PTC excels in etherification of aliphatic alcohols and phenols. In this patent, a secondary diol is etherified to diether in 81% yield using 3 equivalent NaOH and 3 equiv p-chloromethylstyrene using 20 mole% TBAB for 10 hours at 70 C. Toluene is the solvent. It is interesting to note that the diol starting material is not observably soluble in toluene and the reaction works anyway. The NaOH and diol were stirred for 30 min at 70 C before adding the TBAB. The diether product is soluble in toluene.
In another example, a diphenol based on phosphaphenanthrene and hydroquinone was etherified with p-chloromethylstyrene under the same conditions and gave only 65% yield of the diether. The diphenol is about 8 orders of magnitude more acidic than the secondary diol described in the first reaction. So it should be easily neutralized by NaOH immediately and the excess NaOH should not have been needed. The 30 minutes of equilibration before adding the TBAB was likely not needed either due to the instantaneous complete neutralization of a phenol with NaOH. Hydroquinone derivatives are often sensitive to hydroxide and this diphenol was stirred with excess base. We speculate that the lower yield may have been a combination of the diphenol being sensitive to hydroxide during the 30 minutes of stirring and the excess base may also have hydrolyzed some of the p-chloromethylstyrene that was even more active as p-bromomethylstyrene formed in-situ.
Of course, hydrolysis of the chloro/bromomethylstyrene could have happened in the etherification of the diol as well, but at least in the case of the diol, the excess NaOH was at least partially “preoccupied” with forming the di-alkoxide by equilibrium with the diol. This is not the case with the diphenol that deprotonates fully and immediately in the presence of NaOH.
Contact Marc Halpern of PTC Organics to achieve low-cost high-performance green processes for strong base reactions using phase-transfer catalysis.
