Halogen Bond Asymmetry in Solution

Abstract

Halogen bonding is the noncovalent interaction of halogen atoms in which they act as electron acceptors. Whereas three-center hydrogen bond complexes, [D···H···D]⁺ where D is an electron donor, exist in solution as rapidly equilibrating asymmetric species, the analogous halogen bonds, [D···X···D]⁺, have been observed so far only to adopt static and symmetric geometries. Herein, we investigate whether halogen bond asymmetry, i.e., a [D-X···D]⁺ bond geometry, in which one of the D-X bonds is shorter and stronger, could be induced by modulation of electronic or steric factors. We have also attempted to convert a static three-center halogen bond complex into a mixture of rapidly exchanging asymmetric isomers, [D···X-D]⁺ ⇄ [D-X···D]⁺, corresponding to the preferred form of the analogous hydrogen bonded complexes. Using ¹⁵N NMR, IPE NMR, and DFT, we prove that a static, asymmetric geometry, [D-X···D]⁺, is obtained upon desymmetrization of the electron density of a complex. We demonstrate computationally that conversion into a dynamic mixture of asymmetric geometries, [D···X-D]⁺ ⇄ [D-X···D]⁺, is achievable upon increasing the donor-donor distance. However, due to the high energetic gain upon formation of the three-center-four-electron halogen bond, the assessed complex strongly prefers to form a dimer with two static and symmetric three-center halogen bonds over a dynamic and asymmetric halogen bonded form. Our observations indicate a vastly different preference in the secondary bonding of H⁺ and X⁺. Understanding the consequences of electronic and steric influences on the strength and geometry of the three-center halogen bond provides useful knowledge on chemical bonding and for the development of improved halonium transfer agents.

Figure 1

Energy potentials of halogen motion in a three-center [D···X···D]⁺ halogen bond: (a) a symmetric single-well energy potential describes the halogen motion when the D–X bonds are equal and the system is static and symmetric, whereas (b) a symmetric double-well potential may reflect a pair of asymmetric isomers, [D···X–D]⁺ ⇄ [D–X···D]⁺, in dynamic equilibrium, with each form having a shorter and stronger D–X and a longer and weaker D···X bond when the energy barrier between the minima is shallow. The system becomes static and asymmetric if the energy barrier between the two minima is high. Alternatively, if the electron density of the two Lewis bases, D, are different, the halogen motion may either follow (c) an asymmetric single-well potential, or (d) an asymmetric double-well potential with a clear preference for a shorter and stronger bond toward one of the electron donors. The potential energy variation is shown here as a function of Δr, the displacement of X⁺ from the symmetrical position.

Figure 2

[(4-Methyl-2-((2-((4-(trifluoromethyl)pyridin-2-yl)ethynyl)phenyl)ethynyl)pyridine)iodine]⁺ tetrafluoroborate (1) and [(2,2′-(9,10-dimethoxyphenanthrene-3,6-diyl)dipyridine)iodine]⁺ tetrafluoroborate (2) were used as model systems to study a static asymmetric and a dynamic asymmetric halogen bond, respectively. Complex 1 allows optimal N–N distance for the formation of a three-center halogen bond and has an asymmetric electron distribution. Complex 2 has a longer-than-optimal distance between its nitrogens and has a symmetric electron distribution. A mixture of 1 and its monodeuterated isotopologue 1-d was used in IPE NMR experiments to differentiate between a static [N···I···N]⁺ and a dynamic [N···I–N]⁺ ⇄ [N–I···N]⁺ system.

Figure 3

Variation of electronic energy as a function of the position of the iodine in an [N···I···N]⁺ halogen bond, upon varying the N–N distance, r_NN (Å), and the position of the iodine as described by Δr, the elongation of the iodine from the geometrical midpoint of the nitrogen–nitrogen distance. Thus, at Δr = 0 the iodine is centered between the nitrogens, whereas at Δr = 0.5 Å it is 1 Å closer to one of them. The blue line shows the potential curve, corresponding to Figure 1a, for variable r_NN, while the red lines show the potential curves for r_NN kept fixed at 4.30 (solid), 4.88 (long-dashed), and 5.50 Å (short-dashed), respectively, shown both in the 3D plot and projected on the rear border plane. The black line on the right border plane shows the dissociation curve of the [N···I···N]⁺ bond model system. DFT calculations were performed using the M06 exchange and correlation functional and a mixed-level (double-ζ/triple-ζ/augmented triple-ζ) basis set (for details see the Supporting Information).

Figure 4

Potential energy curves of [N···I···N]⁺ halogen bonds: (a) Potential curves of complexes with flexible backbone, i.e., variable r_NN: [bis(pyridine)iodine(I)] (solid line), 4-methylpyridine–iodine(I)–trifluoromethylpyridine (long-dashed line), and methylpyridine–hydrogen(I)–trifluoromethylpyridine (short-dashed line). (b) Potential curves for systems with a rigid backbone, i.e., r_NN kept fixed: r_NN = 4.30 (solid line), 4.88 (long-dashed line), and 5.50 Å (short-dashed line). The energies are given relative to the ground-state energy of the respective system (see the Supporting Information for details).

Scheme 1. General Synthetic Route of [(4-Methyl-2-((2-((4-(trifluoromethyl)pyridin-2-yl)ethynyl)phenyl)ethynyl)pyri-dine)iodine]⁺ BF₄^– (1a) and Its Deuterated Analog 1a-d

Reagents and conditions: (a) 1. DMAE, n-BuLi, dry hexane, −78 °C, N₂; 2. MeOD, −78 °C, 30 min, −78–25 °C in 35 min; (b) TMS-acetylene, PdCl₂(PPh₃)₂, CuI, PPh₃, Et₂NH, MW 120 °C, 27 min; (c) MeOH, rt, 2.5 h; (d) 1,2-diiodobenzene, Pd(PPh₃)₂Cl₂, CuI, Et₂NH, MW 120 °C, 5 min; (e) Pd(PPh₃)₂Cl₂, CuI, Et₂NH, MW 120 °C, 30 min; (f) KF, MeOH, rt, 2.5 h; (g) PdCl₂(PPh₃)₂, CuI, Et₂NH, MW 100 °C, 12 min; (h) 1. AgBF₄, CH₂Cl₂, rt, 15 min; 2. I₂, CH₂Cl₂, rt, 30 min.

Scheme 2. General Synthetic Route to [(2,2′-(9,10-Dimethoxyphenanthrene-3,6-diyl)dipyridine)iodine(I)] tetrafluoroborate (2a)

Reagents and conditions: (a) Bu₄NBr, Na₂S₂O₄, dimethyl sulfate, THF/H₂O, 20 min; (b) Pd(PPh₃)₄, 2-pyridylzinc bromide, THF, 50 °C, overnight; (c) AgBF₄, CH₂Cl₂, 10 min; (d) I₂, CD₃CN, −40 °C.

Figure 5

Aromatic region of the ¹H NMR spectrum of (a) the I⁺ complex 2a, (b) the proton complex 2b, and (c) the free ligand 12 acquired at −40 °C for CD₃CN solution at 500 MHz suggests 2a to be present in solution as a dynamic mixture. The signals of 2b are also broadened but to a lesser extent than those of 2a, suggesting a faster rate of H⁺ exchange compared to that of I⁺ in the corresponding halogen complex.

Scheme 3. Calculated Electronic Energies, (ΔE, kJ mol^–1), Gibbs Free Energies (ΔG²³³, kJ mol^–1), and Bond Distances (r_NN and r_NI, Å) for a Variety of Possible Geometries of 2a and 2b

Energies are given as stabilization energies relative to 14a or 14b, respectively; that is, positive energy values indicate that the respective compound is less stable than 14a or 14b, respectively. For dimeric structures, energies are given per monomer. All species shown have a charge of +2 (dimers) or +1 (others). For the dimer structures, the methoxy functionalities have been omitted to make the presentation of the bonding situation for these structures less crowded. Computational details are given in the Supporting Information.