Triflic Acid Mediated Fries Rearrangement of 3-Dienyl-2-azetidinones: Facile Synthesis of 3-(But-2-enylidene)quinolin-4(3H)-ones

Abstract

β-Lactam-synthon-interceded synthesis of 3-(but-2-enylidene)quinolin-4(3H)-ones has been described via triflic acid mediated Fries rearrangement of 3-butadienyl-2-azetidinones. The described protocol provides a direct access to C-3 functionalized quinolin-4(3H)-ones and does not suffer from the disadvantages ­associated with conventional routes.

Key words

3-dienyl-β-lactam - triflic acid - Fries rearrangement - quinolin-4(3H)-one - β-lactam synthon protocol

• References and Notes

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• 25 Typical Procedure for the Synthesis of Quinolin-4(3H)-one 2 The synthesis of quinolin-4(3H)-one was realized by slow addition of TfOH (10 mmol) to an ice-cold solution of trans-3-butadienyl-2-azetidinones 1 (30 mmol) in DCE (20 mL). After completion of the reaction (monitored by TLC), the reaction mixture was quenched with ice-cold H₂O and extracted into DCE. The removal of solvent under reduced pressure resulted in the isolation of a crude product, which was purified through silica gel column chromatography resulting in the formation of compound 2 in good yields. 3-(But-2-enylidene)-2-phenylquinolin-4(3H)-one (2a) Pale yellow solid; mp 92–93 °C. IR (KBr): 1627, 1684 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 1.86 (d, J = 5.4 Hz, 3 H, CH₃), 5.88 (d, 1 H, J = 15.0 Hz, H²), 6.17 (m, 2 H, H¹ and H³), 7.10 (t, 1 H, J = 7.5 Hz, ArH), 7.26–7.36 (m, 6 H, ArH), 7.54–7.57 (m, 2 H, ArH). ¹³C NMR (75 MHz, CDCl₃): δ = 19.5, 127.0, 127.1, 127.7, 128.2, 128.8, 129.2, 130.2, 130.4, 131.0, 131.2, 135.8, 138.9, 143.1, 153.5, 164.8, 177.4. ESI-MS: m/z = 273 [M]⁺. Anal. Calcd for C₁₉H₁₅NO: C, 83.49; H, 5.53; N, 5.12. Found: C, 83.57; H, 5.65; N, 5.02. 3-(But-2-enylidene)-2-p-tolylquinolin-4(3H)-one (2b) Pale yellow solid; mp 96–97 °C. IR (KBr): 1627, 1685 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 1.88 (d, J = 5.4 Hz, 3 H, CH₃), 2.25 (s, 3 H, CH₃C₆H₄), 5.86 (d, 1 H, J = 15.0 Hz, H²), 6.16 (m, 2 H, H¹ and H³), 7.12 (t, 1 H, J = 7.5 Hz, ArH), 7.30–7.42 (m, 5 H, ArH), 7.57–7.61 (m, 2 H, ArH). ¹³C NMR (75 MHz, CDCl₃): δ = 19.6, 21.5, 127.0, 127.2, 127.8, 128.3, 129.0, 129.2, 130.2, 130.5, 131.2, 135.8, 136.6, 140.3, 143.3, 153.2, 164.6, 177.2. ESI-MS: m/z = 287 [M]⁺. Anal. Calcd for C₂₀H₁₇NO: C, 83.59; H, 5.96; N, 4.87. Found: C, 83.74; H, 6.06; N, 4.72.