Correlation of Intermolecular Acyl Transfer Reactivity with Noncovalent Lattice Interactions in Molecular Crystals: Toward Prediction of Reactivity of Organic Molecules in the Solid State

Intermolecular acyl transfer reactivity
in several molecular crystals
was studied, and the outcome of the reactivity was analyzed in the
light of structural information obtained from the crystals of the
reactants. Minor changes in the molecular structure resulted in significant
variations in the noncovalent interactions and packing of molecules
in the crystal lattice, which drastically affected the facility of
the intermolecular acyl transfer reactivity in these crystals. Analysis
of the reactivity vs crystal structure data revealed dependence of
the reactivity on electrophile···nucleophile interactions
and C–H···π interactions between the reacting
molecules. The presence of these noncovalent interactions augmented
the acyl transfer reactivity, while their absence hindered the reactivity
of the molecules in the crystal. The validity of these correlations
allows the prediction of intermolecular acyl transfer reactivity in
crystals and co-crystals of unknown reactivity. This crystal structure–reactivity
correlation parallels the molecular structure–reactivity correlation
in solution-state reactions, widely accepted as organic functional
group transformations, and sets the stage for the development of a
similar approach for reactions in the solid state.