1-Acetyl-2,3-Dimethylimidazolidine: A Novel Organic Reductant for Transfer Hydrogenation

Abstract

1-Acetyl-2,3-dimethylimidazolidine was synthesized and was shown to be able to directly reduce a series of aromatic, aliphatic and α,β-unsaturated aldehydes as well as imines in high yields.

Key words

1-acetyl-2,3-dimethylimidazolidine - aldehydes - hydrogen transfer - imines - organic reductant

References and Notes

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11

Synthesis of 1-Acetyl-2,3-dimethylimidazolidine (1c) (Scheme 1): 2-Methylimidazoline (4.3 g, 51 mmol) was dissolved in CH₂Cl₂ (15 mL) at 0 °C, followed by the addition of Et₃N (5.2 g, 51 mmol). This solution was then added dropwise to a solution of Ac₂O (5.2 g, 51 mmol) in CH₂Cl₂ (5 mL). After the addition, the reaction mixture was stirred at r.t. for an additional 3 h. The resulting solution was treated with 10% NaHCO₃ (40 mL). After stirring for 0.5 h, the mixture was extracted with CH₂Cl₂, and the organic layers were washed with brine, and dried over anhyd Na₂SO₄. Evaporation of CH₂Cl₂ in vacuo gave 1-acetyl-2-methylimidazoline (5.46 g) as an oil (yield: 85%). This product was sufficiently pure for the next step.
1-Acetyl-2-methylimidazoline (5.8 g, 46 mmol) and MeI (8.6 mL, 138 mmol) were refluxed in Et₂O (30 mL) for 10 h. After cooling to r.t., acetone (15 mL) was added to the mixture. The mixture was stirred for several hours, and the solid obtained was collected by vacuum filtration to give 1-acetyl-2,3-dimethylimidazolinium iodide (8.5 g) as a white solid (yield: 69%). ¹H NMR (300 MHz, CDCl₃): δ = 2.39 (s, 3 H), 2.79 (s, 3 H), 3.41 (s, 3 H), 4.29 (m, 2 H), 4.46 (m, 2 H). ¹³C NMR (75 MHz, CDCl₃): δ = 172.1, 171.2, 55.5, 49.3, 38.5, 28.1, 19.2. IR (KBr): 2941, 1728, 1654, 1446, 1388, 1298, 1174, 1037 cm^-1.
1-Acetyl-2,3-dimethylimidazolinium iodide (0.80 g, 3 mmol) was dissolved in MeCN (10 mL) at 0 °C, followed by the addition of NaBH₄ (0.125 g, 3.3 mmol). After the addition, the reaction mixture was stirred at r.t. for an additional 5 h. The reaction was quenched with H₂O (50 mL). The mixture was extracted with CH₂Cl₂, and the organic layers were washed with brine, and dried over anhyd Na₂SO₄. Evaporation of CH₂Cl₂ in vacuo gave 1-acetyl-2,3-dimethylimidazolidine (1c; 0.42 g) as a clear oil (yield: 97%). ¹H NMR (300 MHz, D₂O): δ = 1.33-1.50 (3 × d, J = 6.3 Hz, 3 H), 2.05-2.11 (3 × s, 3 H), 2.63-2.69 (3 × s, 3 H), 3.27-3.88 (3 × m, 4 H), 4.76-4.90 (m, 1 H). IR (film): 2956, 2381, 1718, 1652, 1419, 1265, 1182 cm^-1. MS: m/z = 142 [M⁺], 127 [M -15], 99 [M - 43]. Anal. Calcd for C₇H₁₄N₂O: C, 59.12; H, 9.92; N, 19.70. Found: C, 59.24; H, 9.89; N, 19.75.
The deuterated 1c (C-2 position) was synthesized by the same procedures except that NaBD₄ was used. ¹H NMR (300 MHz, D₂O): δ = 1.22-1.36 (3 × s, 3 H), 1.93-1.99 (3 × s, 3 H), 2.51-2.56 (3 × s, 3 H), 3.15-3.73 (3 × m, 4 H).

Scheme 1

13

General Procedure for the Transfer Hydrogenation Reaction with Imidazolidine 1c as ReductantProcedure Using Condition A: To a solution of substrate (1 mmol) in MeOH (2 mL) was added a solution of imidazolidine 1c (0.142 g, 1 mmol) in anhyd MeCN (2 mL). The reaction mixture was stirred under reflux and monitored by TLC. Upon completion, the solvent was removed in vacuo and the residue was chromatographed on silica gel to give the desired products.
Procedure Using Condition B: To a solution of substrate (1 mmol) and Mg(ClO₄)₂ (22.3 mg, 0.1 mmol) in MeOH (2 mL) was added a solution of imidazolidine 1c (0.142 g, 1 mmol) in anhyd MeCN (2 mL). The reaction mixture was stirred at r.t. and monitored by TLC. Upon completion, the solvent was removed in vacuo and the residue was chromatographed on silica gel to give the desired products.