Linear templates and hydrogen bonding as general tools to control reactivity in molecular co-crystals

The use of ditopic molecules as linear templates to control reactivity in molecular co-crystals has been explored in context of developing a reliable and general synthetic system. The system, termed template-controlled solid-state synthesis, employs supramolecular interactions, specifically hydrogen bonds, to control reactivity within finite assemblies in co-crystals. The template-controlled solid-state approach has been employed to control [2+2] photodimerization in solids. The inherent modularity of the approach was exploited to maintain similar reactivity among solids based on molecules that are members of a homologous series. That the solids exhibited different crystal packing patterns demonstrated that the modularity of template-controlled solid-state approach allows the decoupling of solid-state reactivity from crystal packing. The modularity was utilized as a foundation to develop a strategy to fine-tune the reactivity of molecular assemblies in the solid. The strategy, that has been termed template-switching, provides the flexibility to construct molecules that have different sizes, shapes and functional group patterns. Specifically, the mentioned properties have been addressed by constructing [2.2]para-, meta- and orthocyclophanes, as well as simple cyclobutane molecules bearing a variety of different substituents. By way of template-switching, the generality of template-controlled solid-state synthesis to build molecules with 2-pyridyl, 3-pyridyl, as well as 4-pyridyl moieties has been established. In context of materials science, template-switching has been employed as a chemical approach to achieve single-crystal-to-single-crystal [2+2] photodimerization under harsh irradiation conditions. In addition, a system that undergoes single-crystal-to-single-crystal desolvation has been serendipitously achieved by template-switching. The ability to construct molecules that carry hydrogen bond-donating, rather than accepting functionalities has been explored by controlling the reactivity of fumaric acid. Benzoxazole derivatives have been explored as alternative hydrogen bond-accepting groups that are more readily degradable than pyridines. Occurrence of polymorphism and pseudopolymorphism in molecular co-crystals has been explored. Template-switching is proposed as a means to overcome the difficulties related to pseudopolymorphism. A pseudoseeding strategy is presented to deliberately construct polymorphs of co-crystals that exhibit different solid-state reactivity.