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

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 group C2/c with an unusually large lattice parameter, a = 82.904 Å. The thickness of each layer L is equal to a′ = a/6 = 13.82 Å, and a = 6a′ originates from a sixfold LLLL′L′L′ sequence with L and L′ 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 group X2/c(α0γ)00, where X = 00; (ii) the lattice parameter a′ and modulation vector q = 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 polytypes nM with lattice parameter a_nM = na′ for n = 1, 2, 3, 4 and 5. A comparison of powder X-ray diffraction patterns available for cimetidine form C with those simulated for the nM polytypes suggests that the powder samples published previously probably contain a mixture of various polytypes.