N-Acyliminium Ion Chemistry on 4-Oxo-N-arylpentanamides
LE3 .A278 2021
2021
Jha, Amitabh
Acadia University
Master of Science
Masters
Chemistry
Heterocycles have significant applications in medicinal chemistry. This importance is presented in the preface of the thesis with discussion leading to heterosteroids. The original plan for this investigation was to prepare analogs of 12,14-diaza-steroids through hetero-Diels Alder reaction between organic nitriles and N-acyliminium ions derived from levulinic acid amides of 2-naphthylamines. To obtain the proof of principle, the levulinic acid amide of aniline was prepared and reacted with benzonitrile in presence of BF3.Et2O as the Lewis acid. This reaction did not produce the expected hetero-Diels Alder adduct. However, a new product was obtained which was characterized as 3-(2-methyl-5-oxo-1-phenylpyrrolidin-2-yl)-4-oxo-N-phenylpentanamide, a dimer of the starting levulinanilide. This dimerization process was found to be unprecedented, unique, and potentially useful in making new heterocycles including heterosteroids. We decided to systematically investigate this chemistry and its usefulness. The starting twelve levulinanilides (and two others related ketoanilides) were prepared in good to excellent yields using three peptide coupling conditions. The conditions for dimerization of levulinanilides were optimized using unsubstituted levulinanilide as the model substrate. Application of the optimized conditions on levulinanilides (and other related ketoanilides) led to synthesis of thirteen new dimers; two examples among these were found to follow a different reaction pathway leading to a new type of cyclized dimer. Plausible mechanisms of these reactions are proposed. All compounds were thoroughly characterized using spectrometric techniques (1H & 13C NMR and ESI-HRMS).
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https://scholar.acadiau.ca/islandora/object/theses:3680
