Current Organic Synthesis - Volume 18, Issue 6, 2021

This review article summarizes the applications of nickel(II) compounds in organic synthesis since 2016. In recent years, the field of nickel(II) catalysis is gaining considerable interest due to readily available, low-cost nickel(II)-compounds and several key properties of nickel. This review article is organized by the reaction type, although some reactions can be placed in multiple sections.

The subclass of compounds that have the nucleus 1, 4-naphthoquinone is the most diverse class of quinones, which have a large number of substances and have useful applications ranging from medicinal chemistry to application in materials with special properties. The introduction of one or two substituents with the sulfur heteroatom in the naphthoquinone nucleus generates products containing alkyl and aryl groups that amplify certain biological properties against bacteria, viruses, and fungi. There are several methods of preparing these compounds, mainly from low molecular weight naphthoquinones with two electrophilic sites capable of reacting with sulfides generating diversity and new classes of compounds, including new sulfur heterocycles and sulfur heterocycles fused with naphthoquinones. These compounds have been shown to be bioactive against several biological targets. This review will describe the methods of their synthesis and, when applicable, their biological activities.

Pyrazolopyrimidines are a privileged class of 5-6 bicyclic systems with three or four nitrogen atoms, including four possible isomeric structures. The significance of this class of compounds is that they can be applied in medical and pharmaceutical fields due to their unlimited biological aptitude, hence it is the basic skeleton of several synthetic drugs. The current review aimed to highlight all the synthetic routes that have been applied to construct the pyrazolo[1,5-a]pyrimidine ring systems up to date. The sections in this study included the synthesis of pyrazolo[1,5- a]pyrimidines by condensation reactions of 5-aminopyrazoles with each of β-diketones, 1,5-diketones, β- ketoaldehydes, α-cyanoaldehydes, β-enaminones, enamines, enaminonitriles, ethers, with unsaturated ketones, unsaturated thiones, unsaturated esters, unsaturated dienones “1,2-allenic”, unsaturated aldehydes, unsaturated imines, and unsaturated nitriles. The routes adopted to synthesize this class of heterocyclic compounds were extended for ring construction from acyclic reagents and multicomponent reactions under catalytic or catalyst-free conditions.

Background: Paclitaxel, a natural diterpenoid compound, has anti-tumor effect by acting on tubulin, whereas coumarin, another kind of natural product, has anti-tumor effect, along with some other effects, such as anti-bacterial-., Moreover, it also possesses fluorescence. Objective: Multi targeting is an effective strategy in drug design to combat tumor. Therefore, a combination of paclitaxel with other active molecular drugs for exploring the novel lead with multi-functions is in demand. Materials and Methods: To synthsize paclitaxel-coumarin conjugate via click chemistry and to investigate anticancer activity by MTT assay and the scratch test. Results and Discussion: The results of MTT assay showed that compared tothe paclitaxel, the anti-tumor activity of the conjugate was significantly improved. The results of flow cytometry showed that the conjugate had a stronger ability to induce apoptosis. The scratch test results showed that the conjugate had better anti- metastasis ability than paclitaxel. Conclusion: These findings indicated that paclitaxel and coumarin had a synergistic effect, which paved the way for the development of paclitaxel through fluorescence.

Aims: The aim of the present research was to synthesize glycoluril derivative 2,4-Bis(4- cyanobenzyl)glycoluril through a convergent scheme. Background: For this purpose, Sandmeyer reaction procedure was employed for the synthesis of said compound. The structure of the pure compound was confirmed by using different spectroscopic techniques, such as 1HNMR, 13C-NMR and (HR-MS) Mass spectrometry. Objective: Convergent synthesis of 2,4-BIS (4-CYANOBENZYL)GLYCOLURIL USING SANDMEYER REACTION and urease inhibition study. Methods: The structure of the pure compound was confirmed by using different spectroscopic techniques such as 1H-NMR, 13C-NMR and (HR-MS) Mass spectrometry. The electronic properties of the newly synthesized compound and thiourea were determined by using density functional theory. Results: Furthermore, the compound was evaluated against urease enzyme and was found to be potent inhibitors with an IC50 value of 11.5 ± 1.50 μM when compared with standard inhibitor thiourea (IC50 = 21.0 ± 1.90 μM). The compound may serve as a lead compound to synthesize new cyano-based bambusuril in the future with enhanced biological properties. Conclusion: We have synthesized a new glycoluril derivative 2,4-Bis(4-cyanobenzyl)glycoluril by the sandmeyer reaction. It has been obtained in the form of light yellowish powder in good yield (96%). Glycoluril based macrocycles have been used in various fields; starting from the 2,4-Bis(4-nitrobenzyl)glycoluril (already reported compound), which has undergone reduction (CH3OH,Pt/C) , diazotization (NaNO2/HCl), cyanation (CuCl/KCN), respectively in order to synthesize the desired new glycoluril derivative. The obtained product will be used as a building block for the synthesis of the cyano based bambusuril marcocycle in the future. The yield of the obtained product has been monitored by using different amounts of cyanating reagent, but the best results are shown by the use of 4 mmol of CuCl/KCN. KCN with CuCl assisted the conversion of diazo group into the cyano group with enhanced yield when used in excess amount. It acts as a catalyst. The solubility characteristic of 2,4-Bis(4-cyanobenzyl)glycoluril has also been determined in different organic solvents. 1H NMR technique proved to be very helpful for the structure determination of our desired product. Benzylic protons give signals at 7.5 ppm and 7.8 ppm, respectively. The downfield peaks confirm the presence of CN group near the benzylic protons. Methine protons show a signal at 5.2 ppm, which ensures the basic skeleton of glycoluril. Ureidyl protons also confirm the synthesis of the heterocyclic 2,4-Bis(4-cyanobenzyl)glycoluril compound. The negative and positive electrostatic potential sites, molecular descriptors, and charge density distribution of frontier molecular orbitals are revealing that 4a with promising sites for electrophilic and nucleophilic attacks would result to enhance the urease inhibition, which is in good agreement with the experimental data.

Aims and Objective: The main objective of the kinetic investigation of the reaction between ethyl acetoacetate 1, ammoniumacetat 2, dimedone 3, and diverse substitutions of benzaldehyde 4-X, (X= H, NO2, CN, CF3, Cl, CH (CH3)2, CH3, OCH3, OCH3, and OH) for generating 4-substituted 1, 4-dihydropyridine derivatives (product 5) was to recognize the most realistic reaction mechanism. The layout of the reaction mechanism was studied kinetically via a UV-visible spectrophotometry approach. Materials and Methods: Among the various mechanisms, only mechanism1 (path1) involving 12 steps was recognized as a dominant mechanism (path1). Herein, the reactions between 1 and 2 (kobs= 814.04 M^-1.min^-1) and also between 3 and 4-H (kobs= 151.18 M^-1.min^-1) can be accepted as the first and second steps (step1 and step2) of the reaction mechanism, respectively. Amongst all steps, only step9 of the dominant mechanism (path1) comprised substituent groups (X) near the reaction center. Results and Discussion: Para electron-withdrawing or donating groups on the compound 4-X increased the rate of the reaction 4 times more or decreased 8.7 times less than the benzaldehyde alone. So, this step is sensitive for monitoring any small or huge changes in the reaction rate. Accordingly, step9 is the rate-determining step of the reaction mechanism (path1). Conclusion: The recent result is in agreement with the Hammett description of an excellent dual substituent factor (r = 0.990) and positive value of reaction constant (ρ= +0.9502), which confirms that both the resonance and inductive effects “altogether” contribute to the reaction center of step9 in the dominant mechanism (path1).