Control of regioselectivity in the dimerisation of trans-cinnamic acid and its derivatives using crystal engineering

Details

Supervisors

Leyssens, Tom

Faculty

Faculté des sciences

Degree label

Master [120] en sciences chimiques, à finalité approfondie

Abstract

Cinnamic acid is a compound that, by dimerisation through a [2+2] photocycloaddition, allows to obtain, α-truxillic and β-truxinic acid. These two acids differ by the position of the phenyl group in the cyclobutane. The phenyl groups are neighbouring groups in truxinic acid while they are more separated in the truxillic acid. These reactions of photocycloaddition can happen in the solid state if the two molecules have parallel double bonds separated by a distance between 3.5Å and 4.2Å. The regiochemistry of the product depends on the orientation of the molecules of cinnamic acid in the solid. The goal of this work is to develop a thermodynamic approach to control the regiochemistry of the products obtained by irradiation of solid compounds, and especially of trans-cinnamic acid. Crystal engineering, in particular the formation of a cocrystal, allows to change the orientation of molecules inside the solid. Our focus is on trans-cinnamic acid. This molecule can crystallise under different polymorphic forms. Two polymorphs are currently known: the α- and β-polymorph. The α-truxillic acid can be obtained by irradiation, in solid state, of the α-polymorph. Concerning the β-truxinic acid, it can be obtained by irradiation, in solid state, of the β-polymorph. But this acid is never obtained pure as the β-polymorph is meta-stable. Indeed, the β-polymorph transforms spontaneously in the stable α-polymorph. This implies that β-truxinic acid synthesis is always accompanied by the formation of α-truxillic acid. Our goal is to find a thermodynamic pathway to this acid. To do so, we try to identify a stable solid phase in which the trans-cinnamic acid molecules are positioned in such a way that they lead to β-truxinic acid. After a screening of forty-three molecules and the study of nine potential cocrystals, it was observed that 4,6-dichlororesorcinol and urea were coformers that allow the synthesis of β-truxinic acid in a controlled manner, leading to pure acid in case of the former. In practice, our approach can also lead to the synthesis of other products such as δ-truxinic acid and ε-truxillic acid. This study will be extended coming year to three trans-cinnamic acid derivatives: 2-ethoxy-trans-cinnamic acid, 2-methoxy-trans-cinnamic acid and 4-coumaric acid.