Synthesis of monomethyl 5,5'-dehydrodiferulic acid

Authors: Zeller, Wayne; Schatz, Paul

Submitted to: Tetrahedron Letters
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/2/2015
Publication Date: 1/8/2015
Citation: Zeller, W.E., Schatz, P.F. 2015. Synthesis of monomethyl 5,5'-dehydrodiferulic acid. Tetrahedron Letters. 56:1076-1079.

Interpretive Summary: Scientists often need to add substances of similar size and properties to mixtures of compounds to assist them in identifying and quantifying materials while using modern instrumentation and techniques. Previously it has been determined that the compound called monomethyl 5,5’-dehydrodiferulic acid is well suited to serve as a reference compound (internal standard) for analysis of ferulic acid derivatives produced during the analysis of forages for fiber digestibility. Previous ways of preparing monomethyl 5,5’-dehydrodiferulic acid resulted in impure material. We developed a new way to synthesize it that eliminates these impurities, and the results of our efforts are described in this paper. The efficient synthetic sequence described should be useful to other scientists needing to prepare reasonable quantities of monomethyl 5,5’-dehydrodiferulic acid for their analyses of ferulic acid derivatives, including scientists who are developing improved forages for cattle diets or biofuel feedstocks.

Technical Abstract: Synthesis of the internal reference compound, monomethyl 5,5’-dehydrodiferulic acid, is described. The synthetic scheme relies on a selective monomethylation of the known compound 5,5-dehydrodivanillin, followed by elaboration into the dehydrodiferulic framework through a dual Horner-Emmons-Wadsworth reaction with methyl diethylphosphonoacetate. Saponification of the ester functionalities provided the target monomethyl 5,5’-dehydrodiferulic acid in 49% overall yield from 5,5-dehydrodivanillin.