N-heterocyclic Chemistry Research Articles

Copper(I)-Catalyzed Nitrosylation/Annulation Cascade of Enaminones with tert-Butyl Nitrite: Access to 1H-1,2,3-Triazole 2-Oxides.

The direct synthesis of triazole 2-oxides has posed a challenge in the field of N-heterocyclic chemistry. A novel copper(I)-catalyzed nitrosylation/annulation cascade of enaminones provides a straightforward route to 1H-1,2,3-triazole 2-oxides by forming new C-N, N=N, and N-N bonds using noncorrosive tert-butyl nitrite (TBN) as both the N and NO sources. The synthetic protocol features easily accessible starting materials, wide substrate scopes, and good tolerance toward various functional groups while avoiding use of explosive azides.

Efficient Green Synthesis, Anticancer Activity, and Molecular Docking Studies of Indolemethanes Using a Bioglycerol-Based Carbon Sulfonic Acid Catalyst.

Indolemethane derivatives are significant molecules in the study of N-heterocyclic chemistry. Herein, we designed and developed a highly efficient green synthesis of indolemethane compounds using a recyclable biodegradable glycerol-based carbon solid acid catalyst under solvent-free conditions at room temperature for 5 min with excellent yields. The synthesized compounds were subjected to cytotoxic activity against prostate (DU145), hepatocellular carcinoma (HepG2), and melanoma (B16) cell lines. The highest cytotoxicity effects were found with 1k (1.09 μM) and 1c (2.02 μM) against DU145, followed by 1a, 1d, 1f, 1n, and 1m between 5.10 and 8.18 μM concentrations. The anticancer activity is validated using molecular docking simulations, and comparing binding energies with the standard drug doxorubicin suggests that the title compounds are well fitted into the active site pocket of the target molecules..

Spectroscopic evidence for 1,2-diiminoethane - a key intermediate in imidazole synthesis.

Simple imines and diimines are common building blocks in organic synthesis, but the compound class is spectroscopically not well characterized. Herein we report the formation of the simplest diimine, namely 1,2-diiminoethane, as well as spectroscopic characterization by cryogenic matrix isolation IR and UV/Vis spectroscopy. Three conformers of 1,2-diiminoethane form after UV irradiation of 1,2-diazidoethane by N2 extrusion at 3 K in solid argon and can be photochemically interconverted. In a matrix isolation pyrolysis experiment at 600 °C with 1,2-diazidoethane as the starting material we observe hydrogen cyanide and formaldimine as the main decomposition products. All experimental findings are supported by deuterium labeling experiments and B3LYP/6-311++G(2d,2p) calculations. Irradiation of 1,2-diazidoethane in aqueous solution leads to the formation of imidazoles as indicated by NMR spectroscopy and GC-MS analysis. Our results underline the key role of diimines as building blocks in N-heterocyclic chemistry.

Copper(II)-Catalyzed C-H Nitrogenation/Annulation Cascade of Ketene N,S-Acetals with Aryldiazonium Salts: A Direct Access to N2-Substituted Triazole and Triazine Derivatives.

Direct synthesis of N2-substituted triazole and triazine derivatives has been a challenge in N-heterocyclic chemistry. Under copper(II) catalysis ketene N,S-acetals, that is, alkylthio-substituted enaminones, efficiently reacted with aryldiazonium salts to allow the regioselective generation of functionally diverse N2-substituted 1,2,3-triazoles and 2,3-dihydro-1,2,4-triazines. The oxidant and base-dependent reaction yielded the five- and six-membered N-heterocyclic products, respectively. The synthetic protocol features broad substrate scopes and good functional group tolerance under mild conditions. The mechanistic studies have revealed that the reaction proceeds via alkenyl azo/imino hydrazone intermediates.

ChemInform Abstract: Indole Synthesis Through Transition Metal‐Catalyzed C—H Activation

AbstractReview: [56 refs.

Functionalized Heteroarylpyridazines and Pyridazin-3(2H)-one Derivatives via Palladium-Catalyzed Cross-Coupling Methodology

A general method for the synthesis of functionalized pyridazinylboronic acids/esters is described involving a directed ortho metalation (DoM)--boronation protocol (Schemes 1 and 2). A comprehensive study of the reactivity of the C-B bond in palladium-catalyzed cross-couplings with aryl/heteroaryl halides is presented. Aryl-/heteroarylpyridazines are thereby obtained in synthetically viable yields (typically 40-75%) although in some cases competing protodeboronation has been observed. A series of pyridazin-3(2H)-one derivatives, including 4,6-diaryl/heteroaryl derivatives, have been obtained from the corresponding 3-methoxypyridazines in straightforward procedures (Schemes 3 and 4). Several X-ray crystal structures of aryl-/heteroarylpyridazines and derived pyridazin-3(2H)-one derivatives are reported. These multi-ring systems are of considerable interest in contemporary N-heterocyclic chemistry.