Control of Regioselectivity in the Dimerization of trans-Cinnamic Acid and Its Derivatives Using Cocrystal Engineering

trans-Cinnamic acid and derivatives can undergo a [2 + 2] photocycloaddition, resulting in the formation of truxinic and truxillic acids. These photoproducts are regioisomers, differing only in the relative arrangement of the acid and phenyl groups on the cyclobutane ring formed. In this contribution, we show that a cocrystal engineering approach can direct the outcome of the reaction (regioisomer) and control the photoreactivity of the compounds in the solid state. For trans-cinnamic acid, cocrystallization with 4,6-dichlororesorcinol yields a thermodynamic pathway to beta-truxinic acid. The otherwise photostable para-methoxy-trans-cinnamic acid can be rendered photoactive to also yield beta-truxinic acid using 5-hydroxyisophthalic acid. Finally, the photoactive para-hydroxy-transcinnamic acid can be rendered photostable by cocrystallization. Cocrystal engineering is thus a valuable tool not only to control photoreactivity but also the obtained outcome of a solid-state photoreaction. We expect to see this approach being applied as a more general procedure for this type of reaction in the future.