Current Organic Synthesis - Volume 17, Issue 2, 2020

Background: Natural products have been received attention due to their importance in human life as those are biologically active. In this review, there are some reports through different methods related to the synthesis of the indolizidine 195B which was extracted from poisonous frog; however, due to respect nature, the synthesis of natural compounds such as indolizidine has been attracted much attention among scientists and researchers. Objective: This review discloses the procedures and methods to provide indolizidine 195B from 1989 to 2018 due to their importance as a natural product. Conclusion: There are several methods to give rise to the indolizidine 195B as a natural product that is highly active from the biological perspective in pharmaceutical chemistry. In summary, many protocols for the preparations of indolizidine 195B from various substrates, several reagents, and conditions have been reported from different aromatic and aliphatic.

Objective: To develop efficient method for the synthesis of naphtha-quinoxaline derivatives via the reaction of β-lapachone with various 1,2-diamines. Methods: A mixture of β-lapachone (1mmol), 1,2-diamine (1mmol) and graphene oxide (20mg) in methanol (3mL) was heated at 60°C, under constant stirring for appropriate time. After completion of the reaction, the catalyst was filtered off, washed with ethyl acetate (3x3mL) and the combined filtrate was washed with H2O, dried (anhy. Na2SO4) and concentrated under vacuum. The residue was chromatographed over a column of silica gel eluting with a mixture of hexane and ethyl acetate in different ratios, to afford the desired product. All synthesized compounds were assigned with the help of analytical and 1H, 13C NMR, IR, and mass spectral studies. Results: To establish the catalytic role of GO in the synthesis of naphtha-quinoxaline derivatives, the reaction of β-lapachone with 3,4-diaminotoluene was selected as a model reaction. The catalytic activity of graphene oxide in comparison with other catalysts like acidic resin amberlyst-15 and solid acid catalyst like montmorillonite K-10 were studied. The reaction was also observed in various solvents such as water, acetonitrile, toluene, dichloromethane, ethanol and 1,4-dioxane using GO as a catalyst. Excellent yields were obtained at 60°C in methanol. The efficacy of the present protocol was investigated by the reaction of β- lapachone with other 1,2-diamines. Conclusion: An attractive green metal free carbocatalyst Graphene Oxide (GO) has been successfully utilized for the expedient synthesis of naphtha-quinoxaline derivatives. GO showed high catalytic activity which is attested by the desired products being produced in shorter time. The main advantage of this method is the reusability of the catalyst which makes the procedure sustainable.

Aim and Objective: In order to preserve the environment from harmful organic solvents, a synthesis of coumarin derivatives was performed in deep eutectic solvents, which are considered as “green” due to their characteristics. Materials and Methods: Choline chloride based deep eutectic solvents (DESs) were employed, both as solvents and as catalysts, in the synthesis of coumarin derivatives via Knoevenagel condensation. In order to find the best DES for coumarin synthesis, 20 DESs were tested for the reaction of salicylaldehyde and dimethyl malonate at 80 °C. Results: Among the twenty tested deep eutectic solvents only five were adequate for this kind of synthesis. The best DES for this reaction was found to be the one composed of choline chloride:urea (1:2). Most coumarin compounds were obtained in good to excellent yield. Compounds 1g, 2g and 2p should be pointed out due to their yields of 85, 88 and 98 %, respectively. 3-Acetylcoumarins 5a, 5c, 5d, 5e, 5f and 5g were synthesized under ultrasound irradiation and were also obtained in excellent yields of 90, 95, 98, 93, 94 and 85 %, respectively. Conclusion: Series of coumarin derivatives were successfully synthesized, either in choline chloide:urea DES at 80 °C or in ultrasound-assisted reaction, from different salicylaldehydes and active methylene compounds. These “green” methods were found to be very effective in Knoevenagel condensation, while DES was recycled for several cycles without any significant influence on the product yield.

Background: The benzimidazoles and benzothiazoles have shown relatively high pharmaceutical and biological activities. In recent years, numerous methods have been developed for synthesis of benzimidazole and benzothiazole derivatives using different catalysts. However, only some of the reported procedures are quite satisfactory and most of them have drawbacks. Herein, we report a convenient method for synthesis of benzimidazole and benzothiazole derivatives using a nickel (II) metal-organic framework (Ni- MOF) as a novel and reusable catalyst. The presence of unsaturated metal centers makes metal-organic frameworks to be used as Lewis acid catalysts. Objective: The primary objective of this study was to describe an efficient method for synthesis of benzimidazole and benzothiazole derivatives. Method: Ni-MOF was prepared using the modified evaporation method and was characterized by FE-SEM, FT-IR, TGA, and XRD techniques.The catalyst was then used to test the synthesis of some benzimidazole and benzothiazole derivatives. The benzimidazoles and benzothiazoles were characterized by Elemental analyses, HNMR and IR techniques. Result: A variety of aromatic aldehydes bearing electron donating groups or electron-withdrawing were reacted with 1,2-phenylenediamine or 2-aminothiophenol using Ni-MOF in good to excellent yields. Conclusion: In summary, a new and highly efficient method was developed and reported for the synthesis of benzimidazole and benzothiazole derivatives using nickel(II) metal-organic framework. The advantages are short reaction times, good to excellent yields, the environmentally benign and simple procedure, stability, nontoxicity, recyclability, and easy separation of the catalyst.

Background: SO3H-functionalized zeolite-Y was prepared and used as a catalyst for the synthesis of 2-aryl-N-benzimidazole-4-thiazolidinones and tri-substituted imidazoles at ambient conditions. Objective: The goals of this catalytic method include excellent yields and high purity, inexpensive procedure and ease of product isolation, the use of nontoxic and heterogeneous acid catalyst, shorter reaction times and milder conditions. Materials and Methods: NMR spectra were recorded on Brucker spectrophotometer using Me4Si as internal standard. Mass spectra were recorded on an Agilent Technology 5975C VL MSD with tripe-axis detector. FTIR spectra were obtained with KBr disc on a galaxy series FT-IR 5000 spectrometer. The surface morphology of nanostructures was analyzed by FE-SEM (EVO LS 10, Zeiss, Carl Zeiss, Germany). BET analysis were measured at 196 °C by a Japan Belsorb II system after the samples were vacuum dried at 150°C overnight. Results: The NSZ was characterized by FT-IR, FESEM, EDX, XRF, and BET. The catalytic activity of NSZ was investigated for synthesis of 1,3-tiazolidin-4-ones in H2O/Acetone at room temperature. Moreover, NSZ was used for synthesis of tri-substituted imidazoles at 60 °C via solvent-free condensation. Different kinds of aromatic aldehydes were converted to the corresponding of products with good to excellent yields. Conclusion: Sulfonated zeolite-Y was as an efficient catalyst for the preparation of N-benzimidazole-2-aryl-1,3- thiazolidin-4-ones and 2,4,5-triaryl-1H-imidazoles. High reaction rates, elimination toxic solvent, simple experimental procedure and reusability of the catalyst are the important features of this protocol.

Background: In continuation of our previous work and the applications of saccharin, we encouraged to investigate the one-pot synthesis of the aryl iodides by the diazotization of the arene diazonium saccharin salts. Objective: Arene diazonium salts play an important role in organic synthesis as intermediate and a wide variety of aromatic compounds have been prepared using them. A serious drawback of arene diazonium salts is their instability in a dry state; therefore, they must be stored and handled carefully to avoid spontaneous explosion and other hazard events. Methods: The arene diazonium saccharin salts were prepared as active intermediates in situ through the reaction of various aryl amines with tert-butyl nitrite (TBN) in the presence of saccharin (Sac–H). Then, in situ obtained intermediates were used into the diazotization step without separation and purification in the current protocol. Results: A variety of aryl iodides were synthesized at a greener and low-cost method in the presence of TBN, Sac–H, glacial acetic acid, and TEAI. Conclusion: In summary, a telescopic reaction is developed for the synthesis of aryl iodides. The current methodology is safe, cost-effective, broad substrate scope, and metal-free. All used reagents are commercially available and inert to moisture and air. Also, the saccharine and tetraethylammonium cation could be partially recovered from the reaction residue, which reduces waste generation, energy consumption, raw material, and waste disposal costs.

Background: Infection is a global threat to human health, and there is an urgent need to develop new effective antibacterial drugs to treat bacterial infections. Objective: To study the antibacterial activity of piperazine substituted chalcone sulphonamides. Materials and Methods: A series of novel piperazine substituted chalcone sulphonamides have been prepared, and in vitro antibacterial activity against Staphylococcus aureus, Bacillus subtilis and Escherichia coli strains were evaluated. Results: The results showed that derivatives 6a, 6c and 6h displayed good antibacterial activity against Bacillus subtilis with MIC values of 4.0-8.0 mg/mL. Conclusion: Piperazine substituted chalcone sulphonamides may be used as potential antibacterial agents.

Background: Bis(indolyl)methane derivatives are widely found in nature with a broad range of biological and pharmacological activities. The development of techniques for the synthesis and functionalization of bis(indolyl)methanes have attracted more and more attention in recent years. Objective: To study the synthesis and biological activity of heterocyclic substituted bis(indolyl)methanes. Materials and Methods: A series of heterocyclic substituted bis(indolyl)methanes (3a-3p) have been prepared by condensation reaction of indole and heterocyclic aldehydes catalyzed by boron trifluoride etherate with high yields. Preliminary in vitro anti-inflammatory in lipopolysaccharide (LPS)-stimulated RAW-264.7 macrophages and cytotoxic activity against human tumor cell lines (A549, Hela and SGC7901) by MTT assay were tested. Results: The result indicated that heterocyclic substituted bis(indolyl)methanes showed good antiinflammatory and selective cytotoxic activity. Especially, compounds 3o, 3p and 3q displayed similar inhibitory effect on the generation of NO to positive control dexamethasone, and compound 3q displayed similar selective cytotoxic activity to 5-FU. Conclusion: Heterocyclic substituted bis(indolyl)methanes may be used as potential anti-inflammatory and anticancer leads.

A series of novel 1,3-thiazole derivatives (5a-i) with a modified phenothiazine moiety were synthesized and tested against cancer cell line MCF-7 for their cytotoxicity. Most of them (5a-i) were less cytotoxic or had no activity against MCF-7 cancer cell line. Material and Methods: The IC50 value of compound (4) was 33.84 μM. The compounds (5a-i) were also evaluated for antimicrobial activities, but no significant activity was observed. The antioxidant activity was conducted for target compounds (5a-i). The IC50 value of compound (5b) was 0.151mM. Results: The total amount of energy, ACE (atomic contact energy), energy of receptor (PDB: 5G5J), and ligand interaction of structure (4) were found to be 22.448 Kcal.mol-1 , -247.68, and -91.91 Kcal.mol-1, respectively. The structure (4) is well binded with the receptor because the values of binding energy, steric energy, and the number of hydrogen bondings are -91.91, 22.448 kcal.mol-1, and 2, respectively. It shows that structure (4) has good cytotoxicity with MCF-7 in vitro. Conclusion: The increasing of docking ability of structures (5a-i) with the receptor is presented in increasing order as (5f)>(5e)>(5g)>(5a)>(5b)>(5d)>(5c)>(5i)>(5h). The structure bearing substitution as thiosemicarbazone (4), nitrogen heterocyclic (5f), halogen (5e), and azide (5g) showed good cytotoxicity activity in vitro.