Selective Amine Recognition Driven by Host–Guest Proton Transfer and Salt Bridge Formation

The stepwise synthesis of ionizable p-tert-butylcalix­[5]­arenes 1a·H
and 1b·H, featuring a fixed cone cavity
endowed with a carboxyl moiety at the narrow rim, is described. Single-crystal
X-ray analyses have shown that in the solid state 1a·H
and 1b·H adopt a cone-out conformation
with the carboxylic OH group pointing in, toward the bottom of the
aromatic cavity, as a result of a three- or two-center hydrogen-bonding
pattern between the carboxyl group and the phenolic oxygen atom(s).
The affinity of amines for calix[5]­arene derivatives 1a·H and 1b·H was probed by 1H NMR
spectroscopy and single-crystal X-ray diffraction studies. These carboxylcalix[5]­arenes
are shown to selectively recognize linear primary aminesover
branched, secondary, and tertiary aminesby a two-step process
involving a proton transfer from the carboxyl to the amino group to
provide the corresponding alkylammonium ion, followed by binding of
the latter inside the cavity of the ionized calixarene. Proton transfer
occurs only with linear primary amines, that is, when the best size
and shape fit between host and substrate is achieved, while the other
amines remain in their noncompeting unprotonated form. The role of
the solvent in the ionization/complexation process is discussed. Structural
studies on the n-BuNH2 complexes with 1a·H and 1b·H provide evidence that
binding of the in situ formed n-BuNH3+ substrate to the cavity of the ionized macrocycle is ultimately
secured, in the case of 1a·H, by the formation of
an unprecedented salt-bridge interaction.