Macrotricycles Featuring a π-Basic Tetrahedral Cavity:  Preference for NH₄⁺ Detected by Electrospray Ionization Mass Spectrometry

Abstract

Cation-pi interactions play an important role in biology. The title compounds are C3-symmetric macrotricycles built from resorcinol, a pi electron-rich arene. They were prepared in up to 18% yield by intramolecular cyclization of 1,3,5-trisubstituted benzene tripods bearing pendant resorcinol groups, with methylene acetal bridges. Positive ESI-MS showed that these receptors recognize NH4+ over K+, and poorly respond to the large t-BuNH3+ cation, suggesting that they bind NH4+ intramolecularly, presumably via cation-pi interactions.

Effect of Substituents on the Molecular Shapes of π‐Basic Macrotricyclic Receptors

“…[13] The synthesis of macrotricycles 1 and 2 has been reported previously. [7] The synthesis of the tripod precursors 5 and 6 of the macrotricycles 3 and 4, respectively, started with functional-group transformations of the resorcinol derivatives 7 and 10 (Scheme 1 and Scheme 2). Accordingly, methyl 4-bromo-3,5-dihydroxybenzoate (7) was treated with MOMCl in the presence of HünigЈs base (iPr 2 NEt) to afford ester 8 in 85 % yield.…”

“…They were obtained in 4.8 and 6 % yields, respectively, which is very much lower than the 18 % yield of 1 obtained under the same reaction conditions. [7] This indicates that the cyclization reactions are hampered by the presence of the bulky Br (for 3) and CH 3 S (for 4) substituents. In support of this assertion, the intermediate macrobicyclic product of two-fold ring closure (4a) was isolated in trace amounts in the course of the chromatographic purification of macrotricycle 4.…”

“…[7] Unlike 2, which shows a well-defined but elongated (cylindrical) cavity in the solid state, 1 has a collapsed structure because the mesitylene "cap" has a weak interaction (ring-to-ring distance of 3.981 Å) with one of the resorcinol-derived aromatic "walls". [7] Hydrogen atoms have been omitted for clarity. Thermal ellipsoids are drawn at the 50 % probability level.…”

“…[5] The problem of fixing either one has been solved by intramolecular bridging or by substituting the phenolic oxygen atoms with appropriate groups (e.g., nPr). [6] We recently reported the synthesis and properties of macrotricyclic molecules 1 and 2 [7] incorporating resorcinol-and mesitylene-derived "walls" and "cap", respectively (Figure 1), and complementing molecular cages derived from hexahomotrioxacalix [3]arene. [8] These compounds the "walls" and the "cap" on the shapes of the macrotricycles in solution ( 1 H NMR), the solid state (X-ray diffraction), and gas phase (calculations).…”

“…Finally, the implications of the structural differences are discussed with regard to the preorganization of receptors 1 and 2 for gas-phase π-complexation properties studied in a previous investigation. [7] Figure 1. Chemical structures of macrotricycles 1-4.…”