Investigation On Methodology For The Synthesis Of Nitrogen-Containing Heterocycles

Nitrogen-containing heterocycles are crucial moieties in a wide range of drug leads. Nitrogen-containing heterocycles of different ring sizes, with different substitution patterns and embedded in various molecular frameworks constitutes extremely important structure classes in the search for bioactivity. Despite the large availability of methods to construct nitrogen-containing heterocycles, there is still a strong need to further explore synthetic methods to efficiently synthesize novel heterocyclic structures. For the stringent and growing environmental regulations, organic chemists are requested to develop clean, economical, and environmentally safer methodologies. We aim at the development of novel methodology for the synthesis of nitrogen-containing heterocyclic structural motifs carried out in water, under solvent-free conditions, microwave irradiation or photolysis. The main work presented in this dissertation can be divided into seven parts:1. 2-Substituted 4-(3H)-quinazolinones have shown biological activities, these types of compounds have not been synthesized in aqueous solvent before. We have developed an aqueous synthesis of 2-substituted 4(3H)-quinazolinones via the condensation of aldehydes with anthranilamide using iron(III) chloride hexahydrate. This method provides several advantages such as being environmentally friendly, simple work-up procedure and high yields (77-93%).2. A synthetic route to unsymmetrical 9-arylacridinediones in aqueous-phase or solvent-free conditions is described. These aqueous and solvent-free conditions give excellent yields that could not be achieved in organic solvents. The current process provides a simple and green method to obtain a variety of novel unsymmetrical acridinediones, which may have potential biological activities.3. An efficient synthesis of N-substituted polyhydroquinolines under solvent-free conditions using DMAP as a catalyst, through reactions of benzylidene malonitriles and cyclic enaminones, is described. Operational simplicity, use of an economically convenient catalyst, high yield and short reaction times are the key features of this protocol.4. A simple and efficient method for the solvent-free synthesis of 2-phenylbenzimidazoles is described. By direct heating aromatic aldehydes, malonitrile and o-phenylenediamine,...