How robust is the hydrogen-bonded amide ‘ladder’ motif?

The well-known hydrogen-bonded ladder displayed by amides in the solid state, is readily disrupted and reduced to an R²₂(8) motif if a competitive hydrogen-bond acceptor is incorporated in the molecular structure of the amide. When a weaker hydrogen-bond acceptor (i.e. –NO₂, –CN, –Cl, –Br) is present, the ladder persists in about every other case, whereas if a stronger hydrogen-bond acceptor is introduced (such as a N-heterocycle), the ladder is very unlikely to appear. If a strong hydrogen-bond acceptor is present, the amideamide dimer ‘survives’ a little over 50% of the time. This conclusion is based upon the synthesis and structural characterization of six pyrazole-decorated benzamides in addition to an examination of relevant data from the CSD. The anti hydrogen atom of the amide moiety is much more likely to engage in an N–HN(heterocycle) hydrogen bond instead of an N–HOC (amide) interaction.