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).

2-Ammonio-5-chloro-4-methyl­benzene­sulfonate, its 1-methyl-2-pyrrolidone and dimethyl sulfoxide monosolvates and a corrected structure of 2,2'-(1,4-phenyl­ene)di(4,5-di­hydro­imidazolium) bis­(4-aminobenzene­sulfonate) dihydrate

2-Ammonio-5-chloro-4-methyl­benzene­sulfonate, C₇H₈ClNO₃S, (Ia), is an inter­mediate in the synthesis of lake red azo pigments. The present structure determination from single-crystal data confirms the results of a previous powder diffraction determination [Bekö, Thoms, Brüning, Alig, van de Streek, Lakatos, Glaubitz & Schmidt (2010). Z. Kristallogr. 225, 382-387]. The zwitterionic tautomeric form is confirmed. During a polymorph screening, two additional pseudopolymorphs were obtained, viz. 2-ammonio-5-chloro-4-methyl­ben­zene­sulfonate 1-methyl-2-pyrrolidone monosolvate, C₇H₈ClNO₃S·C₅H₉NO, (Ib), and 2-ammonio-5-chloro-4-methyl­benzene­sulfonate dimethyl sulfoxide monosolvate, C₇H₈ClNO₃S·C₂H₆OS, (Ic). The mol­ecules of (Ib) have crystallo­graphic m symmetry. The 1-methyl-2-pyrrolidone solvent mol­ecule has an envelope conformation and is disordered around the mirror plane. The structure shows hydrogen-bonded ladders of mol­ecules [graph-set notation C₂²(6)R₂²(12)] in the [010] direction. The benzene groups of adjacent ladders are also stacked in this direction. A different type of hydrogen-bonded ladder [graph-set notation C(6)R₂²(4)R₄⁴(12)] occurs in (Ic). In (Ia), (Ib) and (Ic), the mol­ecules correspond to the zwitterionic tautomer. The structure of the cocrystal of 4-amino­benzene­sulfonic acid with 1,4-bis­(4,5-dihydro­imidazol-2-yl)benzene [Shang, Ren, Wang, Lu & Yang (2009). Acta Cryst. E65, o2221-o2222] is corrected; it actually contains 4-amino­benzene­sulfonate anions and 2,2'-(1,4-phenyl­ene)di(dihydroimidazolium) dications, i.e. 2,2'-(1,4-phenyl­ene)di(4,5-dihydro­imidazolium) bis­(4-amino­benzene­sulfonate) dihydrate, C₁₂H₁₆N₄²⁺·2C₆H₆NO₃S^-·2H₂O. Hence, all known structures of amino­benzene­sulfonic acid complexes contain ionic or zwitterionic mol­ecules; there is no known structure with a neutral amino­benzene­sulfonic acid mol­ecule.

Nimustine hydro­chloride: the first crystal structure determination of a 2-chloro­ethyl-N-nitro­sourea hydro­chloride derivative by X-ray powder diffraction and solid-state NMR

Nimustine hydro­chloride [systematic name: 4-amino-5-({[N-(2-chloro­ethyl)-N-nitroso­carbamoyl]­amino}­methyl)-2-methyl­pyrimidin-1-ium chloride], C₉H₁₄ClN₆O₂⁺·Cl^-, is a prodrug of CENU (chloro­ethyl­nitroso­urea) and is used as a cytostatic agent in cancer therapy. Its crystal structure was determined from laboratory X-ray powder diffraction data. The proton­ation at an N atom of the pyrimidine ring was established by solid-state NMR spectroscopy.