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⁺·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 [21]. 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 ¹H NMR analysis. In tizanidine hydro­chloride, cations and anions are connected by N-H...Cl hydrogen bonds to form layers parallel to (100).

Conformational studies of hydantoin-5-acetic acid and orotic acid

Hydantoin-5-acetic acid [2-(2,5-dioxoimidazolidin-4-yl)acetic acid] and orotic acid (2,6-dioxo-1,2,3,6-tetra­hydro­pyrimidine-4-carb­oxy­lic acid) each contain one rigid acceptor-donor-acceptor hydrogen-bonding site and a flexible side chain, which can adopt different conformations. Since both com­pounds may be used as coformers for supra­molecular com­plexes, they have been crystallized in order to examine their conformational preferences, giving solvent-free hydantoin-5-acetic acid, C₅H₆N₂O₄, (I), and three crystals containing orotic acid, namely, orotic acid dimethyl sulfoxide monosolvate, C₅H₄N₂O₄·C₂H₆OS, (IIa), dimethyl­ammonium oro­tate-orotic acid (1/1), C₂H₈N⁺·C₅H₃N₂O₄^-·C₅H₄N₂O₄, (IIb), and dimethyl­ammonium orotate-orotic acid (3/1), 3C₂H₈N⁺·3C₅H₃N₂O₄^-·C₅H₄N₂O₄, (IIc). The crystal structure of (I) shows a three-dimensional network, with the acid function located perpendicular to the ring. Inter­estingly, the hy­droxy O atom acts as an acceptor, even though the carbonyl O atom is not involved in any hydrogen bonds. However, in (IIa), (IIb) and (IIc), the acid functions are only slightly twisted out of the ring planes. All H atoms of the acidic functions are directed away from the rings and, with respect to the carbonyl O atoms, they show an anti­periplanar conformation in (I) and synperiplanar conformations in (IIa), (IIb) and (IIc). Furthermore, in (IIa), (IIb) and (IIc), different con­formations of the acid O=C-C-N torsion angle are observed, leading to different hydrogen-bonding arrangements depending on their conformation and composition.

Analysis of geometric parameters and packing considerations for triphenylboroxine derivatives, with tris(penta­fluoro­phen­yl)boroxine as an example

Mol­ecules of the title compound [systematic name: 2,4,6-(penta­fluorophenyl)-1,3,5,2,4,6-trioxatriborinane], C₁₈B₃F₁₅O₃, are located on crystallographic twofold rotation axes which run through the boroxine and one of the penta­fluoro­phenyl rings. The boroxine ring (r.m.s. deviation = 0.027 Å) and the penta­fluoro­phenyl rings (r.m.s. deviations = 0.004 and 0.001 Å) are essentially planar. The dihedral angles between the boroxine and the two symmetry-independent benzene rings are 8.64 (10) and 8.74 (12)°. The two benzene rings are mutually coparallel [dihedral angle = 0.80 (11)°]. The packing shows planes of mol­ecules parallel to (01), with an inter­planar spacing of 2.99 Å. Within these planes, all the mol­ecules are oriented in the same direction, whereas in neighbouring planes the direction is inverted. Short B...F contacts of 3.040 (2) and 3.1624 (12) Å occur between planes. The geometric parameters of the boroxine ring in the title compound agree well with those of comparable boroxine structures, while the packing reveals some striking similarities and differences.

Structural characteristics of dibromo­borylated benzene derivatives

The crystal structures of five dibromo­benzene derivatives, namely dibromo­boryl­benzene, C₆H₅BBr₂, (I), 1-dibromo­bor­yl-4-(trimethyl­silyl)­benzene, C₉H₁₃BBr₂Si, (II), 4-bromo-1-(di­bromo­boryl)­benzene, C₆H₄BBr₃, (III), dibromo(di­methyl­am­ino)­(phenyl)­borane, C₈H₁₂BBr₂N, (IV), and dibromo­(di­methyl­sulfanyl)­[4-(trimethyl­silyl)­phenyl]­borane, C₁₁H₁₉BBr₂SSi, (V), have been determined. Compounds (I)-(IV) crystallize with one mol­ecule in the asymmetric unit, but the mol­ecule of (V) is located on a crystallographic mirror plane, implying twofold disorder of the central aromatic ring, the S atom and one of the methyl groups bonded to the S atom. In (I), (II) and (III), the B atom is three-coordinated, and in (IV) and (V) it is four-coordinated. The geometric parameters of the -BBr₂ group in these five structures agree well with those of comparable structures retrieved from the Cambridge Structural Database. The C-B and B-Br bond lengths in the mol­ecules with a three-coordinated B atom are significantly shorter than those in the mol­ecules with a four-coordinated B atom. In the compounds with a three-coordinated B atom, the -BBr₂ group tends to be coplanar with the aromatic ring to which it is attached.