This patent describes the synthesis of derivatives of propane diyl dicinnamate. The inventor used phase-transfer catalysis to perform an esterification of a cinnamate derivative (e.g., potassium cinnamate, sodium dimethoxycinnamate) with epichlorohydrin, that serves as both reactant and solvent in great excess. The esterifications to the glycidyl cinnamate derivative are typically performed for an hour at temperatures of about 65C of 100C. The resulting glycidyl esters are then isolated and reacted with the salt of a second cinnamate derivative, in DMSO as the solvent to form a dicinnamate ester of 2-propanol.
The inventor is to be commended for thinking to use PTC to perform the esterification with epichlorohydrin and also for the thought to use solvent-free PTC conditions. However, there are several additional thoughts that could have likely been used to streamline this 2-step process.
First, the excess of epichlorohydrin is very large. It is so large that it would be worthwhile to consider using an inert solvent such as toluene (with a very similar boiling point to epichlorohydrin) and cut down the excess epichlorohydrin to a minimum.
Once toluene is used for the first esterification, it could be used for the second esterification as well if we leave the phase-transfer catalyst in the system. This could be easily done since the inventor simply filtered off the KCl formed after the first esterification. It is possible that the KCl doesn’t need to be filtered off from the first esterification before simply adding the second cinnamate salt on top of the crude reaction mixture from the first esterification. Reducing unit operations could streamline the process.
Moreover, the inventor recovered the DMSO by distilling it off under reduced pressure. If toluene would be used as the solvent for both steps, while avoiding the isolation of the intermediate, we would achieve less unit operations as well as being able to distill away a much lower boiling solvent of toluene instead of DMSO.
When using toluene as the solvent for both steps, the salt byproducts and the phase-transfer catalyst could be separated from the dicinnamate ester product by dissolving them in water and separating the phases.
In all these concepts could be successfully implemented, advantages would include benefitting from the presence of the phase-transfer catalyst for two esterifications, reducing the excess epichlorohydrin by at least 90%, avoiding isolation of an intermediate, replacing a high boiling solvent with a lower boiling solvent and achieving easy separation of the salts and phase-transfer catalyst from the product.
We might be able to further speed up the reaction by the addition of 1 mole% iodide which might be able to be leveraged to reduce the reaction temperature and/or time. Temperature reduction might be good for stability.
Now contact Marc Halpern of PTC Organics to achieve low-cost high-performance green chemistry by integrating our highly specialized expertise in industrial phase-transfer catalysis with your commercial goals, especially to streamline PTC esterifications and other nucleophilic substitutions.
