Lewis Acid Catalyzed Nenitzescu Indole Synthesis.

Abstract

Indole derivatives R 0140Lewis Acid Catalyzed Nenitzescu Indole Synthesis. -This simple, rapid, and efficient method enables the preparation of hydroxyindoles like (III) from benzoquinone (I) and enamines (II) in good to excellent yields in the presence of weak Lewis acid catalysts using low-polar solvents. The experimental conditions for the realization of the Nenitzescu reaction are defined via a non-redox mechanism. -(VELEZHEVA*, V. S.; KORNIENKO, A. G.; TOPILIN, S. V.; TURASHEV, A. D.; PEREGUDOV, A. S.; BRENNAN, P. J.; J. Heterocycl. Chem. 43 (2006) 4, 873-879; Nesmeyanov Inst. Organoelem. Compd., Russ. Acad. Sci., Moscow 119991, Russia; Eng.) -H. Hoennerscheid 52-120

Indole Based Weapons to Fight Antibiotic Resistance: A Structure–Activity Relationship Study

“…Then, absolute ethanol (8 mL) was added, and the mixture was made and reacted for 12 h. After solvent evaporation under reduced pressure, flash chromatography of the solid residue on silica gel gave a white solid exhibiting the following spectroscopic properties: mp 147−149 °C; Ethyl 1-Benzyl-2-methyl-5-phenethoxyindole-3-carboxylate (9). 30 Anhydrous ZnCl 2 (10% mol) was added to a stirred suspension of p-benzoquinone (1.08 g, 10 mmol) in 30 mL of dry DCM. After having heated at reflux, a solution of crotonamine 19 (2.2 g, 10 mmol) in dry DCM (20 mL) was added in 5 min and stirred at reflux for further 45 min.…”

“…The NMR spectrum was in accordance to that described in the literature. 30 Ethyl 5-Acetoxy-1-benzyl-2-methyl-1H-indole-3-carboxylate (10). Acetic anhydride (0.50 mL, 5.2 mmol) was added to a stirred solution of hydroxyindole 9 (160 mg, 0.52 mmol) in dry pyridine (3 mL), and the mixture was refluxed overnight.…”

“…Ethyl 1-Benzyl-2-methyl-5-(4-(piperazin-1-yl)butoxy)-1H-indole-3-carboxylate (30). The titled product was obtained from chloro intermediate 20c and piperazines as a white solid (72 mg, yield 43%).…”

“…The substituted 5-hydroxyindole 9 was synthesized according to a modified Nenitzescu reaction by refluxing 1,4-p-benzoquinone, zinc chloride, and aminocrotonate 19 in dichloromethane. 30 Compound 19 was prepared from the condensation of ethyl acetoacetate and benzylamine (Scheme 3).…”

Structural Optimization and Biological Evaluation of 2-Substituted 5-Hydroxyindole-3-carboxylates as Potent Inhibitors of Human 5-Lipoxygenase

“…Moreover, method a failed when using 6,7-dimethoxy-1,4-naphthoquinone ( 15 ), quinoline-5,8-dione ( 16 ), or the 2-aryl-1,4-benzoquinones 17 and 18 as reactants from enaminoester 7a . Due to the fact that Lewis acid-promoted Nenitzescu reactions mostly provide better yields, we also used ZnI 2 as catalyst in a wide range of reactions (method b) . Moreover, the desired Nenitzescu products of the reported 1,4-quinones 15−18 − could be successfully synthesized according to method b.…”