Cimetidine, C10H16N6S, form C: crystal structure and modelling of polytypes using the superspace approach

Abstract

The H2 antagonist cimetidine forms many polymorphs, several of which have resisted structural analysis thus far. Using single-crystal X-ray measurements obtained from synchrotron radiation, the crystal structure of cimetidine form C has been solved. This layered structure crystallizes in space groupC2/cwith an unusually large lattice parameter,a= 82.904 Å. The thickness of each layerLis equal toa′ =a/6 = 13.82 Å, anda= 6a′ originates from a sixfoldLLLL′L′L′ sequence withLandL′ differing by 0.5b. This packing is reminiscent of polytypic stacking in metals. A (3 + 1)-dimensional superspace model is derived and used to explain and predict many polytypic modifications. This model is characterized by (i) the (3 + 1)-dimensional symmetry groupX2/c(α0γ)00, whereX= 0\textstyle{1 \over 2}0\textstyle{1 \over 2}; (ii) the lattice parametera′ and modulation vectorq= 1/n(a′*); (iii) the atomic positions of a single molecule of cimetidine form C; (iv) the primary variable, 1/n. The model reproduces the previously solved structure, the 6M polytype, and generates the related polytypesnM with lattice parameteranM =na′ forn= 1, 2, 3, 4 and 5. A comparison of powder X-ray diffraction patterns available for cimetidine form C with those simulated for thenM polytypes suggests that the powder samples published previously probably contain a mixture of various polytypes.