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

Abstract

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].