Unisolable Reactive Intermediate Compounds

When we organic chemists talk about reactive intermediates, often we mean transition states like carbonium ions, radicals, or carbanions that are undetectable by normal analytical methods and that exist at such low levels that they can be treated kinetically as being at some constant but very low concentration throughout a chemical transformation. In addition to these; however, there are authentic substances existing at analytically detectable concentrations that are simply too unstable to be isolated in good yield under convenient conditions. They are also called reactive intermediates. They are intermediates in a reaction sequence rather than a single reaction. The greater numbers of these situations arise when compounds are not stable at convenient isolation temperatures or when compounds are too reactive to be concentrated down to a solid or neat liquid state.  An answer for the problem of handling most of such substances is to ‘telescope’ the first reaction into the second. No attempt is made either to store that first unstable compound or to remove the diluting reaction milieu that surrounds it.

Flow Systems

Some such reactive intermediates are too unstable even for these methods to work. Sometimes the conditions required to obtain a practical rate of formation of the intermediate are still too vigorous to allow it to accumulate without further degradation. For such materials some sort of flow system is required to control how long reagents and starting materials are in contact before the accumulating intermediate is carried into an environment where the subsequent transformation can take place. Such flow reactors are a popular expedient today; however, such methods are not new and do not have to be expensive or high tech.

Flow reactors can be advantageous when the reaction mixture passes through a very viscous intermediate stage where much stronger stirring is required {Om P Goel, Continuous reactor model for the use of butyl lithium in the pilot plant, 1974 ???] ; this can be frequently caused by the low temperature required for the stability of the intermediate.

Sometimes the intermediate is too unstable to remain in the reactor during the time required for the mixing of the reagents on a large scale [J.A. Foulkes and J. Hutton, Synthetic Communications, 9(7), 625-630 (1979).]