The aim of the paper was to estimate the degrees of freedom, i.e. the flexibility, of four compounds (1–4) belonging to the tertiary aromatic o-substituted oxo(thio) amide family in the perspective to exploit them as scaffolds for generating chemical libraries. A combined experimental and theoretical structural study was undertaken. Solid state X-ray structures of all the molecules are presented. Thermochemical data for 3 and 4, i.e. ΔHfus, ΔSfus and Tfus, were discussed on the basis of the solid state results. A survey of the 3D solid state key features retrieved in the Cambridge Crystallographic Database for molecular fragments featuring CO(S) grouping directly bound to a phenyl ring is presented. Results from a molecular modelling approach (both force field and ab-initio based) applied to ad-hoc simplified molecules were discussed both from a geometrical and energetic point of view.