New co-crystals of salicylic acid: from screening to synthesis and structural characterization

Few areas of crystal engineering have, in recent times, received the same amount of attention that has been lavished upon almost any topic dealing with co-crystals. Many co-crystals have been prepared through strong hydrogen bonds, notably between a carboxylic acid and an N-group hydrogen-bond acceptor.[1] To assess the utility of these synthons, we present here our studies on the supramolecular reactions between salicylic acid (SA) with six co-formers (tyramine (Tyr), 1,2-Phenylendiamine (Phen), paracetamol (Par), ibuprophen (Ibu), diglycine (Dig) and triglycine (Trig)). The co-crystals are first screening using Differential Scanning Calorimetry (DSC) and synthesized by Liquid Assisted Grinding (LAG). A single crystal of SA•••Phen and SA•••Trig were obtained by slow evaporation method using methanol as solvent in the first case and a mixture of methanol:water (9:1) in the second case. The mixtures were characterized by thermal analysis (DSC and Thermogravimetric Analysis (TGA)), Powder X-Ray Diffraction (PXRD), infrared spectroscopy (IR) and Single Crystal X-Ray Diffraction (SCXRD) when possible. From the initial screening and data obtained so far, it can be concluded: (i) The co-formers studied, SA•••Phen and SA•••Trig formed a single crystal and the structures were characterized using SCXRD. (ii) SA•••Ibu and SA•••Dig, showed potential to form co-crystals by screening conducted using DSC. Furthermore, the PXRD spectrum showed some significant changes in the samples prepared through the LAG method. (iii) SA•••Par need further investigation, including new crystallizations and study of new ratios between the components. Data obtained for the SA•••Par (1:1), prepared through the slow evaporation of the solvent and LAG method, are not conclusive to observe interactions between these components. Figure 1. New co-crystals from salicylic acid. [1] C. B. Aakeröy, J. Desper, B. M. T. Scott Chem. Comm. 2006, 1445.