Heterogeneous catalysis in protodecarboxylation and c c bond formation 2

Chapter 1: Introduction The aim of this thesis is to develop and study heterogeneous Pd, Cu, and Ag catalysts for C-C bond transformation reactions The Ullmann reaction and decarboxylative cross-coupling are preferred methodologies for C-C bond formation between aromatic rings Both not require the use of preformed organometallic reagents and can be used to prepare biphenyl compounds The biphenyl moiety is a very important structural component of many industrial, agrochemical and pharmaceutical products Thus, the development of more efficient catalytic systems for access to this group of molecules has very high economical and industrial value We also investigated the protodecarboxylation of aromatic benzoic acids over heterogeneous supported catalysts The study of the expulsion of the carboxylate group is important because it is also the rate-determining step in the decarboxylative crosscoupling of aromatic benzoic acids with aryl halides The catalyst is the key to the efficient synthesis of these valuable biphenyl compounds Thus, in this work, various parameters that influence the catalytic properties such as metal loading and pretreatment conditions were studied to understand and correlate the catalyst design to its function The reaction mechanism was also studied to better understand the catalytic process and to optimise the reaction conditions 1.1 Supported nanosized transition metal catalysts in fine chemical synthesis Catalysis is a fundamental area of research as it is a highly important technology used to support industrial processes Several well defined areas of       industrial catalysis include petroleum, pharmaceutical and environmental catalysis The petroleum industries rely heavily on catalysts to manufacture petrochemicals from crude oil [1], while pharmaceutical companies have started to appreciate the benefits of catalysis in the manufacture of chemical compounds with medicinal functions [2] Environmental catalysts are used to remove and degrade toxic waste products from manufacturing effluents [3] and most notably in the car catalytic converter It has been estimated that up to 90 % of all industrial chemical processes were performed with the help of catalysts [4] BASF, a market leader in catalysis, reported total sales of catalyst products worth € 6.4 million in 2011 [5] The importance of industrial catalysis is also reflected by the fact that the annual catalyst demand has been projected to increase by % annually from 2011-2015 Catalysts can speed up the rate of chemical transformations without being consumed in the process They lower the activation energy by providing an alternative reaction pathway which is energetically and sterically favourable Catalysis also lowers by-product formation and maintains high productivity All these factors reduce the costs and time required, and make the processes more environmentally friendly Hence, catalysis is an indispensable tool in the chemical industries as it ensures optimum efficiencies and high process yields 1.1.1 Homogeneous catalysts versus heterogeneous catalysts Catalysts are generally divided into two classes: homogeneous catalysts and heterogeneous catalysts In homogeneous catalysis, the catalysts used are chemical compounds such as general acid, base or organometallic complexes       which dissolve fully in the reaction medium to form a single phase Thus, they have a higher degree of dispersion Due to their molecular nature, each homogeneous catalyst contains only a single type of active site, and high selectivity to a particular product can be achieved However, homogeneous catalysts such as organometallic complexes have poor thermal stability which limits their working temperature to below 200 oC; this is unlike heterogeneous catalysts, which can tolerate higher reaction temperatures Heterogeneous catalysts are usually solids, whereas the reactants are liquids or gases Catalytic reactions using such catalysts take place between two or more different phases Many catalysts are based on precious metals such as palladium, platinum, ruthenium and silver However, in a heterogeneous reaction at a fluid-solid interface, only atoms on the surface of the solid can participate in the reaction High surface area is therefore required for efficient catalysis Due to the high price of the precious metals, they are often dispersed as nanoscale metal particles onto support materials to maximise and stabilise the exposed catalytically active surface Some molecular species such as hydrogen and oxygen adsorb dissociatively onto these nanoparticles by interaction with the d-electrons of the precious metals, allowing hydrogenation and oxygenation reactions to occur under milder conditions [6] The higher activity afforded by the precious metal catalysts compensates for their high price by making it possible to use a very small amount of the catalysts Also, precious metal catalysts have higher thermal stability and are more resistant to oxidation, which can potentially prolong the catalyst life-time However, there are also many catalysts which are made up of non-precious metals such as copper and iron, or metal oxides with Lewis or Brönsted acidic and basic sites       such as zeolites, silica and alumina These catalysts are used effectively in a wide variety of processes, for example metallic Fe in the Haber-Bosch process [7], Cu/ZnO/Al2O3 in methanol synthesis [8], and ZSM-5 zeolites in catalytic steam cracking of hydrocarbons [9] The atoms at the surface of a solid catalyst have an incomplete coordination shell There are more highly coordinated atoms within planes, and coordinatively unsaturated atoms in edges and at corners The amount and type of each active site varies according to the chemical composition, dimension and the form of the solid catalyst particle, as seen in the example of a gold nanoparticle in Fig 1.1 Figure 1.1: A plot of the calculated fraction of Au atoms at the corner (red), edge (blue), and crystal face (green) of a truncated octahedral gold nanoparticle The insert shows the top half of a truncated octahedral gold nanoparticle and the position of the corner, edge and surface atoms [10], [11] The various surface atoms have different catalytic activities and may catalyze different reactions For example, studies conducted by Medlin et al using self-assembled monolayers (SAM) on supported Pd/Al2O3 catalysts have shown that furfurals react differently on various surface sites present on the       Pt(111) surface [12] It was postulated that furfural decarbonylation followed by ring hydrogenation occurs preferentially on threefold terrace sites as it allows the adsorption of the furan ring in a flat-lying manner In contrast, aldehyde hydrogenation to give furfural alcohol and hydrodeoxygenation to give methylfuran occurs primarily at the step edge and defect sites as the furfural binds upright at these sites The results clearly show that several products can be obtained using unmodified supported Pt catalysts; with furan as the primary product The rate of of decarbonylation was about two orders of magnitude higher than that of the aldehyde hydrogenation and hydrodeoxygenation Figure 1.2 Furfural hydrogenation pathways on Pt(111) surface [12] This example show that due to the presence of multiple active sites present on heterogeneous catalysts, the selectivity towards the desired products is normally poorer than with homogeneous catalysts Also, the degree of dispersion, i.e., the ratio of atoms in the surface to the total number of atoms in the particle for such solid catalysts is generally lower than one, compared to homogeneous catalysts where all atoms are active The mechanism of homogeneously catalysed reactions is usually well understood because the catalytically active atoms or molecules are welldefined and can be studied through the use of spectroscopic methods [13] For       heterogeneous catalysts, the exact reaction mechanism is harder to elucidate Nevertheless, the chemical interactions between the components in the reaction mixture and the active sites should be similar in both homogeneous and heterogeneous catalysts This is certainly true if the active sites of both types of catalysts are of similar chemical nature The active site of the catalyst is made up of a specific type of atom or fragment of a molecule or complex The active site can be inherent to the chemical compound or it can be formed upon pre-coordination or pre-chemisorption of reaction components In homogeneous organometallic catalysts, the transition metal ions coordinated to ligands usually make up the active site of the catalyst The ligands are neutral molecules with a lone pair of electrons or charged ions In both cases, they can donate an electron pair into the empty d-orbital of the transition metal ion to form a carbon-metal (C-M) bond The presence of the ligand changes the size, charge, coordination number and electron configuration of the metal ion, which in turn affects its catalytic activity The steric bulk of the ligand can control the type and the binding of reactants to the organometallic complex During reaction, the reactants coordinate to the central transition metal ion of the organometallic complex to form an activated intermediate complex which accelerates the rate of chemical transformation For example, changes in the electronic configuration of the reactants such as alkenes or carbon monoxide coordinated to positively charged metal centres activate the carbon atoms towards nucleophilic attack Insertion of hydride or alkyl ligands is also favoured upon the coordination of unsaturated reactants to the transition metal centre of the organometallic complex β-Hydrogen elimination, which is the reverse of insertion, can take place more easily       through the formation of the intermediate complex Oxidative addition of reactants to the organometallic complex results in the dissociation of the bond within the reactant and brings it into close contact with other reactants for the reaction to take place These examples are shown in Figure 1.3 (a) Nucleophilic attack on coordinated ligands 2+ + CH2 M M CH2 C H2 H2 C OH + H+ OH2 (b) Migratory insertion of alkyl group O O CO OC OC CO C OC CO M M OC CH3 OC CH3 C + CO OC CO M CH3 OC CO CO CO (c) Migratory insertion of hydride/ beta-hydride elimination (reverse) H M CH2 CH2 M H CH2 M C H2 CH2 CH3 (d) Oxidative addition A L L M L L + L L AX M L L X Figure 1.3: Examples of reactions of organometallic complexes In heterogeneous catalysts, the active site is made up of a specific type of surface atom within the larger metal particle In analogy to the homogeneous catalyst complex, the nearest neighbour atoms can be regarded as permanent ligands of the central active surface atom Solvent or reactant molecules can also function as ligands when they adsorb next to the active site and modify its electronic properties The support of the catalyst can also affect the adsorption of the reactant molecules, and the direction of electron flow at the metal-support interface can thereby influence the catalytic properties of the       metal atoms Heterogeneously catalysed reactions begin with the adsorption of the reactant molecules onto the active sites of the metal catalyst surface, forming activated intermediates similar to organometallic complexes Adsorption induces bond dissociation, such as the dissociative adsorption of H2 in hydrogenation reactions, or it can result in the weakening of molecular bonds which favours substitution reactions In this way, the activation energy of the bond transformation is lowered which accelerates the rate of reaction After the bond transformation, the product desorbs from the catalyst surface to allow the next reactant molecule to adsorb onto the active site The strength of the metal-adsorbate bond however cannot be too strong, otherwise it will not be possible for the transformed species to desorb from the catalyst surface The active site will be blocked, and catalytic activity will come to an end One example of a reaction catalysed by heterogeneous catalyst is the iron-catalysed Haber-Bosch process for the synthesis of ammonia The process, as shown in Figure 1.4, begins with the dissociative adsorption of nitrogen and hydrogen on the surface of the iron catalyst The formation of Fe-N and Fe-H is energetically favourable which facilitates the fission of the N≡N and H-H bond The adsorbed N and H atoms combine to form NH3 which readily desorbs from the catalyst surface Figure 1.4: Formation of ammonia on a heterogeneous catalyst surface       Although the chemical interactions between the reactants and homogeneous or heterogeneous catalysts are similar, heterogeneous catalysts are preferred industrially The reason is that homogeneous catalysts are difficult to separate from the products This leads to serious contamination of the products and limits the reuse of the catalysts [14] The loss of expensive metals in the catalysts is also a serious economical drawback The problem of residual metal catalysts in pharmaceutical products is particularly crucial as guidelines have been set by government agencies to limit the amount of metal residues present in these products [15] Extra purification processes using metal scavengers have to be incorporated to reduce the metal content of these products This increases the cost and slows down the production process [16] In contrast, heterogeneous catalysts can be easily retained in fixed bed reactors or separated from the products in the reaction medium through simple filtration, centrifugation or magnetic separation 1.1.2 Heterogeneous catalysts: Supported metal catalysts One important class of heterogeneous catalysts are the supported metal catalysts Such catalysts comprise of one or more catalytically active metal species which are highly dispersed onto a support material to form metal nanoparticles The support materials have high surface area (>100 m2/g) and are usually porous, and these factors help to increase the dispersion and the surface area-to-volume ratio of the catalytically active species The support material also functions to stabilise the small metal nanoparticles Various materials such as alumina (Al2O3), hydrotalcite (Mg6Al2CO3(OH)16·4(H2O)), hydroxyapatite (Ca5(PO4)3(OH)), silica (SiO2), zeolites (aluminosilicate       minerals), cyclodextrins (cyclic oligosaccharides), polyamides and polyamines are used as the solid support The nature of the support used and the specific interactions between the support and the active phase can have a pronounced effect on the outcome of the catalytic reaction This was demonstrated by Touroude and his co-workers, who reported an increased chemo-selectivity (70-80 %) of a Pt/ZnO catalyst used to hydrogenate crotonaldehyde to crotyl alcohol (Figure 1.5) [17] , [18] OH Pt/ZnO O H O x H x H OH H Figure 1.5: Selective hydrogenation of crotonaldehyde to crotyl alcohol The Pt/ZnO catalysts were prepared by wet impregnation of ZnO with an aqueous solution of tetraammineplatinum (II) nitrate, followed by calcination in air at 400 oC for h Upon reduction at 200 oC for h under flowing H2, some of the support, ZnO, is reduced to metallic Zn and dissolves into the Pt to form a Pt-Zn alloy Increasing the reduction temperature to 400 oC results in the total conversion of the Pt into a Pt-Zn alloy The Ptδ Znδ+ entities favoured the adsorption of the C=O bond over the C=C bond of crotonaldehyde The phenomenon was attributed to the use of an easily reducible support and the electronic interactions between the Pt and Zn, resulting in the loss of Pt 5d electrons and disfavouring the adsorption of C=C bond [19] Besides the choice of support and active metal species, other catalyst parameters such as surface composition, morphology and size of the metal nanoparticles will greatly influence the activity of the catalysts Decreasing the 10       In chapter 5, we showed that the Cu loading on the γ-Al2O3 support greatly influences the oxidation state of the Cu species present Based on XPS results, the Cu exists in the form of Cu2O at 2.5 wt % loading, as a mixture of Cu2O and metallic Cu at 5.0 wt % loading, but as essentially metallic Cu at 10.0 wt % loading The test for decarboxylative cross-coupling of potassium 2-nitrobenzoate and iodobenzene clearly showed that the reaction favours the use of 2.5 wt % Cu/Al2O3, giving a moderately high yield of 68.7 % (entry 5) The 2-NBP yield was only 55.0 % when the 10.0 wt % Cu/Al2O3 catalyst was used (entry 1) This tells us that Cu2O has a higher catalytic activity than metallic Cu, not only for protodecarboxylation but also for the decarboxylative cross-coupling An intermediate yield of 57.5 % was obtained for 5.0 wt % Cu/Al2O3 (entry 6) The similar trend in the activity of the supported Cu catalysts for these two reactions indicates that both reactions go through a common intermediate, i.e., the formation of the aryl-copper intermediate Unexpectedly, a 2-NBP yield of only 15.4 % was obtained when the reaction was carried out with the 10.0 wt % Cu/Al2O3 catalyst in the presence of K2S2O8 (entry 7) Based on results in chapter 5, K2S2O8 should be able to positively influence the Cu species present on the 10.0 wt % Cu/Al2O3, but the low yield obtained suggests that the K2S2O8 plays a different role in the decarboxylative cross-coupling reaction 6.3.2.5 Cu·Pd/Al2O3-catalysed decarboxylative cross-coupling From the results obtained above, it is clear that the decarboxylative crosscoupling of potassium 2-nitrobenzoate and iodobenzene is limited by the inherent catalytic activity of the copper catalyst Our studies have shown that 201       the Cu plays a major role in the extrusion of the carboxylate group from the aromatic carboxylic acids However, our results above show that copper does not have much catalytic activity for the coupling of the aryl-copper intermediate with iodobenzene Thus, palladium (Pd) was incorporated into our catalytic system as a second metal, because Pd metal is known to aid in C-C coupling reactions [25] Pd, being a two-electron catalyst, could catalyse the cross-coupling of the aryl-copper intermediate with the aryl halide in a separate catalytic cycle We postulate that by depositing palladium onto the support together with Cu, the close distance between the two metallic species will allow for the quick transfer of the aryl-copper formed upon decarboxylation to the Pd centre, where the cross-coupling can take place To test this hypothesis, bimetallic catalysts comprising of the γ-Al2O3 support with both Cu and Pd were prepared to find out if the close proximity of the two metallic species on the same support favours the selective formation of the cross-coupling product, 2-NBP However, beside NB and 2-NBP, the use of Pd as a co-catalyst resulted in the formation of several other products, notably 2,2’-dinitrobiphenyl (DNBP), 3-nitrobiphenyl (3-NBP) and biphenyl (BP) DNBP is formed from the homocoupling of potassium 2-nitrobenzoate [26], [27] 3-NBP is formed from the cross-coupling of the potassium 2-nitrobenzoate and iodobenzene through C-H activation followed by protodecarboxylation [28], [29] Biphenyl is formed from the homocoupling of iodobenzene Disappointingly, the bimetallic 2.5 wt % Cu · 1.0 wt % Pd/Al2O3 catalysts did not operate as expected In all cases, the yield obtained for 2-NBP were low, ranging from to 14 % (Table 6.10) For CI catalysts, Cu2O 202       and Pd nanoparticles are randomly distributed over the alumina surface, with little or no interaction between the two metals as shown by the XPS data This is expected due to the electronic repulsion of the positively charged catalyst precursors (Cu2+ from Cu(NO3)2 and [Pd(NH3)4]2+ from [Pd(NH3)4]Cl2·H2O) used during deposition Thus, the Cu2O nanoparticles catalyse the decarboxylation of potassium 2-nitrobenzoate, which resulted in the formation of NB and 2-NBP, while the Pd nanoparticles allowed for the formation of 3-NBP (entry 3) The yields for 2-NBP remained low at 5.5 % and showed no improvement over the use of only 2.5 wt % Cu/Al2O3 (entry 1) This indicates the lack of interaction between Cu2O and Pd, which is necessary to couple the catalytic cycles of the decarboxylation and cross-coupling But it is interesting to note that the yield for NB was enhanced by 10 times (entries & 3) This suggests that the Pd species has catalytic activity towards protodecarboxylation and may also play a role in enhancing the catalytic activity of Cu2O towards decarboxylation of aromatic acids when present in close proximity In the case of SI catalysts, Cu2O was deposited after the formation of Pd nanoparticles on the alumina support However, similar to the CI catalysts, no specific interaction between Cu2O and Pd+ could be detected from the XPS data The lower NB yield compared to that of CI catalysts is due to the difference in oxidation state of Pd species (Pd+ vs Pd0) (Table 6.10, entry 2) Also, these positively charged Pd+ species seem to have higher activity towards the formation of 3-NBP A slightly higher yield towards 2-NBP of the SI catalysts (11.4 %) compared to the CI catalysts (5.5 %) was observed This could be due to some contact between the copper and palladium in the SI 203       catalysts Contact between the two metal species could occur in the sequential impregnation when copper gets deposited on top of the pre-formed Pd nanoparticles Table 6.10: Summary of results 2.5 wt % Cu · 1.0 wt % Pd/Al2O3 catalysts Entry Catalyst 2.5 wt % Cu/Al2O3 2.5 wt % Cu·1.0 wt % obtained with bimetallic Conv/ % 12.4 Yield/ % NB 2-NBP 6.7 5.5 DNBP 47.1 24.1 11.4 11.6 72.5 61.8 5.5 5.3 31.8 10.4 5.0 14.1 5.7 44.4 14.5 6.7 8.8 14.4 32.4 10.2 4.3 11.5 6.5 34.7 8.7 7.6 16.0 2.4 52.4 8.4 6.3 21.4 16.2 3-NBP Pd/Al2O3 (SI) 2.5 wt % Cu·1.0 wt % Pd/Al2O3 (CI) 2.5 wt % Cu·1.0 wt % Pd/Al2O3 (SA) 1.0 wt % Cu·1.0 wt % Pd/Al2O3 (SA) 5.0 wt % Cu·1.0 wt % Pd/Al2O3 (SA) 2.5 wt % Cu/Al2O3 + Pd(OAc)2 2.5 wt % Cu/Al2O3 + 1.0 wt % Pd/Al2O3 Pd(OAc)2 5.1 1.9 1.6 1.5 10 1.0 wt % Pd/Al2O3 30.5 14.9 10.1 5.5 Reaction condition: Potassium 2-nitrobenzoate (2 mmol), iodobenzene (4 mmol), K2CO3 (0.3 mmol), 2.5 wt % Cu 1.0 wt % Pd/Al2O3 (0.100 g) or 2.5 wt % Cu/Al2O3 (0.100g) with Pd catalyst (Pd(OAc)2= 0.00211g (0.01 mmol) or 1.0 wt % Pd/Al2O3= 0.100g), DMA, 150 oC, Ar delivered using Schlenk line after purge-and-refill cycles , 24 h, solid reactants were dried in vacuo for at least h before use NB: nitrobenzene; 2-NBP: 2-nitrobiphenyl; DNBP: 2,2’-dinitrobiphenyl; 3-NBP: 3-nitrobiphenyl The strategy used in the preparation of SA catalyst ensured good contact between Cu and Pd species, which had been verified by XPS analysis 204       This catalyst (entry 4) was indeed slightly more selective towards 2-NBP than the CI and SI catalysts Unlike the CI and SI catalysts, the homocoupling product, 2-DNBP, was also observed with the SA catalyst, possibly due to the close proximity of the Cu and Pd species which enabled the coupling of the catalytic cycles for Cu-catalysed decarboxylation and Pd-catalysed homocoupling Unfortunately, it was not possible to enhance the formation of 2-NBP by changing the weight ratio of Cu:Pd from to (entries & 6) In summary, low 2-NBP yields ranging from 5.5 - 14.1 % were obtained with various Cu·Pd bimetallic catalysts This suggests that the deposition of Pd together with Cu onto the γ-Al2O3 support did not significantly enhance the activity of the catalysts towards decarboxylative cross-coupling While the bimetallic catalyst brings the two metallic species onto the same support, reducing the distance between the two species, it may restrict the angle of approach and diffusion of the aryl-copper to palladium centre In view of this possible restriction brought about by bimetallic catalysts, decarboxylative cross-coupling of potassium 2-nitrobenzoate and iodobenzene was carried in the presence of 2.5 wt % Cu/Al2O3 and Pd(OAc)2 or 1.0 wt % Pd/Al2O3 (entries & 8) It is clear the Pd species (Pd(OAc)2 and 1.0 wt % Pd/Al2O3) catalyse the formation of DNBP, 3-NBP as well as NB (entry and 10) Although similar side products are also formed, the use of Pd(OAc)2 and 1.0 wt % Pd/Al2O3 together with 2.5 wt % Cu/Al2O3 enhanced the yield of the 2-nitrobiphenyl by - times (entries 1, & 8) This clearly shows that mobility between the two metal species and 205       intermediates formed is also important in the formation of the decarboxylative cross-coupling product 6.3.2.6 Proposed reaction mechanism Based on the results obtained above, reaction mechanisms for the formation of the various products were proposed (Scheme 6.4) For copper-catalysed decarboxylative cross-coupling, the catalytic cycle begins with the adsorption of the substrate followed by the decarboxylation of the potassium 2-nitrobenzoate and the formation of a surface aryl-copper intermediate as described in chapter Next, a SN2 nucleophilic substitution takes place between the aryl-copper intermediate and the iodobenzene adsorbed on the surface of the catalyst The lone pair from the nucleophilic aryl-copper intermediate attacks the electrophilic carbon of the iodobenzene and forms a C-C bond with it In this process, the iodide anion is expelled and will from potassium iodide with the potassium ion released from potassium 2-nitrobenzoate This explains why potassium carbonate is required in the reaction despite the use of the potassium 2-nitrobenzoate salt 2-nitrobiphenyl is released as the product before the next catalytic cycle begins 206       O O N O O-K+ I Adsorption Cu O Cu O Cu NO2 KI Cross-coupling O O N O Cu O I Cu O Cu O O N O K+ Cu Cu Decarboxylation O O Cu I O Cu K+ O Cu CO2 Scheme 6.4: Proposed mechanism for Cu-catalysed decarboxylative crosscoupling of potassium 2-nitrobenzoate and iodobenzene In the case of the bimetallic Cu·Pd catalysed decarboxylative crosscoupling, a mechanism is proposed based on the mechanism previously reported by Goossen et al for homogeneous catalysis [6] (Scheme 6.5) The proposed mechanism is similar to that of the copper-catalysed decarboxylative cross-coupling One major difference between the two mechanisms is the oxidative addition of the iodobenzene and the subsequent transmetallation of the aryl-copper intermediate to the palladium metal centre The transmetallation step is crucial for the coupling of the two catalytic cycles as it brings the two aryl groups into close proximity A C-C bond is formed between the aryl components on the palladium centre upon reductive elimination, releasing the 2-NBP product 207       O O N O OH 0.5 K2CO3 0.5 CO2 + 0.5 H2O O I O N O oxidative addition Pd(II)L2 Cu O O Cu K+ O Cu I Pd(0)L2 NO2 CO2 transmetallation reductive elimination decarboxylation O2N Pd(II)L2 O Cu KI Scheme 6.5: Proposed mechanism decarboxylative cross-coupling of iodobenzene O N K+ O Cu O Cu for bimetallic Cu·Pd catalysed potassium 2-nitrobenzoate and As for the side products, it was suggested that the formation of 3-NBP results from a Pd-catalysed tandem C-H arylation/protodecarboxylation process (Scheme 6.6) [29] NO2 NO2 NO2 H COOH I COOH + Pd catalyst Pd catalyst - CO2 H Scheme 6.6: Proposed mechanism for formation of 3-NBP For the formation of DNBP, a possible mechanism begins with the Cucatalysed decarboxylation, resulting in the formation of an aryl-copper intermediate (Scheme 6.7) Transmetallation of the aryl-copper intermediate to the Pd(II) centre occurs twice, generating a bisaryl-Pd species DNBP is then released upon reductive elimination and Cu(I) reoxidises the Pd(0) to Pd(II) to regenerate the catalyst [27] 208       O Pd(II)L2 O N Cu Cu(I) Cu O O Pd(0) NO2 Pd(II)L2 NO2 NO2 NO2 O2N Pd(II)L2 O Cu O N O Cu O Scheme 6.7: Proposed mechanism for formation of DNBP 6.4 Conclusion In conclusion, the use of γ-Al2O3 supported copper catalyst was extended to attempt the decarboxylative cross-coupling of potassium 2-nitrobenzoate and iodobenzene Using 2.5 wt % Cu/Al2O3 as catalyst, K2CO3 as base, and carrying out the reaction under Ar atmosphere, 2-nitrobiphenyl could be obtained with a moderate yield of 68 % Similar to results presented in chapter 5, Cu species in the +1 oxidation state have much higher activity towards the decarboxylative cross-coupling reaction than metallic Cu or CuO The fast rate of formation of the aryl-Cu intermediate through the efficient Cu+-catalyzed decarboxylation is attributed to the high activity of the aryl carboxylic acids towards decarboxylative cross-coupling with iodobenzene The lower activity of the metallic Cu and CuO towards decarboxylation, in turn, resulted in decreased yield for the cross-coupling product The use of catalysts that contained both Cu and Pd supported on the same support did not lead to much enhancement in the yield of the desired cross-coupling product, 2209       nitrobiphenyl Instead, it resulted in the formation of side products such as nitrobenzene, 2,2’-dinitrobiphenyl, 3-nitrobiphenyl and biphenyl Based on the results obtained, mechanisms for the formation of the various products were proposed 6.5 References [1] L.J Goossen, F Collet, K Goossen, Isr J Chem., 50 (2010) 617-629 [2] L.J Goossen, G Deng, L.M Levy, Science, 313 (2006) 662-664 [3] L.J Goossen, N Rodríguez, B Melzer, C Linder, G Deng, L.M Levy, J Am Chem Soc., 129 (2007) 4824-4833 [4] L.J Goossen, N Rodríguez, C Linder, J Am Chem Soc., 130 (2008) 15248-15249 [5] L.J Goossen, N Rodríguez, P.P Lange, C Linder, Angew Chem Int Ed., 49 (2010) 1111-1114 [6] L.J Goossen, B Zimmermann, T Knauber, Angew Chem Int Ed., 47 (2008) 7103-7106 [7] L.J Goossen, B Zimmermann, C Linder, N Rodríguez, P.P Lange, J Hartung, Adv Synth Catal., 351 (2009) 2667-2674 [8] P.P Lange, L.J Goossen, P Podmore, T Underwood, N Sciammetta, Chem Commun., 47 (2011) 3628-3630 [9] L.J Goossen, T Knauber, J Org Chem., 73 (2008) 8631-8634 [10] L.J Goossen, B Melzer, J Org Chem., 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using potassium 2-nitrobenzoate, iodobenzene, K2CO3, 2.5 wt % Cu·1.0 wt % Pd/Al2O3 in DMA at 150 oC, Ar 212       Chapter 7: Final Conclusion We have developed heterogeneous catalytic systems for Ullmann coupling of bromobenzenes, protodecarboxylation of aryl carboxylic acids and decarboxylative cross-coupling reactions between aryl carboxylates and iodobenzene These methods are green alternatives for C-C bond formation between aromatic compounds as they not require preformed organometallic reagents This greatly improves the atom efficiency In all cases, the catalysts can be easily separated from the products and reactants, and can be recycled with little loss of activity In the study of the heterogeneous Pd(OAc)2-PEG-EG catalytic system for Ullmann coupling, mixtures of PEG and EG allowed the viscosity and reducing ability of the system to be fine-tuned so that the reaction could proceed to completion with high activity Interestingly, besides the targeted biphenyl, terphenyls were also observed with an average selectivity of 15 % This reaction is an example for direct C-H activation at the aromatic core and constitutes a new way of forming C-C bonds Alumina supported Ag and Cu catalysts were developed for protodecarboxylation of ortho-substituted aromatic benzoic acids Increased metal loading resulted in increasing particle size for the Ag catalysts which ultimately lead to lower activity For Cu catalyst, a change in oxidation state from Cu2O to metallic Cu was observed with increasing metal loading The positively charged oxide (Ag2O layer for Ag catalyst and Cu2O for Cu catalyst) was essential for the transfer and attachment of carboxylate anion through electrostatic interactions Amongst the Ag catalysts with different metal loading, 10 wt % Ag/Al2O3 (without H2 pretreatment) was the most effective 213       catalyst with the highest TOF; its TOF is about 35 times that of homogeneous AgOAc In contrast, for Cu catalysts, it was found that Cu2O and metallic Cu was much more active than fully oxidised CuO, and 2.5 wt % Cu/Al2O3 (with H2 pretreatment for h at 300 oC), which constitute Cu2O nanoparticles, was the most active Unlike Ag/Al2O3 which could only be recycled once, the Cu/Al2O3 catalyst was stable under reaction conditions and could be recycled for three consecutive runs with little loss in activity No leaching of the Cu species was detected when the reaction was conducted at 150 oC Thus, we can conclude that the advantage of using Ag/Al2O3 is that it allows the reaction to be conducted at a lower temperature of 120 oC For Cu/Al2O3, the advantages over Ag/Al2O3 are the lower cost of the metal, truly heterogeneous nature and recyclablity of the catalyst Finally, both 10 wt % Ag/Al2O3 and Cu/Al2O3 catalysts were used in the study of decarboxylative cross-coupling of the potassium salt of 2-nitrobenzoic acid and iodobenzene 10 wt % Cu/Al2O3 showed much better selectivity for 2-nitrobiphenyl (cross-coupling product) while 10 wt % Ag/Al2O3 was more selective for nitrobenzene (protodecarboxylation product) Optimization of the reaction conditions showed that by increasing the amount of iodobenzene and 2.5 wt % Cu/Al2O3 used, up to 75 % selectivity for biphenyls and 83 % total conversion could be achieved However, the use of bimetallic Cu·Pd/Al2O3 catalyst did not lead to much enhancement in the yield of the 2-nitrobiphenyl Instead, it resulted in the formation of side products such as nitrobenzene, 2,2’-dinitrobiphenyl and 3-nitrobiphenyl Good contact between the Cu and Pd species in the SA catalyst seemed to aid in the crosscoupling reaction as expected However, we suspect that the low yield of the 214       cross-coupling products is due to steric restrictions imposed by the fixed positions of the two metal species within a supported metal particle, which does not allow for favourable interaction with the intermediates during the catalytic cycle   215       ... group O O CO OC OC CO C OC CO M M OC CH3 OC CH3 C + CO OC CO M CH3 OC CO CO CO (c) Migratory insertion of hydride/ beta-hydride elimination (reverse) H M CH2 CH2 M H CH2 M C H2 CH2 CH3 (d) Oxidative... 1.37 1.44 1 .28 Density/ g/cm3 12. 38 10.5 8.96 Melting point/ ? ?C 1555 9 62 1085 Electronegativity (Pauling scale) 2. 20 1.93 1.9 Atomic weight f .c. c.: face-centred cubic Pd, Ag, and Cu nanocatalysts... Pd /C in the presence of zinc as reducing reagent (Scheme 1.4) [69] R1 Cl R1 + Zn + OH- R2 mol % Pd /C mol % PEG-400 60- 120 oC, 1 -2 h, H2O R2 + R2 R1 R2 + ZnO + H2O + Cl- R1 where R1= H, CH3 and R2=