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

Abstract

Solid-state synthesis (S 3 ) 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 S 3 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, 1 H and 13 C 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 S 3 reactions whereas the other aldehydes are solids and 5−8 are therefore S 3 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.

Toward an Understanding of the Propensity for Crystalline Hydrate Formation by Molecular Compounds. Part 2

“…Anhydrous forms of 5 – 7 were observed to transform to hydrated forms of 5 – 7 following aqueous slurry and exposure to humidity. Anhydrous samples of 4 – 11 were also subjected to aqueous SDG. ,, Hydrated forms of 5 – 7 were isolated from the SDG experiments.…”

“…1 – 11 were prepared following procedures reported in the literature. − 5 – 9 were prepared by a facile synthetic strategy, co-crystal controlled solid-state synthesis, developed by us . Single crystals of 7· 4H 2 O and 10 were isolated by slow evaporation of a saturated solution of either 7 or 10 in CHCl 3 /MeOH (1:1 v/v) over 5 days.…”

Reversible single-crystal to single-crystal phase transformation between a new Werner clathrate and its apohost

“…1a). 43,44 A 1 : 1 ground mixture of 1,8-NA and 3APy formed an intermediate via SDG when using 120 μL of EtOH. The imide was obtained by heating the intermediate at 185°C for 5 h, affording 5 in 93% yield (Fig.…”

“…In this contribution, we report the solid-state synthesis 2-( pyridin-3-yl)-benzo[de]isoquinoline-1,3(2H)-dione, 5, and its use as a Werner complex ligand. The formation of imides from Cocrystal Controlled Solid-State Synthesis (C 3 S 3 ) has been previously exploited by our group as a mechanochemical approach to prepare ligands [43][44][45] and typically involves solventdrop grinding (SDG) [46][47][48] followed by heating. Advantages of C 3 S 3 include the following: (i) little solvent is required, especially compared to solution-based synthesis methods; (ii) yields are typically high, often approaching quantitative; (iii) new condensation products can be readily accessible from simple organic building blocks.…”

Crystal structure of (E)-N-[4-(1H)-imidazolyl phenyl]-(2-methylphenyl)methanimine, C17H15N3

“…A large number of studies have shown that imidazole-based compounds have good biological activities such as insecticidal, bactericidal, herbicidal, antiviral, anticancer etc. [4][5][6].…”