Spectral and computational studies on regioselective synthesis of 4-oxo-6-phenyl-2-selenoxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile

Abstract The nucleophilic addition reaction of selenourea (1) to each ethyl 2-cyano-3-phenylacrylate (2) and 2-cyano-3-phenylacrylamide (3) was investigated. Three regioisomeric products (A–C) were proposed due to the presence of different electrophilic centers in compounds 2 and 3. Based on the spectroscopic measurement (infrared, NMR) combined with quantum mechanical calculations, a regioselective product; 4-oxo-6-phenyl-2-selenoxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile (A) was identified in both reactions. On the other hand, the conformational analysis and selenol-selenone tautomerism were examined using DFT methods (B3LYP and M06–2X) combined with 6-31 + G (d,p) basis set. The computational outcomes favor selenone-keto tautomeric form where the phenyl ring was twisted by 44.5° with respect to the pyrimidine ring. The regioselectivity and reaction mechanism for possible pathways were theoretically investigated using the calculated energies/atomic charges for intermediates/transition states besides thermodynamic parameters for involved steps. Accordingly, the second nucleophilic addition of amino group to carbonyl carbon was favored, instead of nitrile group in compounds 2 and 3 and led to the formation of regioisomer A. The observed IR bands, 1H and 13C NMR chemical shifts were precisely interpreted supported by the calculated vibrational frequencies and chemical shifts which correlated well to the favored oxo-cyano regioisomeric product (A).