High Yield, Low-Waste Synthesis of a Family of Pyridyl and Imidazolyl-Substituted Schiff Base Linker Ligands

Solid-state synthesis (S³) is an attractive approach to organic synthesis as in principle it offers minimal solvent waste and high yield. However, many functional groups are ill-suited for S³ reactions, which tend to only proceed when substrates are aligned in the solid-state according to the topochemical principle. The aim of this work is to use high yield, low-waste synthetic methods to develop a library of novel Schiff bases that can be utilized as linker ligands to prepare coordination networks. Herein, we report that eight pyridyl- and/or imidazolyl-substituted Schiff bases, 1-8, five of which are new chemical entities, can be prepared via reaction of an amine and an aldehyde without the use of solvent. All eight compounds were prepared via solvent-drop grinding (SDG) in multigram scale in >95% yield and each was characterized by FTIR, ¹H and ¹³C NMR spectroscopies and single crystal X-ray diffraction. One of the aldehydes used is a liquid under ambient conditions so its reactions to form 1-4 are not classified as S³ reactions whereas the other aldehydes are solids and 5-8 are therefore S³ reactions. The SDG solvents were selected in accordance with guidelines used by industry. 1-4 were also prepared quantitatively via addition of the liquid aldehyde (4-pyridinecarboxaldehyde) to a solution of the corresponding amine. That 1-8 contain functional groups suitable for coordinating with metal cations will enable 1-8 to serve as linker ligands in coordination networks as exemplified by 5, which forms a parallel interpenetrated coordination network with square lattice, sql, topology.