The Secondary Amine/Nitric Oxide Complex Ion R2N[N(O)NO]- as Nucleophile and Leaving Group in SNAr Reactions
- 11 April 2001
- journal article
- research article
- Published by American Chemical Society (ACS) in The Journal of Organic Chemistry
- Vol. 66 (9) , 3090-3098
- https://doi.org/10.1021/jo0016529
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.Keywords
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