Facile Synthesis, Pure DFT Calculations, and PM3 Semiempirical MO Method Validation of Regiospecificity of Novel 1,4-Dihydropyrido[2,3-d]pyrimidine Derivatives

Abstract

Reaction of 6-aminothiouracil (or uracil) with equimolar amounts of different ketones or diketones and the appropriate aromatic aldehydes afforded di- and tricyclic linear pyrido[2,3-d]pyrimidine derivatives 4, 6–12, 14, 16–18, 20, and 21, and pyrimido[4,5-b]quinoline derivatives 15 and 19 in good yields. The regiospecificity, which led to the formation of compound 4 not 5, was validated using ab initio at the HF/6–31 G⁺(d,p) level and pure density functional theory (DFT) calculations using BLYP energy functional and the basis set DNP via studying the thermodynamics of their possible conformers and regioisomers. In addition, the total energy of the transition state was calculated for compounds 12 and 13 to determine whether the reaction products were thermodynamically or kinetically controlled. Hence, the linear structures and the regiospecificities of the reactions for the structures reported in this article were established by elemental analysis, spectral data, ab initio calculations, pure DFT, and PM3 parameters.

Keywords:

• Ab initio validation
• acetylacetone
• 6-amino-uracil and thiouracil
• molecular modeling
• trifloroacetylacetone

Notes

Notes. Hartree = 627.51 kcal/mol; RHF, restricted Hartree–Fock.

Note. Hartree = 627.5 kcal/mol.