Current Organic Synthesis - Volume 18, Issue 5, 2021

A series of N, P-ligands bearing carboxyl groups have been synthesized. These have been applied in conjunction with cobalt naphthenate in a facile, economic, and efficient method for the catalytic hydrosilylation of alkenes. In the presence of KO^tBu as an additive, the reaction time and activation energy are greatly reduced.

Background: Hexahydro-2H-pyrano[3,2-c]quinolines are known to have antibacterial, antifungal, and antitumor properties. Great efforts have been made to develop new synthetic methods that lead to the synthesis of valuable libraries. Extensive methodologies, low yields, excessive amounts of catalyst and expensive reactants are some of the limitations of current methodologies. Aims and Objective: Developing a useful and efficient method to construct diversely substituted hexahydro-2Hpyrano[ 3,2-c]quinolines into good to excellent yields through a cationic imino-Diels-Alder/N-debenzylation methodology. Method: The cationic imino-Diels-Alder/N-debenzylation methodology was used for the preparation of substituted hexahydro-2H-pyrano[3,2-c]quinolines. It involves the use of Sc(OTf)3 for activation of cationic imino- Diels-Alder cycloaddition reaction of N-benzylanilines, 3,4-dihydro-2H-pyran and paraformaldehyde in MeCN; and microwave irradiation to shorten reaction time to afford new 6-benzyl-hexahydro-2H-pyrano[3,2- c]quinolines whose catalytic transfer debenzylation reactions with HCO2NH4 in the presence of Pd/C (10%) and methanol give the new 5-unsubstituted pyrano[3,2-c]quinolines in excellent yields. Results: We found that optimal conditions for the preparation of hexahydro-2H-pyrano[3,2-c]quinolines were Sc(OTf)3 0.5 % and acetonitrile at 160°C for 15 min; and using paraformaldehyde obtained the 6-benzylhexahydro- 2H-pyrano [3,2-c]quinolines with excellent yields, while the N-debenzylation process using ammonium formate in the presence of Pd/C and methanol resulted in the synthesis of hexahydro-2H-pyrano [3,2-c] quinolines with quantitative yields (95-98%). Conclusion: We describe an efficient method to synthesize hexahydro-2H-pyrano[3,2-c]quinolines via the cationic imino-Diels-Alder/N-debenzylation methodology using Sc(OTf)3 0.5 % as Lewis Acid catalyst. Excellent yields of the products, use of MW irradiation, short times of reactions, and an efficient and highly diversified method are some of the main advantages of this new protocol.

Iso-octenidine, an isomer of octenidine dihydrochloride, was synthesized and studied for the first time. Iso-octenidine was demonstrated to be 3-fold more soluble in water in comparison to original octenidine, and both substances had remarkably similar antibacterial activity (tested on Escherichia Coli and Micrococcus luteus).

Oxabenzonorbornadiene (OBD) is a useful synthetic intermediate, which can be readily activated by transition metal complexes with great face selectivity due to its dual-faced nature and intrinsic angle strain on the alkene. To date, the understanding of transition-metal catalyzed reactions of OBD itself has burgeoned; however, this has not been the case for unsymmetrical OBDs. Throughout the development of these reactions, the nature of C1-substituent has proven to have a profound effect on both the reactivity and selectivity of the outcome of the reaction. Upon substitution, different modes of reactivity arise, contributing to the possibility of multiple stereo-, regio-, and in extreme cases, constitutional isomers, which can provide unique means of constructing a variety of synthetically useful cyclic frameworks. To maximize selectivity, an understanding of bridgehead substituent effects is crucial. To that end, this review outlines hitherto reported examples of bridgehead substituent effects on the chemistry of unsymmetrical C1-substituted OBDs.

Aims: Novel bi metal organic framework (b–MOF) is synthesized and used as a heterogeneous catalyst for the synthesis of chromeno[4, 3–b]quinolone derivatives via one-pot and solvent-free, four-component reaction of dimedone, aromatic aldehydes, 4–hydroxycoumarin and ammonium acetate at 110°C. Background: b–MOFs can be used as a heterogeneous catalyst in the synthesis of many organic compounds. The active and multi-purpose sites in b–MOFs provide a varied function in their catalytic applications. In this paper, reductive CES method is applied for the synthesis of Ce0.47/Ni0.53–BTC b–MOF. The resulting b–MOF was used as a heterogeneous catalyst for the synthesis of chromeno[4, 3–b]quinolone via one-pot and solvent-free, fourcomponent reaction of dimedone, aromatic aldehyde, 4–hydroxycoumarin and ammonium acetate at 110 °C. Method: Ce0.47/Ni0.53–BTC was synthesized in an electrochemical cell composed of a stainless steel foil with a size of 5cm×5cm centered between two 5cm×5cm sized graphite plates as the anodes by the cathodic current density of 0.2 A/dm² and placed in a solution of cerium nitrate (0.3 g), nickel nitrate (0.3 g), H3BTC (0.2 g) and NaNO3 (0.1 g) in ethanol (500 mL). Ce0.47/Ni0.53–BTC (10 mg) was added to a mixture of dimedone (1 mmol), aromatic aldehyde (1 mmol), hydroxycoumarin (1 mmol) and ammonium acetate (1.5 mmol) and stirred at 110 °C under solvent-free conditions for 45 min. The reaction evolution was controlled by the TLC (hexane:ethyl acetate, 4:1). Then, boiling ethanol was added to the reaction mixture and stirred at room temperature for 15 min. After the reaction completion, the catalyst was separated by centrifuge. Finally, the reaction mixture was placed in an ice bath, which resulted in a white solid product and recrystallized from ethanol to give the pure product. Result: The b–MOF catalyst showed very good efficiency in the synthesis of the desired compounds and can be easily recovered by centrifuge and reused at least five times without a decrease in catalytic activity. Conclusion: In this report, a novel bi metal-organic framework (Ce0.47/Ni0.53–BTC) is synthesized via the cathodic electrosynthesis method. The synthesized b–MOF is fully characterized by several characterization methods. The catalytic activity of Ce0.47/Ni0.53–BTC is investigated in the synthesis of chromeno[4, 3–b]quinolone derivatives via one-pot four-component reaction of dimedone, aromatic aldehyde, 4–hydroxycoumarin and ammonium acetate. The reaction optimization results showed that the highest isolated yield was obtained when the reaction was performed in solvent-free conditions at 110 °C. The catalyst showed to be highly efficient in the synthesis of the desired compounds and performing the reaction utilizing various starting materials gave the products in good isolated yields, which proves the generality and the scope of the method. The catalyst could easily be recovered by centrifuge and reused at least five times without a decrease in catalytic activity.

Background: The continuous need for new anticancer drugs is never-ending task due to cancer resistance to the existing drugs. Objective: This article aimed to design, synthesis, characterization, and anticancer evaluation of cyanopyridines, pyridopyrazolopyrimidines and pyridopyrazolotriazines. Methods: Anticancer activity of the synthesized compounds was determined using MTT assay against three cancer cell lines, namely liver cancer cell line (HepG-2), pancreatic cancer cell line (PANC-1), non-small lung cancer cell line (A-549) and normal fibroblast. Results and Discussion: A series of 3-cyanopyridines (2a,b, 4, 5, 9), pyridopyrimidine (10), pyridopyrazolopyrimidines (11a-c, 12a,b, 18), pyrazolopyridine salt (13) and pyridopyrazolotriazines (16a,b) were synthesized from 3-cyano-4,6-dimethyl-2-pyridone. The synthesized compounds were evaluated in vitro for their anticancer activity and their chemical structures were determined by elemental analysis and spectroscopic data. Conclusion: Some of the synthesized compounds showed remarkable anticancer activities, especially 11a exhibited superior potency to the reference drug cisplatin against A-549 (IC50 = 9.24 μg mL-1 compared to 11.76 μg mL-1 for reference drug) and was found to be safe (IC50 = 66 μg mL-1) for normal fibroblast. Furthermore, compound 16a displayed the highest activity among the tested compounds against HepG-2 (IC50 = 6.45 μg mL-1 equipotent to cisplatin) with the highest safety profile for normal fibroblast (IC50=113.97 μg mL-1).

This article describes the controlled synthesis and characterization of azo oxazolone scaffold compounds containing multifunctional groups such as carbonyl group, imine and carbon-carbon double bond. The reaction of the azo-oxazolone with aromatic amines led to the ring-opening of the azo-oxazolone into the corresponding azo-benzamide derivatives in a short time (average 10 min), resulting in high yield (>90%). All newly synthesized compounds were characterized by the common spectral analysis such as UV, IR, ¹H-NMR, ¹³CNMR, Elemental analysis and MS spectrometry. Objective: The aim of the study was to synthesize new bioactive azo-benzamides by using azo-oxazolone as a synthon utilizing its ring-opening function. Materials and Methods: Azo-benzamide derivatives were prepared in very good yield via ring-opening reaction of azo-oxazolone with aromatic amines in the presence of acetic acid under reflux for few minutes. Results and Discussion: Chemical structures of the newly synthesized compounds were characterized by UV, IR, ¹H-NMR, ¹³C-NMR, Elemental analysis and MS spectrometry. Conclusion: The new azo-oxazolone 4 and azo-benzamide compounds 5a, 5c, 5f, 5h, 5j were screened against Escherichia coli as G(-ve) and Staphylococcus aureus as G(+ve) using ciprofloxacin as a standard. All compounds showed high inhibition potency against E-Coli but low inhibition for S-aureus. Compounds 4, 5c, and 5J showed more reactivity against E-coli. Others: Also, the compounds were tested for their anti-oxidant activity by both DPPH and FRAP methods. The results showed that some compounds possessed moderate anti-oxidant activity in comparison to ascorbic acid as control, typically the compounds bearing OCH3 and OCH2CH3 groups.

Introduction: In continuation of our interest in 2-amino-3-cyano-4.6-diarylpyridines reactions in various fields of organic chemistry which were previously used for the synthesis of many heterocyclic compounds and where dyes generally have many applications especially when benzene or anthraquinone azo dyes are replaced with heterocyclic azo dyes so new derivatives of heterocyclic azo dyes derived from 2-amino-3-cyano- 4.6-diarylpyridines were prepared. Materials and Methods: The IR spectra (KBr), NMR, elemental microanalyses and mass spectra, were performed at different faculties of science in Egypt. Absorption spectra were recorded on Unicam SP 750 in DMF and acetone using 1x 10^-5 mol l^-1 of dye concentration. Optimization was performed using density functional theory (DFT) and time dependent-DFT by applying Becke’s three-parameter hybrid exchange functional with Lee– Yang–Parr gradient-corrected correlation (B3LYP functional). The chemical reagents used in the synthesis were purchased from Fluka, Sigma and Aldrich. Results and Discussion: The structure of the preparing Heterocyclic azo dyes is proven using spectroscopic tools and elemental analysis, and investigation of its absorption spectra indicate the effect of both solvent and substituent on absorption maximum. DFT calculations were performed on some of the selected dyes. Conclusion: Structures of newly synthesized heterocyclic azo dyes were confirmed using elemental analysis, IR, ¹H-NMR, ¹³C-NMR and mass spectral data. DFT theory was used in explaining the electronic properties of some selected dyes, where the energy gap can help in understanding the reactivity behaviour and stability of these compounds. Absorption spectra indicate the effect of both solvent and substituent on absorption maximum.