Letters in Organic Chemistry - Volume 18, Issue 3, 2021

The oxidation of aldehydes is an efficient methodology for the synthesis of carboxylic acids. Herein we hope to report a simple, efficient and recyclable protocol for aerobic oxidation of aldehydes to carboxylic acid by using C3N4 supported silver nanoparticles (Ag/C3N4) as a catalyst in aqueous solution under mild conditions. Under standard conditions, the corresponding carboxylic acids can be obtained in good to excellent yields. In addition, Ag/C3N4 is convenient for recovery and could be reused three times with satisfactory yields.

2, 3-Dihydroquinazolinones are of popular compounds with the diversification of biological and pharmacological activities. Among many discovered methods, there are efficient and convenient methods used for the synthesis of 2, 3-dihydroquinazoline-4 (1H)-one and some new bis 2, 3- dihydroquinazoline-4 (1H)-one derivatives which are reported in this study. The mentioned methods include the two-component condensation of one molecule of anthranilamide and one molecule of pyrazole carbaldehyde using montmorillonite-K10 as a catalyst for the preparation of 2, 3 dihydroquinazoline-4 (1H)-ones. Also, one-pot pseudo-five-component reaction (5MCRs) of two molecules of isatoic anhydride, two molecules of pyrazole carbaldehydes and one molecule of ethan-1, 2-diamine in the presence of the r catalyst (montmorillonite-K10) for the synthesis of bis 2, 3-dihydroquinazoline-4 (1H)-ones. Despite the short times of reactions, high yields of products were obtained, which were validated using FT-IR, ¹HNMR, ¹³CNMR, and elemental analysis. Moreover, the compounds were screened for their antimicrobial activities against two-gram-positive bacterial strains: Staphylococcus aureus and Micrococcus Luteus; and against two-gram-negative bacterial strains, as well: Escherichia coli and Pseudomonas aeruginosa, which all were utilized for antibacterial investigations. The results showed moderate or significant antibacterial activities.

The application of 3,5-bis(trifluoromethyl)phenylammonium triflate (BFPAT) as a convenient new organocatalyst for the synthesis of quinoxaline derivatives is described. In the presence of BFPAT, one-pot synthesis of a wide variety of quinoxaline derivatives was achieved by the reaction of various o-phenylenediamines and 1,2-dicarbonyl compounds in water.

A series of new 2-((1-((1-(4-methoxy-3-nitrophenyl)-1H-1,2,3-triazol-4-yl)methyl)1H-indol- 3-yl)me thylene)malononitrile derivatives were synthesized by the 1,3-dipolar cycloaddition reaction (click reaction) of 2-((1-(prop-2-yn-1-yl)-1H-indol-3-yl)methylene)malononitrile with different aryl azides in the presence of sodium ascorbate and copper sulphate in good yields. The advantages of this method are efficient, clean, high yields, easy workup procedures, and shorter reaction time. These reactions are very facile, giving products by simple processing that does not require purification by column chromatography. Spectroscopic methods confirmed all the newly synthesized compounds.

Novel group of phenoxy-substituted enediyne-triazole conjugates were synthesized by Huisgen [3+2] cycloaddition reaction (Click chemistry) in aqueous media. It was observed that enediynes were stable in aqueous medium and open-air conditions.

Introduction: Mannich reaction is a typical example of a three-component condensation reaction and the chemistry of Mannich bases has been the matter of search by researchers. Here, an efficient procedure for the synthesis of some new Mannich derivatives of simple phenols is described. Methods: In this procedure, a microwave-assisted and solventless condensation was done between different phenols, secondary amines and paraformaldehyde. The reactions proceeded in the presence of the catalytic amount of nano ZnO and tetrabutylammonium bromide (TBAB) in excellent yields. Ten new compounds were synthesized (A1-A10). Chemical structures of all new compounds were confirmed by different spectroscopic methods. We optimized the chemical reactions in different conditions. Optimization reactions were done in the presence of different mineral oxides, different amounts of TBAB and also different solvents. Nano ZnO and TBAB in catalytic amounts and solvent-free conditions were the best conditions. All the synthesized compounds were screened for their antimicrobial activities. Antifungal and antibacterial activities of the synthesized compounds were evaluated against some Candida species, filaments fungi, gram-positive and gram-negative bacteria by the broth microdilution method as recommended by CLSI. Results: The result showed that compounds A2, A3 and A4 against most of the tested Candida species and compounds A5 and A7 against C. parapsilosis and C. tropicalis exhibited considerable antifungal activities. Moreover, compounds A8 and A10 showed desirable antifungal activities against C. neoformance and C. parapsilosis, respectively. The antibacterial activities of the synthesized compounds were also evaluated. Compounds A6 - A10 against E. fecalis and compounds A5, A7, A9 and A10 against P. aeruginosa showed desirable antibacterial activities. Discussion: We have synthesized some new Mannich adducts of poly-hydroxyl phenols in the presence of nano- ZnO as a reusable catalyst, with the hope of discovering new lead compounds serving as potent antimicrobial agents. The advantages of this method are generality, high yields with short reaction times, simplicity, low cost and matching with green chemistry protocols. The antimicrobial studies of Mannich derivatives of phenols showed desirable results in vitro.

The microtubule is composed of αβ-tubulin heterodimers and is an attractive target for the design of anticancer drugs. Over the years, various compounds have been developed and their effect on tubulin polymerization has been studied. Despite great efforts to make an effective drug, no drug has been introduced which inhibit colchicine binding site. In the current work, a series of pyrimidine derivatives were designed and synthesized. Furthermore, their cytotoxic activities were evaluated and molecular docking studies were performed. Twenty compounds of pyrimidine were synthesized in 2 different groups. In the first group, 4,6-diaryl pyrimidine was connected to the third aryl group via thiomethylene spacer. In the second group, this linker was substituted by S-CH2-triazole moiety. The cytotoxic activity of these compounds was evaluated against 4 different cell lines (HT-29, MCF-7, T47D, NIH3T3). Compounds 6d, 6m, 6p showed potent cytotoxic activity against MCF7 cancerous cell lines. Between these compounds, compound 6p did not show cytotoxic activity against NIH- 3T3 (normal cell) cell line. Docking studies show that these compounds occupy colchicine binding site in tubulin protein and probably their anticancer mechanism is inhibition of tubulin polymerization. Altogether, with respect to obtained results, it is attractive and beneficial to further investigation on pyrimidine scaffold as antimitotic agents. Attention to the selectivity index of 6p on MCF7 cell line could be valuable in design new chemical agents for the treatment of breast cancer.

Synthesis of polyhydroquinolines via Hantzsch’s multicomponent reaction (MCR) involves the use of a hygroscopic and moderately toxic ammonium salt as one of the key reactants. In our effort, we have found urea as an effective ammonia surrogate when the MCR was performed in the presence of sulphonic acid-functionalized Wang resin (Wang-OSO3H) as a polymeric and recoverable acidic catalyst under green conditions. Urea is relatively less hygroscopic/toxic than the commonly used ammonium salts used in this MCR. The methodology afforded a range of polyhydroquinolines in good yields. Depending on the nature of reaction conditions employed, the MCR afforded Biginelli product or 1,4-DHPs when the use of 1,3-diketone was omitted.

The aldol reaction which is the most important one among the C-C bond forming reactions, is widely used by synthetic organic chemists to obtain β-hydroxycarbonyl compounds which are important starting components for biologically active compounds in optically pure form. In this research, five Pro-Phe derivatives were synthesized by simple amidation reactions and characterized by their spectral data. Their catalytic activities in asymmetric aldol reaction were investigated. The catalytic activity studies were performed with aliphatic ketones and various aromatic aldehydes. Especially, (S)- methyl 3-mercapto-2-((S)-3-phenyl-2-((S)-pyrrolidine-2-carboxamido)propanamido)propanoate showed good catalytic activities in water at 0oC in the presence of p-nitrobenzoic acid cocatalyst. The enantioselectivities were up to 90.4%, the diastereomeric ratios were up to 97/3 and yields were 99%. The results showed that these organocatalysts were promising organocatalysts for aldol reaction. Besides, this catalyst showed its best catalytic activities in water which is also an important contribution to green chemistry requirements.

Novel polyheterocyclic nitrogen systems such as 2-amino-1H-pyrazolo[5',1':3,4][1,2,4]- triazino[5,6-b]indole-3-carbonitrile 2, which has been synthesized for the first time in the present work, is considered as starting material for the synthesis of more novel polyheterocyclic systems with five fused rings and sometimes eight fused rings via heterocyclization with α,β-bifunctional reagents under different conditions. The formed structures of the products were established from their correct elemental analysis and spectral data. Some of the compounds were evaluated for their antimicrobial activity using the Agar Well Diffusion method. Compounds 2, 4, 5, 6, 8 were found to be biologically active (Supplementary information).