A Novel One‐Pot Synthesis of Substituted Quinolines

Abstract

A synthesis of quinoline derivatives is described via reaction between ethyl bromopyruvate (¼ ethyl 3-bromo-2-oxopropanoate), acetylenedicarboxylate, and isatin (¼ 1H-indole-2,3-dione) in the presence of NaH as a base. Also, these reactions were performed without ethyl bromopyruvate. The reaction in the presence of ethyl bromopyruvate provides regioselectively a quinoline with the ethyl ester group in 4-position. In the absence of ethyl bromopyruvate, the reaction leads to functionalized quinolines with the same ester groups in 2-, 3-, and 4-positions.Introduction. -Heterocyclic aromatic aza compounds, especially quinoline derivatives, are widely present in several natural compounds (e.g., Cinchona alkaloids) [1 -3] and pharmacologically active substances displaying a broad range of biological activity [4 -6]. Quinoline compounds have been found to possess antiasthmatic, antibacterial, anti-inflammatory, and antihypertensive properties [7 -9]. In addition to the medicinal applications, quinolines have been employed in the study of bioorganic and bioorganometallic processes [10]. Quinolines are also known for their formation of conjugated molecules and polymers that combine enhanced electronic, optoelectronic, or nonlinear optical properties with excellent mechanical properties [11]. A number of methods have been reported for the synthesis of quinolines involving a variety of metal catalysts and Lewis acids [12 -15]. Especially the Pfitzinger reaction [16] of isatins with a-methylidene carbonyl compounds is widely used for the synthesis of physiologically active derivatives of substituted quinoline-4-carboxylic acids [17]. However, many of these procedures are not fully satisfactory with regard to operational simplicity, cost of the reagent, drastic reaction conditions, and relatively low yield. Therefore, a simple, general, and efficient procedure is still in demand for the preparation of these important heterocyclic compounds.

Solvent-free synthesis of polysubstituted pyrroles catalyzed by ZnO nanorods

“…In connection with our previous work for the synthesis of zinc oxide nanostructures [31] and our interest in heterocyclic synthesis [32][33][34][35], we report an efficient synthesis of functionalized pyrroles. Thus, the reaction of alkylamines 1 with dialkyl acetylenedicarboxylates 2 and a-chloroketones 3 in the presence of ZnO nanorods (ZnO-NRs, 12 % mol) as catalysts without adding any organic solvent at 70°C led to polysubstituted pyrroles 4 in excellent yields (Scheme 1).…”

A Facile One‐Pot Synthesis of Substituted Quinolines via New Multicomponent Reaction

“…A tentative mechanism for this transformation is proposed in Scheme [15]. Intermediate 7 is formed from the reaction of anionic species of isatin and acetylenic compound 2 , which react with ethyl chloropyruvate to produce anionic species of 8 and 9 .…”

“…Because of their importance as substructures in a broad range of natural and designed products, significant effort continues to be directed toward the development of new quinoline‐based structures and new methods for their construction [8–11]. A number of methods have been reported for the synthesis of quinolines involving a variety of metal catalysts and Lewis acids [12–15]. In this article, as part of our ongoing studies on the multicomponent area, we present herein our results of a novel discovery involving synthesis of quinoline derivatives, using commercially available starting materials in excellent yields.…”

“…In this article, as part of our ongoing studies on the multicomponent area, we present herein our results of a novel discovery involving synthesis of quinoline derivatives, using commercially available starting materials in excellent yields. Thus, the reaction of isatin 1 , activated acetylenes 2 and ethyl chloropyruvate 3 or alkyl 4‐chloroacetoacetate, at 70°C in water as the solvent, produced quinoline derivatives 4 [15] in good yields (Scheme ).…”

A Rapid, Four-Component Synthesis of Functionalized Thiazoles

“…As part of our current studies on the development of new routes in heterocyclic synthesis [15][16][17][18], we describe an efficient one-pot method for the synthesis of functionalized thiazoles.…”