Greener Synthesis of Nitrogen-Containing Heterocycles in Water, PEG, and Bio-Based Solvents

Abstract

The solvents used in chemistry are a fundamental element of the environmental performance of processes in corporate and academic laboratories. Their influence on costs, health safety, and nature cannot be neglected. Quantitatively, solvents are the most abundant constituents of chemical transformations; therefore, acting on solvents and replacing standard solvents with safer products can have a great ecological impact. However, not all green solvents are suitable for the wide scope of organic chemistry reactions. A second point to consider is that 50% of pharmaceutical drugs are nitrogen heterocycles compounds. It therefore appeared important to provide an overview of the more ecological methodologies for synthesizing this class of compounds. In this review, all publications since 2000 that describe green reactions leading to the formation of nitrogen heterocycles using safe solvents were considered. We chose water, PEG, and bio-based solvents for their negligible toxicity. The synthesis of five-, six-, and seven-membered aromatic nitrogen heterocycles using green reactions reported in the literature to date is described.

Ultrasound-Assisted Iodination of Imidazo[1,2-α]pyridines Via C–H Functionalization Mediated by tert-Butyl Hydroperoxide

“…42 A yellow solid, mp = 160−162 °C, yield: 90% (58.24 mg); 1 H NMR (400 MHz, CDCl 3 ) δ 8.20 (d, J = 6.8 Hz, 1 H), 8.06 (d, J = 7.6 Hz, 2 H), 7.61 (d, J = 9.2 Hz, 1 H), 7.48 (t, J = 7.6 Hz, 2 H), 7.39 (t, J = 7. 4 Hz, 1 H), 7.24 (t, J = 8.0 Hz, 1 H), 6.90 (t, J = 6.8 Hz, 1 H); 13…”

“…In the past 20 years, with the development of the chemical and pharmaceutical industries, novel approaches to the synthesis of heterocycles have rapidly emerged. − The development of more green and effective methods to heterocycle synthesis has been a major research interest for green and sustainable chemists because more than 70% of major commercially available synthetic drugs contain at least one N -fused heterocyclic scaffold. − It is worth mentioning that the imidazo­[1,2-α]­pyridine derivatives exhibit a wide range of biological and pharmacological activities, such as antibacterial, antiulcer, antiviral, and antitumor (Scheme ). − As a result, tremendous efforts have been devoted to the synthesis and functionalization of N -fused heterocyclic scaffolds. − Among them, 3-halo imidazo­[1,2-α]­pyridines are great potential intermediates for their diverse reactivity in many types of reactions.…”

Gram-Scale Synthesis of 1,8-Naphthyridines in Water: The Friedlander Reaction Revisited

“…The studied catalysts and solvents used for the Friedlander reaction exhibit high cost, toxicity, high loading, low selectivity, high-temperature dependence, etc., which contribute to environmental pollution, limiting the criteria for green synthesis. , Thus, sustainable approaches need to be explored from a green perspective point of view, and a recent review sheds light on the greener synthesis of quinolone that uses water as the solvent . It is advantageous to choose water as a solvent in the reaction medium . Very recently, Hayes and co-workers reported the synthesis of 1,8-naphthyridine and its derivatives in moderate to good yield , using metal hydroxides (LiOH and KOH) in aqueous-alcohol media.…”

“…28 medium. 29 Very recently, Hayes and co-workers reported the synthesis of 1,8-naphthyridine and its derivatives in moderate to good yield 30,31 using metal hydroxides (LiOH and KOH) in aqueous-alcohol media. Although there are a few reports on the synthesis of quinoline derivatives using the Friedlander reaction in mixed aqueous-alcohol media, using metal-based catalysts such as Fe 3 O 4 -IL-HSO 4 , 31 LiOH•H 2 O 30 makes them unfavorable from the green chemistry perspective.…”

Mutual Diffusivities of Binary Mixtures of Water and Poly(ethylene) Glycol from Heterodyne Dynamic Light Scattering

“…PEGs can be used in pharmaceutical, chemical, cosmetic, and food industries, e.g., as drug delivery systems [2] or for protein modi cations [3,4]. It has also been widely employed as environmentally friendly alternative solvent [5][6][7][8]. In all these applications, polydisperse PEGs are ubiquitously used due to their low cost.…”