Efficient, One-Pot, BF₃·OEt₂-Mediated Synthesis of Substituted N-Aryl Lactams

Abstract

A quick, efficient, one-pot, BF₃·OEt₂-mediated synthesis of substituted N-aryl lactams in good to excellent yields by reaction of various substituted arenes with a variety of ω-azido alkanoic acid chlorides at room temperature is reported.

Key words

substituted arenes - ω-azido-alkanoic acid chloride - Lewis acid - N-aryl lactams

• References and Notes

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• 28 Typical Experimental Procedure for the Synthesis of Substituted N-Aryl Lactams An equimolar amount of substituted arene and the corresponding ω-azido alkanoic acid chloride were taken in anhyd CH₂Cl₂ (25 mL) and stirred for 10 min at r.t. To this mixture, BF₃·OEt₂ (0.1 mol, with respect to arene) was added slowly in 2–3 small portions at r.t. The reaction was continued until completion (cf. Table 1) as confirmed by TLC. The reaction mixture was then poured into distilled H₂O (50 mL) and extracted with CH₂Cl₂. The organic layer was separated and dried over anhyd Na₂SO₄ and then concentrated to afford the desired substituted N-aryl lactam compound. Data of Selected Compounds 1-(3,4-Dimethoxyphenyl)piperidin-2-one (3aa) Colorless oil. ¹H NMR (300MHz, CDCl₃): δ = 1.92–1.95 (m, 4 H), 2.55 (t, J = 6.2 Hz, 2 H), 3.61 (t, J = 5.5 Hz, 2 H), 3.86 (s, 3 H), 3.87 (s, 3 H), 6.77–6.78 (m, 2 H), 6.86–6.88 (m, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 21.3, 23.4, 32.7, 52.0, 55.7, 55.8, 110.0, 111.2, 118.0, 136.4, 147.6, 149.0, 170.0. MS (EI): m/z (%) = 235 (100) [M⁺], 220, 166. HRMS (EI): m/z calcd for C₁₃H₁₇O₃N [M⁺]: 235.1208; found: 235.1208. 1-(3,5-Dimethoxyphenyl)pyrrolidin-2-one (3ba) White solid; mp 85–86 °C. IR (CH₂Cl₂): ν = 1069, 1154, 1208, 1249, 1275, 1324, 1347, 1393, 1478, 1598, 1697, 2841, 2958 cm^–1. ¹H NMR (300 MHz, CDCl₃, TMS): δ = 2.14 (tt, J = 8.4 Hz, 6.6 Hz, 2 H, CH₂), 2.61 (t, J = 8.4 Hz, 2 H, CH₂), 3.80 (s, 6 H, OCH₃), 3.83 (t, J = 6.6 Hz, 2 H, CH₂), 6.27 (t, J = 2.4 Hz, 1 H, Ar), 6.86 (d, J = 2.4 Hz, 2 H, Ar). ¹³C NMR (75 MHz, CDCl₃, TMS): δ = 17.8, 32.9, 48.9, 55.3, 96.4, 98.3, 141.1, 160.7, 174.3. MS (EI): m/z (%) = 221 (100) [M⁺], 192 (23), 178 (9), 166 (75), 162(7), 151 (5), 136 (12), 122(6), 108(5). Anal. Calcd (%) for C₁₂H₁₅NO₃: C, 65.14; H, 6.83; N, 6.33. Found: C, 64.99; H, 6.85; N, 6.25.