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

Abstract

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, 1 H NMR, 13 C NMR, X-ray crystallography and mass analysis techniques. The reaction mechanism was proposed. The hydrogen bond strength (E HB ) versus d (O1·····O7 (w)) distance (kcal.mol -1 ) and corresponding pKa value for the proton of H 3A (in water molecule) in 4b.H 2 O were estimated to be 13.8 kcal.mol -1 and 8.2, respectively.

Review on synthetic approaches towards barbituric acids‐based furo[2,3‐d]pyrimidines

“…In 2015, Noroozi Pesyan et al reported that the reaction of 4‐cyanobenzaldehyde with sodium azide in the presence of catalytic amounts of montmorillonite K10 in refluxing DMF for 24 h gave 4‐(1 H ‐tetrazol‐5‐yl)benzaldehyde (127) and then its reaction with BrCN and some (thio)barbiturates 4 in CH 3 OH resulted 5‐substituted tetrazoles including spiro barbiturates 128 in 60%–80% yields in the presence of triethylamine and/or L‐(+)‐TA as a basic and acidic conditions, respectively (Scheme 45, paths a and b ) [63].…”

4‐Methyl morpholinium bis‐(thio)barbiturates: Synthesis, structure, anticancer evaluation, and CoMFA study

“…[ 15 ] One‐pot reaction of (thio)barbituric acids with aldehydes and cyanogen bromide yield spiro furo[2,3‐ d ] pyrimidines. [ 16–21 ]…”