Zwitterionic-Type Molten Salt: A Mild and Efficient Organocatalyst for the Synthesis of 3-Aminoalkylated Indoles via Three-Component Coupling Reaction

Abstract

A general and efficient method has been developed for the synthesis of 3-aminoalkylated indoles by a three-component coupling of indoles, aldehydes, and amines in the presence of a catalytic amount of zwitterionic-type molten salt under solvent-free conditions. The non-hazardous experimental procedure, mild reaction conditions, and the reusability of the catalyst are the notable advantages of the present method.

Key words

3-aminoalkylated indole - zwitterion - molten salt - organocatalyst - multicomponent

References and Notes

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9

Synthesis of 2-Methyl-3-(morpholin-4-ylpyridin-2-ylmethyl)-1 H -indole (Entry 16, Table 1): A mixture of 2-pyridinecarboxaldehyde (190 µL, 214 mg, 2 mmol), morpholine (350 µL, 348 mg, 4 mmol), and 2-methylindole (262 mg, 2 mmol) was stirred in the presence of 4-(1-imidazolium)butane sulfonate (82 mg, 20 mol%) at 60 ˚C for 2 h. After completion of the reaction (TLC) the reaction mixture was extracted with Et₂O (3 × 10 mL). Evaporation of solvent furnished the crude product which was subjected to column chromatography to obtain the pure product (498 mg, 81%) as a brown solid; mp 145-146 ˚C. IR (KBr): 3502, 2738, 1587, 1460, 1377 cm^-¹. ^¹H NMR (500 MHz, CDCl₃): δ = 8.44 (d, J = 3.0 Hz, 1 H), 8.19 (s, 1 H), 8.07 (t, J = 3.0 Hz, 1 H), 7.80 (d, J = 8.0 Hz, 1 H), 7.55 (t, J = 8.5 Hz, 1 H), 7.15-7.17 (m, 1 H), 7.02-7.10 (m, 3 H), 4.76 (s, 1 H), 3.72-3.79 (m, 4 H), 2.58 (m, 2 H), 2.44 (s, 3 H), 2.37-2.41 (m, 2 H). ^¹³C NMR (125 MHz, CDCl₃): δ = 162.6, 148.6, 136.8, 135.4, 133.4, 127.0, 122.1, 121.8, 121.0, 120.2, 119.6, 110.6, 110.4, 71.1, 67.4 (2 × C), 67.4 (2 × C), 12.5. Anal. Calcd for C₁₉H₂₁N₃O: C, 74.24; H, 6.89; N, 13.67. Found: C, 74.10; H, 6.72; N, 13.58. The catalyst, left in the reaction vessel, was dried under vacuum and was reused for subsequent reactions.