Concise Two-Step Synthesis of γ-Pyrone from Acetone

Abstract

γ-Pyrone (1) is readily accessible in 59% overall yield via 1,1,5,5-tetraethoxy-3-pentanone (10b) and subsequent acidic hydrolysis. The synthesis enables an easy scale up, as demonstrated for intermediate 10b.

Key words

diethoxymethylation - formylation - γ-pyrone - tetraethoxypentanone

References

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10

Preparation of 1,1,5,5-Tetraethoxy-3-pentanone (10b) on a Multi-Gram Scale.
A solution of BF₃·OEt₂ (46.60 mL, 0.36 mol) in CH₂Cl₂ (40 mL) was added dropwise over 15 min to 12 (44.46 g, 0.30 mol) at -30 °C. The stirred reaction mixture was warmed up to 0 °C for 20 min, and then cooled to -78 °C. After addition of absolute acetone (4.41 mL, 0.06 mol), i-Pr₂NEt (55.5 mL, 0.36 mol) was added dropwise over 20 min. The reaction mixture was stirred at -78 °C for 2.5 h, poured into concd NaHCO₃ solution (500 mL), stirred for 10 min, and was then extracted with CH₂Cl₂ (3 × 100 mL). The combined organic layers were washed successively with ice cold 2 N H₂SO₄ (75 mL) and H₂O (2 × 100 mL), and dried (MgSO₄). The solvent was removed under vacuum and the residue was distilled through a Vigreux column to give 10b (10.10 g, 64%) as a light yellow liquid, bp 105 °C/0.18 mbar (bp 71-71.5 °C/0.025 mm). [9] ¹H NMR (250 MHz, C₆D₆): δ = 1.19 (t, J = 7.0 Hz, 12 H, 7-H), 2.79 (d, J = 5.6 Hz, 4 H, 2-H, 4-H), 3.60 (m, 8 H, 6-H), 4.91 (t, J = 5.6 Hz, 2 H, 1-H, 5-H) ppm. ¹³C NMR (62 MHz, C₆D₆): δ = 15.2 (C-7), 48.5 (C-6), 62.3 (C-2, C-4), 99.6 (C-1, C-5), 204.8 (C-3) ppm.

12

Preparation of γ-Pyrone (1) from Tetraethoxypentanone (10b). In a sealed Schlenk flask a solution of 10b (2.62 g, 10.0 mmol) in EtOH (50 mL) and 10% H₂SO₄-H₂O (5 mL) was heated at 80 °C for 24 h. The reaction mixture was then neutralized with NaHCO₃ (1.60 g), and the solvents were removed under vacuum. The residue was extracted with absolute benzene. Concentration of the combined extracts gave 1 (881 mg, 9.2 mmol, 92%) as a light yellow oil, which crystallized rapidly under vacuum. The crystals liquefy at r.t. (mp 32.5 °C). [2] ¹H NMR (250 MHz, C₆D₆): δ = 5.88 (d, J = 6.4 Hz, 2 H, 3-H, 5-H), 6.58 (d, J = 6.3 Hz, 2 H, 2-H, 6-H) ppm. ¹³C NMR (62 MHz, C₆D₆): δ = 118.6 (C-2, C-5), 154.6 (C-3, C-6), 176.5 (C-4) ppm.