Date of Award

8-1-2011

Degree Name

Doctor of Philosophy

Department

Chemistry

First Advisor

Hou, Yuqing

Second Advisor

Tolley, Luke

Abstract

Dynamic isomerization of diethylstilbestrol (DES) makes it difficult to ascertain the active estrogen between its E and Z isomers. An indirect approach has been used in this project to identify the active estrogen. Methoxylated E- and Z-DES (13 and 14) and 9,10-diethylphenanthrene-3,6-diol (15), a closed ring analog of Z-DES, were synthesized and tested for their estrogenicity. The estrogenicity of 13 is higher than that of 14 and 15, which indicates that E-DES is more estrogenic than Z-DES. Dimethylstilbestrol (16), another analog of DES, was also synthesized and tested. Its estrogenicity is lower than that of DES. Non-estrogenic analogs of bisphenol-A were designed based on the observation that (15) is far less estrogenic than DES. Closed ring analogs of bisphenol-A, 3,6-dihydroxy-9,9-dimethylfluorene (34), 2,6-dihydroxy-9,9-dimethylfluorene (35), and 2,7-dhydroxy-9,9-dimethylfluorene (36) were synthesized and they were found to have little or no estrogenicity. An open ring analog of bisphenol-A, 2-(3-hydroxyphenyl)-2-(4-hydroxyphenyl)propane (33) was also synthesized and its estrogenicity is much lower than that of bisphenol-A. Polycarbonate of 36 was also synthesized and its glass transition temperature was measured using differential scanning calorimetry (DSC). Glass transition temperature of polycarbonate of 36 was found to be 199.92 oC, which is about 50o higher than that of bisphenol-A polycarbonate (150 oC). This indicates that polycarbonate of 36 forms a harder plastic than bisphenol-A polycarbonate. Compounds 2,8-dihydroxy-5,5-dioxo-dibenzothiophene (69) and 2,8-dihydroxydibenzothiophene (70) were also synthesized and were tested as non-estrogenic alternatives for bisphenol-S and bisphenol sulfide, respectively. Compound 69 and 70 were found to be less estrogenic than bisphenol-S and bisphenol sulfide respectively agreeing with our hypothesis. Iodane/quaternary ammonium halide in nitromethane was utilized to explore aromatic bromination, N-nitrosation-dealkylation, and benzoate ester formation from benzylamines. Koser's reagent was found to be a suitable iodane for aromatic bromination reaction, whereas for N-nitrosation-dealkylation, IBX gave the best yields. Further, for N-nitrosation-dealkylation reaction, the halides of quaternary ammonium salts play a crucial role. The effectiveness of halides follows F- > Cl- > Br- ~ I-. The lack of N-nitrosation-dealkylation and ester formation in the absence of nitromethane indicates that nitromethane is playing an essential role as well. Yields of benzoate ester from benzyl amines were low (~22%). Optimization experiments will be performed in the future. Plausible reaction mechanisms for these reactions were proposed. Aromatic bromination was thought to be induced either by iodane/halide adduct or by BrOH that was formed from iodane/halide adduct. Ester formation and N-nitrosation-dealkylation were believed to be induced either by alkyl nitrite or by nitrous acid, generated from the reaction of iodane/halide adduct with nitromethane.

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