Crystal structure, Hirshfeld surface analysis, and computational insights into phenoxyacetohydrazones: Hydrogen-bonded dimers and p-stacking interactions

X-ray crystallographic and theoretical study, including Hirshfeld surface analysis of four acylhydrazones, PhOCH2CONH-N--CH-C6H4-X-p (1: X = H; 2: X = F; 3: X =Cl; 4: X = Br), has been carried out: a larger number of this series of compounds 1 has recently been found to possess activity against Trypanosoma cruzi. In the solid state, the four molecules have the (E) arrangement about the C--N bond and the syn arrangement about the NHCO fragment. Two major sub-structures of each compound are present in the solid state: (i) symmetrical R22(8) dimers formed from pairs of classical N-H(hydrazinyl)& ctdot;O(carbonyl) hydrogen bonds and (ii) columns composed of parallel and equally spaced layers of single molecules. The short perpendicular separations of the layers and the overlaps of the delocalised -C(O)-NH-N--CH-C6H4- fragments of the compounds indicate extensive pi-interactions. Calculations, including Hirshfeld surface analysis, provide confirmation of these interactions. While extensive regions of pi-overlap are indicated in the columns, specific pi(C--N) & ctdot;pi(pH) and C-X & ctdot;pi(pH) interactions (X = F, Cl and Br) can be highlighted. Combination of the two major sub-structures results in one-dimensional, two-molecule-wide, infinite structures for all four compounds, with the 1 compound exhibiting a slight difference from the very similar structures of the halo derivatives. The only significant intermolecular interaction, which differs between 1 and the three halo-derivatives, 2-4 is the formation of C-X & ctdot;pi(pH) interactions, in which the halo substituent, in each case, resides above the centre of the phenyl ring. In 1, the hydrogen atom is close to the periphery of the ring: this reflects essentially the differences in the C-X bond lengths. In general, the very similar crystal structures for the three halo derivatives indicate that the significantly different properties of the halogen atoms have only small consequences on the overall crystal structures.