Metastable Macrocyclic Bis-Meisenheimer Adduct

Abstract

An electron-deficient tetranitroazacalixarene is shown to undergo reversible cyanide capture via nucleophilic aromatic substitution, yielding an unprecedented class of metastable dianionic macrocycle incorporating two Meisenheimer units, fully characterized by single-crystal X-ray diffraction, NMR, and electronic absorption spectroscopies. Acting as a chemical fuel, cyanide transiently drives the formation of this adduct, which can spontaneously regenerate the parent macrocycle under mild conditions, representing a rare demonstration of metastability in a Meisenheimer complex. The dynamic behavior of this system, reminiscent of out-of-equilibrium assemblies, is finely tunable through macrocycle concentration, counterion nature, solvent, and temperature. Detailed crystallographic, spectroscopic, and computational analyses reveal that intramolecular hydrogen bonding plays a key role in stabilizing the adduct. Comparative studies with simpler analogues further highlight the importance of macrocyclic preorganization and non-covalent interactions in governing this reversible reactivity.

Keywords: Chemical fuel; Dissipative system; Macrocycle; Meisenheimer complex; Nucleophilic aromatic substitution.

Figure 1

SN_Ar mechanistic pathways (a) and Meisenheimer anions reported in this study (b).

Scheme 1

Synthesis of azacalix[4]arene 1 and Meisenheimer adduct 1•2CN^2‐ .

Figure 2

¹H (a) and ¹³C (b) NMR spectra of compound 1 in CDCl₃ before and after addition of 2.5 equivalents of TBACN. The attributed signals are indicated with colored circles, “s” corresponds to the solvent, the signals marked with * and CN^‐ stem from the free cyanide in solution (see ESI for NMR spectra of TBACN).

Figure 3

Single crystal structures of 1 (column a) and 1•2CN^2‐ (column b) represented as front or elevated side views, with relevant distances indicated in Å. Atomic displacement ellipsoids plot at the 50% probability level.

Figure 4

Evolution of the electronic absorption spectra of 1 (5 × 10⁻⁵ M in CH₂Cl₂) upon addition of TBACN (a). Plot of the proportion of final complex 1•2CN^2‐ depending on the concentration of free cyanide in solution for different initial concentrations (c₀) of 1 (b). Evolution of the electronic absorption spectra of 1•2CN^2‐ (3.8 × 10⁻⁵ M in CH₂Cl₂) over time at room temperature (c). Plot of the normalized variation of absorbance intensity at 463 nm over time depending on the initial concentration of 1•2CN^2‐ in solution (d).

Figure 5

Electron density difference (EDD) plots for selected electronic states. The blue and red regions correspond to zones of decrease and increase of density upon absorption, respectively. Contour: 0.0015.

Figure 6

Experimental UV‐vis titration of macrocycle 1 with TBACN monitored at 463 nm in dichloromethane ([c]₀ = 2.5 × 10⁻⁵ M), and corresponding distribution of species 1, 1•CN^‐ , and 1•2CN^2‐ modeled with Sivuu.

Scheme 2

Proposed dissipative cycle regenerating azacalixarene 1 from 1•2CN^2‐ .

Scheme 3

Synthesis of nitrile‐containing azacalix[4]arene 8.

Figure 7

Fatigue of the addition‐elimination of cyanide on 1 (1 × 10⁻⁵ M in CH₂Cl₂) monitored at 464 nm (a). Evolution of the absorbance at 1•2CN^2‐ (2 × 10⁻⁵ M in CH₂Cl₂, A⁴⁶³  = 1.10 at t  = 0 h) stored at different temperatures (b).

Figure 8

Electronic absorption of compounds 1–3 (a) and the corresponding Meisenheimer adducts (b) in CH₂Cl₂ solvents. Plot of the proportion of final complex depending on the concentration of free cyanide in solution and calculated fits (dashed lines) (c). Plot of the variation of absorbance intensity at 463 nm over time depending on the initial concentration of Meisenheimer adduct in solution (d). In graphs (c) and (d), the concentration of macrocycle is about half of the one used for the model compounds to have the same number of reactive sites on each molecule compared.