 84d 3 4 OCH 1 86e 3 5 OCH 1 86f 3 6 OCH 1 78g 3 7 OCH 1 76h 3 8 OCH 1 62i 3 9 OCH No n.d.j 3 10 OCH 1 n.d.k 3 11 OCH 2 72 3 12 OCH 3 81 3 13 OCH 4 86 3 14 OCH 5 76 3 15 H 1 86 16 H 2 84 17 H 3 86 18 H 4 87 19 H 5 78 20 COOCH 1 89 3 21 COOCH 2 85 3 22 COOCH 3 87 3 23 COOCH 4 90 3 24 COOCH 5 81 3 aIsolatedyields. ReactionsweremonitoredbyGC-MS.Conditions: temperaturerampedto80 ◦C(3min)andheldfor 5b min and 10c min, temperature ramped to 100 ◦C (3 min) and held for 5d min, temperature ramped to 120 ◦C (3 min) and held for 5e min. As the base, Cs COf and DBUg were used. As a solvent, EtOH/H Oh (1:1) mixture was 2 3 2 used. 0.5mol%Pd(OAc)i. Without1j. Onpreheatedoilbath,for5k minwiththermalheatingat120 ◦C.n.d.: not 2 detected. 2.1.2. The Suzuki{Miyaura coupling reaction Among the several methods in biaryl synthesis, the Suzuki{Miyaura cross coupling reaction is a very efficient methodfortheconjugationofphenylboronicacidswitharylhalidesundermildreactionconditions.35 Although 1268 KU(cid:127)C(cid:24)U(cid:127)KBAY et al./Turk J Chem Table 2. The Suzuki{Miyaura coupling reactions of aryl halides with phenylboronic acid. Entry R Salt Yields (%)a 1 OCH 1 81b 3 2 OCH 1 83c 3 3 OCH 1 87d 3 4 OCH 1 90e 3 5 OCH 1 89f 3 6 OCH 1 82g 3 7 OCH 1 75h 3 8 OCH 1 60i 3 9 OCH No 11j 3 10 OCH 1 n.d.k 3 11 OCH 2 87 3 12 OCH 3 89 3 13 OCH 4 94 3 14 OCH 5 86 3 15 H 1 92 16 H 2 89 17 H 3 94 18 H 4 87 19 H 5 86 20 COOCH 1 94 3 21 COOCH 2 90 3 22 COOCH 3 92 3 23 COOCH 4 96 3 24 COOCH 5 88 3 aIsolatedyields. ReactionsweremonitoredbyGC-MS.Conditions: temperaturerampedto80 ◦C(3min)andheldfor 5b min and 10c min, temperature ramped to 100 ◦C (3 min) and held for 5d min,temperature ramped to 120 ◦C (3 min) and held for 5e min. As the base, Cs COf and DBUg were used. As a solvent, EtOH/H Oh (1:1) mixture was 2 3 2 used. 0.5 mol % Pd(OAc)i 1. Without 1j. On preheated oil bath, for 5k min with thermal heating at 120 ◦C. n.d.: 2 not detected. there has been considerable research on this topic, it is still being studied to improve the catalytic system and reaction conditions. For this purpose, we also continued to improve the catalytic system containing new benzimidazolium salts for these reactions. In order to (cid:12)nd the optimum reaction conditions for the Suzuki{ Miyaura coupling reaction, a series of experiments was performed with 4-bromoanisole and phenylboronic acid as model compounds similar to the Heck{Mizoroki reaction mentioned above. It was found that the Suzuki{ Miyauracouplingreactioncatalyzedbybenzimidazoliumsalt(1),Pd(OAc) ,andbasecatalystsystemgavethe 2 highest yield when using DMF/H O mixture as a solvent and K CO as a base at 120 ◦C/300 W microwave 2 2 3 heating for 5 min. A signi(cid:12)cant increase in catalytic reaction yields could not be observed by prolonging the time from 5 to 10 min. Under the optimized conditions, reaction of 4-bromanisole, bromobenzene, and 4- bromoacetophenone with phenylboronic acid gave quite high yield using a catalytic system consisting of 2 mol 1269 KU(cid:127)C(cid:24)U(cid:127)KBAY et al./Turk J Chem % benzimidazole salts (1{5), 1 mol % Pd(OAc) , and 2 equiv. K CO in DMF{H O (1:1) at 120 ◦C by 2 2 3 2 microwave irradiation (300 W) within only 5 min. We also tested the catalytic yields using a conventional heating system in a preheated oil bath for 5 min at 120 ◦C, but the desired product could not be detected. Control experiments showed that the yield of the coupling reaction was dramatically decreased to 11% in the absence of 1. The results obtained under optimum conditions are given in Table 2. Of the three different aryl bromides used in the Suzuki{Miyaura coupling with phenylboronic acid, the ones with electron-withdrawing substituents gave the highest yields (Table 2, entries 20{24). Similar to the Heck{Mizoroki cross coupling reaction results, it can be observed that the electron releasing group on p-substituted benzyl attached to the nitrogenatomofthebenzimidazoliumsaltsslightlyincreasedthecatalyticactivity(Table2, entries13, 18, and 23). The conventional heating was also inefficient in 5 min at 120 ◦C for the Suzuki{Miyaura reaction under optimized conditions (Table 2, entry 10). 2.1.3. The Sonogashira coupling reaction SonogashiracouplingreactionofphenylacetylenewitharylhalidescatalyzedwithPdcomplexesinthepresence ofcopperreagentisoneofthemostusefultechniquesinorganicsynthesesandhasbeenwidelyusedinmanyareas suchasnaturalproductsynthesis,biologicalactivecompounds,andmaterialscience.55 Ingeneral,Sonogashira cross-coupling reactions proceed in the presence of palladium catalyst containing copper(I) compounds as co- catalyst and often suffer from the Glaser-type oxidative dimerization of the alkyne substrate as a side product andthesereactionsneedprolongedreactiontimes. Inordertopreventthissideproductformationandimprove the Sonogashira cross coupling reactions, we used nano copper as co-catalyst instead of Cu(I) salts. After performing a series of test experiments with phenylacetylene and phenyl iodide, we obtained optimum reaction conditions for the Sonogashira cross coupling reactions (Table 3). It was found that the Sonogashira coupling reaction catalyzed by benzimidazolium salt (1), Pd(OAc) , 2 copper nano particle, and basecatalyst system gavethe highest yield whenusing polyethyleneglycol (PEG300) as a solvent and Cs CO as a base at 100 ◦C/300 W microwave heating for 10 min. Under the optimized 2 3 conditions, reaction of phenyliodide, p-tolyliodide, and p-bromonitrobenzene with phenylacetylenegavequite high yield using a catalytic system consisting of 2 mol % benzimidazole salts (1{5), 1 mol % Pd(OAc) , 4 mol 2 % Cu nano particle, and 2 equiv. Cs CO in PEG300 at 100 ◦C by microwave irradiation (300 W) within 10 2 3 min. We also tested the catalytic yields using a conventional heating system in a preheated oil bath for 10 min at 100 ◦C, but the desired product was not detected. Control experiments showed that the coupling reaction yields dramatically decreased to approximately half in the absence of 1. The results obtained under optimum conditions are given in Table 4. Among the three different aryl halides used in the Sonogashira coupling with phenylacetylene, the ones with electron-withdrawing substituents were found to give results similar to those of theHeck{MizorokiandSuzuki{Miyauracrosscouplingreactions. Itcanbe observedthatthe electronreleasing group on p-substituted benzyl attached to the nitrogen atom of the benzimidazolium salts slightly increased the catalytic activity (Table 4, entries 4, 9, and 14). The conventional heating was also inefficient for 10 min at 100 ◦C for the Sonogashira reaction under optimized conditions (Table 3, entry 19). FigureS1(onthejournal’swebsite)showsXRDdiffractionpatternsofcopper(0)nanoparticles. Accord- ing to XRD diffraction, Cu nanoparticles have an Fm-3m face centered cubic structure and crystal parameters using the Jade program according to the Rietveld-re(cid:12)nement method are calculated as a = b = c = 3.889 (cid:23)A. ThestrongpeaksattheBragganglesof36.4◦,43.3◦,50.5◦,and74.1◦ correspondtothe002,111,200,and220 1270 KU(cid:127)C(cid:24)U(cid:127)KBAY et al./Turk J Chem facetsofelementalcopper.56;57 Theparticlesizeofthecorrespondingfacets002,111,200,and220ofelemental copper were determined as 15.3, 27.1, 22.2, and 21.6 nm (21.6 (cid:6) 9.9 nm) using the Debye{Scherrer equation [d = (0.94. (cid:21) )/(FWHM.Cos(cid:18))], respectively. These values were also found experimentally as 14.9, 27.2, CuK(cid:11) 21.8, and 21.0 nm (21.2 (cid:6) 10.0 nm) from the XRD report, respectively. Table 3. Test experiments for optimization of the Sonogashira coupling reactions. Co catalyst Time Temperature Entry Salt Base (0.04 mol) Solvent (min) ◦C Yield,% 1 1 KOH CuI DMF 10 100 55 2 1 KOH CuI DMF 20 100 59 3 1 KOH CuI DMF 10 120 60 4 1 K CO CuI DMF 10 100 66 2 3 5 1 K CO CuI DMF 20 100 67 2 3 6 1 K CO CuI DMF 10 120 68 2 3 7 1 Cs CO CuI DMF 10 100 69 2 3 8 1 Cs CO CuI DMF 20 100 70 2 3 9 1 Cs CO CuI DMF 10 120 70 2 3 10 1 Cs CO CuNPc DMF 10 100 73 2 3 11 1 Cs CO CuNPc DMF 10 120 75 2 3 12 1 Cs CO CuNPc Ethylene glycol 10 100 74 2 3 13 1 Cs CO CuNPc Glycerol 10 100 56 2 3 14 1 Cs CO CuNPc EtOH 10 100 45 2 3 15 1 Cs CO CuNPc PEG300 10 100 94 2 3 16 1 Cs CO CuNPc PEG300 10 120 95 2 3 17 1 Cs CO CuNPc PEG300 10 100 84a 2 3 18 no Cs CO CuNPc PEG300 10 100 43b 2 3 19 1 Cs CO CuNPc PEG300 10 100 n.dc. 2 3 Reaction conditions are same as indicated in the text. Yields are based on aryl bromide. Reactions were monitored by GC-MS. aCuNPcwasused0.02mol. bThesaltwasnotused. Onpreheatedoilbath,for10c minwiththermalheating at 100 ◦C. n.d.: not detected. 2.1.4. Buchwald{Hartwig coupling reaction A number of biological active compounds, herbicides, conducting polymers, and components of organic light- emitting diodes contain arylamines. For many years, these types of compounds have been synthesized by classicalmethods,suchasnitration,reduction,andreductivealkylation,andcopper-mediatedchemistryathigh temperatures, through benzyne addition or direct nucleophilic substitution on electron-poor aromatic halides. However, following the (cid:12)rst reports on palladium-catalyzed C{N coupling by Kosugi et al., on coupling of tin amides with aryl halides in 1994, and two reports by Buchwald and Hartwig in 1995, palladium catalyzed C{N bond forming methodology entered synthetic organic chemistry as a new method. Today, palladium-catalyzed C{N cross-coupling reactions are important tools in both academia and industry.58;59 Despite considerable 1271 KU(cid:127)C(cid:24)U(cid:127)KBAY et al./Turk J Chem Table 4. The Sonogashira coupling reactions of aryl halides with phenylacetylene. Entry R X Salt Yields (%)a 1 H I 1 88 2 H I 2 85 3 H I 3 84 4 H I 4 88 5 H I 5 86 6 CH I 1 72 3 7 CH I 2 69 3 8 CH I 3 73 3 9 CH I 4 81 3 10 CH I 5 79 3 11 NO Br 1 94 2 12 NO Br 2 92 2 13 NO Br 3 93 2 14 NO Br 4 95 2 15 NO Br 5 91 2 aIsolated yields. advances in this area, there are some notable limitations such as time, toxic ligands such as phosphines, and side products. We have published some papers concerning the C{C cross coupling reactions on the Suzuki{ Miyaura and Heck{Mizoroki reactions catalyzed by Pd{NHC and reported promising results.41;44(cid:0)47 In this report, we also tested the efficiency of some benzimidazolium salts that were precursors of NHC ligand on the Buchwald{Hartwig coupling reactions. In order to (cid:12)nd the optimum reaction conditions, we began our studies withthecouplingofanilineandphenylbromide. ItwasfoundthattheBuchwald{HartwigC{Ncouplingreaction catalyzed by benzimidazolium salt (1), Pd(OAc) , and base catalyst system gave the highest yield when using 2 DMF as a solvent and Cs CO as a base at 100 ◦C/300 W microwave heating for 60 min. A signi(cid:12)cant 2 3 increase in catalytic reaction yields was not obtained by prolonging the time from 60 to 90 min. A phase transfer agent, tetrabutylammonium bromide (TBAB), was added to enhance the reactivity. As can be seen from Table 5, TBAB played a crucial role in the C{N coupling reactions (Table 5, entry 13). Under optimized conditions, the reaction of aniline with phenyl bromide gave low yield, using a catalytic system consisting of 4 mol % benzimidazole salts (1{5), 2 mol % Pd(OAc) , and 2 equiv. Cs CO in DMF in the presence of 2 2 3 2 mol % TBAB at 100 ◦C by microwave irradiation (300 W) within 60 min. On the other hand, catalytic conversion yields were found to be moderate to high when using phenyl iodide instead of phenyl bromide. We also tested the catalytic yields using a conventional heating system in a preheated oil bath for 60 min at 100 ◦C, but the yield of the desired product decreased (Table 5 entry 14). The control experiment showed that the couplingreactionyielddramaticallydecreasedto11%intheabsenceof 1. Theresultsobtainedunderoptimum conditions are given in Table 5. 1272 KU(cid:127)C(cid:24)U(cid:127)KBAY et al./Turk J Chem Table 5. The Buchwald{Hartwig coupling reactions of phenyl halides with aniline. Entry X Salt Yields (%) 1 Br 1 n.da 2 Br 1 12b 3 Br 1 49c 4 Br 1 47d 5 Br 1 46e 6 Br 1 32f 7 Br 1 23g 8 Br 1 17h 9 Br 1 29i 10 Br 1 24j 11 Br 1 45k 12 Br no 11l 13 Br 1 37m 14 Br 1 38n 15 Br 2 43 16 Br 3 49 17 Br 4 50 18 Br 5 44 19 I 1 76 20 I 2 72 21 I 3 82 22 I 4 84 23 I 5 70 Reactions were monitored by GC-MS. Conditions: temperature ramped to 100 ◦C (3 min) and held for 10a min, 30b min, 60c min, and 90d min. As the base, K COe KOHf and DBUg were used. As a solvent, EtOH/H Oh (1:1) 2 3 2 mixture DMF/H O (1:1) and toluenej was used. 1 mol% Pd(OAc)k, Without saltl, Without TBABm, On preheated 2 2 oil bath for 60n min with thermal heating at 100 ◦C., n.d.: not detected. 3. Experimental The starting materials and reagents used in the reactions were supplied commercially by Acros, Aldrich, Fluka, or Merck. The solvents were dried by standard methods and freshly distilled prior to use. All catalytic activity experiments were carried out in a microwave oven system manufactured by Milestone (Milestone Start SMicrowaveLabstationforSynthesis)underaerobicconditions. 1HNMR(300.13MHz)and 13CNMR(75.47 MHz) spectra were recorded using a Bruker Avance 300 MHz Ultrashield high performance digital FT NMR spectrometer. InfraredspectrawererecordedasKBrpelletsintherange4000{400cm(cid:0)1 onaPerkinElmerFT- IR spectrophotometer. Elemental analyses were performed by LECO CHNS-932 elemental analyzer. Melting 1273 KU(cid:127)C(cid:24)U(cid:127)KBAY et al./Turk J Chem points were recorded using an Electrothermal-9200 melting point apparatus, and were uncorrected. The structural characterization of copper nanoparticles fabricated was investigated by X-ray diffraction (XRD). An automated Rigaku RadB Dmax X-ray diffractometer with CuK(cid:11) radiation was used. Scan speed was selected as 2◦ min(cid:0)1 in the range of 2(cid:18) = 3{80◦. 1-(4-Bromobenzyl)benzimidazole, 1-(4-chlorobenzyl)benzimidazole, 1-benzylbenzimidazole, 1-(4-methyl- benzyl)benzimidazole, and 1-(4-cyanobenzyl)benzimidazole used in this work as starting compounds were pre- pared according to the literature procedures.60(cid:0)63 Copper nanoparticles were also prepared according to the literature procedure64 and were characterized by X-ray diffraction (XRD) pattern. 3.1. GC-MS analysis GC-MS spectra were recorded on an Agilient 6890 N GC and 5973 Mass Selective Detector with an HP- INNOWAX column of 60-m length, 0.25-mm diameter and 0.25-(cid:22)m (cid:12)lm thicknesses. GC-MS parameters for both Heck{Mizoroki and Suzuki{Miyaura coupling reactions were as follows: initial temperature 60 ◦C; initial time,5min;temperatureramp1,30 ◦C/min;(cid:12)naltemperature,200 ◦C;ramp2,20 ◦C/min;(cid:12)naltemperature 250 ◦C;runtime30.17min; injectorporttemperature250 ◦C;detectortemperature250 ◦C,injectionvolume, 1.0 (cid:22)L; carrier gas, helium; mass range between m/z 50 and 550. 3.2. Synthesis 3.2.1. Synthesis of 1-(4-bromobenzyl)-3-(N-phthalimidoethyl)benzimidazolium bromide, 1 A mixture of 1-(4-bromobenzyl)benzimidazole (1.00 g, 3.48 mmol) and N-(2-bromoethyl)phthalimide (0.90 g, 3.54 mmol) in DMF (5 mL) was re(cid:13)uxed for 4 h. The mixture was then cooled and the volatiles were removed under vacuum. The residue was crystallized from EtOH/EtO (1:1). Yield: 68% (1.28 g); mp 2 259{260 ◦C. (cid:29)(C=N): 1559 cm(cid:0)1, (cid:29)(C=O) 1710 cm(cid:0)1. Calcd for C H Br N O : C, 53.26; H, 3.54; : 24 19 2 3 2 N, 7.76%. Found: C, 53.24; H, 3.54; N, 7.74%. 1H NMR ((cid:14), DMSO-d ): 4.09 (t, 2H, CH -N, J= 6 2 5.1 Hz), 4.84 (t, 2H, CH -N, J= 5.1 Hz), 5.57 (s, 2H, ArCH ), 8.21{7.38 (m, 12H, Ar-H), 9.97 (s, 1H, 2 2 NCHN). 13C NMR ((cid:14), DMSO-d6): 37.3 (CH ), 46.5 (CH ), 49.6 (ArCH ), 114.1, 114.5, 122.5, 123.7 2 2 2 (BrPh-C), 127.3 (phthalimide-C), 127.4 (phthalimide-C), 130.9 (benzimidazole-C), 131.3(benzimidazole-C), 131.7 (phthalimide-C), 131.9 (benzimidazole-C), 132.3 (benzimidazole-C), 133.6 (benzimidazole-C), 135.0 (benzimidazole-C), 143.4 (NCN), 168.2 (C=O). Similar to the procedure above, compounds 2{5 were synthesized from appropriate 1-substituted benz- imidazole and N-(2-bromoethyl)phthalimide. 3.2.2. Synthesis of 1-(4-chlorobenzyl)-3-(N-phthalimidoethyl)benzimidazolium bromide, 2 Yield: 73% (1.50 g); mp 252{253 ◦C. Calc. for C H BrClN O : C, 58.02; H, 3.85; N, 8.46%. Found: C, 24 19 3 2 58.01; H, 3.85; N, 8.42%. IR: (cid:29)(C=N): 1561, (cid:29)(C=O): 1716 cm(cid:0)1. 1H NMR ((cid:14), DMSO-d ): 4.10 (t, 2H, 6 NCH CH -phthalimide, J= 5.1 Hz), 4.85 (t, 2H, NCH CH -phthalimide, J= 5.1 Hz), 5.77 (s, 2H, CH - 2 2 2 2 2 benzyl), 7.45{8.22 (m, 12H, Ar-H), 9.99 (s, 1H, NCHN) ppm. 13C NMR ((cid:14), DMSO-d ): 37.3 (NCH CH - 6 2 2 phthalimide), 46.5 (NCH CH -phthalimide), 49.6 (CH -benzyl), 114.1, 114.5, 123.7, 127.3 (BrPh-C), 127.4 2 2 2 (phthalimide-C), 129.4 (phthalimide-C), 130.6 (benzimidazole-C), 131.3 (benzimidazole-C), 131.7 (phtalim- ide), 131.9 (benzimidazole-C), 133.3 (benzimidazole-C), 133.9 (benzimidazole-C), 135.0 (benzimidazole-C), 1274