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

Crystalline Polymorphism of Organic Compounds 199
leading to “collective stabilisation”, which prevents spontaneous transformation
to Form II.
Structural, thermodynamic, kinetic and mechanistic aspects of phase transformations
among three differently coloured forms of dimethyl 3,6-dichloro-
2,5-dihydroxyterephthalate have been studied by various methods [108] including
simultaneous DSC and optical microscopy using the apparatus shown in
Fig. 8.The three forms,(Y) yellow,(LY) light yellow and (W) white,which exhibit
extraordinary polymorphic behaviour, are now known to be conformational
polymorphs and the transformations among them appear to occur by nucleation
and growth of the new phase outside the domains of the old one, not by
single-crystal to single-crystal transformation. Some perspective on research on
polymorphism can be gained from the concluding remarks of this account
which stress the prevailing lack of understanding of the complexity of phase
transitions and the formidable experimental difficulties experienced in obtaining
reproducible results.
4
Towards Control of Polymorphism
4.1
The Need for Polymorphic Control
In a review sketching the important developments in synthetic organic chemistry
during the past 25 years and predicting future directions [158], it was
emphasised that the exciting synthetic targets today are no longer molecules to
be prepared “for their own sake”, but rather, they are systems possessing specific
functions or properties. The systems which are being pursued with this goal
in mind are largely those whose properties are governed by non-covalent interactions,
as evidenced by the rapid growth of the discipline of supramolecular
chemistry in recent years. In the realm of solid-state chemistry, the goals of
crystal engineering [3] are, analogously, the design and preparation of materials
with specific properties (e.g. metallic conductivity, thermochromism, photoactivity,
second-harmonic generation), these properties being strictly dictated
by the crystalline assembly or supramolecular organization in the solid-state.
Preparation of such assemblies has been severely impeded by the lack of an
underlying theoretical framework for understanding the subtle interplay of
factors determining crystal packing. There is no guarantee, in the first instance,
that a given molecule will form a stable crystal which will survive the treatment
to which it will be subjected. The occurrence of polymorphism (in which both
thermodynamics and kinetics play a role) is an additional complicating factor,
since the three-dimensional array possessing the desired property is but one,
unique arrangement among many alternative arrays having similar free energies,
but lacking that property. As an example, one property of solid materials
currently attracting widespread attention is that of non-linear optical (NLO)
behaviour, whose effect is second-harmonic generation (SHG). This property
has potential for the design of laser devices, optical communications and information
processing. SHG depends on both the molecular hyperpolarizability