Condensation reactions in microflow

Syntheses of imines and enamines are well-known examples of condensation reactions and play an important role in organic chemistry. Syntheses of these chemical compounds consist of two steps: an addition step, in which the nucleophile attacks the carbonyl carbon forming a tetrahedral intermediate and an elimination step, in which water is formed. The removal of water is necessary to shift the reaction equilibrium to the product side. In a batch process a Dean-Stark apparatus is used to remove the water by using an entrainer. Zeolite packed columns are used to bound water in a continuous way. As model reactions, the syntheses of imine 1 and of enamine 2 at various temperatures were investigated.


The reaction of substances with low boiling temperatures to imines/enamines (e.g. alkylamines or ketones like cyclohexanone) is very time-consuming due to the low reaction rates. By using a stainless steel microflow system, high pressure/temperature conditions are realized. The key point in using a pressurized microflow system is to access temperatures above the respective boiling points (at normal pressure), which results in higher reaction rates.



By performing the reaction in that system, the reaction time was shortened, while a comparable yield to the Dean-Stark apparatus was obtained. A drop in yield was observed at high temperatures, which was attributed to desorption of water from the molecular sieves. This indicates a limitation for the reaction conditions, but proves that microflow systems are able to exceed the results of conventional batch processes of condensation reactions.