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

70 A. Nangia · G.R. Desiraju
-NH 2 group similarly donates and accepts a strong hydrogen bond with two different
molecules of 28. The second H-atom participates in the N-H◊◊◊p hydrogen
bond with a third molecule of 28. The hydrogen bonding array in 3-aminophenol
29 is similar to 28. A tetrahedral environment around O- and N-atoms is
maintained in both structures, but unlike in 27 it is not exclusively of the strong
type.
The reason for the “anomalous” structures of 2- and 3-aminophenols compared
with the “normal” structures of 4-aminophenol is understood in terms of
the need to attain herringbone or “T”-shaped geometry of the phenyl rings in
the two structures. The origin of the weaker N-H◊◊◊p and C-H◊◊◊O hydrogen
bonds is then the herringbone geometry of the phenyl rings which makes the
heteroatoms inaccessible for the formation of conventional N-H◊◊◊O hydrogen
bonds. The preference for two weak instead of one strong hydrogen bond is
caused by the optimisation of the herringbone interactions and this is identified
as the primary structural effect in these compounds.
In summary, simple molecules can have complex crystal structures and the
relationship between molecular and crystal structures can accordingly be difficult
to delineate.
The above examples illustrate that connections between molecular and crystal
structures are straightforward or difficult depending on whether there is insulation
or interference between the different sets of significant intermolecular
interactions. Thus, in 4-aminophenol, the crystal structure retains a high degree
of fidelity to other hydroxy-amino systems described by Ermer because the
competing herringbone and hydrogen bonding interactions are effectively
insulated. In 2- and 3-aminophenols, however, the structure determining interactions
interfere with one another and this leads to unexpected crystal structures.
Hanessian’s compounds are somewhat less problematic because they do
not contain aromatic groups. Unfortunately, it is often difficult to anticipate
from a casual inspection of the molecular structure when such insulation will or
will not be present. This then is a major problem in crystal engineering; indeed
it is the problem, and at its heart lies our inability to predict accurately the
supramolecular (crystal) structure of an arbitrary molecule from its molecular
structure.
4.2
Goals and Challenges
The “supramolecular Everest” of predicting the crystal structure of any given
molecule is as challenging and formidable a task today as the total syntheses of
vitamin B 12, gingkolide or palytoxin were in earlier times (Table 1). The subject
of supramolecular synthesis is in its infancy and probably at the same stage of
development as target oriented synthesis was in the 1960s. A set of empirical
chemical principles for the solid state assembly of molecules has been formulated
but its utility in the construction of complex architectures is yet to be completely
demonstrated. This is one of the major goals of current crystal engineering
strategies.