Reaction of Nitric Oxide at the β-Carbon of Enamines. A New Method of Preparing Compounds Containing the Diazeniumdiolate Functional Group

Publisher Website
Google Scholar
Abstract
The reaction of nitric oxide (NO) with enamines has been investigated. Unlike previously reported reactions of NO as a free radical with alkenes, the electrophilic addition of NO to the β-carbon of enamines results in the formation of compounds containing the diazeniumdiolate functional group (−[N(O)NO]-). This reaction between NO and enamines has been shown to be quite general and a variety of enamine-derived diazeniumdiolates have been isolated and characterized. While enamines derived from aldehydes and ketones whose structures allow for sequential multiple electrophilic additions tended to undergo overreaction leading to unstable products, it has been shown that this complication may be overcome by suitable choice of reaction solvent. The products obtained may exist as zwitterionic iminium salts or as neutral species depending upon the structure of the parent enamine. The diazeniumdiolate derived from 1-(N-morpholino)cyclohexene is unique among the new compounds in that it spontaneously releases NO upon dissolution in buffered aqueous solution at pH 7.4 and 37 °C. While the total quantity of NO released by this material (ca. 7% of the theoretical 2 moles) is apparently limited by a competing reaction in which it hydrolyzes to an α-diazeniumdiolated carbonyl compound and the parent amine, this feature may prove to be of great value in the development of multiaction pharmaceuticals based upon this new type of NO-releasing compound. Reports of enzymatic (oxidative) release of NO from previously known carbon-bound diazeniumdiolates also suggest that analogues of these compounds may be useful as pharmaceutical agents. This new method of introducing the relatively rarely studied diazeniumdiolate functional group into organic compounds should lead to further research into its chemical and biological properties.