Revisiting the Passerini Reaction under Eco-Friendly Reaction Conditions

Abstract

α-Acyloxy carboxamides were easily assessed in one step by the multicomponent reaction between carboxylic acids, aldehydes and C-isocyanides (Passerini reaction) using ionic liquids or polyethyleneglycol (PEG 400) as green reaction media.

Key words

Passerini reaction - ionic liquids - polyethylene glycol - green chemistry

References and Notes

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Typical Experimental Procedure.
All three components were mixed in equimolar amounts (1 mmol) in the IL (1.0-1.5 mL) or PEG 400 (1.0 mL) at r.t. under an argon atmosphere and stirring was continued until no starting materials could be detected (TLC). The reaction was then extracted with Et₂O (3 × 5 mL) by simple decantation. The combined organic phases were filtered through a small pad of silica and concentrated at reduced pressure to furnish the crude products in high purity (>90% by ¹H NMR analysis). Analytical samples were obtained after column chromatography (30% EtOAc in hexane).

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All the compounds gave satisfactory spectroscopic data.
Selected Spectroscopic Data
Compound 1: ¹H NMR (300 MHz, CDCl₃, Me₄Si): δ = 1.04 (3 H, d, J _1,2 = 7.2 Hz), 1.07 (3 H, d, J _1,2 = 7.2 Hz), 2.42-2.58 (1 H, m), 4.42 (1 H, dd, J _1,2 = 5.7 Hz and J _gem = 15.0 Hz), 4.56 (1 H, dd, J _1,2 = 6.0 Hz and J _gem = 15.0 Hz), 5.37 (1 H, d, J _1,2 = 4.5 Hz), 6.36 (1 H, br s), 7.22-7.34 (5 H, m), 7.44-7.51 (2 H, m), 7.58-7.64 (1 H, m), 8.05-8.09 (2 H, m). ¹³C NMR (75 MHz, CDCl₃, Me₄Si): δ = 17.0, 18.9, 30.7, 43.0, 78.5, 127.3, 127.4, 128.5, 129.1, 129.6, 133.5, 137.8, 165.4, 169.3.
Compound 11: ¹H NMR (300 MHz, CDCl₃, Me₄Si): δ = 1.02 (3 H, d, J _1,2 = 7.2 Hz), 1.05 (3 H, d, J _1,2 = 7.2 Hz), 1.06-1.22 (3 H, m), 1.24-1.44 (2 H, m), 1.54-1.74 (3 H, m), 1.80-2.00 (2 H, m), 2.39-2.55 (1 H, m), 3.75-3.89 (1 H, m), 5.29 (1 H, d, J _1,2 = 3.9 Hz), 5.86 (1 H, br s), 7.47-7.54 (2 H, m), 7.60-7.66 (1 H, m), 8.07-8.11 (2 H, m). ¹³C NMR (75 MHz, CDCl₃, Me₄Si): δ = 16.8, 18.9, 24.6, 25.3, 30.7, 32.7, 33.0, 47.8, 78.4, 128.6, 129.3, 129.6, 133.5, 165.3, 168.2.