Novel synthesis, ring transformation and anticancer activity of 1,3-thiazine, pyrimidine and triazolo[1,5-a]pyrimidine derivatives

Abstract

Synthesis, heterocyclization and anticancer activity of a new series of heterocyclic compounds are described. Aminothiazine 1 was obtained from the base induced condensation of thiourea, benzaldehyde and ethyl cyanoacetate. The synthesis of N-phenyl amino pyrimidine derivative 2 was obtained as a result of reaction of aniline with compound 1. Compound 2 underwent ring opening and recyclization upon reaction with HCl or H₂O₂/ NaOH to afford the acid derivative 3 or oxazine 4, respectively. Thiazine 1 undergoes ring transformation upon the effect of NH₂OH.HCl to produce pyrimidine derivative 5. Heterocyclization of compound 1 with thiosemicarbazide followed by oxidation with I₂/AcOH afforded triazolopyrimidine 6 and 7, respectively. Alkylation of compound 1 was promoted by reaction of 1 with ethyl iodide to give alkylated thiazine 8 which in turn undergo ring transformation when subjected to reaction with hydrazine hydrate to give pyrazole derivative 9. Refluxing of amino-1,3-thiazine derivative 1 with ethyl bromoacetate in the presence of Et₃N produce the alkylated pyrimidine product 10. Hydrazonolysis of 1,3-thiazine 1 with hydrazine or phenyhydrazine gave pyrimidine derivatives 11a,b, respectively. Compound 11b was cyclized with carbon disulfide or formaldehyde to produce triazolopyrimidines 12 and 13, respectively. Some of the new compounds were screened for anticancer activity and significant results were found for some compounds.

KEY WORDS: 1,3-Thiazine, Pyrimidine, Triazole, Pyrazole, Anticancer activity

Bull. Chem. Soc. Ethiop. 2018, 32(3), 513-522.

DOI: https://dx.doi.org/10.4314/bcse.v32i3.10