Publication Date


Document Type


Committee Members

Kenneth Turnbull (Advisor)

Degree Name

Master of Science (MS)


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


Department or Program

Department of Chemistry

Year Degree Awarded


Included in

Chemistry Commons