Date of Award

Spring 5-6-2017

Document Type

Honors Project

Degree Name

Bachelor of Science



First Advisor

Oldham, Davis

Second Advisor

Sharpless, Charles

Major or Concentration



Di(2-ethylhexyl) phthalate (DEHP) is a chiral persistent organic pollutant that is used as a plasticizer in polyvinyl chloride (PVC). Humans are exposed to DEHP through inhalation, ingestion, and intravenous exposure; it has shown toxicity as an endocrine disrupter and carcinogen. In the body, DEHP is broken down into mono(2-ethylhexyl) phthalate (MEHP), which is subsequently oxidized in various locations on the ethylhexyl chain. Since previous studies of DEHP have ignored chirality, the purpose of this research is to synthesize enantiomerically pure oxidative metabolites of DEHP. One of the oxidative metabolites of DEHP, 2cx-MMHP, was produced by a malonic ester synthesis followed by lithium aluminum hydride (LAH) reduction, esterification with phthalic anhydride, and oxidation in 14% overall yield. A precursor to three of the other oxidative metabolites, mono(2-ethyl-5-hexenyl) phthalate, was prepared in an analogous manner, beginning with the alkylation of diethyl ethylmalonate with 4-iodo-1-butene, in 34% yield. In future work, the terminal alkene of mono(2-ethyl-5-hexenyl) phthalate will be oxidized, yielding 5cx-MEPP, 5oxo-MEHP, and 5OH-MEHP. Then, a resolution step will be incorporated into both syntheses to produce both enantiomers of each metabolite. Enantiomerically pure oxidative metabolites of DEHP would serve as standards in metabolism, biomonitoring, and toxicity studies.

Included in

Chemistry Commons