Nitrogen-containing ligands have been widely used in coordination chemistry and homogeneous catalysis owing to ease of manipulation and the high catalytic activity of their transition metal complexes [1-5]. Many pyridyl-based symmetric ligands, such as 2, 2':6', 2''-terpyridines [6-10], 2, 6-bis(oxazolinyl)  pyridines [11-15], 2, 6-bis(imino)pyridines [16-20], and 2, 6- bis(pyrazoyl)  pyridines [21-25] have been reported and applied in organic synthesis and homogeneous catalysis.

2, 6-Bis(tetrazolyl)pyridines are pyridyl-based multidentate chelating agents containing nine N atoms, and their metal complexes have been applied in functional materials fabrication, coordination chemistry, and catalysis. These ligands can be used in the synthesis of luminescent materials using a self- assembly strategy. Both visible and near-infrared (IR) luminescence emissions of lanthanide cations (Pr, Nd, Sm, Eu, Tb, Dy, Ho, Er, Tm, and Yb) can be efficiently sensitized using 2, 6-bis(tetrazole)pyridine [26, 27]. Furthermore, platinum(Ⅱ) complexes bearing 2, 6-bis(tetrazole)pyridine can be used as luminescent films, dopants for OLEDs, and to form supramolecular polymeric nanofibers [28-31]. Ruthenium complexes based on mixed ligands 2, 2':6', 2''-terpyridine and 2, 6- bis(tetrazole)pyridine have been reported and used in dye-sensitized solar cells to afford novel ruthenium dyes [32-34]. These ligands can also be coordinated with other metals, such as a reported series of homoleptic complexes of 2, 6-bis(tetrazole)pyridine with Co^Ⅱ, Ni^Ⅱ, Cu^Ⅱ, and Zn^Ⅱ [35]. Furthermore, 2, 6-bis(tetrazolyl)pyridine ligands can recover trivalent minor actinides effectively and selectively from HNO₃ media, while exhibiting weak or almost no extraction of trivalent lanthanides with similar chemical properties [36, 37]. However, 2, 6-bis(tetrazolyl)pyridine ligands have rarely been applied in catalytic reactions. In 2016, zinc polymers based on 2, 6-bis(tetrazole)pyridine with different morphologies and particle sizes were obtained and used in the cyclization of aromatic dinitriles with β-aminoalcohols as heterogeneous catalysts [38].

The transfer hydrogenation (TH) of unsaturated substrates catalyzed by transition metal complexes has attracted much attention owing to its capacity for reliable reduction using simple procedures with mild conditions and is considered a prospective alternative to direct hydrogenation [39-43]. Versatile ruthenium(Ⅱ) 2-aminomethylpyridine (ampy) complexes have been reported by Baratta et al. [44-49] and demonstrated very high catalytic activity in the TH and asymmetric TH (ATH) of ketones. Moreover, Noyori ruthenium(Ⅱ) complexes, containing N-sulfonylated 1, 2-diamines as chiral ligands, have been used as efficient catalysts for the ATH of ketones and imines [50-55]. Furthermore, transition-metal complexes bearing a ligand with NH functionality also exhibit high catalytic activity in transfer hydrogenation reactions [56-59]. Although various ligands and their transition-metal complexes have been synthesized for TH, the development of efficient catalytic systems is still needed. We have been interested in developing N-heterocyclic ligands and the corresponding highly effective catalyst system for application in homogeneous catalysis. Various pyridyl-based N-containing ligands and their ruthenium(Ⅱ) complexes have been reported and applied to the TH of ketones [60-65]. Herein, we describe the synthesis and structural characterization of ruthenium(Ⅱ) complexes of 4-chloro- 2, 6- bis(1-(p-tolyl)-1H-tetrazol-5-yl)pyridine with different phosphorus ligands and their catalytic behavior in TH reactions of ketones.

All manipulation of air-and moisture-sensitive compounds was carried out under a nitrogen atmosphere using standard Schlenk techniques. Solvents were dried and distilled prior to use according to literature methods. ¹H and ¹³C{¹H} NMR spectra were recorded on a Bruker DRX-400 spectrometer (Bruker, Germany) and all chemical shift values are referenced to δ_TMS = 0.00 ppm or CDCl₃ (δ(¹H), 7.26 ppm and δ(¹³C), 77.16 ppm). HRMS analysis was performed by the Analysis Center, Dalian University of Technology. All melting points are uncorrected. Thin-layer chromatography (TLC) analysis was performed using glass-backed plates coated with silica gel (0.2 mm). Flash column chromatography was performed on silica gel (200–300 mesh). All chemical reagents were purchased from commercial suppliers and used as received unless otherwise indicated.

4-Chloro-2, 6-bis(1-(p-tolyl)-1H-tetrazol-5-yl)pyridine (2). A mixture of N², N⁶-di-p-tolylpyridine-2, 6-dicarboxamide (1) (20.0 g, 58 mmol), PCl₅ (24.2 g, 116 mmol), and SOCl₂ (120 mL) were heated at 80 ℃ for 3 h. Excess SOCl₂ was removed under reduced pressure and the resulting imidoyl chloride was dissolved in CH₂Cl₂ (100 mL). This solution was then added dropwise to a stirred suspension of NaN₃ (13.6 g, 209 mmol) in DMF (100 mL). After addition was completed, stirring was continued for 16 h at room temperature. The reaction mixture was then treated with water, the organic layer was separated and washed with water (3×200 mL), and all volatiles were removed under reduced pressure. The resultant residue was purified by column chromatography on silica gel (eluent: petroleum ether (60–90 ℃)/CH₂Cl₂ = 2:1, v/v) to afford 2 as a white solid (8.7 g, 35%). m.p. 247–248 ℃. ¹H NMR (CDCl_3, 400 MHz, 25 ℃) δ 8.28 (s, 2 H, pyridyl CH), 7.11 (d, 4 H, J = 8.2 Hz) and 6.92 (d, 4 H, J = 8.3 Hz) (both p-tolyl CH), 2.38 (s, 6 H, p-tolyl CH₃). ¹³C{¹H} NMR (CDCl_3, 100 MHz, 25 ℃) δ 150.7, 147.1, 145.8, 140.6, 131.8, 129.8, 127.2, 124.8, 21.4. HRMS Calcd. for C₂₁H₁₆ClN₉: 429.1217; Found: 429.1212.

Ruthenium complex 3a. Under a nitrogen atmosphere, a mixture of 4-chloro- 2, 6-bis(1-(p-tolyl)-1H- tetrazol-5- yl) pyridine 2 (215 mg, 0.5 mmol), RuCl₂(PPh₃)₃ (480 mg, 0.5 mmol), and CH₂Cl₂ (40 mL) was stirred at 40 ℃ for 4 h. After cooling to ambient temperature, all volatiles were evaporated under reduced pressure. The resultant residue was purified by flash chromatography on silica gel (eluent: CH₂Cl₂/CH₃OH = 10:1, v/v). Recrystallization in hexane–CH₂Cl₂ (3:1, v/v) at room temperature gave ruthenium(Ⅱ) complex 3a as a reddish brown solid (479 mg, 85%). m.p. > 155 ℃ dec. ¹H NMR (CDCl_3, 400 MHz, 25 ℃) δ 7.56, 7.40, 7.33, 7.27, 7.13, and 6.72 (each m, 10:9:3:6:6:6 H, aromatic CH), 2.56 (s, 6 H, p-tolyl CH₃). ¹³C{¹H} NMR (CDCl_3, 100 MHz, 25 ℃) δ 153.25, 153.22, 146.8, 145.1, 144.2, 134.8, 134.7, 134.2, 133.7, 133.3, 133.2, 131.6, 130.8, 129.9, 129.8, 129.3, 128.7, 128.6, 128.5, 127.8, 127.7, 125.5, 125.3, 21.5. ³¹P{¹H} NMR (CDCl_3, 162 MHz, 25 ℃) δ 40.4, 35.0.

Ruthenium complex 3b. Under a nitrogen atmosphere, a mixture of 1, 4-bis(diphenylphosphino)butane (512 mg, 1.2 mmol), RuCl₂(PPh₃)₃ (959 mg, 1.0 mmol), and CH₂Cl₂ (50 mL) was stirred at room temperature for 2 h. Then, 4- chloro- 2, 6- bis(1-(p-tolyl)-1H-tetrazol-5-yl)pyridine 2 (429 mg, 1.0 mmol) was added and the mixture was stirred at 40 ℃ for 4 h. After cooling to ambient temperature, all volatiles were evaporated under reduced pressure. The resultant residue was purified by flash chromatography on silica gel (eluent: AcOEt/CH₃OH = 5:1, v/v). Recrystallization in hexane–CH₂Cl₂ (3:1, v/v) at room temperature gave ruthenium(Ⅱ) complex 3b as a reddish brown solid (754 mg, 71%). m.p. > 180 ℃ dec. ¹H NMR (CDCl_3, 400 MHz, 25 ℃) δ 7.95, 7.62, 7.45, 7.36, 7.28, 7.07 and 6.86 (each m, 4:8:6:2:4:2:4 H, aromatic CH), 2.83, 2.37, 2.11 and 1.79 (each m, 4×CH₂), 2.57 (s, 6 H, p-tolyl CH₃). ¹³C{¹H} NMR (CDCl_3, 100 MHz, 25 ℃) δ 153.2, 145.7, 144.8, 144.4, 136.4, 136.0, 134.0, 133.9, 132.7, 132.2, 131.8, 131.6, 131.5, 131.0, 130.2, 129.3, 129.2, 129.1, 128.1, 128.0, 125.6, 124.3, 33.0, 32.7, 29.3, 29.1, 26.1, 21.7, 20.1. ³¹P{¹H} NMR (CDCl_3, 162 MHz, 25 ℃) δ 40.4, 33.9.

Ruthenium complex 3c. Under a nitrogen atmosphere, a mixture of 1, 5-bis(diphenylphosphino)pentane (106 mg, 0.24 mmol), RuCl₂(PPh₃)₃ (193 mg, 0.2 mmol), and CH₂Cl₂ (10 mL) was stirred at room temperature for 2 h. Then 4-chloro-2, 6- bis(1-(p-tolyl)-1H-tetrazol-5-yl)pyridine 2 (86 mg, 0.2 mmol) was added and the mixture was stirred at 40 ℃ for 4 h. After cooling to ambient temperature, all volatiles were evaporated under reduced pressure. The resultant residue was purified by flash chromatography on silica gel (eluent: CH₂Cl₂/AcOEt/ CH₃OH = 5:5:1, v/v). Recrystallization in hexane–CH₂Cl₂ (3:1, v/v) at room temperature gave ruthenium(Ⅱ) complex 3c as a reddish brown solid (154 mg, 74%). m.p. > 193 ℃ dec. ¹H NMR (CDCl_3, 400 MHz, 25 ℃) δ 7.87, 7.58, 7.44, 7.38, 7.30, 7.23, 6.96, and 6.74 (each m, 4:8:2:4:2:4:2:4 H, aromatic CH), 2.52 (s, 6 H, p-tolyl CH₃), 2.44, 2.17, 1.92, 1.66, and 1.46 (each m, 5×CH₂). ¹³C{¹H} NMR (CDCl_3, 100 MHz, 25 ℃) δ 153.1, 145.3, 145.0, 144.3, 136.0, 135.6, 133.9, 133.8, 131.7, 130.8, 130.0, 129.0, 128.9, 128.8, 127.9, 127.8, 125.4, 123.9, 27.6, 27.3, 26.5, 26.33, 26.26, 26.2, 21.5, 19.85, 19.79, 19.7. ³¹P{¹H} NMR (CDCl_3, 162 MHz, 25 ℃) δ 41.8, 32.2.

Under a nitrogen atmosphere, a mixture of ketone (2 mmol), catalyst 3 (0.01 mmol), and 2-propanol (18 mL) was stirred at 82 ℃ for 10 min. Then, iPrOK solution in 2-propanol (2.0 mL, 0.1 mol/L, 0.2 mmol) was introduced to initiate the reaction. The reaction mixture was stirred at reflux. After the stated time, 0.1 mL of the reaction mixture was sampled and immediately diluted with 0.5 mL of 2-propanol precooled to 0 ℃, and filtered through a short pad of celite to quench the reaction by removing the complex catalyst. The resultant filtrate was used for GC analysis. After the reaction was finished, the mixture was condensed under reduced pressure and subjected to flash silica gel column chromatography to afford the alcohol product. The alcohol products were identified by comparison with authentic samples using NMR and GC analyses.

A mixture of N², N⁶-di-p-tolylpyridine-2, 6-dicarboxamide 1, PCl₅, and SOCl₂ were heated to afford an imidoyl chloride. The ligand, 4-chloro-2, 6-bis(1-(p-tolyl)-1H-tetraz-ol-5-yl)pyridine 2, was then obtained by cycloaddition of the imidoyl chloride to NaN₃ in DMF. Treatment of ligand 2 with ruthenium compounds in CH₂Cl₂ gave complexes 3a–c under reaction conditions (ⅲ) or (ⅳ) (Scheme 1). Due to cyclic tension, complexes 3 with 2, 3, or 6-carbon alkyl chains between the two phosphorus ligands were not obtained under the same conditions. Complexes 3a–c were stable when exposed to air at ambient temperature.

The structures of complexes 3 were supported by NMR analysis in solution. The chemical shifts of the pyridyl CH hydrogen atoms in complexes 3 were shifted upfield by 0.3–0.7 ppm in the proton NMR spectrum compared with those of ligand precursor 2. Complexes 3a–c showed two signals in the ³¹P{¹H} NMR spectra, suggesting that the two phosphorous groups were positioned in different environments. Single crystals of 3b suitable for X-ray crystallographic study were obtained to further validate the complex structure [66]. In the solid state, the cationic metal center of complex 3b was surrounded by tridentate NNN ligand 2, two PPh₂ ligands, and a chloride anion, with another dissociated chloride anion in the vicinity (Fig. 1). The P(1)–Ru–P(2) angle in 3b was 92.54(3)°, suggesting that the two PPh₂ ligands were almost orthogonal to each other. P(1) and Cl(1) were almost linear to each other (P(1)–Ru–Cl(1), 171.32(3)°) and positioned on two sides of the ligand plane. The presence of three Ru–N bonds (2.058(2), 2.079(2), and 2.096(2) Å), two Ru–P bonds (2.3186(8) and 2.3467(9) Å), an Ru–Cl bond (2.4538(8) Å), a N(5)–Ru–P(2) angle of 171.79(6)°, and a P(1)–Ru–Cl(1) angle of 171.32(3)° identified a six-coordinate metal center in complex 3b with a distorted bipyramidal environment.

Ruthenium(Ⅱ) complexes 3a–c were tested as catalysts in the TH of ketones (Table 1). Using 0.5 mol% of 3 as catalyst, with a molar ratio of 200/20/1 for ketone/base/catalyst and iPrOK as the base promoter, transfer hydrogenation of acetophenone was conducted in 2-propanol at 82 ℃. To achieve > 96% yield, corresponding complexes 3a, 3b and 3c were reacted for 1, 1, and 2 h, respectively (Table 1, entries 1–3). Further research into the catalyst activities was performed using 3a and 3b. For o-methylacetophenone, both catalysts required 3 h to reach 97% conversion (Table 1, entries 4 and 5). When o-chloroacetophenone was tested, 3b showed better catalytic activity, with only 20 min needed to reach 97% conversion (Table 1, entries 6 and 7). Furthermore, for cyclohexanone, 3b showed better catalytic activity than 3a (Table 1, entries 8 and 9). Next, 0.5 mol% 3b as catalyst was used in typical reactions, exhibiting very good catalytic activity for the transfer hydrogenation of o-, m-, and p-chloroacetophenone and achieving > 97% conversions for these ketones in 20–40 min (Table 1, entries 7, 12, and 13). Electron-donating substituent-bearing aromatic ketones o-, m-, and p-methylacetophenone required a longer time to be transformed into the target reduction products (Table 1, entries 5, 10, and 11). Propiophenone, 2- acetonaphthone, 2-benzoylpyridine, and benzophenone were also smoothly reduced to their corresponding alcohols in 93%–96% conversions within 1–2 h (Table 1, entries 14–17). Due to the rigidity of the carbonyl rings, 1-tetralone and 9-fluorenone proceeded with the poorest reaction activity affording 70% and 83% conversion after 2 and 0.5 h, respectively, with extended reaction times producing no improvement (Table 1, entries 18 and 19). For the reduction of aliphatic ketones, cyclohexanone and linear 2-heptanone achieved > 95% conversions in 40 min and 3 h, respectively (Table 1, entries 9 and 21), while cyclopentanone was reduced to its desired alcohol in 90% conversion in 2 h, with no further transformation taking place when the reaction time was extended (Table 1, entry 20). The difference between the catalytic activity of complexes 3a–c in the TH of ketones was presumably attributed to the phosphorus ligands. These results suggested that dppb in 3b was more favorable for stabilizing the active catalytic species.

In the ruthenium-catalyzed transfer hydrogenation reaction of ketones, the catalytically active species is usually a Ru(Ⅱ)H complex generated in situ from a Ru(Ⅱ)Cl complex catalyst precursor [49, 62, 64, 67-70]. To confirm the reaction mechanism, complex 3b was treated with iPrOK or K₂CO₃ in refluxing 2-propanol under a nitrogen atmosphere. The ¹H NMR spectrum of the inseparable product mixture showed a doublet of doublets at −6.00 ppm with ²J(H, P) = 107.9 and 24.4 Hz, which suggested the presence of Ru–H functionality. These results implied that complexes 3 could readily generated Ru(Ⅱ)H species in situ under the stated conditions. This Ru(Ⅱ)H species then catalyzes the ketone reduction via a possible inner-sphere pathway (Scheme 2). Unfortunately, expected Ru(Ⅱ)H complex 4b was not successfully isolated.

Ruthenium(Ⅱ) complexes based on 2, 6-bis(tetrazolyl)  pyridine have been successfully synthesized, characterized by NMR and X-ray crystallographic analysis, and applied in the transfer hydrogenation of ketones. The ruthenium(Ⅱ) complex based on 1, 4-bis(diphenylphosphino)butane exhibited better catalytic activity, smoothly reducing various types of ketones to the corresponding alcohols with good catalytic efficiency. The present work demonstrates an efficient pyridyl-based symmetrical Ru(Ⅱ) catalyst for the transfer hydrogenation of ketones.