The solid-state structures of (-)-scopolamine free base, (-)-scopolamine methobromide, (-)-scopolamine hydrobromide trihydrate, and of the pseudopolymorphic forms of (-)-scopolamine hydrochloride anhydrate and 1.66hydrate

(-)-Scopolamine hydrochloride anhydrate gives crystals belonging to the orthorhombic space group P2₁2₁2₁ and at 293(2) K: a = 7.097(2), b = 10.686(2), c = 22.623(2) Å, V = 1715.7(6) ų, Z = 4, R(F) = 0.039, and R(W)(F) = 0.053. (-)-Scopolamine hydrochloride 1.66hydrate yields crystals belonging to the tetragonal space group P4₃2₁2 and at 293(2) K: a = b = 11.843(6), c = 26.211(4) Å, V = 3676(3) ų, Z = 8, R(F) = 0.047, and R(W)(F²) = 0.135. (-)-Scopolamine methobromide affords crystals belonging to the orthorhombic space group P2₁2₁2₁ and at 293(2) K: a = 7.0403(8), b = 10.926(2), c = 23.364(5) Å, V = 1797.2(6) ų, Z = 4, R(F) = 0.039, and R(W)(F) = 0.052. The two hydrochloride pseudopolymorphs were isostructural to the corresponding two hydrobromide analogues. Both hydrohalide hydrated crystals have a water molecule occupying a general position of symmetry, and another water molecule occupying a special position of C₂-rotation symmetry. The hydrated hydrochloride salt also had an additional 0.322(17) partial occupancy water molecule (absent in the hydrobromide sesquihydrate) occupying another special position of C₂-rotation symmetry, i.e., the extra water molecule occupied the special position in statistically ca. one-third of the unit-cells to give a total hydrate stoichiometry of 1.66 molecules of water. While the two hydrohalide anhydrates exhibited extended tropate ester conformations (phenyl-ring antiperiplanar to oxirane moiety) vs. compact conformations (phenyl-ring near the scopine underside) for the two hydrated hydrohalides, all four displayed other common structural features: axial N- methyl stereochemistry, antiperiplanar methylol oxygen/aromatic C(ipso) relationships, and phenyl-ring eclipsing of the C(α)-H bond. The CPMAS ¹³C NMR spectrum of (-)-scopolamine hydrobromide 'trihydrate' shows it to be a conglomerate of (-)-scopolamine hydrobromide sesquihydrate plus two or more hydrated species (three ca. equal intensity carbonyl signals at 5.0 kHz spin- rate). High-speed rotor spinning (e.g., ca. 10 kHz and higher) causes a temperature-induced phase-transition to yield only the sesquihydrate form. The same transformation was noted with a 18 K rotor-temperature increase and an invariant 5.0 kHz spin-rate. The sesquihydrate spectrum remained after spin-rate decrease to 5.0 kHz, but the three component mixture 5.0 kHz spectrum was regenerated after three weeks sample storage within the capped rotor. The (-)-scopolamine free base crystalline melt CPMAS spectrum also shows a mixture of at least three hydrated species.