Ditopic Hexadentate Ligands with a Central Dihydrobenzo-diimidazole Unit Forming a [2x2] Zn 4 Grid Complex

A family of ditopic hexadentate ligands based on the parent compound 2,6-bis(6-(pyrazol-1-yl)pyridin-2-yl)-1,5-dihydrobenzo [1,2-d:4,5-d’]diimidazole ( L ) was developed and synthesized by using a straightforward condensation reaction, which forms the interlinking central benzo[1,2-d:4,5-d’]diimidazole bridge in the ligand backbone. The two secondary amine groups of the benzodiimidazole unit tautomerize and allow the formation of two tauto-conformers, which upon treatment with metal salts forms different isomeric coordination complexes. Here we report six new derivatives ( 1 – 6 ) that can tautomerize (varying the pyrazolylpyridine part) and 14 derivatives ( 7 – 13 ) with different alkyl and benzyl substitution on secondary amino groups (of L ) that prevent the tautomerization. This way, it is possible to study the properties of isomeric coordination complexes and their intrinsic cooperativity by the example of [2x2] grid complexes in the future. A [2x2] Zn 4 complex of the ligand L was synthesized and structurally characterized.

Recently, we reported on a homoditopic ligand L, which consists of two tridentate 2-(1H-imidazol-2-yl)-6-(pyrazol-1-yl) pyridine units interlinked via a central benzo [1,2-d:4,5-d'] diimidazole bridge (red, Figure 1a). [34] This bridging unit can simultaneously undergo two tautomerization processes between a secondary amine and imine functional groups. Besides, conformational isomers can be formed by rotation about the single bonds between the aromatic ring systems in the backbone of the ligand (Figure 1a). The rotational barriers of the single bonds connecting the pyridine and imidazole subunits enable two in-plane conformations, so-called S and C conformations (this denomination arises from their apparent shape, see Figure 1c). These two conformations are stabilized by the interaction between the N-based lone pair electrons and the H atoms of the neighboring aromatic rings (see Figure 1b).
The investigation of a solution sample of L by 1 H NMR spectroscopy revealed that both tauto-conformers are present in the solution and the L S :L C ratio of one was estimated from 1 H NMR studies in (deuterated) DMSO. Both tauto-conformers, L S and L C , can coordinate with metal ions in two tridentate binding pockets.
The different chelating modes of the homoditopic ligand L were read out by coordination with Fe II ions. This read-out took place in parallel, and multiple coordination products differing in their structures and properties have been observed. [34] Among them, the two dominant, isomeric tauto-conformers [Fe 4 (L S ) 4 ] 8 + and [Fe 4 (L C )4] 8 + of the [2x2] Fe II 4 grid-type complexes were isolated as crystals by several steps of fractional crystallization. [34,35,36] In the present work, we describe the synthesis, structures, and properties of some members of this new ligand family with respect to the substitution at the periphery and also to the central part of the ligand backbone, so that the ligands could not tautomerize; thus parallel product formation can be avoided. Here, we also present a coordination complex with Zn 2 + metal ions and describe its properties.

Results and Discussion
The tauto-isomerization processes of the ligands and the formed complexes are interesting in themselves and may give insights regarding the general mechanisms of such tautoisomerization processes. In the following, we will discuss the synthesis of six new ligands with a free NH group at the imidazole subunit but differing in their aromatic backbone. The intrinsic electronic and steric properties of ligand L can be easily adapted, which is apparent from the synthetic procedure shown in Scheme 1. The last step in the ligand synthesis is the condensation reaction of a carboxylic acid derivative (C) and a half equivalent of 1,2,4,5-benzenetetramine tetrahydrochloride in polyphosphoric acid (PPA). The character of the peripheral aromatic rings in the ligand can be determined in the synthetic step (a), where a suitable pyrazole derivative can be chosen (see R: 1-4 in Scheme 1). In the case of a peripheral pyridine substitution, as shown for 5 and 6, we employed the respective [2,2'-bipyridine]-6-carboxylic acid, which was prepared either from 2,2'-bipyridine or 6'-methyl-[2,2'-bipyridine]-6-carboxylic acid in two steps. The final condensation reaction between the carboxylic acid derivative and benzene tetraamine in polyphosphoric acid (PPA) forms the respective ligand (1-6) in good yields.
The synthesized ligands 1 to 6 were entirely characterized by standard methods like 1 H and 13 C NMR spectroscopy, mass spectrometry, and elemental analysis. It was possible to determine the molecular structure of 3 and 5 by X-ray diffraction of single crystals crystallized from deuterated DMSO with a drop of CF 3 COOD. Therefore, we found the compounds in the form of their dicationic triflate salts, showing a twofold protonation of each imidazole moiety ( Figure 2). For comparison, Figure 2 also shows the reported compound L, which was crystallized as a neutral ligand from the DMF solution. All three Figure 1. a) The conformational isomerism and tautomerism of L, b) stabilization of the planar ligand configuration by hydrogen contacts in the depicted conformation, c) the L S and L C conformers of L as found in solution, [34] d) the coordination of L to metal ions (e. g., Fe II ) develops the tautomerism-driven emergence of complexity (schematic representation of the cationic moieties of the isolated isomers of the [2x2] Fe II 4 grid complexes, consisting of L (black bars) and Fe II ions (grey spheres)).

Scheme 1.
Synthesis of the ligands 1 to 6 and the mother compound L (the first line is only for R = pyrazole derivative; in case of R being a pyridine, refer to Experimental section), a) K(pyrazolate), diglyme, 110°C b) NaOH, EtOH/ H 2 O, 55°C c) polyphosphoric acid (PPA), 200°C. structures in Figure 2 show the molecules are in the S configuration (as depicted in Figure 1c).
A detailed examination of the X-ray data shows that the ligand 3 with indazole derivative is not in planar configuration in the crystal lattice. The torsion angles are 18°and 24°, respectively, between the imidazole/pyridine and the pyridine/ indazole subunits. The reason for this torsion is the steric stress caused by the interaction between the hydrogen atoms of two opposite aromatic rings, namely the NH hydrogen of the imidazole and the hydrogen in the 7 th position of the indazole ring. On the other hand, the ligand 5 has a near planar configuration in the crystal lattice. We calculated a plane out of all C and N atoms of the ligand backbone. Then we measured the distance between each carbon and nitrogen atom of the ligand 5 to this plane, calculating an average distance of 0.05 Å. The ligands are arranged in layers, and the distance between two adjacent layers is 3.36 Å. There are also small torsion angles found for L (13°pyrazole/pyridine and 1°pyridine/imidazole) and 5 (1°pyridine/pyridine and 6°pyridine/imidazole), but these are not caused by steric repulsion between H atoms.
We noticed that the protonation state of the ligand has to be carefully controlled during the workup. Otherwise, hydrochloride or phosphate adducts can form depending on the workup procedure. Since these ligands are hardly soluble in organic solvents that are not miscible with water, it is difficult to adjust the pH as quickly as could be done easily in a biphasic system. We suspended the compounds in aqueous/alcoholic media and changed the pH to the sufficient value (see experimental section for the preparation of 1·2HCl and 1), which is time-consuming since it requires time to work with such an inhomogeneous system. The protonation state of the final product was assessed by elemental analysis. Furthermore, the 1 H NMR spectroscopic investigations revealed that the hydrochloride adducts of these ligands 1 to 6 behave slightly different in solution compared to the free ligands.
As mentioned above, both tauto-conformers of L are present in solution, and their ratios could be determined by the integration of the singlet resonances of the central benzene moieties, H α , H β , and H γ . In the case of DMSO (deuterated), we found an equimolar concentration of L S and L C , both in dilute and concentrated solutions. This is different for the HCl adducts of such ligands L, 1, 2, 3, and 4, which were precipitated during the workup under acidic conditions. The 1 H NMR spectrum of 1·2HCl adducts (with a concentration of 10 to 20 mM dissolved in deuterated DMSO) shows just one single resonance for the central benzene moiety corresponding to H α . Furthermore, there is no (or only a very broad) signal for the secondary NH group at about 12.5 ppm. Apparently, we just found the S form of the compound from the NMR experiment. A successive dilution of the sample in 3 steps of one order of magnitude each is shown in Figure 3 for 1 · 2HCl. The relatively sharp Hα resonance ( Figure 3a) becomes broader after dilution of one magnitude ( Figure 3b) and is almost not visible after the next dilution step (Figure 3c). At a concentration of about 0.015 mM, the signals of H α , H β , and H γ re-appear as it was observed for the free ligand. This phenomenon was also observed for the hydrochloride adducts of L, 2, 3, and 4 (see ESI, Figures S2-6). The coordination reaction of the presented ligands with transition metal ions such as Fe 2 + , Co 2 + , Zn 2 + is generally carried out in solvents like acetonitrile, nitromethane, or methanol. The solubility of the ligands in these solvents is very low. Therefore, we can conclude from the 1 H NMR spectroscopic investigation that even for the HCl adducts, both tautoconformers are present in solution and a divergent coordination [34] reaction takes place with at least two main coordination products. The tautomerization of the ligand is interesting and gives access to different coordination modes and products. It is possible to investigate the factors that  influence the isomerization of the formed grid complexes, such as temperature, solvent polarity, or pH.
However, if we want to study, in detail, the influence of the different coordination modes on the properties of the coordination products in the future, it may be advantageous to block the occurring tautomerization equilibrium of the two different tauto-conformers of L by chemical substitution at the secondary amine functionalities forming tertiary amines. The resulting ligands are either in a C-or S-type conformation which are unable to tautomerize and can be separated easily by column chromatography; thus, any parallel product formation is avoided during divergent coordination protocols. So to block the interconversion in ligand L, we treated it with alkyl or benzyl bromides or iodides either in DMF or DMSO as a solvent in the presence of Cs 2 CO 3 as a base, as depicted in Scheme 2.
The seven pairs of prepared derivatives differ in the steric demand of the introduced substituents. Increasing the chain length of the alkyl substituent may influence the crystal packing of the resulting [2x2] Fe II grid complexes in the solid-state and, therefore, also plays a role in the Spin Crossover (SCO) property of these compounds as seen before in mononuclear compounds. [37,38] The synthesized ligands 7 C /7 S to 13 C /13 S were characterized entirely by standard methods like 1 H and 13 C NMR spectroscopy, mass spectrometry, and elemental analysis (see Experimental Section and ESI). It was possible to determine the molecular structure of 8 C , 12 C , and 12 S by X-ray diffraction of single crystals (see Figure 4 and Table S2). The substitution of the secondary amine group of imidazole ring with alkyl and tert-butylbenzene moieties has improved the solubility of the ligands in solvents like chloroform/methanol, and even in diethyl ether in case of 12.
The diverse nature of the prepared derivatives of L will allow in future a detailed study of different metal complexes prepared from these structurally related ligands and may uncover resulting structure-property relationships. As one first example, we want to report on a Zn 4 grid complex prepared from the reaction of equimolar amounts of L with the metal salt Zn(ClO 4 ) 2 · 6H 2 O in acetonitrile. The complex formation leads to a clear yellow solution of a metal complex [Zn 4 (L) 4 ](ClO 4 ) 8 . The 1 H-NMR spectroscopic investigation of a sample of the reaction mixture showed 84 % of the [Zn 4 (L S ) 4 ] 8 + and 16 % of a second complex, [Zn 4 (L C ) 4 ] 8 + isomer, comparing the NMR data with the data of the Fe II grid derivatives described elsewhere. [34] The second data set of the [Zn 4 (L C ) 4 ](ClO 4 ) 8 isomer disappeared after recrystallization. The major fraction of the reaction product was isolated by slow diffusion of diisopropyl ether into the concentrated acetonitrile solution of the complex. The molecular structure of [Zn 4 (L S ) 4 ](ClO 4 ) 8 could be determined by X-ray diffraction of single crystals obtained during this recrystallization process (Figure 5b).
So far, it was not possible to isolate the pure [Zn 4 (L C ) 4 ][ClO 4 ] 8 isomer since both complexes (C and S) are of same color whereas in case of the Fe II grid complexes, they show differences in their spin states. Figure 6 shows the 1 H NMR spectrum of the ligand L for comparison, where the C and the S conformation are in equilibrium, giving, therefore, three signals for the singlet resonances of the central benzene moieties, H α , H β , and H γ [34] (see Figure 1c and Figure 6) and the spectrum of [Zn 4 (L S ) 4 ][ClO 4 ] 8 showing only one resonance H α for this moiety. Besides NMR spectroscopy in solution and X-ray diffraction of single crystals, we also investigated the properties of [Zn 4 (L S ) 4 ][ClO 4 ] 8 in the gas phase by high-resolution ESI-TOF mass spectrometry as shown in Figure 7. The mass spectrum of the reaction mixture following the coordination reaction is shown in the supporting information but has not such a high resolution as the one shown in Figure 7. Scheme 2. Synthesis of the ligand pairs of 7 to 13 starting from the mother compound L (using either DMSO or DMF as a solvent and Cs 2 CO 3 as a base for the reaction with the respective haloalkane or benzyl halide, see also the Experimental Section) different tautomers are chemically stabilized in this way so that an interconversion is not possible anymore.  Figure 8, the absorption maxima (λ max ), and extinction coefficients (ɛ) for the complex are listed in the supporting information. The UV region of the absorption spectrum shows strong bands with maxima at 258 nm, 377 nm, and 394 nm, which corresponds to ligand-centered (LC) π-π* transition bands. In the free ligand L, these bands are slightly higher in energy (see SI- Figure S33).

Conclusion
A family of ditopic hexadentate ligands with a central dihydrobenzo-diimidazole unit based on the mother compound 2,6-bis(6-(pyrazol-1-yl)pyridin-2-yl)-1,5-dihydrobenzo[1,2-d:4,5d']diimidazole (L) were successfully synthesized by condensation reactions. The two tautomerizing secondary amine functions of the benzodiimidazole unit are the origin of two tautoconformers, which can translate into two different isomeric coordination complexes. We reported on six tautomerizing derivatives with different nitrogen containing aromatic subunits with different electronic and steric properties. The resulting [2x2] grid complexes of transition metals, e. g., Fe II , Co II , and the prepared ligands are interesting in themselves, regarding the structure-property relationship of the isomeric complexes and their isomerization equilibrium. The 14 derivatives with different alkyl and benzyl substitution on secondary amino groups do not tautomerize and can give access to only one [2x2] grid  complex tauto-isomer. In this way, it will be possible to study the properties of isomeric coordination complexes and their intrinsic cooperativity on the models of [2x2] grid complexes in the future. Furthermore, we note that grid complexes built from the S form of such ligands show two chiral enantiomers. In the future, we will focus on the deconvolution/separation of these enantiomers and hope to study their properties in detail.

Experimental Section
General Methods: All the reactions were performed under Argon atmosphere using standard Schlenk techniques unless specified. All starting materials were purchased from commercial sources and were used as received. Solvents were freshly distilled over appropriate drying reagents. 1 H and 13 C NMR, COSY, HMQC correlation measurements were recorded using a Bruker Ultrashield plus 500 spectrometer with solvent-proton as an internal standard. Elemental analyses were carried out on a Vario Micro Cube. Infrared spectra were recorded using KBr-pressed pellets with a Perkin-Elmer Spectrum GX FT-IR spectrometer in the region of 4000-400 cm À 1 . Mass spectrometric data were acquired with a MicroTOF-Q II Bruker for ESI-TOF. Electronic absorption and fluorescence spectra were acquired at room temperature for diluted solutions (e. g., 2 × 10 À 6 M) on a Cary 500 Scan UV-VIS-NIR spectrophotometer and a Cary Eclipse fluorescence spectrophotometer, respectively using a 1 cm quartz cell. For Zinc complex, Mass-spectrometric measurements we performed on a SYNAPT G2S-HDMS (Waters, Manchester, UK) using electrospray ionization.

X-Ray Crystallographic Data:
Single crystal X-ray diffraction data were collected on a STOE IPDS II or IPDS2T diffractometer with monochromated Mo Kα radiation (0.71073 Å) at low temperatures. Using Olex2, [39] the structure was solved with the ShelXS [40] structure solution program using Direct Methods and refined with the ShelXL [41] refinement package using Least Squares minimization. Refinement was performed with anisotropic temperature factors for all non-hydrogen atoms (disordered atoms were refined isotopically); hydrogen atoms were calculated on idealized positions. Crystal data and structure refinement parameters are summarized in Tables S1-S3 in ESI.

Ligand 7:
An oven-dried Schlenk-flask was equipped with a magnetic stirrer bar and evacuated by three argon-vacuum cycles. L (0.895 g, 2.02 mmol, 1 eq) and Cs 2 CO 3 (2.64 g, 8.10 mmol, 4 eq) were added and dried under vacuum at 100°C overnight. The flask was flushed with Ar and DMF (40 mL, distilled from CaH 2 ) was added. After 30 min, the suspension was allowed to cool to ambient temperature. The iodomethane (0.855 g, 6.06 mmol, 3 eq, V = 0.375 mL) was added using a syringe. After the addition of the iodomethane the reaction was stopped after 24 h. The DMF was removed by distillation. The residue was taken into a mixture of CHCl 3 /EtOAc and H 2 O. After phase separation, the aqueous layer was extracted twice with CHCl 3. The organic layer was dried over Na 2 SO 4 , filtered, and reduced to dryness. Then the products were purified by column chromatography on silica as a stationary phase and a gradient of CH 2 Cl 2 and MeOH as a liquid phase. Yield: 7S: 0.254 g, 26 %, 7 C: 0.221 g, 23 %.