Synthesis, characterization and in silico studies of some 2-amino-4,6- diarylpyrimidines derived from chalcones

Abstract

Pyrimidine derivatives have garnered substantial research interest over the past decades. This is largely due to their wide range of biological activities as antiviral, diuretic and antitumor agents, as well as their potential therapeutic application in ameliorating several degenerative diseases. In this study, 2-amino-4,6- diarylpyrimidines were synthesized from their respective 1,3-diphenylprop-2-en-1-one (chalcone) precursors. The chalcones were condensed with guanidine carbonate by refluxing in dimethylformamide for 4 hours at 160^oC to obtain the following compounds: 4,6-diphenyl-pyrimidin-2-ylamine (PAA₁), 4-(4-nitro-phenyl)-6- phenylpyrimidin-2-ylamine (PAA₂), 4-phenyl-6-(3,4,5-trimethoxy-phenyl)pyrimidin-2-ylamine (PAA₃) and 4-phenyl-6-(3,4,5-trimethoxy-phenyl)pyrimidin-2-ylamine (PAA₄). TLC analysis was used to monitor the purity of the synthesized compounds, and their melting points were determined using the open capillary method with a Kofler Electrothermal melting point apparatus. They were characterized using IR, ¹H-NMR, ¹³C-NMR and GC - MS. The biological activities of the title compounds were predicted using the Gaussian 16 software suite-36 (for full geometry optimization in chloroform and gas phase) and the SwissADME web tool for lipophilicity and hydrophilicity. The compounds were obtained in good yield, and the characteristic N-H stretch of the -NH₂ group (free and H-bonded) was observed at 3503, 3380 cm^-1 (PAA₁); 3492, 3317 cm^-1(PAA₂); 3194, 3309 cm^-1 (PAA3); and 3466, 3313 cm^-1(PAA4). The amino protons showed a broad peak between 4.47 – 5.31 ppm while the characteristic C2 and C5 of 2-aminopyrimidines resonated at 105.34 and 163.03 ppm respectively. The logP values revealed that the lipophilicity of the compounds decreased in the order: PAA₁< PAA₂< PAA₃< PAA₄. The computations on the optimized geometry established the possible application of the compounds in the synthesis of modern pharmaceuticals.