Tizanidine and tizanidine hydrochloride: on the correct tautomeric form of tizanidine

A crystallization series of tizanidine hydrochloride, used as a muscle relaxant for spasticity acting centrally as an alpha(2)-adrenergic agonist, yielded single crystals of the free base and the hydrochloride salt. The crystal structures of tizanidine [systematic name: 5-chloro-N-(imidazolidin-2-ylidene)-2,1,3-benzothiadiazol-4-amine], C9H8ClN5S, (I), and tizanidine hydrochloride {systematic name: 2-[(5-chloro-2,1,3-benzothiadiazol-4-yl)amino]imidazolidinium chloride}, C9H9ClN5S+center dot-Cl-, (II), have been determined. Tizanidine crystallizes with two almost identical molecules in the asymmetric unit (r.m.s. deviation = 0.179 angstrom for all non-H atoms). The molecules are connected by N-H center dot center dot center dot N hydrogen bonds forming chains running along [2 (1) over bar1]. The present structure determination corrects the structure determination of tizanidine by John et al. [Acta Cryst. (2011), E67, o838-o839], which shows an incorrect tautomeric form. Tizanidine does not crystallize as the usually drawn 2-amino-imidazoline tautomer, but as the 2-imino-imidazolidine tautomer. This tautomer is present in solution as well, as shown by H-1 NMR analysis. In tizanidine hydrochloride, cations and anions are connected by N-H center dot center dot center dot Cl hydrogen bonds to form layers parallel to (100).