Date of Award
PhD (Doctor of Philosophy)
Professor Mauro F. A. Adamo
Isoxazole, Chlorination, Enamine, Epoxide, Indole
The work behind my doctoral thesis has been focused on the study of reactivity of 3,5-dimethyl-4-nitroisoxazole. This compound shows a peculiar reactivity compared to other isoxazole derivatives due to the presence of the nitro group in 4-position. The chemical behavior of 3,5-dimethyl-4-nitroisoxazole has been extensively studied in the last decade with the development of important applications in pharmaceutical chemistry in the preparation of valuable biologically active compounds.
The investigation has been focused in the development of novel procedures for the electrophilic chlorination of 3,5-dimethyl-4-nitroisoxazole. We envisaged that the introduction of one or more chlorine atoms on the methyl group in 5-position of the nitroisoxazole core could bring to the formation of polyfunctional derivatives bearing multiple nucleophilic and electrophilic functionalities on the same molecule. The polyfunctional reactivity of these new type of isoxazole derivatives could then be exploited by means of different kind of reactions to produce important building blocks. In particular the use of 3-methyl-4-nitro-5- trichloromethylisoxazole in haloform-type reactions with different nucleophiles would produce 5-aminoisoxazoles via transition metal-free heteroaromatic amination. On the other hand, reaction of 3-methyl-4-nitro-5- chloromethylisoxazole with aldehydes and ketones would furnish α,β- epoxisoxazoles and α,β-epoxiesters through Darzens condensation. Moreover we decided to study the possibility of expanding the typical reactivity exhibited by the 4-nitroisoxazole core to other heterocyclic compounds like indoles in order to prepare valuable functionalized indoles.
Thus, the preparation of these new classes of isoxazole derivatives and their application in the development of novel chemical transformations could serve as new efficient methodologies in the synthesis of important bioactive compounds in different industrial pharmaceutical fields.
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Monasterolo C. Preparation of polychlorinated isoxazoles and application to organic synthesis [PhD Thesis]. Dublin: Royal College of Surgeons in Ireland; 2016.