Aqueous Instability of δ‐Fluorobutylpiperidines

Abstract

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.

Hydrolysis, polarity, and conformational impact of C-terminal partially fluorinated ethyl esters in peptide models

“…Though, the susceptibility of the fluorine-bearing esters towards natural esterases is still unknown, and systematic investigation of this issue is lacking in the literature. Notably, pH-programmed decomposition of fluoro-organic molecules has been recently reported for few other cases [ 61 – 62 ].…”

Well Defined Rich Electronic Structure: Facile Approach for Nido-Carborane Fused Azaspirodecaniums in Water Solution

“…The facile synthesis of nido-carborane has been reported. 38,39 Referring to these documents, we adopted a mild method which used ethanol as a solvent to give the nido-carborane potassium salt in ideal yield. Finally, the corresponding two intermediates were stirred in distilled water to form a target product bis(4-azaspiro [3.4]octan-4-ium)-nido-ortho-caborane (93%) and bis(5-azaspiro [4.5]decan-5-ium)-nido-ortho-caborane (91%), as shown in Scheme 1.…”