A One-Pot Rearrangement of 2-(N-Alkyl-N-aryl)aminochromone-3-carbaldehyde to N-Alkyl-3-salicyloyl-2-quinolone - An Antileishmanial Agent

Abstract

2-(N-Aryl)aminochromone-3-carbaldehyde does not show any change on heating in acetic acid, but under the same reaction conditions 2-(N-alkyl-N-aryl)aminochromone-3-carbaldehyde rearranges to 3-salicyloyl-2-quinolones, which exhibits antileishmanial activity.

Key words

3-formylchromone - 1-benzopyran - 2-quinolone - 2-amino-3-formylchromone - molecular rearrangement - heterocycles

References and Notes

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25

Typical Experimental Procedure for the Rearrangement of 2-( N -Methyl- N -phenyl)aminochromone-3-carbox-aldehyde (4a) Compound 4a (0.14 g, 0.5 mmol) was heated under reflux in AcOH (3 mL) containing 4 drops of H₂O for 2 h when the absence of 4a was observed by TLC. The reaction mixture was cooled to r.t. and poured into ice-cold water. The resultant acidic mixture was neutralized with NaHCO₃ when a solid began to precipitate. The precipitated solid was filtered, dried in air, and crystallized from benzene-light PE (2:1) to give pale yellow crystalline solid 6a.
N -Methyl-3-salicyloyl-2-quinolone (6a) Yield 0.12 g (86%); mp 182-184 ˚C. IR (KBr): 3036, 1645, 1626, 1589 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 3.78 (s, 3 H, NCH₃), 6.81-6.87 (m, 1 H, 5′-H), 7.04 (br d, J = 8.1 Hz, 1 H, 3′-H), 7.28-7.34 (m, 1 H, ArH), 7.42-7.47 (m, 1 H, ArH), 7.49-7.54 (m, 2 H, ArH), 7.63-7.71 (m, 2 H, ArH), 7.86 (s, 1 H, 4-H), 11.96 (s, exchangeable, 1 H, OH). ^¹³C NMR (75 MHz, CDCl₃): δ = 29.6, 114.3, 118.2, 118.9, 119.2, 119.4, 122.7, 129.8, 130.6, 132.3, 132.9, 136.9, 139.1, 140.5, 159.4, 162.9, 199.0. MS: m/z = 280 [M + H⁺], 302 [M + Na⁺]. Anal. Calcd for C₁₇H₁₃NO₃: C, 73.11; H, 4.69; N, 5.02. Found: C, 72.92; H, 4.60; N, 4.97.