Synthesis and hydrolytic decomposition of 2-hetaryl[1,2,4]triazolo[1,5-c]quinazolines: DFT study

Mechanisms for formation and hydrolysis of biologically active 2-substituted [1,2,4]triazolo[1,5-c]quinazolines were modeled at the SMD/B3LYP/6-31 + G(d) theory level. Obtained results revealed that internal heterocyclization of hetarylcarboxylic acid (3H-quinazolin-4-ylidene)-hydrazides involves a proton transfer from nitrogen atom of quinazoline system to oxygen atom of carbonyl group, cyclization with formation of [1,2,4]triazolo[4,3-c]quinazoline system, elimination of molecule of water. Dimroth rearrangement using the ANRORC mechanism of 2-hetaryl[1,2,4]triazolo[4,3-c]quinazolines leads to 2-hetaryl[1,2,4]triazolo[1,5-c]quinazolines. The rearrangement is catalyzed by molecule of water and consists of an addition of molecule of water to quinazoline cycle that facilitates its sequential opening, rotation of 1,2,4-triazole, cycle closure and elimination of molecule of water. Acid-catalyzed hydrolysis of 2-hetaryl[1,2,4]triazolo[1,5-c]quinazolines involves protonation of nitrogen atom of quinazoline cycle, an addition of molecule of water to protonated [1,2,4]triazolo[1,5-c]quinazoline system, opening of quinazoline cycle, an addition of second molecule of water, elimination of formic acid, and deprotonation. Substituents influence insignificantly on activation barriers for formation and hydrolysis of 2-hetaryl[1,2,4]triazolo[1,5-c]quinazolines.