Microwave-Promoted Michael Addition of Azaheterocycles to α,β-Unsaturat­ed Esters and Acid under Solvent-Free Conditions

Abstract

Regioselective Michael addition of N-9 adenine to ethyl acrylate under microwave activation in solid-liquid solvent-free phase-transfer catalysis using TBAB as catalyst and DABCO as base was extended to tert-butyl acrylate and acrylic acid. Under these conditions and in the presence of a catalytic amount of KOH, first Michael addition of indole and indolylmaleimide to acrylates is also reported.

Key words

microwave irradiation - Michael addition - azahetero­cycles - phase-transfer catalysis - green chemistry

• References and Notes

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• 24 Optimized Procedure for the Synthesis of 1-(2-tert-Butoxycarbonylethyl)indole (7b) Indole 2 (1.77 g, 15 mmol), DABCO (1.681 g, 15 mmol), TBAB (967 mg, 3 mmol) were ground until a homogeneous mass was obtained, then 4b (3.27 mL, 22.5 mmol) was added. The reaction mixture was stirred using a dark magnetic bar for 30 min. KOH (337 mg, 6 mmol) was added, and the mixture was stirred for further 2 min just before irradiation at 200 W in a microwave oven. The reaction mixture was suspended in CH₂Cl₂ (200 mL), washed with H₂O (3 × 200 mL). The organic layer was dried (MgSO₄) and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (cyclohexane–EtOAc = 99:1) to give 3.06 g (83%) of 7b as a brown oil
• 25 Spectral and Analytical Data of Compound 7b ¹H NMR (500 MHz, DMSO): δ = 7.56 (d, J = 8.0 Hz, 1 H, H-7), 7.50 (d, J = 8.2 Hz, 1 H, H-4), 7.35 (d, J = 3.2 Hz, 1 H, H-2), 7.14 (t, J = 8.0 Hz, 1 H, H-6), 7.02 (t, J = 8.2 Hz, H-5), 6.42 (d, J = 3.2 Hz, 1 H, H-3), 4.40 (t, J = 6.7 Hz, 2 H, CH₂N), 2.74 (t, J = 6.7 Hz, 2 H, CH₂CO), 1.32 (s, 9 H, CH₃). ¹³C NMR (500 MHz, CDCl₃): δ = 170.2 (CO), 135.7, 128.7 (Cq-Ar), 127.8 (C-4), 121.4 (C-5), 120.9 (C-7), 119.3 (C-6), 109.1 (C-2), 101.3 (C-3), 80.7 (Cq-t-Bu), 41.7 (CH₂N), 36.0 (CH₂CO), 27.8 (CH₃). IR: ν = 1726 (CO) cm^–1. MS (ESI⁺): m/z (%) = 246.1 (100) [M+H]⁺. HRMS (ESI⁺): m/z calcd for [C₁₅H₁₉N₅O₂ +H]⁺: 246.1489; found: 246.1488
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