Metal-Free Cascade Methylation/Cyclization of N-Alkyl-N-methacryloylbenzamides with Dicumyl Peroxide

Abstract

A metal-free radical cascade methylation/cyclization of a wide range of N-alkyl-N-methacryloylbenzamides by using dicumyl peroxide as the methylating reagent provides a convenient access to a series of methylated isoquinoline-1,3-diones in moderate yields.

Key words

alkylmethacryloylbenzamides - dicumyl peroxide - cascade reactions - methylation - cyclization - isoquinolinediones

• References and Notes

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• 9 4-Ethyl-2,4-dimethylisoquinoline-1,3(2H,4H)-dione (3a); Typical Procedure DCP (0.6 mmol) was added to a stirred solution of N-methacryloyl-N-methylbenzamide (1a; 0.2 mmol) in PhCl (1.0 mL) in a test tube. The tube was sealed, and the mixture was stirred at 120 °C for 17 h. H₂O (5 mL) was added to quench the reaction, and the mixture was extracted with EtOAc (3 × 10 mL). The organic layers were combined, washed with sat. aq NaCl (2 × 10 mL), dried (Na₂SO₄), and concentrated. The residue was purified by column chromatography [silica gel, hexanes–EtOAc (8:1)] to give a colorless oil; yield; 26 mg (60%).IR (KBr): 3066, 2966, 2934, 2876, 1714, 1667, 1606, 1463, 1416, 1361, 764 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 8.26–8.28 (m, 1 H), 7.64–7.68 (m, 1 H), 7.42–7.48 (m, 2 H), 3.41 (s, 3 H), 2.29–2.36 (m, 1 H), 1.86–1.92 (m, 1 H), 1.64 (s, 3 H), 0.56 (t, J = 8.0 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 176.6, 164.5, 143.4, 133.9, 128.7, 127.2, 125.2, 48.3, 36.6, 28.5, 27.0, 9.4. Anal. Calcd For C₁₃H₁₅NO₂: C, 71.87; H, 6.96; N, 6.45. Found: C, 71.68; H, 7.01; N, 6.39.