198 Topics in Current Chemistry Editorial Board: A. de Meijere KN ...

186 M.R. Caira
schematically in Fig. 9. We obtained crystals of a second polymorph of sulphamerazine
[110] by recrystallization from methanol and established the space
group as Pn2 1a, Z=8. This form contains the same hydrogen bonded motif as
shown in Fig. 9, but it is pseudo-centrosymmetric. The two polymorphs are
distinguishable from IR spectra, the form containing the centrosymmetric
dimer (with only one unique N-H◊◊◊N hydrogen bond) yielding only one IR
peak (3453 cm –1 ) assignable ton asNH whereas that containing the pseudo-centrosymmetric
dimer (with two distinct N-H◊◊◊N hydrogen bonds) displayed a
doublet (3493, 3478 cm –1 ).
We recently reported FT-IR spectral data for seven crystalline forms of the
androgen dehydroepiandrosterone [111], showing that differences in both fine
structure and in the locations and intensities of major absorption bands can be
used to distinguish them. X-ray crystal structures of three forms were determined
[112], Form I (a polymorph), Form S1 (a 4 : 1 hydrate) and Form S4 (a
methanol half-solvate). Form I (space group P2 1, Z=4) contains infinite chains
of steroid molecules linked head-to-tail (shown schematically in Fig. 10) by two
crystallographically distinct intermolecular O-H◊◊◊O=C hydrogen bonds,
consistent with two observed O-H stretching bands (3501, 3458 cm –1 ). Doublets
for the O-H absorption bands observed also in both Forms S1 and S4 can be
correlated with distinct O-H ◊◊◊O hydrogen bonds observed by X-ray analysis,
and specifically, with unusual “flip-flop” hydrogen bonding in Form S4. In this
study, attempts to determine the thermodynamic relationships between the
various polymorphic forms were based partly on the application of Burger’s IR
rule [107] which relates IR band positions to relative stabilities.
The use of IR-spectra to distinguish polymorphs from pseudopolymorphs of
the same parent compound, or to distinguish pseudopolymorphs containing
different solvents, is relatively straightforward, since solvent molecules which
are commonly incorporated in pseudopolymorphic crystals (e.g. water, ketones,
alcohols) will exhibit their own characteristic absorption bands. IR spectroscopy
was used to distinguish polymorphs of the antidiabetic drug glibenclamide
from its solvates with pentanol and toluene [113]. Pseudopolymorphs of the
Fig. 9. Schematic representation of the hydrogen bonded dimer occurring in two polymorphs
of sulphamerazine