Chapter-3: Eco-friendly Wacker process 178 3.1 Introduction Palladium (Pd) is an element form platinum group metals (PGMs). Palladium is used in all fields of sciences along with chemical science. Common oxidation states of palladium are 0, +1, +2 and +4. Numbers of reactions are reported in which palladium is used. Palladium catalyzed reaction such as Wacker oxidation,1 Heck reaction,2 Suzuki coupling reaction,3 Sonogashira coupling reaction,4 Hartwig Cross Coupling Reaction5 and Saegusa oxidation6 etc. have gained a lot of importance and popularity in the area of synthetic organic chemistry over a period of time. All these reactions proceed through π complexes. In all these reactions Pd was used in the form of Pd(I/II)7,8,9 .It was shown that Pd can be used as a catalyst in the Pd(0)8,10 form in Heck reaction, Suzuki reaction and Sonogashira coupling reaction. However, in all of the Wacker oxidations reported so far, Pd was used in the form of Pd(II) state. There are no reports of effecting Wacker oxidation using Pd (0) species. Phillips in 1894 oxidised ethylene to acetaldehyde by Pd (II) chloride solutions in acidic medium. During the reaction palladium forms a complex with ethylene, is reduced to Pdo. Latter on Smidt and co-workers (1959) used cupric chloride to regenerate the Pdo catalyst. Smidt’s process was applicable to large scale production due 11 to the final recycling of CuCl back to Cu(II)Cl2 by air. The simplified mechanism of Wacker Oxidation with PdCl2 as the catalyst, and catalytic amounts of copper chloride are used with oxygen to regenerate the active Pd(II) species is shown in Figure 1. Figure 1 179 Palladium decomposition and chlorinated by products limit the use of the Wacker oxidation. Many modifications have been developed allowing for oxidation of more complex targets, but most still utilize the addition of a copper cocatalyst.11 Copper additives severely limit the use of ligands with Pd. Ligand modulation of Pd catalysis has proven to be vital in the development of more effective and asymmetric catalysts for the mechanistically related aerobic alcohol oxidation.12 Conventional Wacker oxidation using homogeneous Pd catalysts often leads to difficulties in isolation of the products, separation of the catalysts from the reaction mixture, and recyclability of the catalysts. Therefore, much effort has been devoted to development of highly efficient Wacker oxidation by heterogeneous catalysts.13,14 Various Pd complex catalysts immobilized on organic or inorganic supports have been reported15,16 for this purpose, but these catalyst systems often have drawbacks such as low catalytic activity, low yield of product and sever dependence of success of the reaction on the structural substituent’s. Copper Chloride is a corrosive chemical cited by DOT, DEP and EPA. It may damage the liver and kidneys. Copper Chloride can affect skin and eye. Breathing of copper chloride can irritate throat, lungs and stomach causing salivation, nausea, vomiting and diarrhea. Prolonged exposure can cause hole in the bone dividing the inner nose.17 So we were interested in developing a catalytic system for the Wacker oxidation that would allow to use oxidants other than copper additives. 180 3.1.1 Literature review Tsuji18 et al (1975): Wacker oxidation of higher terminal alkenes affords methyl ketones rather than the corresponding aldehyde barring a few exceptions (fig. 2). Figure 2 This reaction appears to involve a Markonikov hydration of the complexed double bond followed by oxidation resulting in a one step conversion to methyl ketones. Thus the terminal olefins can be regarded as masked methyl ketones. Wacker oxidation tolerates various19 types of functional groups such as aldehyde, ketone ester, nitrile etc. Application of this type of oxidation to substituted olefins has evolved as synthetic useful tool. Michel Roussel20 et al. (1980) added 30% hydrogen peroxide to a solution of palladium(II) acetate in acetic acid or tert-butyl alcohol at room temperature resulted in an immediate decomposition with evolution of molecular oxygen. When this addition was carried out in the presence of 1-octene, no decomposition was observed and color changes from yellow-orange to deep orange. GLC analysis showed the formation of 2- octanone as the major product (fig. 3). Figure 3 Bodo Betzemeier21 developed a methodology to perform the Wacker oxidation of various polyfunctional olefins under mild conditions leading to the corresponding methyl ketones in the presence of the palladium catalyst in a biphasic solvent system of bromoperfluorooctane and benzene using t-butylhydroperoxide (1.5 - 3.5 equiv) as oxidation agent (fig. 4). Figure 4 181 Timothy et al.22 developed oxidation of terminal olefin to aldehyde and ketone respectively. In this reaction the use of LiCl and CuCl reduced the regioselectivity. The selective formation of aldehyde was 30%, while that of ketone was 70%. This methodology is applied for different condition and mole percentage of co-catalyst was studied (fig. 5). Figure 5 Eric Monflier23 et al developed very useful and efficient Wacker oxidation of higher α- olefins by using a multicomponent catalytic system, i.e. PdSO4/H9PV6Mo6O40/CuSO4 and per (2,6-di-o-methyl)-β-cyclodextrin to obtained the corresponding 2-ketones in high yields (>90 %) (fig. 6). Figure 6 24 Hari Babu Mereyala et al.(1997): A study of Pd(II)Cl2/CuCl catalysed Wacker reaction for the deprotection of prop-2-enyl and prop-1-enyl ethers was reported. In this Pd(II)Cl2 (1 mole equivalent)/CuCl/DMF-H2O/O2/2h catalyzed oxidation of various prop-2-enyl ethers was reported to result in the formation of Wacker ketones (12–51%), hydrolysis products (12–43%) and η2-vinyl complexes of palladium chloride (52–94%) respectively. The corresponding prop-1-enyl ethers under similar conditions react with a catalytic amount of Pd(II)Cl2 (0.2 mole equivalent) rapidly (15–20 min.) to give exclusively hydroxy compounds respectively in good yields (75–97%)(fig. 7). Figure 7 Amos B. Smith et al.25 made modification in the Wacker oxidation of terminal olefins to methyl ketones using substoichiometric amounts of Cu(OAc)2 as a redox shuttle reagent. The modified procedure is generally high yielding despite reduced levels of copper salt and convenient. Importantly, in a problematic case, the conditions 182 suppressed acidic hydrolysis during oxidation of substrate containing an acetonide (fig. 8). Figure 8 Standard Wacker oxidation provides 57% yield. Modified procedure gives 86% yield with 2 eq. Cu(OAc)2 and 84% yield with 0.2 equivalence of Cu(OAc)2 without acetonide hydrolysis. Arata Kishi26et al. (2000) Wacker-type oxidation of cyclopentene to cyclopentanone under dioxygen atmosphere was successfully achieved by the use of Pd(OAc)2 and molybdovanadophosphate supported on activated carbon, [Pd(OAc)2–NPMoV/C], catalyst49. Thus, the reaction of cyclopentene under O2 (1 atm) in aqueous acetonitrile acidified by CH3SO3H in the presence of [Pd(OAc)2–NPMoV/C] at 50°C produced cyclopentanone in 85% yield along with a small amount of cyclopentenone (1%) (fig. 9). Figure 9 Marisa S. Melgo27 et.al (2004) The Wacker oxidation of cyclohexene to cyclohexanone, using the chloride ion-free catalytic system Pd(NO3)2/CuSO4/H3PMo12O40, was investigated at different air pressures, temperatures, and catalyst concentrations. The results show that this system is very efficient and highly selective. After 1 h of reaction at 80 °C and an air pressure of 50 bar, a conversion of 80%, with a turnover frequency of 260 h−1, and a selectivity of more than 99% for cyclohexanone was obtained. Using aqueous hydrogen peroxide and no external pressure, the oxidation was more rapid, giving 80% conversion already after 30 min and 95% conversion after 60 min without the formation of any byproducts (fig. 10). 183 Figure 10 I.A. Ansari et.al (2005)28 A simple and efficient PdCl2/CuCl catalyzed oxidation of alkenes has been successfully developed using a mixture of water and the ionic liquid [bmim][BF4] as solvent. Starting from various types of terminal olefins, the corresponding ketones have been prepared under mild reaction conditions and obtained in good to excellent yields after a simple extraction with diethyl ether. Furthermore, it was possible to recycle and reuse the ionic liquid and the catalytic system (fig. 11). Figure 11 Takato Mitsudome et.al (2006)29 In a recent report palladium-montmorillonite was proven to be highly efficient for the Wacker oxidation of terminal olefins to the corresponding methyl ketones47. The catalyst was reusable while maintaining high activity and selectivity (fig. 12). Figure 12 Candace N. Cornell et al 30 (2006) Direct O2-coupled Wacker oxidation by O2 balloon pressure and catalytic amount of catalyst was described. Use of (−)-sparteine as a ligand on Pd prevents olefin isomerization and leads to selective formation of methyl ketones from terminal olefins in good yields. Enantiomerically pure substrates were oxidized without any type of racemisation (fig. 13). 184 Figure 13 Brian Michel31et al (2010) Michel targeted the use of ligands on Pd(II) to control oxidative processes. In this regard, he developed tert-butylhydroperoxide (TBHP) mediated Wacker-type oxidation, which was shown to be highly selective for the methyl ketone product in the oxidation of terminal olefins, including protected allylic alcohols and the phthalimide substrates. In this process a bidentate ligand (Quinox) along with TBHP was used. It was believed that TBHP undergoes a syn-oxypalladation mechanism, which allows interaction of the group adjacent to the olefin with the Pd center (fig. 14). Figure 14 185 3.1.2 Present work 3.1.2.1 Objective Conventional Wacker process with Pd(II) and CuCl2 leads to the formation of substantial amounts of ecologically hazardous chlorinated by-products.