Theoretical and spectroscopic study of stereoeletronic effects in hydrazide derivatives and organofluorine compounds

Abstract

It’s known that reactivity and conformational equilibrium can be strongly influenced by stereoelectronic interactions, which is related to the overlap of atomic and/or molecular orbitals. Gauche, anomeric, Bohlmann, among others, are directly related to this type of interaction. Thus, different classes of organic compounds were investigated in order to evaluate the contribution of these effects to the conformational stability. The model compounds studied were evaluated theoretically and through analyzes of Nuclear Magnetic Resonance (NMR) and Infrared (IR) spectroscopy. The computational research used the MP2 and ωB97X-D/6-311++G (d,p) levels in several solvents, followed by the analysis of the natural bonding orbitals (NBO) to determine the energetic fractions involved. The quantum theory of atoms in molecules (QTAIM) and the analysis of non-covalent interactions (NCI) were used to characterize possible hydrogen bonds in the compounds. It was found that the electrostatic (P + F -) and hyperconjugative gauche effects (σCH→σ*CF and σCH→σ*CP) don’t seem to determine the conformational equilibrium of the fluorinated organophosphates compounds studied. In this class of compounds, hydrogen bonds look like to be important, but in general, steric and dipole repulsive interactions dictate conformational equilibrium. For N,N-diethyl-(1,1,2,3,3,3-hexafluoropropyl)amine (Ishikawa reagent), the gauche effect plays a significant role in the conformational stability when in highly polar medium. This compound also experiences the generalized anomeric effect, which is determinant for the rotation around the N‒C‒C‒ (F2) bond. The hyperconjugative interaction also has a strong influence on the conformational preference of 2-fluorocyclohexane-1,3-dione, where the equatorial position of the C‒F bond unexpectedly remains in both media. Thus, this system becomes a promising reference for conformational modulation. With respect to hydrazides, the main stabilizing factor of the conformations can’t be attributed to hyperconjugation; however, it is possible to observe that the N‒H stretch vibration mode is really sensitive to this type of interaction, making it efficient to probe the conformation of a congenial portion in larger systems. Notably, the conformational control of organofluorinated compounds by mean of stereochemical interactions goes beyond the well-known gauche effect of fluorine, providing perspectives for the planning of molecules with potential for application, whose stereochemistry of the C‒F bond plays an important role.