Synthesis of new 2‐aryl‐4‐chloro‐3‐hydroxy‐1H‐indole‐5,7‐dicarbaldehydes via Vilsmeier‐Haack reaction

Abstract

New 2‐aryl‐4‐chloro‐3‐hydroxy‐1H‐indole‐5,7‐dicarbaldehydes were synthesized in three steps from acetophenone derivatives. By oxidation of acetophenones to aryl glyoxals using selenium dioxide and condensation with acetylacetone in the presence of ammonium acetate in water 3‐acetyl‐5‐aryl‐4‐hydroxy‐2‐methyl‐1H‐pyrrols were obtained. 2‐Aryl‐4‐chloro‐3‐hydroxy‐1H‐indole‐5,7‐dicarbaldehydes were synthesized via Vilsmeier‐Haack reaction of pyrrole derivatives in moderate yields. J. Heterocyclic Chem., (2010).

Unravelling the synthetic and therapeutic aspects of five, six and fused heterocycles using Vilsmeier–Haack reagent

“…The proposed mechanism involves a series of interconnected reactions, starting from the addition of (23) to iminium salt (1), progressing through iminoalkylation and cyclization of bis-iminium salt (24) to enamine (25), followed by the elimination of dimethylamine. The resulting bis-iminium salt (26) undergoes hydrolysis, culminating in the synthesis of 2-aryl-4-chloro-3-hydroxy-1 H -indole-5,7-dicarbaldehydes (27) as the final product 93 ( Scheme 57 ).…”

“…In 2010, Eftekhari et al 93 reported 2-aryl-4-chloro-3-hydroxy-1 H -indole-5,7-dicarbaldehydes from 3-acetyl-5-aryl-4-hydroxy-2-methyl-1 H -pyrroles using V. H. reagent in cold condition for 1 hour followed by stirring the reaction mixture at 55 °C for 2 hours and further stirred overnight at room temperature in average yield. The resulted products were expected to display a wide range of biological activities ( Scheme 58 ).…”