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Facile synthesis of quinoline in water


The article by Dr. Bimal Banik and colleagues is published in Current Organic Chemistry, 2020

Organic synthesis in water has attracted the attention of chemists for several years. Water is considered as nature's universal solvent and possesses distinguished physical and chemical properties. It exhibits powerful hydrogen bonding and a wide temperature range to stay in liquid state. In recent years, many organic transformations use water as the solvent system. Other interesting features of water are that the pH of water is often varied, salting-in or salting-out effects can be induced by adding additives such as salts or surfactants, cyclodextrins etc. But water was neglected as a reaction solvent by organic chemists due the concept that all the reactants must be soluble in the reaction media. The earliest known reactions of organic synthesis in water include Wohler's urea synthesis and, Baeyer and Drewsen's indigo synthesis. The situation remained the same until Breslow showed how water can enhance the reaction rate of the Diels-Alder reaction. Water has become an admired reaction medium after the contribution of the Sharpless and Breslow groups. According to Jung and Marcus, approximately 25% of water molecules possess free hydroxyl groups at the interface and may form potential H-bonding with the substrates.

The use of water as the solvent system has advantages like ease of product isolation, high heat capacity and unique redox stability. In the last few years, quinoline and its derivatives have attracted both synthetic and biological chemists because of its diverse chemical and pharmacological properties. They exhibit significant activity against several viruses including antimalarial, antibiotic, anticancer, anti-inflammatory, antihypertensive, tyro kinase PDGF-RTK inhibition and anti-HIV properties. Moreover, the quinoline ring system occurs in various natural products, usually in alkaloids, and is often used for the design of many synthetic compounds with diverse pharmacological properties. There are a number of natural products of quinoline skeleton used as a medicine or employed as lead molecule for the development newer and potent molecules. For instance, quinine was isolated as the active ingredient from the bark of Cinchona trees and has been used for the treatment of malaria. Its structure determination and SAR studies resulted in discovery of newer antimalarial drugs like chloroquine, primaquine, mefloquine etc.

The quinoline structural motif is readily available through a number of classical synthetic routes and from commercially available reagents. The Friedländer synthetic method, Skraup, Combes and Doebner-Miller syntheses are good examples. Moreover, the Conrad-Limpach, Gould-Jacobs and Camps routes for the synthesis of quinolones are widely used methods. All classical methods have similar disadvantages, requiring highly acidic and/or oxidizing media, high temperatures and long reaction times. Moreover, most of these synthetic routes have selectivity problems with meta-substituted substrates and its versatility is limited by the reactivity of the methylene carbon involved in the aldol reaction. Although efficient and versatile, classical routes towards the synthesis of quinolines present environmental concerns as most synthetic routes use a large excess of reagents and produce a significant amount of toxic waste.

Over the last decades, scientists are putting constant efforts to develop environmentally friendly synthetic methodology for quinoline derivatives. A significant amount of efforts has been put forwarded to synthesize quinoline moieties by following greener protocols. Microwave irradiation and activation of bonds by light exposure are also documented by several groups in addition to catalyst-free reaction. In this article, we report water-mediated organic reactions resulting in the synthesis and functionalization of quinoline moieties. Some of these transformations are highly regioselective. The synthesis of qionoline in water is covered in detail in a review, Facile Synthesis of Quinolines in Water, authored by Banik et al., in Current Organic Chemistry.

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Author Information:

Gongutri Borah1, Preetismita Borah2, Arnav Bhuyan1 and Bimal K. Banik*3

1Chemical Science and Technology División, CSIR-North East Institute of Science and Technology, Jorhat, Assam, India, 785006;

2 Agrionics, v1(a), CSIR-Central Scientific Instruments Organisation, Sector 30C, Chandigarh, India, 160030;

3Research Development & College of Natural Sciences and Human Studies, Prince Mohammad Bin Fahd University, Al Khobar, Kingdom of Saudi Arabia; Email: