Magnetic Nanoparticle Assisted Bulk Scale Synthesis of Quinazoline Synthon

Abstract

Quinazolines are unique class of compounds possessing exceptional antibacterial activity. Quinazolines class obtains its typical antibacterial activity due to its toxicity from‘hetero’ ring. Known to be the last line of protection against deadly TB bacteria, there are about twenty different quinazoline compounds used in pharma industry. One of the widely used precursors for synthesis of these drugs is 4-chloro-2-phenylquinazoline. In the present research, aminobenzamide and benzoyl chloride are reacted to obtain the cyclized intermediate, 2-phenylquinazoline, which on subsequent treatment with POCl3 forms in 4-cholro-2-phenyl quinazoline. This reaction takes about four days to finish with maximum yield of around 60%. A modification was done using silica coated magnetic nanoparticles (Fe3O4@SiO2) as solid support to further improve the yields attaining about 80% and reduction of reaction time to half. Based on the results obtained, it was concluded that the solid support facilitates the adsorption of acid chloride and also provides the catalytic surface for condensation reaction, due to the acidic nature of the silica gel. The POCl3 reaction uses the nanosilica surface to produce 4-chloro phenyl-2-qinazoline in 80% overall yield. The reason for improved yield could be increase in acidic surface area which could speed up the quinazoline cyclization. Though material chemistry supports are known to improve reaction yields, use of silica coated magnetic nanomaterials towards the quinazoline synthesis is reported for the first time. The characterization data of Fe3O4@SiO2 particles has shown that batch to batch consistency exists in synthesis and it can be used in the pharma industry.