Current Organic Chemistry - Volume 29, Issue 4, 2025

Palladium-catalyzed reactions are widely used for creating carbon-carbon and carbon-heteroatom bonds, with the Heck reaction being particularly valuable for forming rings of various sizes, including medium-sized rings. Recent reports have shown the synthetic potential of intramolecular Heck reactions for assembling rings of seven or more members. While the regioselectivity of this cyclization is often unpredictable in the absence of directing groups, the reductive Heck cyclization strategy can help minimize this issue. Nickel catalysts are also valuable due to their abundance and environmentally friendly nature, playing a pivotal role in producing biologically significant carbocycles and heterocycles. The use of both Pd(0) and Ni(0) catalysts, with or without chiral ligands, has been successful in forming five to nine-member ring heterocycles and carbocycles in a simple, cost-effective manner. This review provides a comprehensive survey of the literature from the past decade on the use of reductive Heck cyclization methodology, including mechanistic details as needed.

Concerning polycyclic heterocyclic compounds, fused triazolopyrimidines and their substituted analogs have been studied recently from a chemical and biological point of view. Triazolopyrimidines have eight different positional isomers based on their structural arrangement and nitrogen atom positions. The present review concerns synthesizing 1,2,4-triazolo[4,3-c]pyrimidines and 1,2,4-triazolo[1,5-c]pyrimidines fused with a five-membered ring containing one heteroatom. The 1,2,4-triazolo[4,3-c]pyrimidines can be prepared by closing the triazole ring on the 4-hydrazinopyrimidine ring, and the 1,2,4-triazolo[1,5-c]pyrimidines can be prepared by closing the triazole ring on the 4-iminopyrimidine-3-amine ring. The transformation of 1,2,4-triazolo[4,3-c]pyrimidine to the more thermodynamically stable isomer triazolo[1,5-c]pyrimidine derivatives via Dimroth rearrangement under different reaction conditions is also discussed. Moreover, the biological activity of both series is presented.

Di-tert-butyl peroxide (DTBP) is one of the most widely used organic peroxides in a variety of oxidative transformations. The main factors contributing to the increasing use of DTBP are its affordability, minimal environmental impact, great effectiveness, and capacity to substitute scarce or dangerous heavy metal oxidants. We have reviewed critically and succinctly the noteworthy applications of DTBP in heterocyclic ring constructions from 2014 onwards in this decennial update. The main components of this evaluation are the pros and cons of its use, the scope of a synthetic organic transformation, and mechanistic logistics.

A series of N-(substituted)-4-methyl aniline derivatives (4a,b, 5a,b, 6, 7, 8, and 9) has been designed and synthesized, and their biological activities were also evaluated as potential anti-tumor and tubulin enzyme inhibitors. Among all compounds, compound (8) showed the most potent tubulin aromatase enzyme inhibitory activity in vitro with an IC50 of 157.3 pg/mL compared to the reference inhibitor Dox (IC50 = 227.4 pg/mL). A docking simulation was performed to insert compound (8) into the crystal structure of human aromatase at the active site to determine the probable binding model. Based on the previous results, compound (8) with potent inhibitory activity on tumor growth could be employed as a potential anticancer agent.

An efficient protocol is reported for synthesizing arylidene adducts, pyridine derivatives, in excellent yields by treating 2-cyano-N-(4-(1-(2-(2-cyanoacetyl) hydrazineylidene)ethyl)phenyl)acetamide with quinoline-3-carbaldehydes, 2-arylidenemalono-nitriles, and acetylacetone in EtOH, respectively. In addition, dithiadiazole and dithiophene adducts were synthesized from one pot reaction using phenyl isothiocyanate, and either hydrazonyl chloride or 2-bromo-1-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazole-4-yl)ethan-1-one in DMF containing potassium hydroxide. The structure of novel products was elucidated using spectroscopic data and elemental analyses. The synthesized compounds were evaluated for their antimicrobial activities. The compounds showed antibacterial and antifungal activities against the tested G-ve and G+ve bacteria and against the tested fungi. The MIC was mostly in the range of 100-500 µg/mL. Molecular docking was used to analyse interactions between the compounds and antimicrobial target proteins. The molecular docking simulation showed lower binding energy with different types of interaction at the active site of Sterol 14-demethylase of C. albicans, Fdc1 proteins of A. niger, DNA Gyrase of E. coli, and LasR, an activator of exotoxin. An expression of P. aeruginosa indicates that these compounds could inhibit the enzyme and cause promising antimicrobial effects.