Oxidant Effect of H₂O₂ for the Syntheses of Quinoline Derivatives via One-Pot Reaction of Aniline and Aldehyde

Abstract

A convenient one-pot method for the synthesis of substituted quinolines via the reaction of aniline and aldehyde in the presence of a Lewis acid (AlCl₃) and an oxidant (H₂O₂) has been developed. Hydrogen peroxide was found to promote the reaction by its function as a hydrogen hunter, hindering the formation of by-product N-alkylaniline. The effect of the oxidant on the yield and selectivity was studied. When the molar ratio of aniline, n-butyraldehyde, and H₂O₂ was 1:3:0.5 at 25 °C, the yield of 3-ethyl-2-propylquinoline was improved from 64% (reaction without H₂O₂) to 84% (with H₂O₂), and the quinoline selectivity was improved to almost 100%. Moreover, the reaction time was obviously reduced. The substituent effect was also investigated in this work.

GRAPHICAL ABSTRACT

Keywords:

• Aldehyde
• aniline
• hydrogen peroxide
• oxidation
• quinoline derivatives

Notes

^a The ratio of aniline–butyraldehyde–AlCl₃ was 1:3:1 in CH₂Cl₂ at 25 °C.

^b The equiv of H₂O₂ was based on aniline.

^c The yield of the by-product (N-butylaniline) was 7%.

^a The ratio of aniline–butyraldehyde–AlCl₃–H₂O₂ was 1:3:1:0.5 in CH₂Cl₂.

^b GC yields; isolated yields are in parentheses.

^a The ratio of aniline–butyraldehyde was 1:3 in CH₂Cl₂.

^b GC yields; isolated yields are in parentheses.

^a Aniline (1 mmol), aldehyde (3 mmol), and AlCl₃(1 mmol) in CH₂Cl₂, at 25 °C.

^b GC yield; isolated yields are in parentheses.

^c The product was isolated by recrystallization by using methanol as solvent.

^d Accompanied by 17% of N-butylaniline.