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.

Automated summary

In this study, the mechanisms for the formation and hydrolysis of biologically active 2-substituted [1,2,4]triazolo[1,5-c]quinazolines were investigated using theoretical modeling. The results revealed that internal heterocyclization and Dimroth rearrangement are crucial steps in the formation and hydrolysis processes, respectively, and are catalyzed by water molecules. The influence of substituents on the activation barriers for these reactions is insignificant.