Dicarbonyl compounds in the synthesis of heterocycles under green conditions

Carbon–carbon and carbon-heteroatom bond forming reactions are strategically employed for the generation of a variety of heterocyclic systems. This class of compounds represents the most general structural unit, present in many natural compounds. They are recognized for their valuable biologically properties and wide range of applications in medicinal, pharmaceutical, and other related fields of chemistry. This is an updated review on the use of dicarbonyl compounds under environmentally friendly conditions to access a series of heterocyclic structures, e.g., quinoxaline, quinazolinones, benzochalcogenazoles, indoles, among others. Synthetic protocols involving copper-catalyzed, multicomponent and cascade reactions, decarboxylative cyclization, recycling of CO2, and electrochemical approaches are presented and discussed.

New Sustainable Synthetic Routes to Cyclic Oxyterpenes Using the Ecocatalyst Toolbox

Cyclic oxyterpenes are natural products that are mostly used as fragrances, flavours and drugs by the cosmetic, food and pharmaceutical industries. However, only a few cyclic oxyterpenes are accessible via chemical syntheses, which are far from being ecofriendly. We report here the synthesis of six cyclic oxyterpenes derived from ß-pinene while respecting the principles of green and sustainable chemistry. Only natural or biosourced catalysts were used in mild conditions that were optimised for each synthesis. A new generation of ecocatalysts, derived from Mn-rich water lettuce, was prepared via green processes, characterised by MP-AES, XRPD and TEM analyses, and tested in catalysis. The epoxidation of ß-pinene led to the platform molecule, ß-pinene oxide, with a good yield, illustrating the efficacy of the new generation of ecocatalysts. The opening ß-pinene oxide was investigated in green conditions and led to new and regioselective syntheses of myrtenol, 7-hydroxy-α-terpineol and perillyl alcohol. Successive oxidations of perillyl alcohol could be performed using no hazardous oxidant and were controlled using the new generation of ecocatalysts generating perillaldehyde and cuminaldehyde.

Highly diastereoselective cascade [5 + 1] double Michael reaction, a route for the synthesis of spiro(thio)oxindoles

The first diastereoselective synthesis of spirothiooxindoles is reported via the Michael reaction between thiooxindoles and dibenzalacetones. The reaction was conducted without any catalyst or additive under green conditions, i.e., ethanol as the solvent and at room temperature. In addition, the described robust method benefits from scalability, simple work-up, and column chromatography-free purification. This work demonstrates the art of governing regio- and stereoselectivity, which has been discussed in the light of Density Functional Theory calculations. Our method represents the first synthesis of spiro[cyclohexanone-thiooxindoles] with the relative configuration of the aryl moieties at the cyclohexanone ring as cis. The obtained cis-spirothiooxindoles, can be used to afford cis-spirooxindoles, which their synthesis had not been explored before. According to our molecular docking studies, cis-spirooxindoles demonstrate higher binding affinities than corresponding trans-spirooxindoles for the OPRT domain of the Leishmania donovani uridine 5′-monophosphate synthase (LdUMPS). Thus, the reported method may eventually be utilized to develop new hit compounds for leishmaniasis treatment.

Pd Doped on TCH@SBA-15 Nanocomposites: Fabrication and Application as a New Organometallic Catalyst in the Three-Component Synthesis of N-Benzo-imidazo- or -thiazole-1,3-thiazolidinones

In this study, Pd(II)/TCH@SBA-15 nanocomposites were synthesized by the grafting of 3-chloropropyltriethoxysilane and thiocarbohydrazide on SBA-15 and subsequent deposition of palladium acetates through the ligand–metal coordination method. The structure and morphology of this nanoporous nanocomposite was thoroughly identified by Fourier transform infrared spectroscopy, field emission scanning electron microscopy, transmission electron microscopy, energy-dispersive X-ray spectroscopy, X-ray diffraction, thermogravimetric analysis, atomic absorption spectroscopy, and Brunauer–Emmett–Teller instrumental analyses. Furthermore, the catalytic activity of this nanocomposite was investigated in the three-component synthesis of 3-benzimidazolyl or benzothiazoleyl-1,3-thiazolidin-4-ones via a reaction of 2-aminobenzimidazole or 2-aminobenzothiazole, aromatic aldehydes, and thioglycolic acid in an acetone–H2O mixture under green conditions. The Pd/TCH@SBA-15 nanocatalyst is demonstrated to exhibit a high catalyzing activity in the three-component reaction of the synthesis of N-heterocyclic thiazolidinones with good to excellent yields. One of the advantages of the suggested method is the direct application of the thiocarbohydrazide ligand to stabilize Pd nanoparticles through formation of a stable ring complex without creating an additional Schiff base step. Moreover, this organometallic nanocatalyst can be recycled several times with no notable leaching or loss of performance.

Highly Diastereoselective Cascade [5+1] Double Michael Reaction, a Route for The Synthesis of Spiro Thio-Oxindoles

The first diastereoselective synthesis of spiro-thiooxindole is reported via Michael reaction between thiooxindoles and divinyl ketones. The reaction was conducted without any catalyst or additive under green conditions, i.e., ethanol as the solvent and room temperature. This study showed the art of governing regioselectivity in which novel spiro frameworks were generated in high yields. In addition to simple and column chromatography-free purification, the high diastereoselectivity makes this protocol very robust. The regio- and stereo- selectivity of the reaction has been discussed in light of the theoretical calculations, and molecular docking has been performed on the reaction products. Our method presents the first synthesis of cis-spiro thiooxindoles, which can be used to generate cis-spiro oxindoles. According to our docking studies, the latter demonstrates higher binding affinities towards the LdUMPS than corresponding trans-spiro oxindoles and may be utilized to develop new hit compounds for leishmaniasis treatment.

Synthesis of (E)-2-(1H-tetrazole-5-yl)-3-phenylacrylenenitrile Derivatives Under Green Conditions Catalyzed by New Thermally Stable Magnetic Periodic Mesoporous Ognosilica Embedded With ZnO Nanoparticles

ZnO nanoparticles embedded on the surface of magnetic isocyanurate-based periodic mesoporous organosilica (Fe3O4@PMO-ICS–ZnO) was prepared through modified environmental-benign procedure for the first time and was properly characterized by appropriate spectroscopic and analytical methods or techniques used for mesoporous materials. The new thermally stable Fe3O4@PMO-ICS–ZnO materials with proper active sites, uniform particle size and surface area were investigated for the synthesis of medicinally important tetrazole derivatives through cascade condensation and concerted reactions as a representative of the Click Chemistry concept. The desired 5-substituted-1H-tetrazole derivatives were smoothly prepared in high to quantitative yields and good purity under green conditions. Low catalyst loading, very short reaction time and the use of green solvents such as EtOH and water instead of carcinogenic DMF as well as the possibility of easy separation and recyclability of the catalyst for at least five consecutive runs without significant loss of its activity are notable advantages of this new protocols compared to other recent introduced procedures.

Molecular Iodine-Mediated Synthesis of 2-Azaanthraquinones from [3.3.3]Propellanes via a Metal-Free Rearrangement

A novel iodine-mediated rearrangement of heterocyclic [3.3.3]propellanes under green conditions is described. This metal-free transformation for the straightforward synthesis of substituted 2-azaanthraquinones proceeds via ring opening/dissociation of C–O and C–N bonds/intramolecular C(sp3)–C(sp3) bond formation/ring expansion/aza-ring closure/1,3-N to N alkyl migration. High atom-efficiency, synthetically useful yields, easily accessible starting materials, and mild reaction conditions are advantages of this process.