Regiochemistry of cyclocondensation reactions in the synthesis of polyazaheterocycles

• Published in: Beilstein journal of organic chemistry 2017-02, Vol.13 (1), p.257-266
• Main Authors: Campos, Patrick T, Rodrigues, Leticia V, Belladona, Andrei L, Bender, Caroline R, Bitencurt, Juliana S, Rosa, Fernanda A, Back, Davi F, Bonacorso, Helio G, Zanatta, Nilo, Frizzo, Clarissa P, Martins, Marcos A P
• Format: Article
• Language: English
• Subjects: Benzimidazoles; Carbon; Chemistry; Chromatography; DFT-B3LYP; Ethanol; Full Research Paper; Intermediates; Nitrogen; Phenylenediamine; polyazaheterocycles; pyrazinone; pyrido[1,2-a]pyrimidinone; pyrimido[1,2-a]benzimidazole; quinoxalinone; Reaction mechanisms; thiazolo[3,2-a]pyrimidinone
• ISSN: 1860-5397; 2195-951X; 1860-5397
• DOI: 10.3762/bjoc.13.29

The syntheses of several polyazaheterocycles are demonstrated. The cyclocondensation reactions between β-enaminodiketones [CCl C(O)C(=CNMe )C(O)-CO Et] and aromatic amidines resulted in glyoxalate-substituted pyrido[1,2- ]pyrimidinone, thiazolo[3,2- ]pyrimidinone and pyrimido[1,2- ]benzimidazole. Pyrazinones and quinoxalinones were obtained through the reaction of these glyoxalates with ethylenediamine and 1,2-phenylenediamine derivatives. On the other hand, the reaction of glyoxalates with amidines did not lead to the formation of imidazolones, but rather -acylated products were obtained. All the products were isolated in good yields. DFT-B3LYP calculations provided HOMO/LUMO coefficients, charge densities, and the stability energies of the intermediates, and from these data it was possible to explain the regiochemistry of the products obtained. Additionally, the data were a useful tool for elucidating the reaction mechanisms.