Synthesis of New Tetrazole Derivatives of Spiro- and Bis-barbiturates

• Published in: Journal of the Chinese Chemical Society (Taipei) 2015-11, Vol.62 (11), p.959-967
• Main Authors: Kashani, Elmira, Pesyan, Nader Noroozi, Sahin, Ertan
• Format: Article
• Language: English
• Subjects: 4-(1H-Tetrazol-5-yl) benzaldehyde; Bond strength; Drugs; Hydrogen bonds; Intermolecular hydrogen bonding; Intramolecular hydrogen bonding; Spiro-barbiturates; Tetrazole; X-ray
• ISSN: 0009-4536; 2192-6549
• DOI: 10.1002/jccs.201500257

This work described the synthesis of the first and unprecedented examples of 5‐aryl‐1H‐tetrazoles including spiro‐ and bis‐(thio)barbiturates, generated from the reaction between 4‐(1H‐tetrazol‐5‐yl)benzaldehyde with (thio)barbituric acids and cyanogen bromide (BrCN) in the presence of triethylamine, providing good overall yields. Tetrazoles based on bis‐(thio) barbiturates were also obtained in the absence of BrCN under the same conditions. The structures were characterized by IR, 1H NMR, 13C NMR, X‐ray crystallography and mass analysis techniques. The reaction mechanism was proposed. The hydrogen bond strength (EHB) versus d (O1⋅⋅⋅⋅⋅O7 (w)) distance (kcal.mol−1) and corresponding pKa value for the proton of H3A (in water molecule) in 4b.H2O were estimated to be 13.8 kcal.mol−1 and 8.2, respectively. The first and unprecedented examples of 5‐aryl‐1H‐tetrazoles including spiro‐ and bis‐(thio)barbiturates were synthesized, providing in good overall yields new type tetrazoles. The hydrogen bond strength (EHB) versus d (O1⋅⋅⋅⋅⋅O7 (w)) distance (kcal.mol−1) and corresponding pKa value for the proton of H3A (in water molecule) in 4b.H2O were estimated to be 13.8 kcal.mol−1 and 8.2, respectively.