Rationalizing and Adapting Water-Accelerated Reactions for Sustainable Flow Organic Processes

Area of Science:

• Green Chemistry
• Sustainable Manufacturing
• Reaction Engineering

Background:

• Water-accelerated reactions, where reactants have low water solubility, offer significant sustainability potential in chemical manufacturing.
• Limited mechanistic understanding of these reactions hinders their broader application and optimization.
• Existing knowledge gaps impede the rational design of efficient and environmentally friendly chemical processes.

Purpose of the Study:

• To establish a theoretical framework for calculating rate acceleration in water-accelerated reactions.
• To computationally estimate changes in activation free energy (ΔG‡) and correlate them with experimental data.
• To rationalize the kinetics and influencing factors of a model Henry reaction.

Main Methods:

• Development of a theoretical framework to calculate reaction rate acceleration.
• Computational estimation of activation free energy (ΔG‡) changes.
• In-depth kinetic study of the Henry reaction between N-methylisatin and nitromethane.
• Design and implementation of a multiphase flow process with continuous phase separation and recycling.

Main Results:

• The theoretical framework successfully correlates computational estimations of ΔG‡ changes with experimental data for water-accelerated reactions.
• Rationalization of the Henry reaction kinetics, including its independence from mixing, kinetic isotope effect, and varied salt effects (NaCl, Na2SO4).
• Demonstration of superior green metrics for the developed multiphase flow process (PMI-reaction = 4, STY = 0.64 kg L⁻¹ h⁻¹).

Conclusions:

• The established theoretical framework provides a basis for understanding and predicting rate acceleration in water-accelerated reactions.
• The study offers mechanistic insights into factors influencing reaction kinetics, such as mixing and salt effects.
• The developed multiphase flow process highlights the practical application of these findings for sustainable chemical manufacturing and in silico discovery.