Computer-Aided Synthesis of Dimerized Eugenol

S Fujisawa, M Ishihara, I Yokoe
2004 Internet Electronic Journal of Molecular Design   unpublished
Motivation. Eugenol, an antioxidant is used as a fragrance, a flavoring agent, and in dental materials. As an adverse effect, eugenol causes allergic contact dermatitis, possibly due to its prooxidant activity and the formation of eugenol-quinone methide (compound 1). We recently reported that dimer of eugenol, dehydrodieugenol A (compound 2) showed the less cytotoxicity and greater antiinflammatory activity than parent eugenols. Therefore, we examined high-yielding methods of producing dimers
more » ... f producing dimers of eugenol. Method. Dimerization of eugenol was carried out in CuCl(OH)/trimethylenediamine (TMEDA) in dichloromethane in air at 20° C. Dimerization reaction pathway of eugenols was evaluated from a PM3 semiempirical calculation. Results. The simplicity and excellent yield of approximately 79% made it the method of choice for preparing this compound, 2. In contrast, compound 3, dehydrodieugenol B was not synthesized from eugenols. The experimental result was supported by the PM3 calculation, which suggested that compound 3 could be synthesized from eugenols with six-coordinating metals, but not with four-coordinating metals such as copper. Conclusions. Dehydrodieugenol (2) was synthesized from eugenols in approximately 79% yield. This dimerization reaction pathway was estimated by the PM3 calculation.