Publication Date
2007
Document Type
Thesis
Committee Members
Kenneth Turnbull (Advisor)
Degree Name
Master of Science (MS)
Abstract
In this research, 5-methylsydno-[3,4-a]quinazoline was synthesized via multiple methodologies, the best of which yielded the target compound in 50 % overall yield for the six steps. Synthesis of this compound in reasonable yields and exploration of its chemical behavior is of particular interest as a putative NO-prodrug. As an initial approach to the synthesis and accumulation of the compound of interest, attempts were made to optimize the existing synthetic pathway to its precursors. The starting material, 3-(2-acetylphenyl)sydnone, was prepared in 3 steps from commercially available starting material in good yields. This sydnone compound was then converted to the versatile intermediate, 3-(2-acetylphenyl)sydnone oxime. This conversion was accomplished by two distinct means, one of which was a novel microwave-assisted synthesis. Following its synthesis, 3-(2-acetylphenyl)sydnone oxime was converted to several reactive intermediates (O-acetate, O-tosylate, O-mesylate) in order to evaluate their utility with regards to cyclization to the aforementioned sydnoquinazoline. With respect to cyclization, 3-(2-acetylphenyl)sydnone oxime was treated with trifluoroacetic acid, which resulted in the target sydnoquinazoline in low yields. The reactive intermediates were also treated under thermal conditions, with the O-tosylate and O-mesylate species resulting in the target fused-ring sydnone in very low yields. These more reactive sydnones were exposed also to lithiation conditions to explore the possibility of base-induced cyclization to the desired sydnoquinazoline. Under these conditions, the O-tosylate and O-mesylate were treated with lithium diisopropyl amide. The O-tosylate resulted in the formation of the target quinazoline in moderate yields, while the O-mesylate resulted in formation of the target compound in good yields. Indeed, by adjustment in the amount of base employed, an up to 80% yield of the desired fused-ring sydnone could be realized; a considerable improvement over the methods previously employed.
Page Count
82
Department or Program
Department of Chemistry
Year Degree Awarded
2007
Copyright
Copyright 2007, all rights reserved. This open access ETD is published by Wright State University and OhioLINK.
