Letters in Organic Chemistry - Volume 19, Issue 9, 2022

A rapid and highly efficient methodology for the synthesis of 1, 2, 4-triazolidine-3-thiones derivatives has been developed in the presence of a catalytic amount of guanidine hydrochloride using water as a solvent. The reaction of thiosemicarbazide with different aryl aldehydes resulted in the formation of title compounds in good yields (85-95%) with a convenient reaction time (20-30 min). The key advantages of this approach include shorter reaction time, energy efficiency, easy work-up procedure, and wide substrate scope tolerance. Furthermore, the catalyst was recycled without significant loss of its catalytic activity.

Among the large variety of nitrogen and oxygen-containing heterocycles, 1,3,4- oxadiazole, the scaffold, has attracted considerable attention owing to its ability to show an extensive range of pharmacological actions. According to literature investigations, prepared 1,3,4- oxadiazole and its derivative are pharmacologically significant and consist of a variety of activities, such as anticonvulsant, anticancer, antioxidant, anti-inflammatory, antibacterial, antidiabetic, etc. These heterocyclics are formed mainly by the cyclization reactions of various reactants under diverse reaction circumstances. Therefore, significant efforts of organic chemists have been directed towards the synthesis of new drug candidates containing 1,3,4-oxadiazole subunits connected to an established potential pharmacophore to improve the efficacy and potency. This article aims to highlight recent publications on the various synthesis techniques of 1,3,4-oxadiazole and related compounds over the previous ten years (2011–2021). The purpose of this review is to help researchers by summarizing several synthetic strategies for synthesizing oxadiazole.

In this report, a hybrid terpyridine (tpy) ligand functionalize with magnetic support was synthesized to obtain well-dispersed Ru NPs with a 2.0±0.5 nm mean size. This material was further analyzed using different analytical techniques before utilizing it as a catalyst for the CO2 hydrogenation reaction. A noticeable application of Ru-deposited magnetic nanoparticles as catalysts was observed during the CO2 hydrogenation. We successfully synthesized the formic acid with a high TON value under high-pressure reaction conditions. Easy recovery of the catalyst under the applied magnetic field helped us to reuse the catalyst up to 6 times with good TON and TOV value.

The present study explores a new method for the fabrication of NaA nanozeolite as a simple and efficient catalyst for producing 3-aminoimidazo [1,2-a] pyridines via the 3-component reaction of aldehydes, 2-aminoperidines and isocyanides under solvent-free conditions. The production of the organic template-free (OTF) NaA nanozeolite was performed at room temperature. The prepared nanozeolite was identified by X-ray diffraction (XRD), Fourier Transform infrared spectroscopy (FT-IR), Field Emission Scanning Electronic Microscopy (FESEM), N2 sorption isotherm and Particle Size Analysis (PSA). The particle sizes of synthesized spherical NaA nanozeolite were under 100 nm via the FESEM method. BET surface area, total pore volume, and mean pore diameter of the created sample were attained to be 362 m²g^-1, 0.44 cm³ g^-1 and 5.9 nm, respectively. The developed method has some advantages, such as OTF production of NaA nanozeolite, a simple synthesis method with short reaction time and easy separation using filtration, and the ability to recycle and reuse the catalyst several times without reducing its efficiency.

Six macrocyclic Schiff bases bearing hydroxyethyl pendants have been synthesized in high yields via [2 + 2] condensation between the rigid dialdehydes and 2-[bis(2-aminoethyl)amino]ethanol or 1-[bis(2-aminoethyl)amino]-2-propanol at 0°C for 12 hours in the CH3CN/H2O mixture. Solubility discrepancies between macrocyclic products and raw materials in selected solvents enable a facile separation and high yields, avoiding any intractable chromatographic purification. This straightforward synthetic protocol provides a relatively facile resolution with potential widespread applications for the synthesis of Schiff bases.

The mechanism of metal-catalyzed spiroketalization of propargyl acetonide is explored by employing DFT with the B3LYP/6-31+G(d) method. Acetonide is used as a regioselective regulator in the formation of monounsaturated spiroketal. The energies of transition states, intermediates, reactants and products are calculated to provide new insight into the mechanism of the reaction. The energetic features, validation of the observed trends in regioselectivity are conferred in terms of electronic indices via FMO analysis. The presence of acetonide facilitates a stepwise spiroketalization as it masks the competing nucleophile, and thus hydroxyl group present exclusively acts as a nucleophile. The vinyl gold intermediate 3 is formed from 2 via activation barrier TS1. This is the first ring formation, which is 6-exo-dig cyclization. The intermediate 3 is converted into allenyl ether 4, which isomerizes to the intermediate oxocarbenium ion 5 via activation barrier TS2. The intermediate 5 cyclizes to 6 via TS3. This is the second ring formation. The intermediate 6 on protodeauration turns into 6,6-monounsaturated spiroketal 7. It is concluded that acetonide as a protecting group serves the purpose, and thus a wide range of spiroketals can be prepared regioselectivity.

Aims: This study aims to synthesize thiazolidine-4-one compounds with a pyrimidine nucleus and evaluate against different species of bacteria, fungi, protozoa, and the malaria parasite. Background: Microwave irradiation was the best method for synthesizing the thiazolidin-4-one ring system. It took only 15 minutes for synthesizing thiazolidin-4-one while the conventional method required 12 hours. The rapid reaction was the main concern of this research. Objective: Pyrimidine and Thiazolidin-4-one nucleus have broad-spectrum biological activity and when it is introduced with other hetero atoms containing moiety, many types of biological activities have been found; antimicrobial, anti-tuberculosis, anti-protozoa, antimalarial are the main activities. The activity of these compounds inspired us to do extra research on Thiazolidin-4-one fused pyrimidines with different functional groups. The aim of this study is to synthesize a combination of these two ring systems in less time by using a microwave irradiation method and to evaluate new compounds for different bioactivity. Methods: 2-(4-Chlorophenyl)-3-(4-(substituted phenyl)-6-(substituted aryl) pyrimidin-2-yl) thiazolidin- 4-ones (6A-J) were synthesized by microwave irradiation to save energy and time. The structure of all newly synthesized motifs was characterized by spectral analysis (¹H NMR, ¹³C NMR, IR, spectroscopy) and screened for antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pyogenes, antifungal activity against Candida albicans, Aspergillus niger, Aspergillus clavatus, anti-tuberculosis activity against M. tuberculosis H37RV, antimalarial activity against Plasmodium falciparum and anti-protozoa activity against L. mexicana and T. cruzi. Results: Because of microwave irradiation synthesis, time period is very less for preparing the new compound. Biological response given by compounds 6B, 6C, 6D, 6E, 6G, 6H, and 6J was found excellent. Conclusion: Good yield with purity of the newly synthesized thiazolidine-4-one compounds obtained in less time by using microwave irradiation. The biological response of some of the compounds of this series was found excellent.

The photochemical reaction of pyrylium cation with water to give a cyclopentene derivative has been studied at the DFT/B3LYP/6-31G+(d,p) level of theory. The calculation is in agreement with an electrocyclic disrotatory reaction from the S1 singlet excited state, giving a cyclopentene epoxide cation that can react with very low activation energy (2 kJ mol-1) with water to give the corresponding adduct. CASSCF calculations allowed to identify a conical intersection in the S1 state, giving the cyclopentene epoxide cation.

An environmentally benign, simple, rapid synthesis of 1,2,4-triazolidine-3-thiones at room temperature is reported using amino acid-derived Brønsted acidic ionic liquid L-proline nitrate [Pro+NO³ -] from aldehyde and thiosemicarbazide in an aqueous medium. A cost-effective and energy-efficient catalyst with the reusability of up to five cycles without significant loss in the catalytic activity makes this protocol superior. A faster reaction and easy work-up with excellent yields are the added advantages of this protocol.

The work describes a detailed account of the Lewis acid-catalyzed preparation of structurally variant alkoxymethyl halides. A series of Lewis acids with different halogenating agents are evaluated for the cleavage of bis-alkoxymethanes, where several readily available Lewis acids were found to exhibit high catalytic potential. SOCl2 with MgCl2 was found to be one of the best combinations for the facile and efficient preparation of structurally diverse alkoxymethyl halides under solvent-free conditions. The efficacy of the methodology was established to obtain a wide range of mixed acetals through alkoxymethylation of phosphorus, sulfur, nitrogen, and oxygen containing nucleophiles. The present procedure has significant advantages including simplicity, generality, rapidity, and availability of reagents.

X-ray crystal and Hirshfeld surface analyses of 2-hydroxy-7-methoxy-3-(2,4,6- trimethylbenzoyl)naphthalene and its 2-methoxylated homologue show quantitatively and visually distinct molecular contacts in crystals and minute differences in the weak intermolecular interactions. The title compound has a helical tubular packing, where molecules are piled in a two-folded head-to-tail fashion. The homologue has a tight zigzag molecular string lined up behind each other via nonclassical intermolecular hydrogen bonds between the carbonyl oxygen atom and the hydrogen atom of the naphthalene ring. The dnorm index obtained from the Hirshfeld surface analysis quantitatively demonstrates stronger molecular contacts in the homologue, an ethereal compound, than in the title compound, an alcohol, which is consistent with the higher melting temperature of the former than the latter. Stabilization through the significantly weak intermolecular nonclassical hydrogen bonding interactions in the homologue surpasses the stability imparted by the intramolecular C=O…H–O classical hydrogen bonds in the title compound. The classical hydrogen bond places the six-membered ring in the concave of the title molecule. The hydroxy group opposingly disturbs the molecular aggregation of the title compound, as demonstrated by the distorted H…H interactions covering the molecular surface, owing to the rigid molecular conformation. The position of effective interactions predominate over the strength of the classical/nonclassical hydrogen bonds in the two compounds.

A new, simple method for the synthesis of N,N-diethyl-m-methylbenzamide (DEET) from m-toluic acid and diethylamine using 1,1'-carbonyl-di-(1,2,4-triazole) (CDT) as a coupling agent has been performed. The basic principles of activated carbonyls have been explored with the ability to prepare new amides easily. All reaction by-products are water-soluble as well as removed by filtration, the reaction could be purified easily in an aqueous solution by liquid-liquid extraction, and the product DEET was high purity. This experimental efficiency is about 94-95%, purity (HPLC): 97-98%.

A new β-dihydroagarofuran-type sesquiterpenoid named 1α,2α,5α,11-tetraacetoxy-8α- (trans-p-coumaroyl)-β-dihydroagarofuran (1), together with five known compounds (2-6), was isolated from the CHCl3-soluble extract of the stems of Celastrus orbiculatus. The structure of the new compound was elucidated with spectroscopic physicochemical analyses. All isolates were evaluated for in vitro cytotoxic activity against four human cancer lines, including HepG2, MCF-7, A549, and HCT-116 cells. Among them, compounds 1 and 6 showed potent cytotoxic activities against HepG2 cells with IC50 values of 8.78 ± 2.31 and 10.28 ± 1.15 μM, respectively. In addition, compound 6 exhibited significant cytotoxic activity against HCT-116 cells with an IC50 value of 6.37 ± 2.52 μM.

Eugenol (4-allyl-2-methoxyphenol) is a natural phenolic compound present in certain aromatic plants; however, it is generally extracted from the essential oil of Eugenia caryophyllata (Syzygiumaromaticum) (L.) Merr. and L.M. Perry. This bioactive natural compound has generated considerable biological interest with well-known antimicrobial and antioxidant actions. This study aimed at evaluating eugenol derivatives as antimicrobial and antioxidant agents with the aid of molecular dynamic simulation. The starting material was extracted from cloves using hydrodistillation. Two eugenol derivatives, acetyleugenol (4-allyl-2-methoxyphenylacetate) and epoxyeugenol 4-(2,3- Epoxypropyl)-2-methoxyphenol, were prepared and tested against two strains Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The results have revealed that the three compounds (eugenol, acetyleugenol, and epoxyeugenol) possess important potentials for inhibition against E. coli and S. aureus. The antioxidant activity of eugenol derivatives was evaluated by reacting with DPPH (1,1- diphenyl-2-picrylhydrazyl), and it was reported that the epoxyeugenol was the most active compound. The molecular docking scores of three compounds and the amino acids in the active site pockets of the selected proteins of the two bacteria have approved and explained the biological experimental outcomes.

In-silico studies are used for the prediction of the properties of several novel materials using the computer simulation technique. The present study describes the complete description of the molecular vibrations and electronic features of the title compound by this technique. 7-(4-nitrophenyl)benzo[6, 7]chromeno[3,2-e]pyrido[1,2-a]pyrimidin-6(7H)-one was prepared by the multicomponent reaction of 2H-pyrido[1,2-a]pyrimidine-2,4(3H)-dione, 2-naphthol and p-nitrobenzaldehyde. The structure of the compound was confirmed by UV, IR, NMR (¹H, ¹³C), and mass spectroscopic studies. The compound was further subjected to quantum chemical calculations at the level of Hartree-Fock (HF) method using Lan2DZ basis set to compute polarizability, hyperpolarizabilities, AIM approach, Natural bond orbital analysis, complete vibrational assignments, Mulliken charges, spectral analysis and HOMO-LUMO energies.

1,5-Disubstituted tetrazoles are vital drug-like scaffolds usually encountered as valuable bioisosteres of the cis-amide bond. In this article, we reported the synthesis of some novel medicinally relevant pyrazole centered 1,5-disubstituted tetrazoles using ultrasound irradiation via a one-pot 4-C reaction from various pyrazole originated aldehyde, amine, isocyanide, and sodium azide. All the synthesized derivatives were characterized by IR, ¹H NMR, ¹³C NMR, spectroscopic techniques, and mass analysis. This ultrasound-assisted green protocol has several advantages like mild reaction condition, high yield, catalyst and solvent-free reaction protocol, 15 minutes reaction time and easy workup.

Aims: This work aims to widen the scope of methodologies to prepare functionalized N-alkenylcarbazates. Background: Alkenylcarbazates are generally prepared via Aza-Baylis-Hillman reactions, nucleophilic attack on ketones or a tandem carbometallation/amidation reaction of alkynes. Objective: The objective of this work is to develop a method to prepare functionalized Nalkenylcarbazates that alleviates the problem encountered in the above methods (use of electron deficient alkenes, use of stoiechiometric amounts of metal, access to symmetrical dicarbazates only). Methods: Use of copper-catalyzed cross-coupling between vinylic diiodide and carbazates to prepare functionalized N-alkenylcarbazates. Results: Various β-iodovinylcarbazates were synthesized with up to good yields. The highest yields were obtained using dicarbazates. Functionalization of β-iodovinylcarbazate demonstrated that the vinyl iodide moiety of these molecules can be substituted by a variety of functional groups via transition metal-catalyzed coupling reactions. Conclusion: Copper-catalyzed cross-coupling reaction is efficient to prepare functionalized N-alkenylcarbazates.