Investigation of structural effects on the reactivity of heterocyclic bioactive compounds

Tese de dout., Química, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2008

In the course of this investigation, structural effects on the reactivity of a series of heterocyclic compounds, in particular tetrazole and benzisothiazole derivatives, submitted to different chemical environments, were explored. The photochemistry of several representative tetrazoles was considered in solution and for the compounds trapped in a rigid matrix of solidified argon at cryogenic temperatures. UV-excitation resulted in photofragmentation of tetrazoles with a wide range of exit channels. Important mechanistic questions concerning the photodecomposition of allyl-tetrazolyl derivatives in different solvents were answered, and new synthetic methodologies for the preparation of heterocyclic compounds, such as pyrimidinones or oxazines, from allyl-tetrazoles, were developed. For the matrix-isolated compounds, since the obtained fragments in general stay in the matrix cage where they are formed, no subsequent cross-reactions involving species resulting from photolysis of different reactant molecules can occur. This fact introduced a useful simplification for the interpretation of the reaction mechanisms. FTIR spectroscopy provided experimental frequencies and intensities of characteristic absorptions of the matrix-isolated chemical species, both for reagents and photoproducts. The analysis of experimental data was assisted by their direct comparison with the vibrational spectra theoretically calculated for the single molecule in vacuum. Spectroscopic characterization of a number of relatively unusual or highly reactive molecules, formed from photolysis of matrix-isolated tetrazoles, is presented for the first time. Novel tetrazolyl and benzisothiazolyl naphthylmethylic ethers were synthesized and the development of experimental conditions for their palladium-catalysed hydrogenolysis, using a hydrogen donor or molecular hydrogen, was carried out successfully. Structural effects on the reactivity of the heteroaromatic ethers were investigated. Furthermore, new benzisothiazole-tetrazolyl derivatives differing on the spacer-group used for linkage of the two heterocyclic systems were designed, produced and tested as multidentate ligands in coordination reactions with transition-metal complexes.