A theoretical study of atropisomerism in N-(2-methylphenyl)-N′-(2-methylphenyl) thiourea and its inclusion in the β-cyclodextrin

β-cyclodextrin and its derivatives form inclusion complexes with a wide variety of guest molecules, including isomers and enantiomers. The main purpose of the present theoretical investigation is to predict the enantio-discrimination of N -(2-methylphenyl)- N ′-(2 methyl phenyl) thiourea and to study in details the inclusion process of the N -(2-methylphenyl)- N ′-(2 methyl phenyl) thiourea with the β-cyclodextrin using static quantum calculations. The compound presents three pairs of atropisomers that can possibly be experimentally separated by inclusion within the cavity of the β-cyclodextrin. Therefore, it appears of interest to study, in the first part, the model compound, the so called N -(2-methylphenyl)- N ′-(2-methylphenyl) thiourea 1. We were interested then in the identification of the possible conformers of this compound. All conformers were fully optimized at different levels of theory. The relative energies of all possible conformers are given and discussed. Our calculations showed, as expected, that the π-stacking conformer with respect to other structures is the most stable. In the second part, we were interested then to evaluate the host–guest complex stabilization through the formation of the inclusion compounds for the 1:1 association. The inclusion process pathways are described and the most stable structures of the different complexes are sought through a global search of the potential energy surface. Graphical Abstract