Novel Microwave-Assisted Processes For The Green Synthesis Of Heterocycles
Dr. Béla Török, Associate Professor, Department of Chemistry, University of Massachusetts Boston, Boston, MA, USA

Nitrogen containing heterocycles are the core part of many important biologically active compounds and are of exceptional interest in medicinal applications. The importance of these compounds provides significance and actuality for developing new methods for their syntheses. Heterogeneous catalysis, including solid acid catalyzed reactions is an important tool for green organic synthesis. Solid acids serve as contemporary, environmentally friendly alternatives to traditional acids. Coupled with the efficiency of microwave irradiation these processes are promising options to many current protocols. In this work our recent efforts on the development of green, microwave-assisted technologies will be illustrated.

NH₂-containing compounds (amines, amides, sulfonamides) readily underwent cyclization and successive electrophilic annelation with bidentate alkylation agents (2,5-hexanedione, 2,5-dimethoxytetrahydrofuran) under solvent-free conditions in the presence of a strong solid acid. Our choice, K-10 montmorillonite is an extremely versatile catalyst: it is a strong acid with high surface area, excellent thermal stability and it absorbs microwaves. The combination of K-10 and microwave irradiation provides very efficient, yet environmentally benign circumstances for the cyclialkylations. This enabled us to synthesize a wide variety of 5-membered N-containing het-erocyclic compounds, such as pyrroles, indoles and carbazoles in excellent yields in short times.

In an extension of cyclizations, the unique combination of a bifunctional K-10/Pd/C catalyst with microwave activation made the direct synthesis of various substituted pyrazoles possible in a three-step one-pot domino reaction. K-10 initiates the condensation and cyclization reactions and Pd dehydrogenates the intermediate to the desired pyrazoles. This new environmentally friendly synthetic methodology provides very higher yields (91-98%) in short reaction times for the preparation of the target compounds without the isolation of the pyrazoline intermediate. The same concept of bifuntional metal-acid catalysis was extended to the one-pot synthesis of pyridines via domino cyclization-dehydrogantion approach from multicomponent systems. This method is an effective contemporary one-pot modification of the Hantzsch synthesis.