Synthesis and biological activity evaluation of Heterocyclic compounds containing quinazolone and quinazoline moieties

Abstract

This study deals with the synthesis and reactions of the 6-iodo-2-ethoxy-4H-benzo[d][1,3]oxazin-4-one 3 and its derivatives. The benzoxazinone derivative 3 was synthesized by treatment of 2-amino-5-iodobenzoic acid 1 with ethyl chloroformate in pyridine to give the 2-ethoxycarbonylamino-5-iodobenzoic acid 2 followed by a ring closure in acetic anhydride (Scheme I). The benzoxazinone derivative 3 was used to prepare quinazolinone derivatives via reaction with different nitrogen nucleophiles. Reaction of benzoxazinone derivative 3 with p-toluidine in refluxing ethanol afforded the corresponding quinazolinone derivative 4, while with o-anisidine in boiling ethanol yielded the urea derivative 5 (Scheme I). Treatment of benzoxazinone 3 with p-aminoacetophenone and/or p-aminobenzophenone afforded iodophenylcarbamate derivatives 6a,b (Scheme I). Compound 6a was recycled in freshly distilled acetic anhydride to give the desired quinazolin-4(3H)-one 7, which on treating with benzaldehyde in refluxing ethanol gave chalcone 8 (Scheme I). On the other hand, aminolysis of benzoxazinone 3 with piperidine and/or morpholine gave phenylcarbamate derivative 9 and carboxmide derivative 10, respectively (SchemeI). When benzoxazinone derivative 3 was reacted with sodium azide in boiling acetic acid it yielded the tetrazol derivative 11 together the imidazole derivative 12 (Scheme I). The 3-hydroxyquinazolinone derivative 13 was yielded on refluxing of benzoxazinone 3 with hydroxylamine hydrochloride in pyridine for 3 hrs (Scheme I). Moreover, hydrazinolysis of benzoxazinone derivative 3 yielded the 3-aminoquinazolinone derivative 14 (Scheme I). On the other hand, when benzoxazinone 3 was allowed to react with formamide in boiling ethanol for 2 hours, the amino quinazolinone 15 was isolated (Scheme I). In the context, 2-hydrazinylquinazolin-4(3H)-one 14 was expected to be highly reactive compound and is used as intermediate for synthesis of many heterocyclic compounds. The hydrazino and amino functions were suitably situated to react with different electrophilic reagents. Thus, the 2-hydrazinyl- quinazolin-4-one 14 reacted with benzaldehyde in boiling ethanol and [1,2,4,5]tetrazino[6,1-b]quinazolin-6-one 16 was produced (Scheme II). Moreover, interaction of 2-hydrazinylquinazolin-4-one 14 with phenylisothiocyanate yielded the [1,2,4,5]tetrazino[6,1-b]quinazolin-6-one derivative 17 (Scheme II).