Current Organic Synthesis - Online First

In this study, using a novel design and readily available starting materials, various quinoline derivatives were synthesized by replacing imidates and amidines. Additionally, in heterocyclic chemistry, a four-component reaction involving alkynes, isatoic anhydride, trichloroacetonitrile, and various amines or alcohols yielded 4-hydroxy-quinoline-3-carboximidamide (imidate) with satisfactory efficiency. Using an inexpensive copper(I) catalyst, DMF as the solvent, and ultrasonic conditions for 40 minutes, the synthesis and characterization of new compounds can be achieved without the need for ligands or oxidants. The combination of readily available starting materials, mild reaction conditions, catalytic systems, and simple purification procedures facilitates the synthesis of a diverse range of substituted 4-hydroxy-quinoline derivatives, including those containing amidine and imidate skeletons.

In this study, isatoic anhydride was employed to trap the triple bond. A copper-catalyzed reaction of alkynes, isatoic anhydride, trichloroacetonitrile, and various amines or alcohols was carried out to synthesize substituted quinoline derivatives containing amidine and imidate skeletons, as illustrated in Scheme 1. In this reaction, isatoic anhydride, at 80°C in DMF, released carbon dioxide to generate an active intermediate. This intermediate reacted with the triple bond of the compound formed from the terminal alkyne and the amidine derivative through a [4+2] cycloaddition to produce the desired quinoline product. The advantages of this method include its simplicity and safety, the use of inexpensive materials and catalysts, ultrasonic-assisted reaction conditions that improve efficiency and speed, and good yields (72-93%). This approach is, therefore, highly attractive for the synthesis of substituted quinoline derivatives. In this study, new quinolines containing amidine and imidate skeletons were synthesized with potential for further biological evaluation.

To start the synthesis of compound 5a, the required starting materials, including aniline 2a, phenylacetylene 3a, trichloroacetonitrile 1, and isatoic anhydride 4, were selected. In the next step, the reaction conditions were optimized by changing the catalyst and different solvents. Among the copper catalysts investigated, CuI gave satisfactory results. Among the solvents, DMF was also the solvent of choice. Finally, the reaction was carried out in DMF using (0.019 g) 10 mol% CuI as catalyst, (0.100 g) 1.0 mmol Et3N as base, (0.142 g) 1.0 mmol of trichloroacetonitrile, (0.093 g) 1.0 mmol of aniline, and (0.163 g) 1.0 mmol of isatoic anhydride under ultrasonic irradiation at a power of 60 W.

The structure of all the synthesized compounds (5a-m) was determined by mass spectral data, IR, ¹H-NMR, and ¹³C-NMR. For example, the mass spectrum of 5a showed a molecular ion peak at m/z = 339. The ¹H-NMR spectrum of 5a showed three singlets for the OH (δ = 8.13 ppm) and two NH (δ = 5.03 and 5.96 ppm) groups with confirmed multiplets for the phenyl protons. The ¹³C-NMR spectrum of 5a exhibited 17 signals in agreement with the proposed structure. The NMR spectra of the rest of the compounds were found to be similar to 5a due to the different substitutions on the ring.

In this study, a new protocol was used to synthesize a variety of 4-hydroxy-quinoline-3-carboxyimidamides (imidates) using alkynes, isatoic anhydride, trichloroacetonitrile, and various amines or alcohols in the presence of available copper(I) iodide catalyst, under ultrasonic conditions for 40 minutes at room temperature in DMF solvent to prepare various quinolines with substituted imidate and amidine derivatives. The combination of readily available starting materials, efficient catalysis by the copper catalyst, mild reaction conditions, the use of ultrasonic conditions to improve reaction speed and efficiency, and ease of purification collectively contributes to the high yields of the synthesized compounds. Using this method, 13 new quinoline-based compounds, including those with amidine and imidate skeletons, with potential for biological evaluation, were synthesized.

In this study, novel 1-(3-cyano-4,6-dimethyl-2-oxopyridin-1(2H)-yl)-3-phenylthiourea 2, 3-phenylthiazolidin-4-one 3, and arylidene-4-thiazolidinone derivatives 5a-k were synthesized in excellent yields. The produced compounds underwent assessment for their antimicrobial properties. Efficient and easy procedures for synthesizing arylidene-4-thiazolidinones 5a-k were delineated.

3-phenylthiazolidin-4-one 3 was achieved by reacting 1-(3-cyano-4,6-dimethyl-2-oxopyridin-1(2H)-yl)-3-phenylthiourea 2 with ethyl 2-bromoacetate in EtOH, employing anhydrous sodium acetate at reflux temperature. Furthermore, a sequence of arylidene-4-thiazolidinone derivatives 5a-k was synthesized by condensing 4-thiazolidinone 3 with different aromatic and heterocyclic aldehydes in a refluxing EtOH-containing piperidine. The binding mechanism of the thiazolidine derivatives to the dihydrofolate reductase (DHFR) and rhomboid protease proteins was determined by docking studies.

Compounds 2, 5c, 5d, 5g, and 5i exhibited germicidal effects against both Gram-negative and Gram-positive bacteria. Furthermore, these compounds exhibited antifungal properties. The MIC ranged from 250 to below 500 μg/mL. The docking study revealed a strong correlation between the docking solutions and the experimental observations.

The structure of new compounds was identified by analytical and spectroscopic data. Certain thiazolidines showed exceptional antibacterial and antifungal properties. These interactions require more investigations that are comprehensive

8-Hydroxyquinoline derivatives are compounds isolated from plants that possess a wide range of pharmacological activities. In our previous work, a series of novel 8-hydroxyquinoline derivatives was synthesized. Among them, the compound 5c, 7-((4-(o-tolyl) piperazine-1-yl) methyl)-5-nitroquinolin-8-ol, demonstrated broad-spectrum antifungal activity against five plant pathogenic fungi with EC50 values ranging from 4.69 to 12.61 μg/mL.

This investigation principally focused on determining the potential mechanisms of compound 5c using Botrytis cinerea (B. cinerea) as a model.

The electron microscope observations revealed that after being treated with compound 5c at 5 μg/mL, the mycelia became obviously curved, collapsed, and its integrity of the cell membrane was eventually destroyed.

The compound 5c influenced the production of reactive oxygen species, loss of mitochondrial membrane potential, and nuclear morphology. In addition, compound 5c inhibited the enzyme activities related to mitochondrial function.

These findings will deepen our insights into the mechanisms of action of 8-hydroxyquinoline against B. cinerea and open new directions for the future development of effective antifungal agents to control phytopathogenic fungi.

Soil sample pretreatment is a critical step in soil analysis, often involving complex processes and the use of organic solvents, which can lead to environmental pollution and inefficiency. In this regard, traditional methods are time-consuming and prone to human error, rendering them unsuitable for large-scale soil surveys. To address these challenges, this study proposes a novel rapid soil pretreatment method employing a device that integrates ultrasonic extraction with pure water and capillary electrophoresis using capacitively coupled contactless conductivity detection (CE-C4D). This study aims to enhance the efficiency and accuracy of soil nutrient analysis while minimizing environmental impact.

Ultrasonic extraction using pure water as a solvent, combined with CE-C4D detection, was employed for rapid and efficient analysis of soil nutrients, particularly potassium and phosphorus. Parameters influencing ultrasonic extraction, including frequency, treatment time, and the relationship between solution factors and cavitation yield, were optimized through both simulations and experiments. Cavitation yield was assessed using iodine release, conductivity measurement, and fluorescence analysis. Additionally, the sound pressure distribution within the extraction tube was simulated, and temperature changes during ultrasonic treatment were monitored. The pretreatment device and detection method were validated using standard soil samples.

The optimal ultrasonic extraction parameters were identified as a frequency of 1.7 MHz and a treatment time of 10 minutes, resulting in the most effective cavitation yield. The use of pure water as a solvent improved both the efficiency of soil pretreatment and the environmental sustainability of the process. The CE-C4D system successfully detected available potassium and phosphorus in standard soil samples with high accuracy, showing trends consistent with standard values and relative standard deviations (RSD, n=4) of less than 5%. Blind tests on soil samples also demonstrated minimal error, with RSD (n=4) below 4%.

This study presents a portable and efficient ultrasonic extraction device for soil pretreatment coupled with a custom-designed CE-C4D detector for the rapid analysis of available potassium and phosphorus. The use of pure water as a solvent significantly reduces environmental impact, simplifies the process, and enhances testing efficiency, reducing the required testing time from 15-20 days to within 30 minutes. This innovation provides a reliable solution for on-site soil analysis, offering potential applications in large-scale soil surveys and routine soil testing.

This study aimed to synthesize a series of new 3-(halophenyl)-1-phenyl-1H-pyrazole moieties and survey the antitumor properties of these compounds.

3-(halophenyl)-1-phenyl-1H-pyrazoles (4a-j) were prepared by reaction of phenyl hydrazine (3) with different halogen aromatic aldehydes 1a-j and malononitrile (2) in C2H5OH and piperidine. The reaction took place under microwave irradiation settings for two minutes at140°C.

Three human cancer cell lines were used as in vitro test subjects for compounds 4a - j. Three cell lines from mammals HeLa (a cell line for human cervical cancer), MCF-7 (a cell line for human breast cancer), and PC-3 (a cell line for human prostate cancer), all with 5-fluorouracil as the standard reference drug were used.

A series of novel 3-(halophenyl)-1-phenyl-1H-pyrazoles were synthesized in this work. All substances had their anticancer properties assessed.