Solid-state stereochemistry of anhydrous (-)-scopolamine hydrobromide

The solid-state structure of anhydrous (Nr,C_α-S)-(-)- scopolamine hydrobromide [(-)-hyoscine], an acetylcholine antagonist, has been determined by single crystal X-ray diffraction analysis. (-)-Scopolamine hydrobromide [anhydrous form] gives crystals belonging to the orthorhombic P2₁2₁2₁ space group, and at 298 K: a = 7.348(1), b = 10.482(1), c = 22.867(1) Å, V = 1 761.26(1) ų, Z = 4, R(F) = 0.053, and R_W(F) = 0.049. The (S)-absolute configuration was determined from the effects of anomalous dispersion of the bromide atom. The N-methyl group exists in an axial configuration similar to that previously described for the hemihydrate. However, in the anhydrous form the tropate residue exhibits a different conformation from that noted for the hemihydrate. The tropate ester moiety in (Nr,C _α-S)-(-)-scopolamine hydrobromide [anhydrous form] and (Ns,C_α-S)-N-butylhyoscinium bromide both exhibit very similar crystalline-state conformations, while that in the hemihydrate form is reasonably similar to (Ns,C_α-S)-(-)-hyoscyamine hydrobromide [(-)-atropine].