Temperature-Controlled Cyclization of Anthranilic Acids to 2-Thioxoquinazolin-4-One or Thiazoloquinazolinone Derivatives Under Microwave Irradiation

Abstract

Investigation of the microwave-assisted condensation of anthranilic acid derivatives with ethylpiperidine isothiocyanates into 2-thioxoquinazolin-4-ones revealed an intramolecular cyclization into 2,3-dihydro-5H-thiazolo[2,3-b]quinazolinones. The study of reaction parameters demonstrated that temperature is a key factor controlling this transformation, while anthranilic acid substituents further modulate the reaction outcome. Here we report the promotion of the intramolecular cyclization to thiazoloquinazoline at high temperatures (200°C), whereas lower temperature (125°C) selectively favors the formation of 2-thioxoquinazolin-4-one in good yield. These findings provide refined conditions for the synthesis of 2-thioxoquinazolin-4-one derivatives and expand the way to synthesize 2,3-dihydro-5H-thiazolo[2,3-b]quinazolinone derivatives of potential medicinal interest.