(497a) The E-Factor of the Thin Film and Its Characterization to Understand Why Water Influences a Heck Alkynylation
Synthesis in batch and continuous-flow were also studied by defining the E-factor in terms of the characteristics of the aqueous-organic interfacial film. First-principle calculations, where ligand substitution is infinitely fast with respect to the diffusive flux, predicted less chemical waste in continuous-flow than batch operation. Interestingly, the concentration of hydrophilic phosphine ligand influenced mass transport limitations and the E-factor of the thin film. Increasing the ligand concentration beyond a critical value increased the E-factor of the thin film above its minimum, and it also introduced mass-transfer-limitations. Finite changes in the ligand concentration could explain ambiguous results when performing aqueous-phase catalyzed Heck alkynylations, and potentially Pd-catalyzed C-C cross-couplings in general. The reactivity of useful ligands could be masked during discovery and mass transport limitations introduced during manufacture. Our understanding of the E-factor of the thin film broadly impacts the sustainable discovery and manufacture of fine chemicals, materials, natural products, and pharmaceuticals.â?
 Hu, C., Shaughnessy, K.H., and Hartman, R.L. â??Influence of water on the deprotonation and the ionic mechanisms of a Heck alkynylation and its resultant E-factorsâ?, Reaction Chemistry & Engineering, 1 (2016) 65-72.