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

Supramolecular Synthons and Pattern Recognition 85
cetanalide, HXACAN, is also dimorphic with synthon 58 being present in both
the forms. As in resorcinol, linear and nearly tetramer geometries are obtained
in forms B and A respectively. Alternating molecules that are utilised in the
generation of synthon 58 are related by translation in form B, while such a relation
exists between successive molecules in form A (Fig. 7).
In some cases, there are distinctive occurrences of the same functionality
within a molecular skeleton and so the same synthons can be formed in different
ways and locations, leading to polymorphism. Synthons 3 and 59 are typical
for primary carboxamides and synthons 60 and 61 are common in
aza-heterocycles and imines (Fig. 8). Pyrazine carboxamide, PYRZIN, an antituberculosis
drug, is a rare example of a compound with four or so different
polymorphic forms (A–D; it is possible that there also exists a fifth form, E, very
similar to form A). In each of these forms, a combination of N-H◊◊◊O synthons 3
and 59 and N-H◊◊◊N and C-H◊◊◊N synthons 60 and 61 are optimised by the
carboxamide and pyrazine functional groups. Form C has a planar sheet structure
whereas the molecules are arranged to form linear ribbons in the other
polymorphs. Forms A, B and C contain the common dimer synthon 3, but it
should be noted that one or more of the other synthons 59–61 are also optimised
and this is what leads to the differences between these polymorphs. Form
D has an interesting non-centrosymmetric packing that is characterised by
synthon 61 and the unusual synthon 62.
Of course, there are some cases where the polymorphs have completely different
crystal structures, that is totally different synthons are seen in the various
forms. Kinetic factors become significant here. 3-Hydroxybenzoic acid,
2,5-dihydroxybenzoic acid and 2,6-dihydroxybenzoic acid (LEZJAB) are all
HEXCAN 58
A B
Fig. 7. Polymorphs A and B of 4-hydroxyacetanilide (HEXCAN)