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

• Published in: Structural chemistry 2024-02, Vol.35 (1), p.97-104
• Main Authors: Pylypenko, Olena O., Sviatenko, Liudmyla K., Shabelnyk, Kostyantin P., Kovalenko, Sergiy I., Okovytyy, Sergiy I.
• Format: Article
• Language: English
• Subjects: Carbonyl groups; Carbonyls; Chemistry; Chemistry and Materials Science; Computer Applications in Chemistry; Formic acid; Hydrazides; Hydrolysis; Nitrogen; Physical Chemistry; Protonation; Theoretical and Computational Chemistry
• ISSN: 1040-0400; 1572-9001
• DOI: 10.1007/s11224-023-02251-8

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 (3 H -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.