Regioselective cyclization reaction of 2-imino-2H-chromene-3-carboxamide with triethyl phosphonoacetate; a combined spectral and computational studies

Abstract The regioselectivity for cyclization reaction of 2-imino-2H-chromene-3-carboxamide with triethyl phosphonoacetate was investigated by means of quantum mechanical calculation combined with infrared and NMR spectral analysis. Density functional theory (DFT) using B3LYP method at 6-31G(d,p) and 6-311++G(d,p) basis sets were used. Two possible pathways for this reaction were explored which resulted in the formation of two regioisomeric products with different ring skeletons; benzoxaphosphorino[3,4-c]pyridine (BOPP) and chromeno[3,4-c]azaphosphinine (CAP). Initially, the tautomeric stability for both products (BOPP and CAP) was predicted in favor of the hydroxy-keto tautomeric structure (S-3/S-6). The 1H-, 13C and 31P NMR chemical shifts were also computed for BOPP and CAP using GIAO-B3LYP/6-311++G(d,p) calculations in DMSO solvent modeled by the PCM method. The computational results revealed that the BOPP regioisomer (S-3) was favored with an energy difference of 9.44 kcal/mol. With the help of the calculated frequencies and chemical shifts, the observed infrared bands and NMR resonances were confidently assigned and a better match for BOPP regioisomer was achieved. In addition, the proposed mechanism for both reaction pathways was theoretically studied based on the calculated electronic structure for reaction intermediates and thermodynamic parameters for the involved steps. The obtained results preferred the pathway which led to the formation of BOPP as a regioselective product.