SYNTHESIS AND STRUCTURAL STUDIES OF BENZIMIDAZOLE BASED SALTS AND THEIR METAL COMPLEXES

Abstract

the development of molecules of pharmaceutical or biological interest. The various benzimidazole derivatives have miscellaneous therapeutic applications viz., antiulcers, antihypertensives, antivirals, antifungals, anticancers and antihistaminics and s Benzimidazoles are typical nitrogen-containing heterocyclic and aromatic compounds in which six-membered benzene molecules are fused with five-membered imidazole moiety. The benzimidazole is a very useful structural motif for ome important drugs are omeprazole, pimobendam, mebendazole etc. The well-known benzimidazole compound in nature is N-ribosyl-dimethylbenzimidazole, which serves as an axial ligand for cobalt in vitamin B12. The benzimidazole and its derivatives have been widely used as a versatile ligand in the coordination as well as in supramolecular chemistry. It has a strong tendency to coordinate with the metal centers, which can lead to materials with potential applications in various fields. They are also used for the preparation of co-crystals and salts with other moieties and it has been found that their properties and reactivity’s are often better than the sum of the properties of each individual component. Benzimidazole is commercially available and the usual synthesis involves the condensation of o-phenylenediamine with formic acid, or with the equivalent trimethyl orthoformate. This method is very useful for the preparation of derivatives of benzimidazoles by altering the carboxylic acid. It is important to mention that benzimidazole and its derivatives promote intra and inter-molecular interactions, such as hydrogen bonding and π- stacking, which results in the formation of molecular aggregates. The different positional isomer of pyridine dicarboxylic acid are also well known for the formation of supramolecules because of their capability of forming robust dimeric and catemeric synthons through O-H···O type hydrogen bonds. It has also a very strong tendency to coordinate with the metal ions either by pyridyl nitrogen or through carboxylic group. For the sake of convenience, the work embodied in the thesis is presented in the following chapters. The first chapter of the thesis is the general introduction and presents an up to date survey of literature related to (i) the co-crystallization of benzimidazole ligands with organic as well as inorganic acids (ii) their chelation with metal complexes and (iii) their different application in various fields viz., fluorescence properties, biological activities etc. The different type of co-crystal, salts and metal complexes related to the present research have been post in the context of the cited work. Some salts of pyridine dicraboxylic acid (various positional isomers) with different benzimidazole bases have been synthesized and characterized by different physico-chemical methods are described in the second chapter of the thesis. The reaction of pyridine-2,3-dicarboxylic acid (2,3-PDCAH2), pyridine-2,4-dicarboxylic acid (2,4-PDCAH2), pyridine-2,5-dicarboxylic acid (2,5-PDCAH2), pyridine-2,6- dicarboxylic acid (2,6-PDCAH2), pyridine-3,4-dicarboxylic acid (3,4-PDCAH2) and pyridine-3,5-dicarboxylic acid (3,5-PDCAH2) with different benzimidazole bases e.g., 1,4-bis(1H-benzimidazol-2-yl)butane (H2BBBu) and tris(1H-benzimidazol-2- yl)methyl)amine (H3NTB) resulted into the formation of salts viz., [(H4BBBu)2+.(2,3- PDCA)2-], [(H4BBBu)2+.(2,4-PDCA)2-], [(H4BBBu)2+.(2,5-PDCA)2-], [(H4BBBu)2+.(2,6-PDCA)2-.H2O], [(H4BBBu)2+.2(3,4-PDCAH)-.2H2O], [(H4BBBu)2+.(3,5-PDCA)2-.3H2O], [(H5NTB)2+.2(2,3-PDCAH)-.DMF], [(H4NTB)+.(2,4-PDCAH)-.2CH3OH.H2O], [(H5NTB)2+.(2,5-PDCA)2-.DMF], [(H4NTB)+.(2,6-PDCAH)-.C2H5OH.CH3OH.H2O], [(H5NTB)2+.(3,4-PDCA)2-.DMF], [(H6NTB)3+.(3,5-PDCA)2-.(3,5-PDCAH)-.DMF]. During salt formation either one or both the proton has been transferred from the carboxylic acid to the nitrogen of the benzimidazole based ligand bearing lone pair of electron. An attempt has also been made to incorporate metal in the above prepared salts. These complexes are (H3BBPr)+[Zn(2,3-PDCAH)3]-, (H3BBBu)+[Zn(2,3-PDCAH)3]-, (H3BBHex)+[Zn(2,3- PDCAH)3]-, (H4BBPr)2+[Ni(2,6-PDCA)2]2-.7H2O, (H4BBBu)2+[Ni(2,6-PDCA)2]2- and (H4BBHex)2+[Ni(2,6-PDCA)2]2-.CH3OH. All the compounds consist of a protonated cationic benzimidazole based ligand and an anionic metal complexes core. These salts and metal complexes have been characterized by different methods including elemental analysis, IR and single crystal X-ray crystallography. Due to the presence of nitrogenrich benzimidazole bases, each salt and metal complexes contain infinite two or three dimensional structures held together by primary N-H···O, N-H···N, O-H···N, O-H···O hydrogen bonds and secondary C-H···O, C-H···π interactions. The third chapter of the thesis deals with the preparation of some salts and cocrystal of different benzimidazole ligands such as N,N,N',N'-tetrakis(1H-benzimidazol- 2yl)methyl)ethane-1,2-diamine (H4EDTB) and N,N,N′,N′-tetrakis(1H-benzimidazol2ylmethyl) propane-1,3-diamine (H4PDTB) with various inorganic and organic acids viz. HClO4, HCl, HNO3, H3PO4, HBr, HF, CF3COOH and CH3COOH. The reaction of acids with different benzimidazoles in aqueous methanol/DMSO resulted into the formation of salts and co-crystal, viz., [(H8EDTB)4+.4(ClO4)-.H2O], [(H8EDTB)4+.4(Br)- .4DMSO], [2(H7EDTB)3+.3(SiF6)2-.14H2O], [(H8EDTB)4+.4(H2PO4)-.2H3PO4], [H4EDTB.2CH3COOH], [(H8PDTB)4+.4(ClO4)-.H2O], [(H8PDTB)4+.4(Cl)-.2H2O], [(H8PDTB)4+.2(H2PO4)-.(H7P3O12)2-.3H3PO4], [(H8PDTB)4+.4(NO3)-], [2(H5PDTB)+.2(CF3COO)-.5H2O] and [(H8PDTB)4+.3(ClO4)-.(H2PO4)-]. These salts and co-crystal have been characterized by different methods including elemental analysis, IR spectroscopy, UV-Visible spectroscopy, and single crystal X-ray crystallography. During salt formation the proton has been transferred from the acid to the nitrogen of the benzimidazole based ligand bearing lone pair of electron, while in the case of co-crystal no proton has been relocated. The selectivity of these ligands has also been checked through anion selectivity test and shows that these ligands are superiorly selective for perchlorate anion. The colorimetric test of these ligands shows that the methanolic solution of the ligands (H4EDTB and H4PDTB) are orange-red in color but after addition of the acids the color changes to light blue to dark blue. These salts and co-crystal have also been used for photoluminescence studies. The fourth chapter of the thesis deals with the synthesis of mono and dinuclear zinc (II) and cadmium (II) complexes with N,N,N',N'-tetrakis(1H-benzimidazol- 2yl)methyl)ethane-1,2-diamine (H4EDTB) and N,N,N′,N′-tetrakis(1H-benzimidazol- 2ylmethyl)propane-1,3-diamine (H4PDTB). The reaction of Zn(NO3)2.6H2O, Cd(NO3)2.4H2O and Zn(ClO4)2.6H2O with H4EDTB and H4EDTB resulted in the formation of [Zn(H4EDTB)](NO3)2.CH3OH, [Cd(H4EDTB)NO3]NO3.CH3OH.2H2O, [Zn(H4EDTB)](ClO4)2, [Zn(H4PDTB)](NO3)2.DMF, [Cd2(H4PDTB)(1-NO3)2(2- NO3)2.H2O].2H2O and [Zn2(H4PDTB)(H2O)2.(DMF)2](ClO4)4.2H2O. These complexes have been characterized by different methods including elemental analysis, IR spectroscopy and single crystal X-ray crystallography. These complexes showed pentato hepta-coordination number depending on the presence of different types of counter ions and the difference in the ligands. Both the zinc complexes are six coordinated derived from zinc nitrate either with H4EDTB or H4PDTB and the two counter nitrate anion are present in the lattice. The cadmium nitrate with H4EDTB forms a seven coordinated mononuclear system whereas with H4PDTB forms a dinuclear system with different coordination number. The photoluminescence properties of these metal complexes have also been studied with absorption and emission spectra and revealed that they shows luminescence due to the complexation resulting in the enhancement in rigidity of the molecule. The starting materials, reagents, synthetic procedures, experimental details and various spectroscopic measurements are described in the fifth chapter of the thesis. Methods for the preparation of different type of ligands, organic salts, co-crystal and metal complexes have also been reported in this chapter.