A phen–terpy conjugate whose chelate coordination axes are orthogonal to one another and its zinc complex

Abstract

A new highly rigid ditopic ligand has been prepared which consists of a terpy fragment connected through its 4′ position to the 3 position of a phen nucleus via a 1,4-phenylene linker. The chemical structure of the presently reported two-chelate ligand is such that the coordination axes of the two chelates are orthogonal to one another. The reaction of this phen–terpy conjugate with Zn²⁺ affords in good yield a dimeric structure, as shown by ES-MS and ¹H NMR spectroscopies.

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Multisite ligands containing two or several aromatic polyimines and their complexes have been extensively used in relation to electron and energy transfer processes, most of the time with ruthenium(II) centres and other d⁶ transition metals.¹ They have also been utilised extensively to construct elegant multinuclear architectures such as grids,^2a helical complexes,^2b,c racks,^2d,eetc. or new topologies such as knots³ or rotaxane dimers.⁴ As far as we know, two-site ligands whose chelate coordination axes are orthogonal to one another are not common. Such compounds should favour the formation of multinuclear complexes with well defined geometries and nuclearities.⁵ Once incorporated in macrocyclic systems, they should also allow the synthesis of multi-rotaxanes. The coordination principle is given in Fig. 1.

Fig. 1 Formation of M(A)(B) complexes should lead to oriented cyclic structures. Depending on the coordination sphere geometry of the transition metal used, various rings and nuclearities could be obtained.

The present report deals with the synthesis and the properties of such a two-site ligand, containing a 2,2′:6′,2″-terpyridine unit (terpy = tridentate chelate) attached to a 1,10-phenanthroline nucleus (phen = bidentate chelate). The rigid linker used (1,4-phenylene) connects the two chelates via appropriate positions (4′ position of terpy and 3 position of phen) so that the coordination axes are perpendicular to one another. The phen–terpy ligand 1 is represented in Scheme 1 as well as the synthetic route leading to it. It should be noticed that both chelating units are very distinct from one another (A of Fig. 1 is the phen unit, and B the terpy fragment). If the complexed metal M has a strong preference for 5-coordinate situations, M(A)(B) complexes should be strongly favoured versus symmetrical complexes of the M(A)₂ or M(B)₂ type.

Scheme 1 Reagents and conditions: (i) 4-bromobenzaldehyde, MeOH–NaOH_(aq), 30 min; (ii) I₂, pyridine, reflux 1 h, rt 14 h; (iii) NH₄OAc, AcOH, reflux 7 h, rt 14 h; (iv) Pd(dppf)Cl₂, KOAc, B₂neo₂, dioxane, 80 °C, 18 h; (v) Pd(PPh₃)₄, Na₂CO₃, p-anisylboronic acid, toluene–H₂O, reflux, 14 h; (vi) Pd(PPh₃)₄, Na₂CO₃, reflux, 30 h.

Compound 2 had previously been made by reacting Grignard reagents with the nitrile derivative.⁶ We developed a new efficient route inspired by the procedure described by Holm,⁷ which upon lithiation of the brominated precursor and addition of N,N-dimethylacetamide afforded 2 in 52% yield. Two parallel reactions were then carried out. On one hand, azachalcone 3 was obtained by classical aldol condensation of 2 and 4-bromobenzaldehyde, and subsequent dehydration of the intermediate^8,9 (86%). On the other hand, reaction of 2 with iodine in pyridine¹⁰ yielded the pyridinium iodide 4 (74%). Precursors 3 and 4 were then allowed to react according to the classical Kröhnke synthesis^8,11,12 and terpyridine 5 was obtained in 60% yield. The functionality at the back of the terpyridine was then modified by changing the bromine atom for a boronic ester function in the presence of bis(neopentyl glycolato)diboron according to the well described procedure.¹³ Compound 6 was thus obtained in quantitative yield from 5. The precursor used for the phenanthroline fragment was 3,8-dibromo-1,10-phenanthroline which was synthesized following the usual procedure.^14,15 It was then dissymetrized by a statistical Suzuki coupling reaction^15,16 on p-anisylboronic acid, and the mono-coupled product 7 was isolated in 46% yield. A last Suzuki coupling reaction^13,15,16 between 6 and 7 under classical conditions yielded the phen–terpy conjugate 1 (24%), containing seven conjugated 6-membered aromatic rings.

Zn²⁺ forms stable 5-coordinate complexes and it is most of the time sufficiently labile to allow formation of coordination compounds under thermodynamic control. This metal was thus selected for complexation studies with ligand 1. It should be noticed that non-distorted trigonal bipyramid geometries, with their two A and B chelates orthogonal to one another, are expected to favour formation of 4-metal centre assemblies similar to that represented in Fig. 1. By contrast, other 5-coordinate geometries such as, for example, square pyramid or distorted trigonal pyramid, should afford smaller rings such as 3-metal assemblies or even dinuclear species. For entropic reasons, the reaction between Zn²⁺ and 1 is expected to lead to the smallest possible complex, the size of the species obtained having nevertheless to be compatible with the coordination constraints imposed by the metal and the ligand. If distortion of Zn²⁺ coordination sphere and/or of the ligand backbone costs less than the entropic price needed to build the large ideal 4-metal species, lower nuclearities will be formed. This is the case in the present system. To our surprise, the dimer was the sole complex formed, without formation of tetramer nor even trimer complexes. The reaction is represented in Fig. 2 along with a molecular model (Chem 3D software) of the complex.

Fig. 2 Reaction between 1 and Zn²⁺ leading to the dimer complex, and its molecular model (Chem 3D software).

The coordination reaction of Zn²⁺ to 1 was carried out by mixing equimolar amounts of respectively 1 in CH₂Cl₂ and Zn(OTf)₂ in MeOH. The resulting orange solution was allowed to stir for 28 hours, the solvent was then evaporated, the crude mixture was taken up in methanol, filtered, and the filtrate evaporated to dryness. The dimer complex [Zn₂·(1)₂]⁴⁺·4OTf⁻ was obtained in good yield (78%) as a yellow solid. It is only sparingly soluble in common organic solvents. At this stage, it is difficult to know if, in solution, the Zn²⁺ centres are really 5-coordinate or if the counterion (CF₃-SO₃⁻ = OTf⁻) participates in the Zn²⁺ complexation. The X-ray structure of a recently published hexanuclear complex with Borromean rings as organic backbone¹⁷ showed that 6-coordinate Zn²⁺ complexes with Zn(N)₅(OTf⁻) coordination spheres are stable. The dimer complex with two 6-coordinate Zn²⁺ centres is moreover certainly less strained in terms of organic ligand distortion than the putative analogous complex in which the Zn²⁺ centres would be 5-coordinate. The chemical structure of [Zn₂·(1)₂]⁴⁺ (M) was proven by electrospray ionization mass spectroscopy (ES-MS) and ¹H NMR spectroscopies. ES-MS analysis of the yellow solid revealed three major peaks at mass-to-charge (m/z) ratios of 342.6, 506.4, and 834.6, corresponding to [M]⁴⁺, [M + OTf]³⁺, and [M + 2OTf]²⁺, respectively, a situation that is consistent with the proposed dimer compound [Zn₂·(1)₂]·4OTf.

DOSY (diffusion-ordered spectroscopy) experiments¹⁸ carried out on a solution of the yellow solid in MeOD (Fig. 3) revealed unambiguously the presence of a single species, characterized by its diffusion coefficient (D = 470 μm² s⁻¹; monomer 1 in CD₂Cl₂: D = 1000 μm² s⁻¹) and its hydrodynamic radius (r_H = 8.5 Å; monomer 1: r_H = 5.3 Å).

Fig. 3 DOSY experiment on the dimer complex in MeOD, and zoom on the aromatic region of the spectrum. Apart from the MeOH broad signals, a single product is present.

Computational simulation of the hydrodynamic radius of an ellipsoid object which matches with the experimental value of the radius enabled us to predict the size of the product in solution: a = 14 Å and b = c = 6 Å. The object is thus a prolate ellipsoid, which is consistent with the proposed dimer compound [Zn₂·(1)₂]·4OTf. The ratio a/b being approximately around 2, it would nevertheless be impossible to exclude the possibility of having an oblate ellipsoid (a = b = 14 Å and c = 6 Å) which would be more consistent with the geometry of the tetramer species. But considering the results of both ES-MS and DOSY experiments, we can tell that the sole product formed during the complexation process is the dimer species [Zn₂·(1)₂]·4OTf. Moreover, ¹H NMR clearly shows what was expected for a dimer species: the geometry around the zinc centre is so distorted that the p₂ proton of the phen part of one monomer points right into the shielding cone of the central ring of the terpy fragment of the other monomer, and consequently the p₂ proton signal is strongly shifted upfield (Δδ = 2.82 ppm).

In conclusion, a new phen–terpy conjugate 1 has been synthesized which contains two chelates whose coordination axes are perpendicular to one another. Whereas the expected structure for the Zn²⁺ complex formed with ligand 1 was that of a tetramer ([Zn₄·(1)₄]⁸⁺), a dimer was the sole product observed. The present example tends to indicate that entropy is a prevailing factor in the complexation process: the reaction leads to the smallest possible complex in spite of probable distortion of the Zn²⁺ coordination sphere and constraints within the organic ligand 1. Obviously, the use of other transition metal centres than Zn²⁺ with more demanding stereoelectronic requirements, making distortion more difficult, should favour formation of trimers or tetramers.

Experimental

General

¹H, ¹³C NMR and DOSY spectra were acquired either on a Bruker AVANCE 300 (300 MHz) or a Bruker AVANCE 500 (500 MHz) spectrometer, using the deuterated solvent as the lock and residual solvent as the internal reference. Mass spectra were obtained by using a Bruker MicroTOF spectrometer (ES-MS). Pd(PPh₃)₄ and Zn(OTf)₂ were commercial products.

Syntheses

Phen–terpy conjugate 1. To a degassed solution of 3-bromo-8-(4-methoxyphenyl)-1,10-phenanthroline (7, 49 mg; 0.134 mmol) and Pd(PPh₃)₄ (7.8 mg; 0.007 mmol) in 10 mL of toluene were added, under argon, 1 mL of a degassed solution of 2 M aqueous Na₂CO₃ and a solution of 4′-(4-(neopentyl glycolatoboron)phenyl)-5,5″-dimethyl-2,2′:6′,2″-terpyridine (6, 62 mg; 0.138 mmol) in 5 mL of toluene. It is very important to respect the following sequence in the additions: (a) dibromophenanthroline in toluene, (b) 3 vacuum–argon cycles, (c) addition of the catalyst, (d) 3 vacuum–argon cycles, (e) addition of the degassed solution of Na₂CO₃, (f) 3 vacuum–argon cycles, (g) addition of the degassed solution of the boronic ester. The reaction was monitored by TLC, and after 30 h reflux, the reaction mixture was allowed to cool to room temperature. The solvent was removed by rotary evaporation and the crude mixture was taken up in CH₂Cl₂ and washed with water. The combined organic layers were dried over Na₂SO₄ and the solvent evaporated. Chromatography (aluminium oxide, CH₂Cl₂ to CH₂Cl₂–MeOH (99 ∶ 1)) gave 20 mg (0.032 mmol; 24%) of pure product 1 as a white solid. ¹H NMR (for atom numbering see ESI†) (300 MHz, CDCl₃) δ (ppm): 2.44 (s, 6H, H_CH3), 3.90 (s, 3H, OCH₃), 7.08–7.11 (dm, 2H, 8.8 Hz, H_o1), 7.67–7.71 (dm, 2H, 8.1 Hz, 2.0 Hz, 0.5 Hz, H₄–H_4″), 7.72–7.75 (dm, 2H, 8.8 Hz, H_m1), 7.88 (d, 2H, 1.5 Hz, H_p5–H_p6), 7.91–8.11 (dd, 4H, 8.3 Hz, H_o2–H_m2), 8.34 (d, 1H, 2.3 Hz, H_p7), 8.46 (d, 1H, 2.3 Hz, H_p4), 8.57 (m, 2H, H₆–H_6″), 8.56–8.58 (d, 2H, 7.4 Hz, H₃–H_3″), 8.75 (s, 2H, H_3′–H_5′), 9.42 (d, 1H, 2.25 Hz, H_p9), 9.50 (d, 1H, 2.25 Hz, H_p2). ¹³C NMR (300 MHz, CDCl₃) δ (ppm): 160.07 (i); 156.19 (2′); 153.80 (2); 149.62 (6); 149.43 (4′); 149.36 (p9); 149.30 (p2); 146.02 (p12); 145.40 (p3); 144.72 (p11); 138.68 (y); 137.44 (4); 135.46 (p8); 134.92 (x); 133.57 (5); 133.41 (p4); 132.59 (p7); 130.00 (p); 128.69 (m1); 128.67 (p14); 128.37 (p13); 128.21 (o2); 127.97 (m2); 127.24 (p6); 127.06 (p5); 120.96 (3); 118.16 (3′); 114.78 (o1); 55.47 (OCH₃); 18.48 (CH₃). EI-MS, m/z exp.: 622.254 (1, calc. for [M + H]: 622.260). DOSY (CD₂Cl₂, 500 MHz): D = 1000 μm²/s; r_H = 5.3 Å.

Dimer [Zn₂·(1)₂]·4OTf. Phen–terpy conjugate 1 was suspended in 0.25 mL of CH₂Cl₂. A solution of Zn(OTf)₂ in CH₃OH (23.8 mg in 1 mL) was prepared, and 0.25 mL were added to the ligand suspension, which became clear and orange. The reaction mixture was allowed to stir for 28 h, the solvent was then evaporated and the crude mixture taken up in methanol, filtered, and the filtrate evaporated to dryness yielding [Zn₂·(1)₂]·4OTf as a yellow solid (10.5 mg; 78%). ¹H NMR (500 MHz, CD₃OD) δ (ppm): 2.37 (s, 6H, H_CH3), 4.02 (s, 3H, OCH₃), 6.68 (s, 1H, H_p2), 7.35–7.37 (d, 2H, 8.85 Hz, H_o1), 7.64–7.66 (dm, 2H, 8.0 Hz, H_m2), 8.12 (m, 2H, H₄), 8.14–8.16 (dm, 2H, 8.0 Hz, H_o2), 8.20 (m, 4H, H_p5–H_p6–H_m1), 8.25 (m, 2H, H₆–H_6′), 8.44–8.46 (d, 1H, H_p9), 8.76–8.78 (d, 2H, 8.1 Hz, H₃–H_3′), 8.94 (m, 1H, H_p4), 9.04 (s, 2H, H_3′–H_5′), 9.39 (s, 1H, H_p7). EI-MS, m/z exp.: 342.592 (calc. for [Zn₂(1)₂]⁴⁺: 342.590); 506.439 (calc. for [Zn₂(1)₂, OTf]³⁺: 506.438); 834.681 (calc. for [Zn₂(1)₂, 2OTf]²⁺: 834.637). DOSY (CD₃OD, 500 MHz): D = 470 μm² s⁻¹; r_H = 8.5 Å.

Acknowledgements

We thank the Région Alsace and the CNRS for financial support to BC.

References

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Footnote

† Electronic supplementary information (ESI) available: Structure and atom numbering for Phen–terpy conjugate 1. See DOI: 10.1039/b511762c

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