Synthesis of Novel Vinylbenzyl Ethers

Objectives: The use of adhesion promoting cyclodextrin derivative monomers for dental applications requires a diluent divinyl comonomer capable of crosslinking and containing a hydrolytically stable ether linkage. The goal is to synthesize a series of vinylbenzyl ether monomers using vinylbenzyl chloride and reactants containing two or more hydroxyl groups. The hypothesis is that the proposed vinylbenzyl ether monomer can be synthesized by the Williamson ether synthesis. Methods: Numerous runs were conducted utilizing the Williamson ether synthesis to promote S_N2 (bimolecular nucleophilic substitution) reactions to form the desired ether links. Initially, triethylene glycol was used as a diol in the presence of a strong base, NaOH, and utilizing Finkelstein reaction conditions. Glycerol was also used under the same reaction conditions, as well as by phase-transfer catalysis. Finally, the reaction was run using sorbitol with phase transfer catalysis at varying temperatures. The reactions were followed with the use of TLC, FT-IR, MALDI, and NMR. Results: In each synthesis, solution NMR analysis showed product, as well as, unreacted vinylbenzyl chloride with a product yield of approximately 10-22%. In addition, the synthesis involving sorbitol showed a side product identified as divinylbenzyl ether. In several cases, the reaction mixtures polymerized, even when multiple inhibitors were added in excess. The inhibitors appear to be washing out of the monomer into the aqueous NaOH layer. Conclusions: The vinylbenzyl ethers are synthesizable by the Williamson ether synthesis and feasible as diluent comonomers for cyclodextrin derivatives. However, a higher yield needs to be obtained. Alternative reaction conditions and/or polyols need to be explored to improve monomer yield and prevent premature polymerization from occurring. This work was supported by NIDCR DE05129, NIST, and the ADA/ADAF.