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

Abstract

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 amide⋯amide 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–H⋯N(heterocycle) hydrogen bond instead of an N–H⋯OC (amide) interaction.