Cascade Reaction of Isatins with 1,1-Enediamines: Synthesis of Multisubstituted Quinoline-4-carboxamides

Abstract

A one-step methodology for the synthesis of multisubstituted quinoline-4-carboxamides was developed by simply refluxing a mixture of isatins 1 and various kinds of 1,1-enediamines 2-4 in a reaction catalyzed by NHSOH. As a result, a series of quinolone-4-carboxamides were produced through a novel cascade reaction mechanism. This reaction involved the formation of the quinoline ring accompanied by the formation of an amide bond in one step. Accordingly, this protocol is suitable for combinatorial and parallel syntheses of quinolone-4-carboxamide drugs or natural products.

Choline Chloride-Based Deep Eutectic Systems in Sequential Friedländer Reaction and Palladium-Catalyzed sp3 CH Functionalization of Methyl Ketones

“…Likewise, the quinolines are an important class of heterocyclic compounds, 39−41 owing to their potential pharmacological properties, namely, antimalarial, 42,43 antibacterial, 44,45 antiasthmatic, anti-inflammatory, 46,47 antihypertensive inhibiting properties, and so forth. Despite numerous methods including Friedländer, 48−50 Combes, 51,52 Conrad-Limpach, 53 Doebner von Miller, Skraup and Camps quinoline synthesis, and so forth, 54−57 reported previously, herein, we report the DES-assisted Friedländer quinoline synthesis.…”

Copper‐Catalyzed Aerobic Oxidative Ring Expansion of Isatins: A Facile Entry to Isoquinolino‐Fused Quinazolinones

“…In recent years, the synthesis of nitrogen‐containing heterocycles has been actively explored through isatin ring‐expansion. Common methods for the ring‐expansion reaction of isatins and their derivatives are as follows: 1) ring‐expansion through the cleavage of the C2—N1 bond with enamines to synthesize multisubstituted quinoline‐4‐carboxamides derivatives; [ 6 ] 2) ring‐formation through the insertion of atoms into the C2—C3 or C3—C4 bond. [ 7 ] For example, Zou and co‐workers reported an efficient and practical method for the construction of benzimidazo[l,2‐ c ]quinazolin‐6‐ ones through the cleavage of the C2—C3 bond and insertion of heteroatoms using molecular oxygen as the oxidant.…”

Synthesis of Quinoline‐4‐carboxamides and Quinoline‐4‐carboxylates via a Modified Pfitzinger Reaction of N‐Vinylisatins

“…[10] Along this line, several modifications of the classical Pfitzinger reaction have been reported for the direct construction of fused quinoline-4-carboxamides which are based on the substitution of the carbonyl compound with imidates, [11] vinylic amines, [12] heterocyclic ketene aminals, [13] enaminones, [14] and 1,1-enediamines. [15] In contrast, only one process has been published for the direct production of quinoline-4carboxylates. [16] To our knowledge, since the Halberkann modification, which led to the formation of 2-hydroxyquinoline-4-carboxylic acids by using N-acylated isatins (Scheme 1b), [17] no further modifications of N-substituted isatins have been published for the construction of quinolines.…”