Structure of N-cyano-N'-methyl-N''-(2-{[(5-methyl-1H-imidazol-4-yl)methyl]thio}ethyl)guanidine (cimetidine) monohydrochloride monohydrate, C10H17N6S+.Cl−.H2O

Abstract

Abstract. M r = 306.82, monoclinic, P2/c, a = 11.542(3), b=10.859(3), c=11.632(3)A, fl= 91.09 (2) ° , V= 1457.5 (7)A 3, z=4, Dm= 1.391 (1), D x = 1.398 Mg m -a, 2(Cu Ka) = 1.5418 A, /t = 2.362mm -1, F(000)= 648, T= 293 K, final R = 0.046 for 2478 independent reflections. Both N atoms of the imidazole ring are protonated and hydrogenbonded to a CI-ion and an N atom of the cyano group of an adjacent molecule, respectively. The CI-ion is further linked with the N atom of the neighboring guanidine group by a hydrogen bond, consequently forming a 20-membered ring consisting of two cimetidine molecules and two C1-ions related by a center of symmetry, respectively.

Combining the Advantages of Powder X-ray Diffraction and NMR Crystallography in Structure Determination of the Pharmaceutical Material Cimetidine Hydrochloride

“…The hydrogen-bonding pattern in the anhydrous form of cimetidine hydrochloride reported here is significantly different from that in the monohydrate form . The monohydrate contains N3–H···N14 hydrogen bonds between cimetidinium cations together with N12···H–O and N15–H···O hydrogen bonds between cimetidinium cations and water molecules.…”

“…In contrast, the crystal structure of the hydrochloride salt of cimetidine (Figure ) has never been reported, presumably as a consequence of the challenge of growing a single crystal of this material suitable for single-crystal XRD. Furthermore, we note that cimetidine hydrochloride has a high propensity to undergo hydration in an ambient atmosphere to form a monohydrate phase (the crystal structure of which has been reported). The anhydrous phase of cimetidine hydrochloride may be obtained by solid-state dehydration of the monohydrate phase, although this procedure yields a microcrystalline powder of the anhydrous phase.…”

“…This method of referencing does not require assignment of the peaks except when two peaks overlap, which occurs in the present case for C2 and C4, and for C8 and C16. Additional GIPAW calculations on the anhydrous form of cimetidine hydrochloride and the monohydrate form of cimetidine hydrochloride are included in Supporting Information. The results from these calculations confirm that the sample analyzed in our experimental solid-state 13 C NMR study was indeed the anhydrous form of cimetidine hydrochloride.…”