Catalyst-Free Alkylation of Quinoxalines in Water

Abstract

A catalyst-free nucleophilic allylation of quinoxalines in water has been developed, enabling efficient synthesis of versatile, functionalized C3-alkylated quinoxalin-2(1H)-ones. This method selectively activates the imine moiety through hydrogen-bonding interactions, shunning conventional strategies that require transition metals, photoirradiation, or elevated temperatures. Remarkably, the reaction exhibits accelerated kinetics in water, due to strong hydrogen-bonding effects that facilitate reactant aggregation.

Keywords

C3-alkylated - Catalyst free - Water - Quinoxalin-2(1H)-ones - Hydrogen bonding

Publication History

Received: 02 November 2025

Accepted after revision: 27 January 2026

Accepted Manuscript online:
27 January 2026

Article published online:
17 February 2026

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• 14 Experimental Procedure The mixture of 1-methylquinoxalin-2(1H)-one 1a (0.2 mmol), potassium allyltrifluoroborate 2a (0.3 mmol) in 1 mL H₂O were stirred at room temperature. After the completion (as indicated by TLC), the mixture was extracted with ethyl acetate. The combined organic phase was dried over Na₂SO₄ and concentrated in vacuo. The residue was further purified by column chromatography on silica gel using PE/EA (5:1) to afford the desired products 3a as a brown solid (67% yield). ¹H NMR (600 MHz, CDCl₃) δ 6.95–6.91 (m, 1H), 6.91 (d, J = 0.8 Hz, 1H), 6.87–6.83 (m, 1H), 6.70–6.66 (m, 1H), 5.84–5.75 (m, 1H), 5.22 (d, J = 10.1 Hz, 1H), 5.15 (dd, J = 17.1, 1.3 Hz, 1H), 3.84 (dd, J = 10.0, 3.3 Hz, 1H), 3.37 (s, 3H), 2.73–2.68 (m, 1H), 2.39–2.30 (m, 1H); ¹³C NMR (151 MHz, CDCl₃) δ 167.52, 134.47, 133.85, 129.15, 123.77, 119.81, 119.62, 114.76, 114.71, 55.52, 35.98, 29.23; HRMS (ESI): calcd for [C₁₂H₁₄N₂ONa]⁺ 225.0998, found 225.099.