The secondary amine/nitric oxide complex ion R2N[N(O)NO]- as nucleophile and leaving group in SNAr reactions

J. E. Saavedra, A. Srinivasan, C. L. Bonifant, J. Chu, A. P. Shanklin, J. L. Flippen-Anderson, W. G. Rice, J. A. Turpin, K. M. Davies, L. K. Keefer

Research output: Contribution to journalArticle

Abstract

Ions of structure R2N[N(O)NO]- and their alkylation products have seen increasing use as nitric oxide (NO)-generating agents for biomedical research applications. Here we show that such diazeniumdiolate anions can readily displace halide from a variety of electrophilic aza- or nitroaromatic substrates to form O2-arylated derivatives of structure R2N-N(O)=N-OAr. The site of arylation and the cis arrangement of the oxygens were confirmed by X-ray crystallography. Displacement by various nucleophiles showed R2N[N(O)NO]- to be a reasonably good leaving group, with rate constants for displacement by hydroxide, methoxide, and isopropylamine that were between those of chloride and fluoride in the SNAr reactions we surveyed. The Meisenheimer intermediate could be spectrally observed. These O2-aryl diazeniumdiolates proved capable of reacting with the nucleophilic sulfur of the HIV-1 p7 nucleocapsid protein's zinc finger assembly to eject the zinc, disrupting a structural motif critical to viral replication and suggesting possible utility in the drug discovery realm.

Original languageEnglish (US)
Pages (from-to)3090-3098
Number of pages9
JournalJournal of Organic Chemistry
Volume66
Issue number9
DOIs
StatePublished - May 4 2001
Externally publishedYes

ASJC Scopus subject areas

  • Organic Chemistry

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    Saavedra, J. E., Srinivasan, A., Bonifant, C. L., Chu, J., Shanklin, A. P., Flippen-Anderson, J. L., Rice, W. G., Turpin, J. A., Davies, K. M., & Keefer, L. K. (2001). The secondary amine/nitric oxide complex ion R2N[N(O)NO]- as nucleophile and leaving group in SNAr reactions. Journal of Organic Chemistry, 66(9), 3090-3098. https://doi.org/10.1021/jo0016529