Synthesis, Structure Determination and Catalytic Activity of a Novel Ruthenium(II)

This work reports the synthesis, structure and catalytic activity of a novel ruthenium(II) complex, [RuCl(dppb)(44bipy)(4-pic)]PF 6 (where dppb = 1,4-bis(diphenylphosphine)butane; 44bipy = 4,4’-dimethyl-2,2’-dipyridyl; 4-pic = 4-picoline). The molecular structure and catalytic activity were studied by Fourier transform infrared (FTIR), UV-Vis and nuclear magnetic resonance (NMR) spectroscopies, cyclic voltammetry, and X-ray crystallography, while the electronic structure was investigated by density-functional theory (DFT) and time dependent DFT (TD-DFT) methods. Electrochemical studies showed the substitution of the chlorido ligand from the precursor by the 4-pic ligand, exhibiting the Ru II /Ru III process at 1.21 V. The structure of the compound was optimized using DFT simulations and showed data similar to the X-ray structure. The UV-Vis absorption spectrum showed a good agreement with TD-DFT simulations. The highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) energies were determined at the Becke, 3-parameter, Lee-Yang-Parr (B3LYP) level. The study of the catalytic activity in the transfer hydrogenation of ketones by the 1 H NMR showed efficient transfer hydrogenation reaction at 60 ºC, employing acetophenone as substrate and resulting in a high conversion. The formation of two ruthenium-hydride species was observed.


Introduction
Several research groups on reactions catalyzed by transition metal compounds have been dedicated to the study of new compounds due to various academic and industrial applications. Reactions of transfer hydrogenation by alcohols as the hydrogen source catalyzed by metal complex have been widely reported as an effective protocol, and in this area, ruthenium catalysts stand out. [1][2][3][4] Geoffrey Wilkinson and co-workers 5 studied these compounds that show enhanced stability, good selectivity and high catalytic activity. They examined the proprieties of ruthenium/rhodium/phosphine complexes in catalytic hydrofunctionalization reactions such as hydroacylation, hydroboration and hydrosilylation of alkenes. 2,3,5 Moreover, many studies have investigated the proprieties of Wilkinson's catalyst and analogues, resulting in a wide range of applications of these complexes such as anticancer and antibacterial drugs. [6][7][8] The hydrogenation of ketones to alcohols using isopropanol as a hydrogen source has attracted wide attention because isopropanol is a common and cheap solvent; isopropanol and the by-product of the hydrogenation transfer reaction, acetone, are volatile which simplify the purification of the product; the reaction does not need pressurized hydrogen gas, nor does it produce hazardous waste. This hydrogenation transfer reaction can be performed in basic medium. Therefore, developing substances with catalytic proprieties under neutral conditions is highly recommended, mainly utilizing more sustainable and economic catalytic systems for this kind of hydrogenation reaction. [9][10][11][12] In previous works, [13][14][15] our research group reported on the catalytic profile of some complexes of [Ru(P-P)(N-N)L] type (P-P = biphosphine; N-N = bipyridine and L = mono/ bidentade ligand), showing that the ruthenium(II) complexes perform well as precursors in the hydrogenation of non-polar double bonds, transfer hydrogenation of polar double bonds, hydroformylation/hydrogenation, hydroformylation/acetalization and oxidation of alkenes. 13 Among these works, Rodrigues et al. 14 demonstrate that Ru II /Ru III complexes tested as hydroformylationhydrogenation catalysts can produce up to 92% (isolated yield) of ethanol cyclohexane, without using additives, showing high versatility as a catalytic agent. 14 Another highlight is a study carried out by Higuera-Padilla et al. 15 which determines the complex catalytic mechanism of hydrogenation of ketones to alcohols with isopropanol as a hydrogen source, monitoring the reaction in situ by rapid injection and in real time using 1 H nuclear magnetic resonance (NMR) spectroscopy techniques. 15 This shows that the reaction mechanism involves the formation of a hydride species and ketone followed by the reduction of ketone substrates, answering the main question of catalysis, the chemical reactions involved in the catalytic process.
In this study, we report on the synthesis, full characterization and theoretical calculations of a new ruthenium(II) complex with 4-picoline ligand. The structure of the complex was determined in crystalline state by X-ray crystallography. The structural analysis and characterization of the complex, in solution, were performed by NMR techniques ( 1 H, 13 C{ 1 H}, 1 H-1 H correlated spectroscopy (COSY), 1 H-13 C heteronuclear multiple bond coherence (HMBC) and 1 H-13 C heteronuclear single quantum coherence spectroscopy (HSQC)), infrared, UV-Vis spectroscopies, conductivity, cyclic voltammetry, elemental analysis and density-functional theory (DFT) calculations. Herein the catalytic activity of this complex is described, in a hydrogen transfer reaction from isopropanol to ketones. Different reaction conditions were used, which include different organic substrates, to produce alcohols. In situ high-field NMR spectroscopy was used to monitor the hydrogen transfer reaction in real-time with rapid injection NMR spectroscopy, which is a reliable tool for structural analysis and determination of reaction rates and yields.

Instrumentation
Elemental analyses were performed in a Fisons EA 1108 model (Thermo Scientific, Waltham, USA). The IR spectrum was recorded on a FT-IR Bomem-Michelson 102 spectrometer (Vancouver, Canada) in the 4000-400 cm -1 region using solid samples pressed in KBr pellets. UV-Vis spectra were recorded in a HP8452A (diode array) spectrophotometer (Avondale, USA). All solvents and reagents employed in this work presented analytical grade and were purchased from Sigma-Aldrich Brazil (São Paulo, Brazil). Solutions with the concentrations of 1.0 × 10 -4 mol L -1 in dimethyl sulfoxide (DMSO) and quartz cells of 1.0 cm path length were used in the analysis. The electrochemical measurements (cyclic voltammetry) were performed in an electrochemical analyzer, BAS model 100B/W MF-9063 Bioanalytical Systems Instrument (West Lafayette, USA). The measurements were performed in dichloromethane solution (degassed with argon) at room temperature with tetrabutylammonium perchlorate (TBAP) as supporting electrolyte. The electrodes used (working and auxiliary) were platinum and Ag/AgCl as the reference electrode and the ferrocene in this system is oxidized at 0.43 V (Fc + /Fc). The 1 H, distortionless enhancement by polarization transfer (DEPT)-135 and advanced 2D NMR techniques such as gradient enhanced, 1 H-1 H COSY and 1 H-13 C correlation HSQC were used. These analyses were performed in acetone-d 6 as a solvent in a 5 mm sample tube at 293 K in Bruker Ascend 600 MHz equipment (Ettlingen, DE). For 1 H and 13 C NMR resonances, splitting was reported as s = singlet, d = dublet, t = triplet and m = multiplet.

X-ray crystallography
Single crystals of C4B-4pic were obtained by slow evaporation of solvent (acetone/methanol, 1:1 v/v) at room temperature. Single-crystals were selected and the intensity data were measured with the crystal at 293 K using the Enraf-Nonius Kappa-CCD diffractometer with graphite monochromated Mo Kα radiation (λ = 0.71073 Å) and the structures were solved by direct method using SHELXT. Non-hydrogen-atom positions were determined by Fourierdifference map analyses with refinements carried out with the SHELXL package using full-matrix least squares on F2 with anisotropic displacement parameters. 17 All H-atoms were stereochemically positioned and refined with the riding model. The visualization of the structure and tables with selected bond lengths and angles were generated using the Olex2 18 and Mercury 19 software.

Theoretical methods
Full geometry optimizations were performed from the crystallographic coordinates using the Becke's parameter hybrid functional combined with the Lee-Yang-Parr correlation functional (B3LYP) in Gaussian 09 package. 20 For ruthenium atoms, the Lanl2dz pseudopotential was used, while for light atoms, a full electron polarized double-zeta basis set 6-31G* was adopted. 21,22 Vibrational frequency analysis showed that optimized structure were real minima (no imaginary frequencies). [23][24][25][26] Time dependent DFT (TD-DFT) calculations were performed to obtain the UV-Vis analyzed using the Chemissian software in order to compare to experimental data. 27,28 Monitoring the catalytic reaction by NMR spectroscopy The study by NMR of the hydrogen transfer reaction from 2-propanol to one cyclic, one linear and one aromatic ketone, representing the different existing classes, was carried out in 5 mm NMR tubes in Bruker Ascend 600 MHz equipment. 1 H NMR spectra were acquired in deuterated benzene (C 6 D 6 ), with sixteen scans, 30° pulse, acquisition time of 1.99 s and 1 s relaxation delay. Spectra were recorded at every 50 s, equivalent to approximately 600 spectra per reaction time. The reagents were added to NMR tubes, mixed and inserted into the spectrometer. After tube insertion in the probe, it was mandatory to allow a suitable time (10 min) to achieve thermal equilibrium. Sample temperature was established at 60 °C and controlled by the variable temperature heater of the probe. Following this, the catalyst precursor was injected through a cannula, coupled to a syringe and mechanically mixed by rapidly pushing and pulling, as was previously reported. 15,29,30 Measurements began upon catalyst injection. The yield of the process was calculated by taking into account the relative integrals of ketone and alcohol.
The reaction was followed by 31 P{ 1 H} NMR, where the precursor consumption pathway can be followed, [RuCl 2 (44bipy)(dppb)] in methanol/dichloromethane (1:1, v/v), which has two doublets spectrum, at 30.42 and 43.92 ppm, with J 39.2. After adding the 4-pic and KPF 6 , we see the change in the spectrum to give two very close doublets with the appearance of a false singlet, as shown in Figure 3. This close proximity of the doublets shows that the two phosphorus atoms of the complex are in very similar chemical environments. This can be explained by the fact that one atom of phosphorus is trans to the N of the diiminic ligand, and the other atom of phosphorus is trans to the N of the 4-pic ligand.
The one-dimensional (1D) and two-dimensional (2D) 1 H and 13 C NMR experiments enabled the assignment the [Ru(dppb)(44bipy)(4-pic)Cl]PF 6 configuration. 1D 1 H and 13 C NMR, 2D 13 C-1 H HSQC, 13 C-1 H HMBC and 1 H-1 H-COSY in acetone-d 6 confirm the purity and the proposed structure and the assignment of the hydrogen and carbon atoms are shown in Figures S2-S6 (SI section). The 1 H spectrum is shown in Figure 4, where two major regions can be observed: an aliphatic region of 1.10-4.16 ppm totaling 17 H, attributed to 8 H from the -CH 2groups of the phosphine; and 9 H referring to the three methyl groups (-CH 3 ), consisting of 2 groups of the diiminic ligand and 1 of the 4-pic ligand. In the aromatic region of hydrogen, between 6.58-9.08 ppm with an integral of 30 H, there were 20 H of the 4 phenyl groups of the phosphine, 6 H of the diiminic ligand and 4 H of the 4-methylpyridine ligand. The experiment obtained for 1 H-1 H COSY identified the couplings between the more deshielded hydrogen 9.08 and 8.89 ppm which are attributed to the hydrogen neighboring the diimine nitrogen, which couples with the methyl groups of the diiminic ligand (2.56 and 2.39 ppm). In addition, the methyl group from the 4-pic ligand (2.07 ppm) couple to the hydrogens from the neighboring methyl groups from the 4,4'-bipyridine molecule. The hydrogens of the phenyl  groups were not assigned to specific hydrogens because they are overlapped.
The 13 C{ 1 H} and DEPT-135 spectra are shown in Figure S3 (SI section) and the carbon type of each signal can be observed, -CH 3 -, -CH 2 -, -CHor -C-, which together with the data of 1 H- 13  The FTIR spectra of the precursor [RuCl 2 (dppb)(44bipy)] and of the [RuCl(dppb)(44bipy)(4-pic)]PF 6 complex, shown in Figure S1 (SI section), are very similar to each other due to the chlorido ligand, because the ligand inserted in the complex does not present any characteristic functional group different from the precursor complex, resulting in few alterations in the profile of the bands presented in the FTIR spectra. When compared to the spectrum of the complex with that of the precursor, it is not possible to notice significant modifications in the spectrum because in the precursor there is already the stretching band νCH sp3 at 2848 and at 2922 cm -1 and at 3062 cm -1 referring to νCH arom of the groups. Thus, the main evidence of the reaction is the appearance of the band at 845 cm -1 for the combination band νP-C and νP-F.
The precursor and the new complex were characterized by cyclic voltammetry (CV) experiments in 0.1 mol L -1 TBAP solution in dichloromethane, showing that both compounds are electroactive and the electrochemical behavior shows the change of the chemical environment in the coordination sphere of the metal, after the reaction.
The behavior of the reaction can be followed by tracing the redox process in the precursor in approximately 0.76 V, which corresponds to the redox Ru II /Ru III process, while the product of the reaction shows the metal oxidation process at higher value, at 1.21 V, indicating the change in the coordination sphere of the metal, when a chlorido ligand is replaced by the 4-pic ligand. The voltammograms can be found in Figures S7 and S8 (SI section). In this reaction, the substitution of a donor sigma bond (Cl) ligand by a π-acceptor ligand (4-pic) can be seen removing the electronic density of the metal, which causes the displacement of the oxidation processor to the higher potential in the cyclic voltammogram. These data are in accordance with reports in the literature for Ru II complexes with phosphine and diimine ligands. 31,32 The details of the X-ray structure obtained for the new complex are explained in the Experimental section and the structural data are given in Table 1. The molecular structure of the complex is displayed as an ORTEP representation in Figure 5, and selected bond distances and angles are shown in Table 2.
Observing the crystallographic data, it can be confirmed that in the coordination sphere of the complex there are two bidentate ligands (44bipy and dppb), a chlorido ligand and a 4-pic ligand, and the PF 6 is the counter ion. The complex crystallizes in a monoclinic P2 1 /n centrosymmetric group, with one molecule per asymmetric unit and the structure is in accordance with the NMR, IR and cyclic voltammetry results.
The compound has distorted octahedral geometry, with a large deviation from the ideal angle of 90°, where P(1)-Ru-P(2) is 93.44°, N(1)-Ru-N(2) is 77.84° and Cl-Ru-N4pic is 87.11°, which are very close to values shown for similar complexes. The Ru-N4pic bond lengths are 2.330 Å, Ru-P(1) is 2.342 Å and the bond length of the P trans to the 4pic ligand, Ru-P(2), is slightly lower with 2.330 Å. 8,13,16,21 The selected bond lengths are shown in Table 2 and are in accordance with the data available in the Cambridge Crystallographic Data Centre (CCDC) database when the data are compared with bond lengths and angles for all similar structures available in the Crystal Structure Database (CSD) using the Mogul software. 33

Computational analysis
It is already well established in the literature t h a t r u t h e n i u m ( I I ) c o m p o u n d s a r e l ow s p i n diamagnetic, and therefore have the electronic state (dxy) 2 (dxz) 2 (dyz) 2 (dz 2 ) 0 (dx 2 -y 2 ) 0 in the ground state. This means that the structure was optimized in the singlet state by the analysis of the absence of imaginary frequencies. 34 The optimized structure of the complex [RuCl(dppb) (44bipy)(4-pic)] + at the DFT/B3LYP level was superimposed with the data obtained experimentally for the sake of comparison, as shown in Figure 6.
The selected bond lengths and angles are shown in Table 2, which corresponds to the optimized geometrical parameters of the compound at the DFT/B3LYP level and the experimental data. It can be observed that the optimized structure is in accordance with the crystallographic data obtained, as already reported in the literature where the B3LYP functional presented accurate results to predict geometric parameters, which are very close to the experimental data. [35][36][37][38][39] It is of the utmost importance to know the physicochemical parameters of the system and its energy from the frontier orbitals (highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO)) that provides valuable quantum information. Thus, the energy of the frontier orbitals were calculated 0.89/-0.51 a-c and α-γ: unit cell parameters; Z: formula unit per unit cell; F(000): structure factor in the zeroth-order case; F 2 : squared structure factor; R 1 and wR 2 : R-factor and weighted R-factor, respectively.   Figure 7. 40,41 The HOMO orbital is centered mainly on the d(Ru) and p x orbitals of the Cl atom, and the LUMO orbital is centered on the 44bipy diiminic ligand. The calculated gap for the HOMO and LUMO orbitals was 3.1062 eV. TD-DFT calculations were performed in order to predict UV-Vis spectrum for the first 80 excitations and the results were compared with the experimentally obtained UV-Vis spectrum. Theoretically and experimentally obtained UV spectra are in good agreement and both indicate two main absorption peaks, which are summarized (excitation energies, wavelength and oscillator strengths) in Table 3.
The difference of the wavelengths between theoretically and experimentally obtained UV spectra is around 10 nm, which is in good agreement. (Figure S10, SI section).
The band located at 290 nm in the experimental spectrum appears at 280 nm in the theoretical spectrum is due to a transition of the type π-π*, which has the greatest contribution of the HOMO-11 → LUMO transition (34.1%). The second band of the experimental spectrum is at 438 nm, which is correspondent to the peak located at 450 nm in the theoretical spectrum. This transition is of the metal-to-ligand charge-transfer (MLCT) type since the transition is from the Ru-centered orbitals (dπ), the π * type orbitals of the Cl ligand and bipyridine ligands. This transition is mainly formed by the HOMO-2 → LUMO orbitals with 88.0% of contribution and HOMO → LUMO 4.4% of contribution. All the theoretical data showed good agreement with the experimental data, which corroborates the theoretical model used.
NMR techniques are widely used to detect multiple reactive intermediates, providing thereby important information concerning the involved reaction mechanism. 15 The Figure 9 allows to follow the catalytic reaction with the expansion of the 1 H NMR spectra, the hydrogen transfer reaction using isopropanol as a hydrogen donor, precatalyst [RuCl(dppb)(44bipy)(4-pic)]PF 6 complex,   and acetophenone as substrate. Beforehand, the reaction monitored by NMR spectroscopy from 6.8 to 7.8 ppm, showed the three acetophenone signals, at 7.77, 7.36, and 7.26 ppm. During the reaction, these three peaks decreased with a concomitant increase of three peaks at 7.23, 7.12, and 7.02 ppm, which can be attributed to the reduced product, acetophenol. During the reaction, the formation of the acetone singlet at 1.9 ppm and the acetophenol doublet at 1.32 ppm were observed. The spectra in Figure 9 demonstrate the continuous formation of the products during a 6 h reaction. The transfer hydrogenation reaction was also performed using hexanone and methyl ethyl ketone as substrate and monitored with NMR. The data presented in Table 4 show the efficiency of the C4B-4pic complex in the hydrogenation transfer reaction at 60 ºC. The pre-catalyst shows efficient conversion of the product, always higher than 80%. In articles previously published in the literature, 15,42 it is common to use nitrogen atmosphere, in addition to high temperature (82 ºC) and a catalyst load between 0.1 to 1 mol%. A recent study 15 used temperatures of 40 and 50 ºC, a catalyst load of 5% and a reaction time between 24 to 30 h.
These observations reinforce that the use of an inert atmosphere was needless, with an acceptable reaction time.
The catalyst load is similar and the in situ conditions were performed in the NMR equipment. It is worth mentioning that the reaction itself occurs only in the presence of the pre-catalyst and the base. A widely accepted mechanism for catalytic activity of ruthenium complexes in the base-assisted transfer hydrogenation from isopropanol to ketones involves the dissociation of the chlorido ligand, as well as the coordination of the hydride species. A plausible mechanism for the catalytic activity of the Ru II complex used here is presented in Figure 10.   It was previously proposed by Aydemir et al. 43 that the first step comprised the removal of the isopropanol more acidic hydrogen by the base, as well as the formation of ions that react with the pre-catalyst A, forming the Ru-iso-propoxyde species B. The B intermediate undergoes β-hydride elimination and forms the ruthenium species C, D and acetone. Then, the hydride intermediates C and D react with the carbonyl carbons of ketones substrate and lead to the alkoxyde substrates E and F. Finally, the alkoxide substrates react with another isopropanol molecule (in excess), restoring the intermediate B by releasing the respective alcohol derived from the substrate.
In order to corroborate the proposed mechanism, NMR spectra of solutions containing isopropanol, base and the pre-catalyst A were acquired, as shown in Figure 11. The insets in the spectra evidence two groups of signals, one doublet of doublets (dd) around -14.0 ppm, and one triplet (t) at approximately -14.4 ppm. Weak signals were attributed to the coupling between hydrogen and phosphorous atoms of the hydride intermediates, which  occurs at a low concentration (0.1%). The dd signal is originated by the coupling with one phosphorus-trans and one phosphorus atom in the cis position. The t signal is attributed to the coupling of the hydride with two phosphorus atoms in the cis position.
The 1 H NMR experiments allowed to observe the formation of two species of ruthenium hydride in the initial stage of the hydrogen transfer reaction. 42 The hydride generated can be observed until the end of the reaction.

Conclusions
We have described the synthesis of a mononuclear ruthenium(II) complex, which presents an octahedral geometry around the metal center, containing two bidentate ligands (phosphine and diimine) and two monodentate ligands (chlorido and 4-picoline) suggested by FTIR and 31 P{ 1 H}, 1 H and 13 C{ 1 H} NMR spectroscopy, where the ligand 4-picoline is trans to the phosphorous atom of the phosphine ligand. This structure was confirmed by single crystal X-ray diffraction. The calculations by DFT methods at the B3LYP/Lanl2dz/6-31G* level of theory are in agreement with experimental structural parameters. In the frontier molecular orbitals, the HOMO is centered mainly on the d(Ru) orbitals and the p x orbitals of the Cl atom, while the LUMO is centered mainly on the 44bipy diiminic ligand. The HOMO-LUMO gap was calculated at 3.1062 eV. Analysis of the UV-Vis spectrum of the complex showed good agreement of the experimental and the calculated data, which showed a difference of only 10 nm for the two main absorptions peaks. The study of the catalytic activity in the transfer hydrogenation of ketones by the 1 H NMR technique showed that the complex is efficient on the transfer hydrogenation reaction at 60 ºC and uses acetophenone as substrate with good conversion, where two ruthenium-hydride species are formed at the initial stage of the hydrogen transfer reaction during 6 h. The yield of the hydrogenation process was higher than 80% in the concentration studied, and the results obtained are as good as those presented in the literature showing that the complex could be used as a catalyst for the transfer hydrogenation reaction of acetophenone.
The data of all NMR experiments as well as potential energy distribution analysis and some theoretical results, geometric and electronic parameters are available free of charge at http://jbcs.sbq.org.br as PDF file.