Publication Date


Document Type


Committee Members

Kenneth Turnbull (Advisor)

Degree Name

Master of Science (MS)


In the present work, a synthetic route to the formation of a sydno[3,4- a]indolone was explored in the hope of attaining the first example of a fused-ring sydnone with an sp2-hybridized bridge. Formation of this product and exploration of its chemical behavior was anticipated to be of particular interest to the formation of NO-releasing prodrugs. A direct synthetic pathway to yield the target sydnoindolone starting from 3-(2-methoxycarbonylphenyl)sydnone and reaction with a base was proposed and explored. Attempted formation and isolation of the target sydnoindolone proved impossible under a variety of different conditions, undoubtedly due to the instability of this intermediate. To "work around" this proposed instability, a "trapping" protocol for the sydnoindolone was explored. Thus, the ester starting material was treated with LDA (or LHMDS) at -78°C for 10 minutes whereupon another organolithium base was added, with the expectation that the latter would intercept the intermediate sydnoindolone. Indeed, when this approach was utilized with methyl, phenyl and butyl lithium, the corresponding fused-ring sydnoindoles were formed in yields ranging from 15-44%. A brief exploration of optimization of the process was explored using methyl lithium as the second base / nucleophile. The relative success of this approach led to extension to other nucleophiles such as a Wittig and three Grignard reagents. The former did not provide the desired alkenyl product but the latter did form the corresponding fused-ring sydnoindoles, albeit (where comparison could be made) in lower yield than from the use of the organolithium species. With this new avenue to the fused-ring sydnoindoles in hand, it was elected also to further test their reactivity. Unfortunately, reactions (acids, base followed by alkyl halide) carried out upon 5-hydroxy-5-methylsydno[3,4- a]indole as the test molecule in attempts to affect the alcohol moiety proved to be futile as recovery of the sydnoindole resulted. However, preparation of 5-hydroxy-5-vinylsydno[3,4- a]indole from the use of vinyl magnesium bromide as the "trapping" reagent provided a more reactive species, especially under acidic conditions. Reactions of this new sydnoindole with acids yielded surprisingly stable, fused-ring alkenyl sydnones with an sp2-hybridized bridge and, accordingly, these valuable findings stimulated an attempt to increase the efficiency of the process leading to the formation of 5-hydroxy-5-vinylsydno[3,4- a]indole. It was conjectured that the target molecule would be available directly from 3-phenylsydnone by a known dilithiation protocol followed by treatment with methyl acrylate and, indeed, this process was more successful, though the overall yield was still very low.

Page Count


Department or Program

Department of Chemistry

Year Degree Awarded


Included in

Chemistry Commons