Microwave-assisted Synthetic Scheme of Novel Schiff Base Congeners of Pyrimidine Nuclei by Using Water as Solvent: A Green Approach to Synthesis

Abstract

Aim: The research work aims to develop a sustainable microwave-assisted scheme for the synthesis of 4-(benzylidene amino)-6-phenylpyrimidine-5-carbonitrile congeners. Background: 4-(benzylidene amino)-6-phenylpyrimidine-5-carbonitrile scaffolds are novel molecules having various pharmacological activities, such as neurodegenerative, antimicrobial, and anticancer. Schiff base congeners are considered efficient pharmacophores for research. These activities are due to the presence of azomethine (CH=N) group in the Schiff base compounds. Objectives: The aim of the study was to synthesise different novel Schiff base scaffolds of pyrimidine nuclei by green chemistry in good yield. Methods: The 4-(benzylidene amino)-6-phenylpyrimidine-5-carbonitrile scaffolds were prepared by two-step reactions. Both steps were microwave-assisted. The first step was to synthesize 4-amino-6- phenylpyrimidine-5-carbonitrile as an intermediate compound. This compound was synthesized by using benzaldehyde, malononitrile and formamidine hydrochloride. The reaction conditions are as follows: temperature- 101°C, pressure- 300W, time- 50min. The final Schiff base congeners were obtained by reacting them with various aromatic aldehydes in the second step. The yield, reaction condition, and time consumption were all very acceptable for the green synthetic methods rather than the conventional schemes. Results: Microwave-assisted method was more efficient. The reactions were less time-consuming, and the overall yield of the all-synthesized compounds was in the range of 72-81%. The synthesized congeners were characterized by different spectroscopic methods. The main functional group, azomethine, was considered by the IR peak at 1611 cm-1 wavelength. Conclusions: This microwave-assisted synthetic method thus emerges as more eco-friendly due to a much-reduced usage of organic solvents, leading to less harmful residues. Using this scheme, we synthesized different Schiff base congeners with satisfactory chemical yields.