Synthesis and Reactivity of 3′,5′-Dichloro-1H-spiro(quinazoline-2,4′-[1,2,6]thiadiazin)-4(3H)-ones

Abstract

A three-step synthesis of 3?,5?-dichloro-1H-spiro(quinazo-line-2,4?-[1,2,6]thiadiazin)-4(3H)-ones starting from 3,4,4,5-tetra-chloro-4H-1,2,6-thiadiazine is presented. The latter reacts with 2-aminobenzonitriles to give 2-[(3,5-dichloro-4H-1,2,6-thiadiazin-4-ylid-ene)amino]benzonitriles, which affords, after hydration, the respective benzamides. Upon heating at reflux in EtOH or HFIP, the benzamides intramolecularly cyclize onto the thiadiazine C4 position to give 3?,5?-dichloro-1H-spiro(quinazoline-2,4?-[1,2,6]thiadiazin)-4(3H)-ones. Single crystal X-ray crystallography supports the structure of two analogues. The chloride displacement of these new spiroquinazolinones was demonstrated by Stille coupling, and by reaction with methoxide to afford both the mono and bis-methoxy derivatives.