Solvent- and Catalyst-Free Environmentally Benign High Hydrostatic Pressure-Assisted Synthesis of Bioactive Hydrazones and the Evaluation of Their Stability Under Various Storage Conditions.

Our group has seen great promise in using substituted diaryl-hydrazones to alleviate oxidative stress in preeclampsia. Specifically, fluorinated diaryl-hydrazones have shown great efficacy, confirmed via antioxidant assays and animal trials using pregnant mice. In addition to efficient antioxidant properties, these diaryl-hydrazones are also considered non-toxic. While the synthesis of these compounds is relatively simple, it commonly utilizes undesirable solvents and glacial acetic acid as the catalyst; additional solvents are needed for the isolation of the desired products, which negatively affects the green synthesis of the hydrazones. To combat this possible industrial roadblock, we have begun incorporating the use of hydrostatic high pressure (HHP) in the synthesis. The use of HHP allowed us to synthesize substituted diaryl-hydrazones in a 1:1 molar ratio without the need for solvents or acid catalysts. The optimized procedure can produce nearly quantitative yields, leading to an easier isolation of the products. Different HHP methodologies, such as constant high-pressure treatment and cycling (with different number of cycles, holding and decompression times) were applied and cycling was observed to be the most efficient activation for the majority of the reactions. Stability experiments were also conducted with one of the products and observed that although the solid-state storage does not alter the hydrazone, storing it in various solvents may significantly decrease the concentration of the active component which should be considered when performing the biochemical/biological assays.