Letters in Organic Chemistry - Volume 20, Issue 8, 2023

An efficient and environmentally-friendly protocol for the synthesis of 2- (arylamino) thiazoles has been investigated. The two-step, three-component reaction of aryl ketones, Nbromosuccinimide, and thiourea derivatives was performed using [bmim][BF4] ionic liquid as a solvent in one pot and gave products in good to excellent yields. Furthermore, the ionic liquid could be reused up to the 5^th time without a considerable decrease in the reaction yield. Thirteen thiazoles were obtained in high yields (78-89%) under mild conditions (ambient temperature and relatively short reaction time) and their structures were confirmed by NMR data.

[Hydroxy(tosyloxy)iodo]benzene mediated the oxidative cleavage of pyridyl hydrazones to regenerate aryl ketones efficiently. Reaction occurred by simply stirring the hydrazone with hypervalent iodine reagent in dichloromethane at room temperature, where aryl ketones are produced up to 90% yield.

A convenient, efficient method for synthesising indole-3-substituted-2-benzimidazoles and benzothiazoles was carried out using N-arylation followed by condensation-oxidation protocol. Narylation of 1H-indole-3-carbaldehyde was carried out via CuI/DMED to yield 1-(3-((tertbutylsulfonyl) methyl)phenyl)-1H-indole-3-carbaldehyde. Condensation using various o-phenylenediamines in the presence of CAN/DMF as oxidant furnished the desired 2-(1-(3-((tert-butylsulfonyl) methyl)phenyl)-1H-indol-3-yl)-1H-benzo[d]imidazole. In addition to simple o-phenylenediamines, 1,2-arylenediamines substituted with withdrawing and donating groups, heterocyclic-2,3-phenylene diamines are well tolerated and give good yields of up to 74% yield. As simple reaction between ophenylenediamines and 1H-substituted indole-3-carboxyaldehyde give indole-3-substituted-2- benzimidazoles with moderate to good yields. These novel indole-derived benzimidazoles and benzothiazoles have shown their efficacy as anti-cancer agents with various cancer K-562, MDA-MB231, colon-205 cell lines.

An important bioactive heterocycle having several uses in medicinal chemistry, synthetic organic chemistry, material chemistry, and natural product is indole along with its analogues. Many bioactive indole-based heterocycles have important antibacterial, anti-inflammatory, analgesic, antiviral, antimalarial, chemotherapeutic, antifungal, and anti-TB effects, as well as antioxidant capabilities. Several well-known medications, including tadalafil, rizatriptan, sumatriptan, and fluvastatin are indole- based potential bioactive compounds. Based on the existing and latest evidence, researchers have focused on developing indole-based compounds with novel biological and pharmacological properties for decades. Owing to useful bioactivities, we have described many bioactive indoles and their synthetic methods in this review article.

Indole is an important heterocyclic molecule having a number of pharmacologically useful properties. Adolf von Baeyer synthesized indole by reducing oxindole in the presence of a catalytic amount of zinc dust in 1866. A number of studies have been conducted and many more are in the pipeline to investigate the medicinal potential of indole and its derivatives. Indomethacin, Indolmycin, Oxypertine, Yohimbine, Pindolol, and Delavirdine are indole containing drugs that are in high demand in the market. The present study aims to highlight the indole nucleus containing drugs developed by researchers over the last 25 years, with a focus on antibacterial and antifungal properties present in these drugs. The mode of action and Structure–Activity Relationship (SAR) of indole derivatives, which are responsible for antibacterial and other relevant actions, are also highlighted in the present review. To aid scientists in exploring future potential in this domain, the present study includes the key qualities and highlights of each research activity done by researchers especially related to synthetic derivatives of Indoles. All the available information on Indole derivatives was collected via electronic search (using Pubmed, SciFinder, Scirus, Google Scholar, and Web of Science) and the resources available in Central Library, IFTM University, Moradabad were also referred. The present review is based on literature collected and studied over the previous 23 years. This article will aid researchers in the development of new molecules with indole derivatives undoubtedly which must have improved antibacterial and other properties.

Firstly, 2-amino aromatic ketones were synthesized by o-acylation of p-substituted anilines with nitrile under Sugasawa conditions, and the yield was up to 90.1%. Then, 4-pyridinylquinoline derivatives were synthesized by Friedlander reaction with α-methylene ketones, and the yield was up to 81.9%. The structures of five 2-amino aromatic ketones and eighteen substituted quinolines were characterized by MS, ¹H NMR, and ¹³C NMR. The structures were further confirmed by single crystal X-ray diffraction, which was consistent with the expected structures. Analyzing the crystal structure, it was found that compounds 4j and 4q crystallized in the monoclinic with the P21/n space group, respectively. Compounds 2c, 2d, 2e, and 4n crystallized in the triclinic with the P-1 space group, respectively. Of which compound 4n crystallized in the triclinic space group P-1 with two crystallographically independent but chemically equivalent molecules in the asymmetric unit. The two independent molecules were found to possess different orientations of the chlorine, methyl, pyridyl, and acetyl groups relative to the core (quinoline) two-ring system. This work provides a simple, straightforward synthetic protocol for preparing 4-pyridinylquinoline derivatives.

A three-component reaction under ultrasound irradiation and with a catalytic amount of citric acid was presented for the synthesis of a series of 2-aryl-quinazolin-4(1H)-ones with excellent efficiency and short reaction time. This one-pot reaction with 2-aminobenzonitrile, ammonium hydroxide or glycine and benzaldehydes is a clean and safe route for the environment at room temperature. Mild reaction conditions, green environment, excellent performance, simple method and reduction of environmental consequences are the advantages of the present method. The structures of many synthesized 2-aryl-quinazolin-4(1H)-one compounds were confirmed by ¹H, ¹³C NMR and FTIR spectral data and elemental analysis.

A coordination polymer Zr-CIA was developed and employed as a stable and effective catalyst for the alkylation of amines with alcohols or benzyl amines. The Zr-CIA as a new coordination polymer was prepared from 1-(carboxymethyl)-1H-indole-3-carboxylic acid and ZrCl4 through a simple and effective solvothermal method and characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), powder X-ray diffraction (XRD), fourier transform infrared (FT-IR), nitrogen adsorption-desorption and X-ray photoelectronic spectroscopy (XPS). The polymer exhibited not only high catalytic activity for the alkylation reaction, but also good reusability in more than five cycles. Meanwhile, mechanistic investigations were carried out to study these reactions.