TEMPO-Derived Task-Specific Ionic Liquids for Oxidation of Alcohols

Abstract

A novel 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) radical bearing an ionic liquid-type appendage has been prepared, and its catalytic activity for the selective oxidation of alcohols to the corresponding carbonyl compounds in ionic liquid-aqueous biphasic conditions has been investigated. The ionic liquid-supported TEMPO radical shows catalyst properties similar to those of non-supported counterpart in terms of activity and selectivity, and can be easily recycled and reused without loss of activity and selectivity.

ionic liquids - alcohols - carbonyl compounds - oxidation - TEMPO

References

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General Procedure for the Attachment of One TEMPO Unit.
To a stirred solution of 4-hydroxy-2,2,6,6-tetramethyl-piperdine-1-oxyl (1, 0.86 g, 5 mmol) and chloroactic acid (0.40 g, 5 mmol) in CH₂Cl₂ (25 mL) at 0 °C under argon, DCC (1.03 g, 5 mmol) and DMAP (0.15 g, 1.25 mmol) were added and the reaction mixture was stirred for 12 h at r.t. The solid materials formed were filtered off and the filtrate was washed with 1 M HCl (5 mL) followed by sat. NaHCO₃ (10 mL) and brine (10 mL). The organic phase was dried over MgSO₄ and evaporated under reduced pressure, and then filtered through a short flash chromatography (EtOAc-hexanes 1:4) providing chloroacetic acid 2,2,6,6-tetra-methyl-1-oxy-piperidin-4-yl ester(2) as a red powder (1.14 g, 92%). Then 1-methylimidazole (0.46 g, 5.6 mmol) was added to a solution of 2 (1.00 g, 4 mmol) in MeCN (30 mL) and the resulting solution was stirred for 48 h at 80 °C. After that, the solvent was removed in vacuum and the residue was washed with acetone to give 3 as a light red powder (1.30 g, 98%). Compound 4 was prepared by stirring 3 (1.00 g, 3 mmol) with KPF₆ (0.66 g, 3.6 mmol) in acetone (30 mL) at r.t. for 48 h. After this, the insoluble by-products were filtered off and the acetone was removed in vacuum to afford 4 as a pink powder (1.27 g, 96%). As excepted, this charged TEMPO 4 is preferentially soluble in [bmim]PF₆ and insoluble in water. All these novel compounds were stable in air and characterized by ¹H NMR, ¹³C NMR, FTIR spectro-metry, mass spectrometry and elemental analyses ref. 20.

<A NAME="RU34204ST-20">20</A>

To samples containing nitroxyl radical residues was added one drop of neat phenylhydrazine to the NMR sample tube immediately prior to analysis in order to reduce in situ the paramagnetic center to the corresponding hydroxylamine species.
Compound 2: mp 55 °C. ¹H NMR (400 MHz, CDCl₃): δ = 5.14 (s, 1 H), 4.10 (s, 2 H), 1.97 (t, 2 H, J = 0.8 Hz), 1.83 (t, 2 H, J = 1.2 Hz), 1.28 (s, 6 H), 1.14 (s, 6 H). ¹³C NMR (400 MHz, CDCl₃): δ = 20.37, 31.93, 41.21, 43.29, 68.47, 166.79. IR (KBr, selected data): 1751.93, 1204.23, 1161.84, 791.67 cm^-1. Anal. Calcd for C₁₁H₁₉ClNO₃: C, 53.12; H, 7.70; Cl, 14.25; N, 5.63. Found: C, 53.17; H, 7.74; N, 5.67. MS (ESI): m/z calcd [M]⁺: 248.73; found: 248.40.
Compound 3: mp 191 °C. ¹H NMR (400 MHz, DMSO): δ = 9.14 (s, 1 H), 7.54 (s, 1 H), 7.36 (s, 1 H), 5.24 (s, 2 H), 5.04 (s, 3 H), 3.90 (s, 3 H), 1.90 (t, 2 H, J = 0.8 Hz), 1.50 (t, 2 H, J = 1.2 Hz), 1.10 (s, 6 H), 1.07 (s, 6 H). ¹³C NMR (400 MHz, DMSO): δ = 166.43, 137.73, 123.66, 123.27, 68.92, 57.93, 49.54, 43.37, 35.89, 32.06, 20.32. IR (KBr, selected data): 1745.13, 1175.20, 1221.89 cm^-1. Anal. calcd for C₁₅H₂₅ClN₃O₃: C, 54.46; H, 7.62; N, 12.70. Found: C, 54.58; H, 7.59; N, 12.72. MS (FAB): m/z calcd [M]⁺: 295.38; found: 294.7.
Compound 4: mp 53 °C. ¹H NMR (400 MHz, DMSO): δ = 9.04 (s, 1 H), 7.36 (s, 1 H), 7.27 (s, 1 H), 5.20 (s, 2 H), 5.04 (s, 3 H), 3.89 (s, 3 H), 1.91 (t, 2 H, J = 0.8 Hz), 1.50 (t, 2 H, J = 1.2 Hz), 1.10 (s, 6 H), 1.08 (s, 6 H). ¹³C NMR (400 MHz, DMSO): δ = 166.38, 137.69, 123.68, 123.29, 69.09, 58.03, 49.59, 43.41, 35.87, 32.09, 20.37. IR (KBr, selected data): 1745.13, 1225.18, 1178.83, 839.76 cm^-1. Anal. calcd for C₁₅H₂₅F₆N₃O₃P: C, 40.91; H, 5.72; N, 9.54; P, 7.03. Found: C, 40.81; H, 5.62; N, 9.30; P, 7.23. MS (FAB): m/z calcd [M]⁺: 295.38; found: 294.9.

<A NAME="RU34204ST-21">21</A> Anelli PL. Biffi C. Montanari F. Quici S. J. Org. Chem.  1987,  52:  2559 

<A NAME="RU34204ST-22">22</A>

General Procedure for all Oxidation Runs.
An alcohol (0.80 mmol), 4 (0.008 mmol, 3.54 mg) and dodecane (0.24 mmol) used as the internal standard in GC-analysis were dissolved in [bmim]PF₆ (2 mL) followed by 0.16 mL aq KBr (0.5 M). After cooling the mixture at 0 °C, 2.7 mL of aq NaOCl diluted to a concentration of 0.37 M and buffered to pH 8.6 by NaHCO₃ was added and the reaction mixture stirred vigorously. After the oxidation, the IL phase was separated and the resultant carbonyl compounds could easily be separated from the IL medium by simple extraction with Et₂O (4 × 5 mL), which was analyzed by GC. The IL containing catalyst can subsequently be re-used for a new reaction cycle. The combined organic extracts were dried with Na₂SO₄, and evaporated to dryness. The residue was purified by silica gel flash chromatography eluting with EtOAc-petroleum ether.