The interplay between hydrogen bonding and π-π stacking interactions in the crystal packing of N1-thyminyl derivatives, and implications for the photo-chemical [2π+2π]-cycloaddition of thyminyl compounds

The solid-state photo-chemical dimerisation of thyminyl derivatives occurs when two thyminyl units are aligned in such a way that the olefinic moieties are separated by a distance of less than 4.2 angstrom. When irradiated with >270 nm UV, the thyminyl olefinic groups undergo [2 pi + 2 pi]-cycloaddition to form a dimeric cyclobutane derivative. However, the design and execution of [2 pi + 2 pi]-cycloaddition reactions can be challenging due to the requirement to produce molecular crystals with the necessary olefinic alignment. In this investigation, the crystallographic and solid-state photo-chemical reactions of six N1-thyminyl derivatives are studied. Only one derivative, thyminyl propanamide (7), was found to undergo [2 pi + 2 pi]-cycloaddition in the crystalline state. As such, quantum chemical methods were employed to study the photo-chemical transition states of the derivatives, as well as the strengths of typical intermolecular interactions that were observed in their crystal structures (such as pi-pi stacking between the thyminyl rings, Watson and Crick style hydrogen bonding and hydrogen bonding between functional groups of N1 substituents). These results were used to rationalise the solid-state photo-reactivity of more complex bis-thyminyl monomers.