Synthesis of IL-Supported Phosphine Oxide-Based Pincer Ligand

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EXPERIMENTAL

General

THF was distilled from sodium-benzophenone ketyl, CH2Cl2 was distilled from calcium hydride, and DMF was distilled from and stored over molecular sieves. All other reagents and solvents were obtained from commercial sources and were generally used without further purification. Column chromatography was carried out on silica gel (300-400 mesh). 1H NMR spectra were recorded at 500 MHz, 13C NMR spectra were recorded at 125 MHz, using TMS as internal standard. Mass spectroscopy data of the product were collected on a MS-ESI instrument.

Synthesis of dimethyl 5-hydroxy-1, 3-benzenedicarboxylate 1

To a stirred mixture of 5-hydroxyisophthatic acid (9.10 g, 0.05 mol) and methanol in an ice-salt bath was slowly added a catalytic amount of sulfuric acid (3 mL). After addition, the reaction mixture was stirred in an ice-salt bath for 0.5 h, then at room temperature for 1 h, and was refluxed for 5 h. After it was cooled to room temperature, the reaction mixture was neutralized with aqueous sodium carbonate solution and then acidified by concentrated hydrochloric acid. Water was added and the resulting mixture was extracted with dichloromethane to give a white solid. Crude dimethyl 5-hydroxy-1, 3-benzenedicarboxylate 1 was recrystallized from methanol. Yield 10.10 g (84%). 1H NMR (500 MHz, CDCl3, TMS): δ 8.25 (s, 1 H, Ph-H), 7.79(s, 2 H, Ph-H), 6.49(s, 1 H), 3.95(s, 6 H, -OCH3). MS (ESI): m/z 241 ([M+H]+).

Synthesis of dimethyl 5-allyloxy-1,3-benzenedicarboxylate 2

Dimethyl 5-hydroxy-1,3-benzenedicarboxylate 1 (2.40 g, 0.01 mol) was dissolved in dry DMF(20 mL), and then K2CO3 (2.21 g, 0.016 mol) was added, and stirred for 2 h, then ally1 bromide (1.20 g, 0.01 mol) was added. The mixture was stirred 9 h at 70 ℃ after which DMF was evaporated. The crude product was treated with water (100 mL). The reaction mixture was extracted with dichloromethane (100 mL), and dried over Na2SO4. The organic layer was concentrated, and gave white solid 2. Yield 2.44 g (92%). 1H NMR (500 MHz, CDCl3, TMS): δ 8.24 (s, 1 H, Ph-H), 7.78(s, 2 H, Ph-H), 6.06-6.03(m, 1 H, allyl-H), 5.43-5.39(d, J=4.5 Hz, 1 H, allyl-H), 5.30-5-28(d, J=3.1 Hz, 1 H, allyl-H), 4.54-4.53(m, 2 H, allyl-H), 3.95(s, 6 H, -OCH3). MS (ESI): m/z 288([M+Na]+).

Synthesis of 5-allyloxy-1,3-benzenedimethanol 3

LiALH4 (4.50 g, 0.12 mol) was suspended in dry THF (200 mL) and a solution of diester 2 (16.40 g, 0.06 mol) in THF (100 mL) was slowly added. The mixture was refluxed for 12 h after which THF was evaporated. The resulting paste was dissolved in dichloromethane (100 mL) and cooled to 0 ℃ and 2 M HCl (100 mL) was slowly added, after which the layers were separated. Extraction of the aqueous layer with dichloromethane (3 × 100 mL) and drying of the combined organic layers gave, after removal of the solvent, 3 as a white solid. Yield 11.20 g (93%). 1H NMR (500 MHz, CDCl3, TMS): δ 6.91 (s, 1 H, Ph-H), 6.84 (s, 2 H, Ph-H), 6.05-6.02 (m, 1 H, allyl-H), 5.42-5.38 (d, J=5.0 Hz, 1 H, allyl-H), 5.29-5-27 (d, J=3.3 Hz, 1 H, allyl-H), 4.63 (s, 4 H, -CH2-), 4.54-4.53 (m, 2 H, allyl-H), 1.95 (s, 2 H, -OH). MS (ESI): m/z 195 ([M+H]+).

Synthesis of O-Allyloxy-3,5-bis(chloromethyl)benzene 4

A suspensionof 3 (1.94 g, 0.01 mol) in 50 mL of dichloromethane was prepared. Pyridine (2.20 mL, 0.03 mmol) was added and the resulting mixture was cooled to 0 ℃. Then, thionyl chloride (2.5 mL, 0.03 mmol) was added dropwise to the mixture, resulting in the eventual dissolution of the starting material. The ensuing homogeneous solution was stirred at room temperature for 18 h. After the reaction, the organic phase was washed with water (3×30 mL), 1 N HCl (2×10 mL), and brine (2×10 mL) and then dried over MgSO4. The solvent was removed under reduced pressure and the isolated yellowish solid was dried under vacuum, yielding 2.29 g (88%) of the dichloride: 1H NMR (500 MHz, CDCl3, TMS): δ 6.98 (s, 1 H, Ph-H), 6.89(s, 2 H, Ph-H), 6.03-6.02(m, 1 H, allyl-H), 5.43-5.39(q, J=6.7 Hz, 1 H, allyl-H), 5.30-5.28(q, J=3.3 Hz, 1 H, allyl-H), 4.54-4.53(m, 2 H, allyl-H), 4.52(s, 4 H, -CH2-). MS (ESI): m/z 261 ([M+H] +, 35Cl), 263 ([M+H]+, 37Cl).

Synthesis of phosphine oxide ligand 5

Dropwise addition of allyl-protected 1,3-bis(chloromethyl)-benzene(2.61 g, 0.01 mol) in THF to a solution of PPh2Li (0.022 mol) in THF/hexane (prepared in situ by dropwise addition of PPh2H in THF to a solution of BuLi in hexanes at -40 ℃) afforded a pale yellow solution, which was stirred overnight. The volatiles were removed, and the oily white solid was dissolved hot EtOH (100 mL), and then added H2O2 (3 mL). The mixture was refluxed overnight after which EtOH was evaporated. The residue was purified by extraction into dichloromethane (100 mL) to give an oily material. The crude product was purified by flash columnchromatography (CH2Cl2/EtOAc/MeOH), and gave the oily white solid 5. Yield 4.43 g (75%). 1H NMR (500 MHz, CDCl3, TMS): δ 7.67-7.63 (m, 8 H, Ph-H), 7.50-7.40 (m, 12 H, Ph-H), 6.64 (s, 1 H, Ph-H), 6.49 (s, 2 H, Ph-H), 5.91-5.83 (m, 1 H, allyl-H), 5.26-5.22 (q, J=6.3 Hz, 1 H, allyl-H), 5.17-5.15 (q, J=3.3 Hz, 1 H, allyl-H), 4.22-4.21 (d, J=5.0 Hz, 2 H, allyl-H), 3.52-3.50 (d, J=10.0 Hz, 4 H, -CH2-). MS (ESI): m/z 614 ([M+Na]+).

Deprotection reaction of 5 to prepare compound 6

To a stirred solution of allyl-protected compound 5 (5.91 g, 0.01 mol) in MeOH (100 mL) was added catalytic amounts of Pd(PPh3)4 (0.05-1.00 mol%) under a nitrogen atmosphere. The slightly yellow solution was stirred for 5 min, and K2CO3 (5.52 g, 0.04 mol) was added. The action was monitored by TLC. The reaction was completed in 1-3 h. The reaction mixture was concentrated in vacuo, and the residue was treated with 2 M HCl. The aqueous solution was extracted with dichloromethane. The organic layer was washed with brine, dried over Na2SO4, and concentrated in vacuo. The crude product was purified by flash columnchromatography (hexanes/EtOAc), and gave the oily white solid 6. Yield 5.01 g (91%). 1H NMR (500 MHz, CDCl3, TMS): δ 9.82 (s, 1 H, Ph-OH), 7.69-7.60 (m, 8 H, Ph-H), 7.47-7.37 (m, 12 H, Ph-H), 6.74 (s, 1 H, Ph-H), 6.44 (s, 2 H, Ph-H), 3.46-3.44 (d, J=13.0 Hz, 4 H, -CH2-). MS (ESI): m/z 552 ([M+H]+).

Synthesis of compound 7

Compound 6 (5.51 g, 0.01 mol) was dissolved in dry DMF (20 mL), and then K2CO3 (2.21 g, 0.016 mol) was added. 1,2-Dibromoethane (18.8 g, 0.1 mol) was added to the mixture. The mixture was stirred 9 h at 50 ℃ after which DMF was evaporated. The crude product was treated with water (100 mL). The reaction mixture was extracted with dichloromethane (100 mL) and dried over Na2SO4. The organic layer was concentrated, and obtained the oily white solid 7. Yield 5.40 g (82%). 1H NMR (500 MHz, CDCl3, TMS): δ7.69-7.60 (m, 8 H, Ph-H), 7.47-7.37 (m, 12 H, Ph-H), 6.74 (s, 1 H, Ph-H), 6.44 (s, 2 H, Ph-H), 4.54-4.52(t, J=3.8 Hz, 2 H, -CH2-), 3.61-3.49 (t, J=4.2 Hz, 2 H, -CH2-), 3.44-3.42 (d, J=13.5 Hz, 4 H, -CH2-). 13C NMR (125 MHz, CDCl3): δ 150.6, 138.2, 135.0, 131.5, 129.6, 128.6, 121.5, 111.9, 76.1, 43.2, 39.8. MS (ESI): m/z 658 ([M+H]+, 79Br), 661 ([M+H]+, 81Br).

Compound 7 bonded on IL to prepare compound 8

Equimolar amounts of 1-methylimidazole (0.82 g, 0.01 mol) with 7 (6.57 g, 0.01 mol) was refluxed at 70 ℃ for 72 h. The resulting crude product was washed with ethyl acetate and dried under vacuum, and compound 8 was obtained. Yield 6.89 g (93%). 1H NMR (500 MHz, CDCl3, TMS): δ10.85 (s, 1 H, imidazolium-H), 8.32 (s, 1 H, imidazolium-H), 7.65 (s, 1 H, imidazolium-H), 7.71-7.68 (m, 8 H, Ph-H), 7.49-7.39 (m, 12 H, Ph-H), 6.76 (s, 1 H, Ph-H), 6.46 (s, 2 H, Ph-H), 4.53 (s, 3 H, -CH3), 4.52-4.50 (t, J=3.8 Hz, 2 H, -CH2-), 3.63-3.50 (t, J=4.2 Hz, 2 H, -CH2-), 3.46-3.44 (d, J=14.0 Hz, 4 H, -CH2-). 13C NMR (125 MHz, CDCl3): δ 158.6, 138.8, 135.3, 134.5, 131.0, 130.0, 129.7, 129.3, 128.6, 128.2, 127.9, 120.2, 112.1, 70.1, 35.0, 25.8. MS (ESI): m/z 661([M]+).