Letters in Organic Chemistry - Online First

An easy and efficient procedure was developed for the synthesis of isoxazole derivatives in good to excellent yields (53–85%) via the reaction of substituted β-chloroacrylonitrile under classical and microwave conditions. The synthesized compounds were evaluated in vitro and in silico for their antibacterial activity against E. coli, B. subtilis, S. aureus, and P. aeruginosa. Antibacterial screening revealed that compound 3a exhibited the strongest inhibition against E. coli and B. subtilis (MICs 12.5 and 25 µg/mL, respectively), while compound 3c showed the highest activity against P. aeruginosa (MIC 50-100 µg/mL). Molecular docking studies confirmed these results, showing more favorable binding energies (–8.4 to –9.0 kcal/mol for compounds 3a–3c) compared to gentamicin (–5.0 to –6.4 kcal/mol). The docking targets included β-lactamase (1BTL), penicillin-binding protein (1DQ9), tyrosyl-tRNA synthetase (8H1B), and outer membrane protein OprM (2UV0). This combined in vitro and in silico evaluation has highlighted compounds 3a, 3b, and 3c as the most promising antibacterial agents, with strong binding affinities and significant inhibitory effects against pathogenic bacteria.

N-(1-Phenylethyl)maleimide derivatives are valuable intermediates for the synthesis of complex organic molecules, including chiral building blocks for asymmetric synthesis. Traditional synthetic methods often involve hazardous solvents, limiting their environmental compatibility and industrial applicability. The aim of this study was to develop a sustainable, efficient, and solvent-free synthetic protocol for the preparation of both chiral and achiral N-(1-phenylethyl)maleimide derivatives. This was followed by separation and analysis using chiral High-Performance Liquid Chromatography. An efficient, solvent-free methodology was employed to synthesize N-(1-phenylethyl)maleimide derivatives. The resulting chiral compounds were separated enantiomerically by chiral chromatography to obtain optically pure enantiomers. All products were characterized to confirm purity and enantiomeric excess. The solvent-free protocol enabled the synthesis of both chiral and achiral N-(1-phenylethyl)maleimide derivatives in high yields and purity. The enantiomeric resolution technique provided efficient isolation of optically pure chiral compounds. The approach demonstrated significant improvements in sustainability, operational simplicity, and scalability. This environmentally benign, solvent-free synthesis offers a practical alternative for the production and isolation of N-(1-phenylethyl)maleimide derivatives. The protocol enhances the sustainability and practicality of accessing the chiral intermediate for further synthetic applications.

The peach fruit moth is a significant pest of fruit crops. The primary component of its sex pheromone is (Z7)-eicosene-11-one (Z7-20-11kt). Using ethyl 4-bromobutyrate as the starting material, a Wittig reaction was conducted to synthesize ethyl (Z7)-undecenoate. This intermediate was subsequently hydrolyzed and acylated to yield (Z7)-undecenoyl chloride, which was then coupled with N,O-dimethylhydroxylamine to form the Weinreb amide 6. Finally, 6 was reacted with nonylmagnesium bromide to afford the target product Z7-20-11kt. The novelty of this synthetic route lies in the reductive addition of the Weinreb amide to a nonyl Grignard reagent to construct the ketone carbonyl group. This method utilizes relatively low-cost starting materials, achieves an overall yield of 35%, and has been successfully scaled up to kilogram-scale production. Field trials confirmed that the synthesized Z7-20-11kt exhibits a potent trapping effect against the target pest.

Heterocycles containing nitrogen, especially pyrazole derivatives, have garnered significant interest because of their notable biological activity and structural diversity. Pyrazole, a five-membered heterocyclic ring containing two nitrogen atoms, has become a key building block in the design of bioactive compounds with applications across various fields, including drug discovery, medicinal chemistry, agrochemistry, organometallic chemistry, and coordination chemistry. The diverse biological activities of pyrazole derivatives, such as antibacterial, anti-inflammatory, anticancer, analgesic, anticonvulsant, anthelmintic, antioxidant, and herbicidal activities, make them highly sought after for the development of therapeutic agents and agrochemicals. However, conventional methods for synthesizing pyrazoles often require harsh reaction conditions, such as toxic solvents, high temperatures, high pressures, and long reaction times. These processes not only pose safety risks but also lead to increased energy consumption, higher costs, and less environmentally friendly practices. With an emphasis on safer, more effective, and time-saving techniques, this review seeks to offer insights into more sustainable methods for preparing these valuable heterocyclic compounds that reduce the need for such harsh conditions. This review offers a possible solution to the problems associated with conventional synthesis.

Benzotriazole-mediated thiophene-3,4-imido-L-amino acid esters (L-phenylalanine methyl ester, L-tyrosine methyl ester, and L-aspartic acid methyl ester) were synthesised from thiophene-3,4-dicarboxylic acid via thiophene-3,4-anhydride to model the reactions of aromatic, phenolic, and polar amino acids, respectively. In synthetic studies, L-amino acids were first reacted with thiophene-3,4-anhydride to produce thiophene intermediates with a carboxylic acid group in the 3-position and an amide group in the 4-position. These intermediates' carboxylic acid functions were then activated using the N-acylbenzotriazole method. This resulted in an in situ cyclisation reaction that was distinct from conventional N-acylbenzotriazole reactions. This reaction formed the target products -thiophene-3,4-imido-L-amino acid esters- in good yields. The electrochemical properties of the thiophene-3,4-imido amino acid ester derivatives, which are free from the 2,5-position of thiophene, were investigated. The structures of thiophene-3,4-imido amino acid esters were examined using ¹H and ¹³C NMR spectroscopy.

Thiazole, a five-membered heterocyclic compound containing sulfur and nitrogen, is widely used in medicinal chemistry. Its fundamental structure is found in many physiologically active chemicals with antibacterial, anticancer, anti-inflammatory, and antidiabetic properties. Thiazole compounds with interesting medicinal value have been thoroughly investigated for their potential as therapeutics. Due to its varied reactivity, thiazole is a significant building block for chemical synthesis, and its derivatives show attractive pharmacological properties. Still, lots of modifications are required in the thiazole derivatives to enhance their potential. The main goal of this review is to investigate several synthesis methods for thiazole and its derivatives, as well as their pharmacological characteristics. This review summarizes the ever-expanding body of chemical knowledge and has significant implications for drug development. A systematic literature search was conducted across major databases, including Google Scholar, ScienceDirect, PubMed, Scopus, Springer, and Web of Science, using keywords related to thiazole derivatives. It involves a systematic literature review, critical analysis, and synthesis of existing research. This review thoroughly discusses the various synthetic approaches and their potential, which will be useful to the drug discovery community and facilitate the synthesis and development of novel, potent thiazole derivatives that may serve as lead molecules for the treatment of various diseases.

A novel electrochemical iodocyclization of N-alkylated alkenyl ureas has been developed, offering a direct and sustainable route to iodinated imidazolidin-2-ones. The method utilizes in situ electrooxidation of potassium iodide (KI) to generate active iodine species, eliminating the need for catalysts or external oxidants. Reactions proceed under mild conditions (room temperature, methanol) and exhibit broad substrate scope, tolerating various aryl substituents. Moderate to good yields (up to 72%) have been achieved. Mechanistic studies, including radical trapping and cyclic voltammetry, suggest a cationic pathway initiated by anodic iodide oxidation. Compared to traditional harsh methods, this electrochemical approach provides a greener, operationally simple synthesis of these privileged heterocycles.

For the first time in this paper, the effect of organic dyes on the thermal conductivity of polyvinyl alcohol (PVA) films was studied. This is crucial for the development of thermostable PVA films, which are utilized in various engineering and technological fields, including optoelectronics, mechanical engineering, space exploration, medicine, and others. In the course of the work, it was revealed that oriented PVA films are characterized by the phenomenon of anisotropy of thermal conduction (ηλ), which is manifested in the fact that thermal conductivity in the direction of orientation (λ||) is higher than in the direction perpendicular to the orientation (λ⊥). Unstretched and stretched PVA films do not have significant thermal conductivity anisotropy. Colored stretched PVA films have anisotropy of thermal conductivity. The factor that causes anisotropy of thermal conduction is an organic dye.

This study reports a rapid and efficient method for the synthesis of the novel substituted sulfonyl-imino-amidine (or imidate) compounds from the copper-catalyzed [3+2] azide-alkyne cyclization (CuAAC) reaction with isocyanides and amines or alcohols under ultrasonic conditions. Considering the extensive utility of N-sulfonylketenimine in the synthesis of new organic compounds, this study explored the use of different isocyanides with diverse electron-donating groups and aliphatic and aromatic alcohols or amines to trap the N-sulfonylketenimine intermediates prepared from copper acetylide and sulfonyl azides under mild conditions. The reactions were investigated with different copper (I) catalysts and various solvents. Finally, experimental results confirmed that the best catalyst for carrying out the reaction with the most suitable efficiency and rate is copper iodide, and the most suitable solvent is THF. It is noteworthy that this study provides the first examples of sulfonyl-imino-amidines (or imidates). Performing the reaction under ultrasonic conditions improves the yield of products and the reaction rate. Among the advantages of this method are a single-step reaction, the use of a cheap copper iodide catalyst with readily available starting materials, short reaction time under ultrasonic conditions as an energy source, and easy purification of the products in good yield. IR, Mass, ¹H, and ¹³C NMR spectroscopy methods were used to identify the synthesized products. Finally, 11 new compounds from the sulfonyl-imino-amidine (or imidate) family were synthesized and identified with desirable yields. The synthesized products contain a variety of functional groups, including sulfonimine, amidine, and imidate, which have the potential to undergo diverse biological evaluations.