Synthesis, configuration and properties of some new 3,4,5-substituted oxazolidin-2-ones

Abstract

Novel 3,4,5-substituted-oxazolidin-2-ones containing piperazine, 1-(4-chlorophenyl) piperazine, benzhydrylpiperazine, morpholine and piperidine rings were synthesized via Mannich reaction. The stereochemistry of syn and anti-isomers was assigned using the observed differences in the chemical shifts of the oxazolidinone ring protons and the values of vicinal coupling constants (³J) between the two protons of the oxazolidin-2-one ring. For all compounds NOE (Nuclear Overhauser Effect) NMR spectra were measured in order to prove additionally the position of the substituents in the oxazolidin-2-one ring. Some physic chemical, steric and electronic properties of the compounds were determined in order to establish the similarity between the synthesized and reference compounds. The performed computations showed that the anti-isomers possessed lower electronic energies in comparison to these of syn-compounds. The nucleus-nucleus repulse energies (NRE) and the highest occupied molecular orbital energies (HOMO) of the anti-isomers are higher than the HOMO and NRE energies of syn-compounds. The Connolly Solvent Accessible Surface Area (SAS) and Connolly Molecular Surface Area (MS) values of anti-isomers are lower than these of syn-isomers. The same relations were observed for the reference compounds. Probably the differences in the electronic and steric properties are responsible not only for the higher LD₅₀ value of the reference anti-compound, but also may contribute to the higher toxicity of the prepared anti-Mannich bases in comparison to that of the syn-diastereoisomers.