Project Type
Poster
Publication Date
4-14-2022
Department or Program
Chemistry and Physics
College
College of Arts and Sciences
Faculty Mentor #1
Oldham, Davis
Abstract
Di(2-ethylhexyl) phthalate (DEHP) is a widely used chiral plasticizer whose primary metabolite (MEHP) and secondary oxidative metabolites have been shown to have peroxisome proliferating and endocrine disrupting effects in mice. The synthesis of these oxidative metabolites is necessary to study their binding affinity to nuclear receptor PPAR. Here, the first step in these syntheses, the construction of the alkyl side chains, was optimized by comparing GC-MS data showing percent composition of the desired alkylation product under varying reaction conditions. The most successful yield with the fewest byproducts was obtained when using LDA as the base, tert-butyl butanoate as the starting ester, and 4-iodo-1-butene as the alkyl chain. This yielded t-Butyl 2-ethyl hex-5-enoate (1) (92.5% conversion of starting ester, 45% yield) which can then be reduced to a primary alcohol, esterified with phthalic anhydride, and oxidized to produce 5-oxo MEHP. Future work will focus on implementing these improved reaction conditions in the synthesis of the alkyl chains for the remaining oxidative metabolites and exploring methods for the selective synthesis of enantiomers of these compounds rather than racemic mixtures. Comparing the binding affinity between these will be a means for determining if a chiral component to phthalate toxicity is present.