467198 The E-Factor of the Thin Film and Its Characterization to Understand Why Water Influences a Heck Alkynylation

Wednesday, November 16, 2016: 8:30 AM
Franciscan A (Hilton San Francisco Union Square)
Chuntian Hu1, Kevin H. Shaughnessy2 and Ryan L. Hartman1, (1)Department of Chemical and Biomolecular Engineering, New York University, Brooklyn, NY, (2)Department of Chemistry, The University of Alabama, Tuscaloosa, AL

This presentation will highlight our discoveries recently reported[1] on why water influences cationic deprotonation, anionic deprotonation, and the ionic mechanism of a Heck alkynylation. Classical chemical reaction engineering theory was applied to characterize mass transfer in the aqueous-organic system. Estimation of Hatta modulus values < 0.02 enabled analyses of Gibbs free energies for all three mechanisms. It was discovered that water potentially switches the rate-determining steps of cationic and anionic deprotonation. Oxidative addition of organohalide to form a Pd-complex, coordination of the alkyne with the oxidative addition adduct, or ligand substitution could govern either catalytic cycle. Hydrogen-bonding is one possible explanation. Molecular-level process intensification has the potential to broadly impact the continuous-flow manufacture of fine chemicals and pharmaceuticals.

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.”

[1] Hu, C., Shaughnessy, K.H., and Hartman, R.L. “Influence of water on the deprotonation and the ionic mechanisms of a Heck alkynylation and its resultant E-factors”, Reaction Chemistry & Engineering, 1 (2016) 65-72.

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