Exploring mechanochemistry for organic synthesis

This thesis describes an investigation into performing organic synthesis under mechanochemical conditions. Procedures were developed for the selective mono- and difluorination of 1,3-dicarbonyls and the one-pot, two-step synthesis of fluorinated pyrazolones under ball milling. Attempts to perform a two-step mechanochemical synthesis of difluoromethylthioethers led to exciting results demonstrating that ball milling can lead to alternative reactions occurring. Finally, some initial results into the generation and reaction of organomanganese reagents under mechanochemical conditions are reported. Initial investigations into the use of mechanochemistry for organic synthesis focused on the mechanochemical formation of the C-F bond, with a particular focus on differences in selectivities observed under different milling conditions. It was found that electrophilic fluorination of 1,3-dicarbonyls could be achieved under ball milling conditions using Selectfluor. The selectivity of this process could be significantly enhanced using Liquid Assisted Grinding with acetonitrile as an additive. The possible causes of this observed change in selectivity were investigated. Further work developing a one-pot, two-step mechanochemical process was performed. A procedure for the synthesis of fluorinated pyrazolones was developed and some of the key considerations when attempting one-pot mechanochemical procedures were established by a careful optimisation. Conditions compatible with both the heterocycle formation step and the fluorination step were found and a range of fluorinated pyrazolones successfully synthesised by this method. It was observed that mechanochemistry could be used to alter the chemoselectivity of a reaction while attempting the synthesis of difluoromethylthioethers. After detailed study, a hypothesis to the origin of this alteration in selectivity was proposed. Finally, some initial results into the use of mechanochemical methods to activate manganese metal for applications in synthesis are presented