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Over the last several years, chemists and engineers have identified the utility of using twin-screw extruders for performing large-scale organic chemistry mechanochemically. This equipment is convenient as it is familiar to several relevant industries for its use in formulation, and it is also well-equipped for temperature control and intense grinding of materials. However, the research and development scale of mechanochemistry is just like that of conventional synthesis: milligrams. These milligram-scale reactions are performed in batch-type reactors, often a ball mill. Commercially available ball mills do not have strict temperature control, limiting the information that can be obtained to inform the scale-up process reliably. This work uses an in-house modified, temperature-controlled, ball mill to bridge the knowledge gap regarding predictable, well-informed, economical, and reliable mechanochemical scale-ups. Included in this work is the first extrusion example of a nucleophilic aromatic substitution. 

Abstract Managing endangered species in fragmented landscapes requires estimating dispersal rates between populations over contemporary timescales. Here, we developed a new method for quantifying recent dispersal using genetic pedigree data for close and distant kin. Specifically, we describe an approach that infers missing shared ancestors between pairs of kin in habitat patches across a fragmented landscape. We then applied a stepping‐stone model to assign unsampled individuals in the pedigree to probable locations based on minimizing the number of movements required to produce the observed locations in sampled kin pairs. Finally, we used all pairs of reconstructed parent‐offspring sets to estimate dispersal rates between habitat patches under a Bayesian model. Our approach measures connectivity over the timescale represented by the small number of generations contained within the pedigree and so is appropriate for estimating the impacts of recent habitat changes due to human activity. We used our method to estimate recent movement between newly discovered populations of threatened Eastern Massasauga rattlesnakes (Sistrurus catenatus) using data from 2996 RAD‐based genetic loci. Our pedigree analyses found no evidence for contemporary connectivity between five genetic groups, but, as validation of our approach, showed high dispersal rates between sample sites within a single genetic cluster. We conclude that these five genetic clusters of Eastern Massasauga rattlesnakes have small numbers of resident snakes and are demographically isolated conservation units. More broadly, our methodology can be widely applied to determine contemporary connectivity rates, independent of bias from shared genetic similarity due to ancestry that impacts other approaches.