Pseudopolymorphs of chelidamic acid and its dimethyl ester

Abstract

Different tautomeric and zwitterionic forms of chelidamic acid (4-hydroxypyridine-2,6-dicarboxylic acid) are present in the crystal structures of chelidamic acid methanol monosolvate, C7H5NO5·CH4O, (Ia), dimethylammonium chelidamate (dimethylammonium 6-carboxy-4-hydroxypyridine-2-carboxylate), C2H8N+·C7H4NO5−, (Ib), and chelidamic acid dimethyl sulfoxide monosolvate, C7H5NO5·C2H6OS, (Ic). While the zwitterionic pyridinium carboxylate in (Ia) can be explained from the pKavalues, a (partially) deprotonated hydroxy group in the presence of a neutral carboxy group, as observed in (Ib) and (Ic), is unexpected. In (Ib), there are two formula units in the asymmetric unit with the chelidamic acid entities connected by a symmetric O—H...O hydrogen bond. Also, crystals of chelidamic acid dimethyl ester (dimethyl 4-hydroxypyridine-2,6-dicarboxylate) were obtained as a monohydrate, C9H9NO5·H2O, (IIa), and as a solvent-free modification, in which both ester molecules adopt the hydroxypyridine form. In (IIa), the solvent water molecule stabilizes the synperiplanar conformation of both carbonyl O atoms with respect to the pyridine N atom by two O—H...O hydrogen bonds, whereas an antiperiplanar arrangement is observed in the water-free structure. A database study andab initioenergy calculations help to compare the stabilities of the various ester conformations.