PALLADIUM, RUTHENIUM AND COPPER COMPLEXES AS EFFICIENT CATALYSTS FOR DIFFERENT ORGANIC TRANSFORMATIONS

Abstract

The thesis entitled “Palladium, Ruthenium and Copper Complexes as Efficient Catalysts for Different Organic Transformations” is reported in seven chapters. In the present work is aimed to design and synthesis of pincer-type ligand (NpyNimOph), unsymmetrical pincer-ligands (NpyNinCary) and bidentate (NimNpy) Schiff bases. These ligands were characterized through different analytical techniques such as UV-visible, IR, NMR, ESI-MS, CHNS spectroscopy. These ligands were utilized for the synthesis of different type of complexes mainly palladium, ruthenium and copper complexes. These synthesized complexes were characterized by UV-visible, IR, NMR, ESI-MS, CHNS spectroscopy. Complexes were characterized by X-ray crystallography. These complexes were utilized as catalysts. These catalysts were utilized for different novel methodology involving CC, CN bonds formation using different reactions like Suzuki–Miyaura reaction, allylation of aldehydes, direct arylation of thiazoles and isoxazoles, arylation of imidazoles, Mizoroki-Heck reaction, α‐alkylation of ketones and amide with alcohols, synthesis of quinolines, Chan-Lam coupling reaction. One–pot [1,2,4] triazinium cationic species were synthesized from copper (II) assisted imine CH bond activation. The synthesized compounds were characterization through different analytical techniques such as 1H NMR, 13C NMR, GC-MS ESI-MS and single crystal X-ray crystallography. The thesis has been divided into seven chapters of convenience and clarity, and organized as follows: Chapter 1: General Introduction and The Reactivity of Palladium, Ruthenium and Copper Complexes: The Chemical System and Physical Methods The concept of Catalysis was presented for the first time in 1820 by J. J. Berzelius in his annual review articles to the Royal Swedish Academy of Sciences. Later, M. Faraday assumed (without elucidation) that the hydrogen and oxygen have to adsorb at platinum surface in order for the electrolysis of water take place. In 1835, Berzelius defined and described the observed phenomenon as a Catalysis. This term continued for the chemical society and the scientists until 1900, where W. Ostwald (Nobel laureate in chemistry 1909) accomplished the definition of the catalyst as “A substance which influences the rate of a chemical reaction without itself undergoing any permanent chemical change.” According to this definition, the catalysis is recognized as a kinetic phenomenon. Over the past few decades, transition metal complexes were well-explored in biology as well as catalysis. Palladium complexes catalyzed CC bond forming reactions are essential and frequently exploited in synthesis of pharmaceuticals and organic materials on both in laboratories as well as in industry. Several functionalized palladium complexes have been reported for various reactions namely hydrogenations, hydrophosphinations, C–H functionalization, Hiyama reaction, Suzuki–Miyaura reactions, Sonogashira coupling reactions Mizoroki–Heck reactions and Buchwald–Hartwig reactions etc. In the same line up, alkylation of carbonyl via borrowing hydrogen (BH) has emerged as an efficient and green choice for the formation of C−C bonds. Direct α-alkylation of ketones with primary alcohols has been functionalized under by transition metal complexes. This type of acceptorless dehydrogenative C−C coupling can be applied for the synthesis of aromatic N-heterocyclic compounds such as quinolines, pyrimidines, pyrroles, and others. The annulation reactions of γ-amino- and 2-amino benzyl alcohols with ketones or alcohols currently require expensive iridium and ruthenium catalysts. C−N bond formations via metal-catalyzed have opened a new avenue in the context of efficiency and applicability. Copper-catalyzed Chan–Lam coupling of boronic acids with nucleophiles to form carbon-heteroatom bonds contributes an alternative pathway. This reaction needs milder condition compared to the related Ullmann–Goldberg reaction or the analogous Buchwald–Hartwig coupling reaction. Nitrogen containing heterocycles cations are an important class because it exhibits in several biological and pharmacological active compounds. In addition, these types of nitrogen containing heterocycles cations also utilized in DNA probes, fluorescent dyes, ionic liquids. The nitrogen containing heterocycles mainly synthesized by condensation reaction. Recently, transition metal catalyzed also immerged area for the synthase of heterocycles under mild condition. Chapter 2: Rational Design of Sterically Hindered and Unsymmetrical NpyNimOph Pincer-Type Ligands and Their Palladium(II) Complexes: Catalytic Applications in Suzuki–Miyaura Reaction and Allylation of Aldehydes Palladium(II) complexes C1-C4 [Pd(L1 to L4)Cl] derived from pincer-type tridentate ligands having NpyNimOph donors were synthesized from ligands L1H to L4H (where L1H = (2-phenyl- 2-(pyridin-2-ylmethyl)hydrazono)methyl)phenol, L2H =[2-((2-phenyl-2-(pyridinyl-2-ylmet hyl)hydrazono)methyl) phenol], L3H = [2-((2-benzyl-2-phenylhydrazono) methyl)-4,6-di-tert- butylphenol], and L4H = [2-((2-benzyl-2-phenylhydrazono)methyl)-6-(tert-butyl)-4-methoxy phenol where H stands for dissociable proton) in quantitative yields. Synthesized ligands L1H to L4H and corresponding palladium(II) complexes C1-C4 were characterized by NMR, IR and ESI-MS spectroscopic studies. Molecular structures of ligand L4H and complexes C1 and C3 were determined by X-ray crystallography. Complexes C1-C4 were utilized as catalysts to investigate Suzuki–Miyaura cross-coupling upon catalyst loading 0.01 mol%. These catalysts also catalyzed allylation of aldehydes up to 95% yield upon catalyst loading 0.5 mol% with broad substrate scopes. Theoretical and experimental investigation was performed to speculate reaction pathway of Suzuki–Miyaura cross-coupling reaction. A reaction model has also proposed for allylation of aldehydes in the presence of allyltributylstannane. Chapter 3: Ferrocenyl Palladacycles Derived from Unsymmetrical Pincer-Type Ligands: Evidences of Pd(0) Nanoparticle Generation During the Suzuki–Miyaura Reaction and Applications in the Direct Arylation of Thiazoles and Isoxazoles A new family of ferrocenyl-palladacycle complexes Pd(L1)Cl (Pd1) and Pd(L2)Cl (Pd2) were synthesized and characterized by UV-visible, IR, ESI-MS, and NMR spectral studies. The molecular structures of Pd1 and Pd2 were determined by X-ray crystallographic studies. Palladacycle catalyzed Suzuki–Miyaura cross- coupling reactions were investigated utilizing the derivatives of phenylboronic acids and substituted chlorobenzenes. Mechanistic investigation authenticated the generation of Pd(0) nanoparticles during the catalytic cycle and the nanoparticles were characterized by XPS, SEM and TEM analysis. Direct C–H arylation of thiazole and isoxazole derivatives employing these ferrocenyl-palladacycle complexes were examined. The reaction model for the arylation reaction implicating the in situ generation of Pd(0) nanoparticles were proposed. Chapter 4: Palladium-based Catalysts Supported by Unsymmetrical XYC-1 Type Pincer Ligands: C5 Arylation of Imidazoles and Synthesis of Octinoxate Utilizing Mizoroki-Heck Reaction A series of new unsymmetrical (XYC-1 type) palladacycles (C1-C4) were designed and synthesized with simple anchoring ligands L1-4H (L1H= 2-((2-(4-methoxybenzylidene)-1-phenylhydrazinyl)methyl)pyridine, L2H= N,N-dimethyl-4-((2-phenyl-2-(pyridin-2-ylmethyl) hydrazono)methyl)aniline, L3H= N,N-diethyl-4-((2-phenyl-2-(pyridin-2-ylmethyl)hydrazono) methyl) and L4H= 4-(4-((2-phenyl-2-(pyridin-2-ylmethyl)hydrazono) methyl)phenyl) morpholine, H= dissociable proton). Palladacycles (C1-C4) were characterized by several spectroscopic studies. Molecular structure of catalysts (C1-C4) were further established by single X-ray crystallographic studies. The catalytic performance of palladacycles (C1-C4) was explored with the direct Csp2−H arylation of imidazoles with aryl bromide derivatives. These palladacycles were also applied for investigating of Mizoroki-Heck reactions with aryl bromides and acrylate derivatives. During catalytic cycle in situ generated Pd(0) nanoparticles were characterized by XPS, SEM and TEM analysis and a possible reacion pathways were proposed. The catalyst was employed in gram-scale synthesis of octinoxate (2-ethylhexyl-4-methoxycinnamate) which is utilised as a UV-B sunscreen agent. Chapter 5: Efficient Organoruthenium Catalysts for α‐Alkylation of Ketones and Amide with Alcohols: Synthesis of Quinolines via Hydrogen Borrowing Strategy and their Mechanistic Studies A new family of phosphine free organometallic ruthenium(II) catalysts (Ru1-Ru4) supported by bidentate NN Schiff base ligands (L1-L4 where L1= N,N-dimethyl-4-((2-phenyl-2-(pyridin-2-ylmethyl)hydrazineylidene)methyl) aniline, L2= N,N-diethyl-4-((2-phenyl-2-(pyridin-2-yl methyl)hydrazineylidene)methyl)aniline, L3= N,N-dimethyl-4-((2-phenyl-2-(pyridin-2-yl) hydrazineylidene)methyl)aniline and L4= N,N-diethyl-4-((2-phenyl-2-(pyridin-2-yl)hydraz ineylidene)methyl)aniline) were prepared and characterized. These half-sandwich complexes acted as catalysts for CC bond formation and exhibited excellent performance in the dehydrogenative coupling of ketones and amides. In the synthesis of C–C bonds alcohols were utilized as the alkylating agent. A broad range of substrates, including sterically hindered ketones and alcohols, were well tolerated under the optimized conditions (TON up to 47000 and TOF up to 11750 h-1). This ruthenium (II) catalysts were also active towards the dehydrogenative cyclization of o-amino benzyl alcohol for the formation of quinolines derivatives. Various polysubstituted quinolines were synthesized in moderate to excellent yields (TON up to 71000 and TOF up to 11830 h-1). Control experiments were carried out and ruthenium hydride intermediate was characterized to support the reaction mechanism and probable reaction pathway of dehydrogenative coupling reaction.Chapter 6: Sterically Hindered NNO Pincer-type Copper(II) Complexes: Synthesis, Efficient and Versatile Catalysis of CN coupling under Base Free Condition A new family of copper complexes (C1-C4) was synthesized and characterized by UV-visible, IR, ESI-MS spectral studies. The molecular structures of copper complexes C2, C3 and C4 were established by single-crystal X-ray diffraction methods. These copper complexes are active catalysts for the CN coupling reaction under base free condition. Complexes were found to be the most efficient catalyst for CN coupling reaction between substituted phenylboronic acid and imidazoles derivatives. These catalysts activated of aryl silane bond for the formation of CN. These copper catalysts also useful for CN coupling between sulfonyl azides and phenylboronic acid under base free condition. Chapter 7: Unprecedented Copper-assisted Cyclization Reaction: Onepot Synthesis of [1,2,4] triazinium Cations During Metal Complex Formation and Application in Protein Binding One–pot [1,2,4] triazinium cationic species (C1-C3) were synthesized from Cu2+ assisted imine CH bond activation followed by cyclization of Ligands L1-3H (L1H= 2-((2-(4-methoxybenzylidene)-1-phenylhydrazinyl)methyl)pyridine, L2H= N,N-dimethyl-4-((2-phenyl -2-(pyridin-2-ylmethyl)hydrazono)methyl)aniline, L3H= N,N-diethyl-4-((2-phenyl-2-(pyridin-2-ylmethyl)hydrazineylidene)methyl)aniline. [1,2,4] triazinium cationic species (C1-C3) were characterized by single-crystal X-ray diffraction. These cationic species show solid state fluoresces property. These cationic species also utilized for DNA intercalative binding and protein binding studies. Control experiments were carried out and some of intermediate was characterized by ESI-MS spectroscopy to explain the reaction pathway of copper(II) assisted cyclization reaction.