I. A crossover mechanistic investigation of the Wolff vs. photo-Favorskii Rearrangement of Diazo-p-Hydroxyacetophenone: Methoxy substituent effects on p-Hydroxyphenacyl cage II. Exploratory studies of hydroxyquinoline-based phototriggers

alpha-Diazo-p-hydroxyacetophenone (1.165), both a model compound and a synthetic precursor to other p-hydroxyphenacyl (pHP) derivatives, has been synthesized and its photochemistry explored. alpha-Diazo-p-hydroxyacetophenone (1.165 ) itself is a unique structure for investigating the influence of a substituent effect on the known rearrangement of alpha-diazoacetophenones which could follow a photo-Wolff or photo-Favorskii rearrangement pathway. Photochemical and photophysical studies on diazo pHP 1.165 in aqueous acetonitrile provided insight into the mechanism of nitrogen (N2) release and its rearrangement to the major product, 4hydroxyphenylacetic acid (PAA). X-ray crystallographic data and 1 H NMR spectroscopy of diazo pHP 1.165 reveal that the syn (s-Z) form is the dominant conformation both in the crystalline state and in solution. These observations are in strong agreement with the reported data for similar alpha-diazoketones by Kaplan et al. and also by others. The triplet sensitized photolysis of diazo pHP 1.165 was unsuccessful with mangiferin (a xanthone derivative) and 4,4'dicarboxylic benzophenone. However, quenching studies with molecular oxygen reduced the efficiency of the reaction by 50%, revealing the involvement of the triplet excited state in the photo-decomposition of diazo pHP 1.165. The Stern-Volmer quenching studies with oxygen produced a triplet life time of 15 ns and a rate of 6.6 x 107 s-1 for the photoreaction in aqueous acetonitrile (1:1). Additional studies in collaboration with Tuscano et al. using timeresolved IR spectroscopy revealed a ketene intermediate, defining this as a Wolff rearrangement pathway. Photorelease of N2 from diazo pHP 1.165 was not sensitized with either mangiferin or benzophenone, and the observed ketene intermediate from timeresolved IR studies, suggesting that the N2 release occurs predominantly through the singlet manifold. However, the role of the quenchable triplet excited state by oxygen is not clear at this point. Thus, the major pathway of N2 photorelease from diazo pHP 1.165 is the Wolff rearrangement, whereas the Favorskii rearrangement might be less likely pathway.;Convenient, high yield, one pot syntheses of other pHP based chromophores were developed by expanding the alpha-diazo- p-hydroxyacetophenone (1.165) chemistry to include additional leaving groups and substituents on the hydroxyacetophenone. Strategies were developed for the synthesis of pHP caged carboxylates, sulfonates, phosphates, phenolates and amino acids and the "diazo approach" was extended to include the synthesis of ortho and meta substituted pHP caged diethyl phosphates. The light induced release of diethyl phosphoric acid and N2 in aqueous acetonitrile was studied. UV/vis spectroscopy studies on solvent effects, pH effects, substituent effects and the effects of the leaving group were examined. The effects caused by ortho vs. meta substitution on the pHP chromophore were altered the quantum yields for release, e.g., ortho methoxy substituted pHP derivatives were 50% higher in quantum yields than meta methoxy derivatives. The neighboring methoxy group participation in N2 release from the ortho and meta methoxy substituted derivatives 4-(2-diazoacetyl)-3-methoxyphenyl acetate 1.204 and 4-(2-diazoacetyl)-2-methoxyphenyl acetate 1.198a demonstrated neighboring methoxy participation. Ortho methoxy 1.204 led to cyclization to 6-acetoxy-3-coumaranone along with the rearranged acid, whereas meta methoxy 1.198a only produced the rearranged acid.;In another study, a series of 8-hydroxyquinoline based photoremovable protecting groups were designed, synthesized, and their photochemistry explored. UV/vis spectroscopic studies, solvent effects, pH effects, and effects of the leaving group were examined. From these, it was demonstrated that the photochemistry of 1,5-substituted 8-hydroxyquinolines is dependent on the nature of the leaving group and the presence or absence of oxygen. The photorelease of diethyl phosphate from 2-(8-(benzyloxy)quinolin-5-yl)-2-oxoethyl diethyl phosphate (2.44) was observed. However, 8-hydroxyquinoline benzoates, i.e., 2-(8-hydroxyquinolin-5-yl)-2-oxoethyl benzoate 2.37 and 2-(8-benzyloxy)quinolin-5-yl)-2-oxoethyl benzoate 2.39 instead formed 2-(benzoyloxy)acetic acid 2.46 and quinoline-5,8-dione 2.47. Singlet oxygen, generated by 8-hydroxyl-5-acetylquinoline photosensitization of the oxygen present in nondegassed studies, oxidized the caged benzoates. Interestingly, the photolysis of benzyl protected diethyl 2-(8-hydroxyquinoline-5-yl) 2-oxoethyl phosphate, 2.44, with or without degassing with argon, gave diethyl phosphoric acid as the major photoproduct. This behavior can be rationalized by the fact that the phosphate group is a better leaving group and can compete favorably with oxidation by singlet oxygen generated by 8-hydroxyl-5-acetylquinoline photosensitization. For the benzoate derivatives, the singlet oxygen reaction with quinoline is more rapid than loss of the poorer leaving group (benzoate). Furthermore, no reaction occurs in the absence of oxygen. Finally, zinc chelated benzoate ester 2.40 was found to be photochemically inert.