1,4,2-Dioxazol-5-ones as Isocyanate Equivalents: An Efficient Synthesis of 2-Quinolinones via β-Keto Amides

Abstract

Under thermal conditions, 1,4,2-dioxazol-5-ones are known to undergo decarboxylation followed by Lossen’s rearrangement to yield isocyanates. Described herein is the in situ trapping of the resulting isocyanates with carbon nucleophiles to synthesize β-keto amides. Furthermore, a general and mild method for the conversion of the resulting β-keto amides into quinolin-2-ones is reported.

Key words

dioxazolones - isocyanates - keto amides - quinolinones - Lossen rearrangement

Publication History

Received: 08 June 2021

Accepted after revision: 08 September 2021

Article published online:
28 September 2021

• References and Notes

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• 12 3-(4-bromophenyl)-3-oxo-N-phenylpropanamide t-BuOK (2.0 mmol) was added in one portion to a stirred solution of 4-bromo acetophenone (2a, 1 mmol), and the 1,4,2-dioxazol-5-one 1a (1.2 mmol) in toluene (2 mL) at r.t., and the mixture was stirred at 110 °C for 1–2 h until the reaction as complete (TLC). The mixture was then cooled to r.t. and H₂O (5 mL) was added. The mixture was extracted with EtOAc (3 × 10 mL) and dried (Na₂SO₄), and the solvent was removed under reduced pressure. The residue was purified by chromatography [silica gel, hexane–EtOAc (8:2)] to give an off-white solid; yield: 120 mg (62%). ¹H NMR (400 MHz, CDCl₃) δ = 9.13 (br s, 1 H), 7.93 (d, J = 8.4 Hz, 2 H), 7.69 (d, J = 8.3 Hz, 2 H), 7.58 (d, J = 7.9 Hz, 2 H), 7.37 (m, 2 H), 7.15 (t, J = 7.5 Hz, 1 H), 4.10 (s, 2 H). ¹³C NMR (100 MHz, CDCl₃) δ = 195.2, 163.6, 137.5, 134.7, 132.3, 130.1, 129.0, 127.4, 125.1, 120.2, 45.9; ESI-MS: m/z [M+2H]⁺ for C₁₅H₁₂BrNO₂ = 320.02; found 320.05. 4-(4-Bromophenyl)quinolin-2(1H)-one (4a1); Typical Procedure A reaction tube equipped with a stirrer bar was charged with 3-(4-bromophenyl)-3-oxo-N-phenylpropanamide (3aa; 0.314 mmol) and PPA(0.159g, 0.471 mmol). The tube was sealed, and the mixture was stirred at 100 °C (oil bath) under N₂ for 20–40 min, then cooled to r.t. H₂O (2 mL) was added, and the mixture was extracted with EtOAc (3 × 5 mL) and the combined organic layers were dried (Na₂SO₄). The solvent was removed under reduced pressure, and the residue was purified by chromatography [silica gel, hexane–EtOAc (6:4)] to give Light yellow solid; yield: 65 mg (58.02%); mp 264-265 °C. ¹H NMR (400 MHz, DMSO-d ₆): δ = 11.94 (s, 1 H), 7.75 (d, J = 8.1 Hz, 2 H), 7.53 (t, J = 14.7, 11.2 Hz, 1 H), 7.48–7.39 (m, 3 H), 7.42–7.32 (m, 1 H), 7.15 (t, J = 7.6 Hz, 1 H), 6.42 (s, 1 H). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 161.67, 150.76, 139.72, 136.29, 132.13, 131.35, 131.19, 126.44, 122.74, 122.48, 121.85, 118.50, 116.30. HRMS-ESI: m/z [M +2H]⁺ calcd for C₁₅H₁₂BrNO; 300.9925; found: 300.9920.