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 α(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], C(9)H(8)ClN(5)S, (I), and tizanidine hydrochloride {systematic name: 2-[(5-chloro-2,1,3-benzothiadiazol-4-yl)amino]imidazolidinium chloride}, C(9)H(9)ClN(5)S(+)·Cl(-), (II), have been determined. Tizanidine crystallizes with two almost identical molecules in the asymmetric unit (r.m.s. deviation = 0.179 Å for all non-H atoms). The molecules are connected by N-H···N hydrogen bonds forming chains running along [2 ̅11]. 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 (1)H NMR analysis. In tizanidine hydrochloride, cations and anions are connected by N-H···Cl hydrogen bonds to form layers parallel to (100).
Institut für Anorganische Chemie, J. W. Goethe-Universität Frankfurt, Max-von-Laue-Strasse 7, 60438 Frankfurt am Main, Germany.
Sándor L
SL
Bekö
Silke D
SD
Thoms
Martin U
MU
Schmidt
Michael
M
Bolte
D003000:Clonidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009125:Muscle Relaxants, Central / Q000737:chemistry* / Q000494:pharmacology
D009125:Muscle Relaxants, Central; C023754:tizanidine; D003000:Clonidine