Gaining insights into difficult chemistry: sensitive and reductive chemistry

Preparation of a Grignard reagent:  Grignard reactions are highly exothermic and the concentration of the organic halide needs to remain at lower than a pre-specified concentration.  Dangerously high concentrations can occur due to addition of excess organic halide prior to reaction initiation or due to reaction stalling after initiation allowing an increase in organic halide as addition continues. These reactions are ideally suited to in situ monitoring in order to ensure the organic halide remains below the specified concentration and to precisely determine reaction endpoint.

Amide synthesis via reactive acid chloride intermediate:  The inherent reactivity within these functional groups can be problematic and can lead to unwanted side-reactions, by-products and impurities. Typical chromatographic conditions often cause decomposition of acid chlorides and activated acids. Derivitization is possible, but is time consuming and may introduce other uncertainties. Other offline analytical techniques pose a challenge to produce timely and accurate analytical data. In addition, reactions of these reactions are exothermic and therefore pose potential safety and scale-up concerns.  In situ monitoring can provide critical information about reactive, unstable intermediates and can eliminate the errors and delays due to offline analysis.