Letters in Organic Chemistry - Volume 19, Issue 12, 2022

Aim and Objective: A novel amino acid ionic liquid was synthesized, characterized, and approved as an efficient and recyclable catalyst for synthesizing xanthenediones and DHPMs in water at reflux temperature. Materials and Methods: The ionic liquid was synthesized by a two-step method. In the first step, pyridine- N-sulfonic acid was prepared by the reaction of pyridine with chlorosulfonic acid. In the second step, the reaction of as-prepared ionic liquid with glycine in water afforded the desired amino acid ionic liquid. Then, the ionic liquid was fully characterized by FT-IR, ¹H NMR, ¹³C NMR, MS, TG/DTG, and Hammett acidity function. Results: We disclose a new strategy to incorporate glycine as the amino acid-based cation in the ionic liquid structure. The prepared IL exhibited remarkable catalytic activity in synthesizing xanthendiones and DHPMs in water at reflux temperature. Conclusion: We have developed a green and efficient amino acid ionic liquid to synthesize xanthenediones in water at reflux temperature. The advantage of this protocol is highlighted by the novelty of the ionic liquid, using H2O as the solvent, simple work-up, high yields, and short reaction times.

A two-step procedure was applied to couple zerumbone, a natural sesquiterpene, with thiols 8a-k to obtain a small library of ten novel zerumbone derivatives 9a-k with full-length library data of spectra including ¹H-, ¹³C-NMR, and HRMS. The tautomerization of 9a, 9b, and 9c was revealed in DMSO and discussed in the case of 9c. The series of 9a-k together with zerumbone 1 was evaluated for their in vitro cytotoxic activity using three human cancer cell lines, HepG2, A549 and HeLa. The results revealed that all zerumbone derivatives had cytotoxic activity against HepG2, A549, and HeLa cells that was 4-20 times stronger than zerumbone.

Aim: The study aims to optimize and synthesize benzimidazole derivatives. Background: Benzimidazoles are essential intermediates and scaffolds for biological activity and drug substances. The reported syntheses of benzimidazoles suffer from disadvantages like longer reaction time using a catalyst, which makes the method costly, and the use of strong corrosive acids and toxic reagents that increase environmental hazards. Objectives: One-pot synthesis of 2-aryl benzimidazole from ortho-phenylenediamine and aryl aldehyde. Method: Herein disclosed a catalyst-free, one-pot synthesis of 2-aryl benzimidazole. Results: Different 2-aryl benzimidazoles were synthesized in good yields via the condensation reaction of aryl aldehyde and ortho-phenylenediamine in acetonitrile as a solvent at room temperature. The method is very simple and convenient, with good yields. The formation of the desired product is affected by the substituent of aryl aldehydes. Electron donating substituents are shown to have a higher time in the completion of a reaction than electron-withdrawing substituents. Conclusion: One-pot synthesis of benzimidazole was found to be simpler and economical.

Aim: To synthesize and characterize organomercury complexes. Background: Organomercury complexes have reported for different antimicrobial activities. Objectives: Synthesis of organomercury complexes with piperidine thiohydrazide ligand and characterization, applications. Methods: Complexes were synthesized by modified reported methods. Spectral (IR, UV, 1HNMR) and TG/DTA analyses were used to characterize the generated complexes. For some of the complexes produced, chemical kinetic characteristics such as activation energy, order of reaction, heat of reaction, and apparent activation entropy were determined. The antimicrobial activities were also reported. Results: In these synthesized complexes, the thiohydrazides act as bidentate ligands, coordinating through the thiol Sulphur and terminal nitrogen. Elemental and spectral data of the ligand and complexes show that the compounds are pure enough. Conclusion: Every synthesized complex is diamagnetic in nature. The complexes have better antibacterial activities against Z. mobilis than E. coli, with A. niger > Cerveleria in case of antifungal activities.

Background: α-Glucosidase inhibitors have been found as the main tool for the treatment of type 2 diabetes. In this respect, the synthesis of a new series of amino-oxoethylcinnamamide derivatives containing α,β-unsaturated carbonyl-based moiety, was developed to be evaluated for their anti-α- Methods: The title compounds were synthesized via the Ugi reaction of cinnamic acid, isocyanides, aromatic aldehydes, and amine derivatives at ambient temperature. All newly synthesized derivatives were screened for their in vitro α-glucosidase inhibitory activity. Results: Among synthesized compounds, derivative 5b displayed promising anti-α-glucosidase activity (IC50 = 115.6 μM), approximately 6-fold more potent than the standard drug (acarbose, IC50 = 750.0 μM). Moreover, kinetic characterization of enzyme inhibition was performed to understand the mechanism of inhibition. To determine the mode of binding interactions of prepared compounds with the enzyme, molecular docking studies were also conducted. Conclusion: Ugi products merit to be investigated in anti-diabetic drug discovery developments.

Background: The methods of dehydration of alcohols frequently suffer from the following drawbacks: high reaction temperature, toxic catalysts, high catalyst loading, and difficulty to remove catalysts. Therefore, the development of a new catalyst for the dehydration of alcohols is still of importance. Methods: Graphite oxide is used as a catalyst for dehydration of alcohols. Results: Graphite oxide is used as a catalyst for dehydrating tertiary and secondary alcohols to the corresponding alkenes as well as dehydrating primary alcohols and diols to the corresponding ethers and cycloethers in moderate to excellent conversion rates and good selectivity. Conclusion: In these reactions, GO prepared by the improved Hummers method showed high catalytic activity. As an efficient catalyst, GO is easily available, cheap, weakly acidic with low toxicity, and well tolerant to various functional groups.

Background: In this study, the synthesis and characterization of a novel kind of NiO-supported CuO nanoparticles (CuO/NiO nanocatalyst), as an efficient and recyclable catalyst, were carried out. Methods: Nanocatalyst was characterized by XRD, BET, FESEM, EDS, HRTEM, TGA and DSC analysis. It was used in the three-component synthesis reaction between barbituric acid, malononitrile and various aromatic aldehydes for the synthesis of pyrano[2,3-d]pyrimidinone derivatives. Results: The advantages of using CuO/NiO nanocatalyst in this reaction are high yields of products, a decrease in the reaction times and easy separation of catalyst from the reaction mixture, and the reaction being performed in one-pot. Conclusion: The CuO/NiO nanocatalyst can be recycled for five consecutive cycles without significant degradation in its catalytic activity.

Aims: The development of a sensitive and visual analytical method for detecting and monitoring the change of pH has always attracted great interest because it plays a significant role in chemical reactions, environmental monitoring, and biological systems. Methods: In this paper, a simple condensation reaction from readily available substrates 2-hydroxy-1- naphthylaldehyde and malononitrile has been carried out to produce probe L with good aggregationinduced luminescence, and its chemical structure was confirmed by ¹H NMR, ¹³C NMR and ESI-MS. Objective: There is a conjugated system containing two electron-withdrawing cyano groups and an electron- donating hydroxyl group in probe L's molecular structure, exhibiting obvious fluorescence intensity and visible color change through intramolecular charge transfer (ICT) under different pH conditions. Results: Probe L assumes excellent fluorescence intensity in a DMF/H2O (1:9, v:v) mixed solvent system, and exhibits good reversibility in a very narrow range of pH values (pH = 12.5∼13). In addition, probe L can also selectively identify solvent DMSO by the induction of fluorescence quenching. Conclusion: Probe L can be used for the analysis and visual detection to pH change in DMF/H2O system, and it may also be used as the indicator for the detection and monitoring of trace amounts of DMSO.

Aims: Synthesis of dihydropyrimidinones derivatives. Background: carrying out reactions in the green route and organic solvent-free conditions. Objective: Regioselective Michael addition of dihydropyrimidinones to acrylic esters. Methods: The reaction proceeded in the presence of K2CO3/TBAB, a media of inorganic base K2CO3 and organic ionic salt TBAB (tetrabutylammonium bromide) at 100°C. Results: A series of new dihydropyrimidinone derivatives using aza-Michael addition reaction were synthesized under solvent-free conditions. Conclusion: The reaction is characterized by high efficiency, relatively short reaction time, high yields, simple environmentally friendly reaction conditions. Other: The reaction of acrylic esters with dihydropyrimidinones produced N3-substituted derivative of dihydropyrimidinones with 85-95% yields in 6 h.

Kadsura coccinea is a folk medicine from the family Schisandraceae. Clinically, it has been used to treat many diseases like chronic gastritis and rheumatoid arthritis (RA). Lignans and triterpenes are the main constituents of it. In this paper, phytochemical research on the root of K. coccinea was carried out, leading to the isolation of a previously undescribed 3,4-secolanostane (1). Its structure was established by means of comprehensive spectral analysis, including ECD calculation. Furthermore, bioactivity assay revealed that 1 could elicit a moderate immune-suppressive activity, showing an IC50 value of 8.32 ± 0.13 μM against ConA-induced T-cell proliferation and with IC50 value of 15.58 ± 0.25 μM against LPS-induced B-cell proliferation. The results indicate that 1 might be used in the treatment of rheumatic diseases.

Microbial transformation of β-caryophyllene (1) by suspended cell cultures of the plant pathogen fungus Aspergillus niger, resulted in the production of one major metabolite. This metabolite was identified as (3aR,11aS, E)-9-methyl-4-methylene-3a,4,7,10,11,11a-hexahydro-2H-furo[3,2- c]oxecine-2,6(3H)-dione (2), by different spectroscopic methods. Metabolite 2 was found to be a new compound. The proposed pathway for the synthesis of compound 2 was also explained.

A series of new spirothiadiazole oxindoles were synthesized by the reaction of 4-amino-5- mercapto-3-[(1H-indol-3-yl)methyl]-1,2,4-triazole and isatin derivatives. The reaction of spiro [indole] thiadiazoles with formaldehyde and piperidine afforded the corresponding Mannich bases. The structures of newly synthesized compounds were characterized by IR, 1D-NMR, 2D-NMR, and LC/MS spectral data.

Many therapeutically important nucleoside analogues can be synthesized from versatile azidonucleoside intermediates. We have synthesized 3’-xylo-azidonucleoside analogues of thymidine and 2’-deoxyadenosine via Mitsunobu-DPPA and triflate-lithium azide strategies. On comparing the two azidation strategies on nucleoside analogues, we found that Mitsunobu-DPPA azidation is better than triflate-lithium azide azidation in terms of yield and reaction conditions.

A concise and efficient synthesis of styryllactone derivative, goniothalesdiol A, has been achieved in the six longest linear steps with 17.7% overall yield. The key steps of our synthesis involved PdCl2-mediated Wacker-type oxidative cyclisation and one-pot tandem Wittig olefination- Michael addition.

A tandem system that enabled the synthesis of 2-substituted benzo[b]furans from 2- halophenols and aryl acetylenes catalyzed by Ni/5-bromo-2,2’-dipyridine was explored. The protocol was found effective for one-pot cascade coupling cyclization reaction producing benzo[b]furan compounds, and heteroaryl substrates were observed to be compatible for this system as well, giving corresponding products in 20-70% yields.