Forskning ved Københavns Universitet - Københavns Universitet


Aqueous Instability of δ-Fluorobutylpiperidines

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

In a series of partially fluorinated N-propyl- and N-butylpiperidine derivatives, three compounds were found to exhibit unexpected instability under mild biophysical assay conditions. These compounds carry a single terminal fluorine in the δ-position of an N-butyl group as a common structural feature. An adjacent fluorine substituent at the γ-position significantly slows down the reactivity. All other compounds, having either no or more than one fluorine substituent at the δ-position are chemically inert under all assay conditions. The reactivity of the labile compounds is traced to an intramolecular ring-closing fluorine substitution reaction by the moderately basic piperidine unit, leading to a spiro-pyrrolidinium salt. The chemical lability of δ-monofluorinated or γ,δ-difluorinated N-butylpiperidine derivatives even under very mild biophysical assay conditions constitutes a caveat to the molecular design of partially fluorinated alkylamines.

Udgave nummer6
Sider (fra-til)431-437
Antal sider7
StatusUdgivet - 17 mar. 2017

ID: 195958758