Beginning in the mid-1960's synthetic nucleoside derivatives of polyazaindolizines and polyazaindenes were studied for their anticancer activities. The most promising nucleosides for anticancer activity were pyrrolo-, imidazo-, and s-triazolo- pyrimidines and triazines. Syntheses of 1,2,4-triazolo 3,4c -1,2,4-triazine-7-oxide, 1,2,4-triazolo 3,4c pyrazine-7-oxide and 1,2,4-triazolo 2,3c pyrazine-7-oxide were achieved by the cyclization of the appropriate 3-hydrazinoazine N-oxide with diethoxymethyl acetate. When different one carbon cyclization agents react with the 3-hydrazinoazine-1-oxides they did not produce the expected polyazaindene-7-oxides. The reaction of formic acid with 3-hydrazino-1,2,4-triazine-1-oxide or 3-hydrazinopyrazine-1-oxide produced the 3-formylhydrazino derivatives. Similarly, the reactions of the 3-hydrazino -pyrazine-1-oxide and -triazine-1-oxide with benzaldehyde, acetic anhydride, or phenylisothiocyanate produced the 3-benzylideno, 3-acetyl, and 3-(4-phenylthiosemicarbizide) derivatives, respectively. The direct N-oxidation of imidazo 1,2a pyrazine with meta-chloroperbenzoic acid produced the imidazo 3,4c pyrazine-7-oxide. Proton nuclear magnetic resonance analyses of the polyazaindenes N-oxides has produced a set of shielding and deshielding parameters for ring protons. The mass spectral information obtained for the polyazaindene N-oxides suggests that the five membered ring of polyazaindene N-oxide has a decreased reactivity to electrophilic reagents when compared to the parent compound. The nitrogen-15 nuclear magnetic resonance spectra obtained for selected polyazaindenes were used to predict the percentage of contribution between two ground state resonance contributing structures. The nitrogen-15 nuclear magnetic resonance spectra of several substituted pyridine, pyrazine, pyrimidine and 1,2,4-triazine derivatives and their N-oxides were correlated with substituent contributions and ground state contributing structures. From this data, correlations between the nitrogen-15 chemical shifts and aromatic electron deficiency have been established.
| Identifer | oai:union.ndltd.org:pdx.edu/oai:pdxscholar.library.pdx.edu:open_access_etds-1217 |
| Date | 01 January 1986 |
| Creators | Sheets, Roger Martin |
| Publisher | PDXScholar |
| Source Sets | Portland State University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Dissertations and Theses |
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