Heterogeneous reactions for organic synthesis have always been challenging problem statement for reaction engineering to scale up with a focus on selectivity towards a desired reaction. The convolution of the fact that the solid base catalyzes the reaction by dissolving a trace amount by addition of water to an organic solvent system can make optimization of selectivity towards a desired product an extremely experiment heavy endeavor. Herein, we present a case study of using a heterogeneous base along with a trace amount of water to catalyze an organic reaction. We show the dependence on the hydrate forms of the base, the impact of mixing, type of base, process volumes and process temperature on scalability of the reaction in batch setting. We discuss the design of a DOE and a parallel kinetic model to aid potential scale up.[1-5]
References
Manna, A. and A. Kumar, Why Does Water Accelerate Organic Reactions under Heterogeneous Condition? The Journal of Physical Chemistry A, 2013. 117(12): p. 2446-2454.
Motokura, K., M. Tada, and Y. Iwasawa, Heterogeneous Organic Base-Catalyzed Reactions Enhanced by Acid Supports. Journal of the American Chemical Society, 2007. 129(31): p. 9540-9541.
Cortes-Clerget, M., et al., Water as the reaction medium in organic chemistry: from our worst enemy to our best friend. Chemical science, 2021. 12(12): p. 4237-4266.
Butler, R.N. and A.G. Coyne, Organic synthesis reactions on-water at the organic–liquid water interface. Organic & biomolecular chemistry, 2016. 14(42): p. 9945-9960.
