Preparation of Propargyl Amines in a ZnCl₂–Dimethylurea Deep-Eutectic Solvent

Abstract

The coupling of an aldehyde, an amine, and an alkyne to yield propargyl amines was performed in a deep-eutectic solvent composed of zinc chloride and dimethylurea. The deep-eutectic solvent acts simultaneously as catalyst and solvent giving access to a variety of propargyl amines, which were isolated in moderate to very good yields.

Key words

deep-eutectic solvent - zinc chloride - dimethylurea - A³-coupling - propargyl amine

• References and Notes

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• 24 General Procedure for the Synthesis of Propargyl Amines The aldehyde was added to the DES (for preparation of DES, see the Supporting Information), followed by the amine (1.5 equiv) and the alkyne (1.5 equiv), and the reaction was performed at 80 °C for 20 h. For workup, the hot reaction mixture was diluted with 2 mL water and extracted four times with 5 mL EtOAc. The combined organic layers were dried over Na₂SO₄, and the product was isolated applying flash column chromatography (gradient of EtOAC in PE). 4-​[1-​(4-​Iodophenyl)​-​3-​phenyl-​2-​propyn-​1-​yl]​-morpholine (5) 4-Iodobenzaldehyde (232 mg, 1.0 mmol) was reacted with morpholine (131 μL, 1.5 mmol) and phenylacetylene (165 μL, 1.5 mmol). The reaction was performed in 1 g of melt, prepared from 0.31 g ZnCl₂ and 0.69 g DMU; yield 336 mg (82%). ¹H NMR (300 MHz, CDCl₃): δ = 7.73–7.69 (m, 2 H), 7.57–7.51 (m, 2 H), 7.43–7.40 (m, 2 H), 7.37–7.32 (m, 3 H), 4.74 (s, 1 H), 3.80–3.68 (m, 4 H), 2.63 (t, J = 4.5 Hz, 4 H). ¹³C NMR (75 MHz, CDCl₃): δ = 137.8, 137.4, 131.9, 130.6, 128.5, 128.4, 122.7, 93.6, 89.0, 84.3, 67.1, 61.4, 49.9. ESI-MS: m/z calcd for C₁₉H₁₈INO [MH]⁺: 404.0512; found: 404.0533. EA (%, theoretical values in brackets): C, 56.50 (56.59); H, 4.36 (4.50); N, 3.38 (3.47).