Last week, two patents that were published using PTC also used THF as solvent and both appear to use conditions that were somewhat disappointing. One will be described in the PTC Tip of the Month here and the other will be described in the PTC Reaction of the Month below.
US Patent 9,422,305 describes the etherification of a diol with epichlorohydrin to form the diglycidyl ether (bisepoxide). The disappointing warning sign is that the inventors used 14 equivalents of epichlorohydrin and 12 equivalents of NaOH when they needed only 2 equivalent in theory. Why would they need such huge excesses of reactants?
The inventors note “intense” stirring of a huge excess of the epichlorohydrin in the presence of the concentrated NaOH while dropping in the diol “slowly”. It may be speculated that the intense stirring could promote hydrolysis of the epichlorohydrin, especially since the diol is being added last leaving the epichlorohydrin open to attack before the diol is available to consume the epi. Addition of THF could also promote hydrolysis by co-dissolving some water/base with the epichlorohydrin and organic epoxide product.
Unless a PTC system is transfer rate limited (etherifications are typically intrinsic reaction rate limited not transfer rate limited), in cases in which there are water-sensitive reactants and products, it is usually preferable to reduce the agitation efficiency and allow the phase-transfer catalyst to bring the reactants together while minimizing non-catalyzed interfacial hydrolysis of the sensitive functional group (epoxide in this case). In addition, PTC enables us to use a less polar solvent that would reduce contact between hydroxide and the epoxide keeping them separated in different phases. All this would possibly reduce the huge excess of epi being used.
One impressive aspect of this reaction is that the etherification to the glycidyl ether takes place at room temperature. Many PTC etherifications with epichlorohydrin are reported at temperatures of about 80oC. The bromide of TBAB is likely forming epibromohydrin in situ that is more reactive than epichlorohydrin, thereby co-catalyzing the reaction.
In short, we expect that by using a non-polar solvent to separate the base from the epoxide starting material and product, avoiding over-agitation and better choice of base (perhaps with potassium salt to enhance the formation of an omega phase), the large excess of starting materials can be avoided.
To learn more about how to optimize PTC etherifications to improve process performance and profit, now contact Marc Halpern of PTC Organics.
