This patent exemplifies the desire of process chemists to achieve high yield, high reactor volume efficiency and low excess reactant to produce an agricultural fungicide.
The reaction is a PTC esterification that uses TBAB as the phase-transfer catalyst and xylene as the solvent. The obvious role of the quat is to transfer the carboxylate anion into the xylene phase and the inventors explicitly note that “using an aromatic hydrocarbon solvent as a poor solvent can suppress an increase in viscosity even for a high-concentration slurry and maintain stirrability, compared to the case of using the polar solvent.” They further explain that they achieve a high volume efficiency, in this case 33.4%) by using a low amount of solvent which is easily recoverable.
PTC almost always provides the opportunity to achieve high atomic efficiency by bringing reactants together, especially in solid-liquid PTC systems. In this case, the excess chloromethyl phenoxybenzene is used in 0.7 mole% excess without resorting to using solvent such as DMSO that may be good for the nucleophilic substitution but are not desirable from the standpoints of solvent recovery and yield loss due to entrainment of product into aqueous streams when attempting to wash out the polar solvent into water. As mentioned above, polar solvents also result in a slurry that is difficult to agitate for these reactants.
Though not noted in the patent, it is reasonable to assume that the bromide of the TBAB is co-catalyzing the reaction by forming bromomethyl phenoxybenzene in situ. This may be important since nucleophilic esterifications often require high temperature so any technique that reduces the reaction temperature is desirable.
The ester product is obtained as a high purity crystalline material in 92.8% yield after an easy and practical workup.
This procedure is a good example of how phase-transfer catalysis enables process chemists to develop low-cost high-performance green chemistry that is easy and practical to execute in both the lab and the production plant.
If you want to similarly achieve the lowest cost, highest performance green chemistry esterifications in the least investment of valuable R&D resources, now contact Marc Halpern of PTC Organics to explore joint development though PTC Process Consulting, PTC Contract Research or PTC Technology Licensing.
