Conformational analysis of menthone, isomenthone, and several of their imines by NMR spectroscopy and molecular modelling: effect of group electronegativities on 3JHH

Abstract

The conformational analysis of menthone ( trans -2-Isopropyl-5-methylcyclohexanone), isomenthone ( cis -2-Isopropyl-5-methylcyclohexanone), and several imines derived from these compounds was performed by 1 H-NMR and the experimental Boltzmann distributions were compared with molecular modelling calculations. Menthone was found adopting a conformation with both methyl and isopropyl groups equatorially oriented at room temperature (21¿23¿C). On the other hand, isomenthone exists in an equilibrium containing ca . 79% of a conformer in which the isopropyl group is axial and the methyl equatorial. The menthone imines, in general, contain about 20% of a diaxial chair conformation and the isomenthone imines have the isopropyl group axial and the methyl equatorial. The conformational differences between these molecules is explained as a competition of pseudo allylic A (1,3) interactions between the isopropyl group and the non-bonded pair of electrons of the heteroatom, and axial-axial interactions between the alkyl chains and the protons of the ring. It was also found that semiempirical, low level ab initio , and DFT calculations poorly reproduced the experimental results due to the small energy differences (<2 kcal/mol) between conformers. <p> Proton-proton three bond coupling constants were recorded for the bornyl and menthyl acetate series ?O 2 CCH 3 , ?O 2 CCCl 3 , and ?O 2 CCF 3 , as well as for other derivatives, in order to observe the effect of group electronegativities, on 3 J HH . The experimental coupling constants were found to be the same, within experimental error, between the three acetates and the corresponding alcohol. In addition, a good linear correlation was observed when the 3 J HH 's were plotted against first atom electronegativity (r = 0.97) instead of group electronegativity; therefore, it is suggested that atomic electronegativities might be good enough to empirically describe substituent effects on 3 J HH .