Sandeep Malik

A series of fused [1,2,4]triazolo[4,3‐b]pyridazine derivatives was synthesized via hypervalent iodine‐mediated oxidative cyclization of hydrazone intermediates using iodobenzene diacetate under mild, metal‐free conditions. This method was applied to diverse 6‐(4‐nitrophenyl)‐substituted triazolopyridazines with various aryl and heteroaryl groups, producing the target compounds in good to excellent yields with broad substrate tolerance. All compounds were characterized by FT‐IR, ¹ H NMR, ¹³ C NMR, and HRMS. Their antiproliferative activity was tested against the human triple‐negative breast cancer cell line MDA‐MB‐231 using the sulforhodamine B (SRB) assay. Compound 3c, containing a 3,4‐dimethoxyphenyl substituent, showed the highest activity, suggesting a beneficial effect of electron‐donating groups. Molecular docking against cancer‐related proteins showed favorable binding, especially with Topoisomerase IIα, though these computational results are preliminary and don't confirm the exact molecular target. This study presents an efficient synthesis strategy and identifies compound 3c as a promising lead for further biological and medicinal chemistry research.

An efficient alternative methodology for the selective functionalization of anilides has been developed through the synergistic combination of PIDA and copper(II) acetate monohydrate in acetic acid. A comparative analysis with previously reported methodologies has been carried out. The developed protocol offer a practical and effective alternative to conventional methods employing expensive or toxic heavy-metal catalysts, highlighting the versatility and cost-effectiveness of copper salts in C-H functionalization reactions. The methodology was operationally simple and proceeds under mild reaction conditions, affording ortho -functionalized products in good to excellent yields. The obtained results were found to be consistent with reported palladium and cobalt-mediated protocols, while differ from Lewis acid promoted methodologies. Additional advantages of this approach include shorter reaction times, high reaction efficiency, and a simplified work-up procedure that avoids chromatographic purification. A plausible reaction mechanism involving ortho -assisted metal chelation has also been proposed.

Hydrazo compounds have displayed significant roles in both biological and physical aspects, such as spinamycin as a potent growth inhibitor against fungi and rat sarcoma cells, hydrazo tocopherol as a component of vitamin E, and electron-rich hydrazo-linked triazines as energetic materials. In this study, a metal-free approach was proposed for the synthesis of hydrazo-linked 5-(4- aryl)-1H-1,2,4-triazoles. The methods for the synthesis of 5-(4-aryl)-1H-1,2,4-triazoles initiated by the reaction of aldehyde with semicarbazide. The resulted compound, 5-(4-aryl)-1H-1,2,4-triazol-3- ol, upon reaction with phosphorous oxychloride yielded 3-chloro-5-(4-aryl)-1H-1,2,4-triazoles. These synthesized compounds upon fusión with various aryl and hetero aryl substituted hydrazines provided desired hydrazo moieties. Synthesized hydrazo compounds were characterized by spectroscopic techniques, viz. 1H-NMR, FT-IR and mass spectrometry. In this study, a series of novel hydrazo- linked 5-(4-aryl)-1H-1,2,4-triazoles were synthesized. The methodology proposed in this study eliminates the use of complicated procedures and heavy metals.

An efficient approach for the tosyloxyl group transfer in several N-arylbenzamides has been achieved using HTIB (Koser’s reagent) under mild reaction conditions. Its simplicity, efficiency, and reduced reliance on hazardous reagents make it an attractive choice for chemists seeking sustainable alternatives. The proposed methodology offered single-step para-selective tosyloxylation, ensuring the prevention of the synthesis of mixtures of ortho and meta-isomers. The corresponding products were obtained with moderate to excellent efficiency. The current approach eliminated the need for harsh, acidic, and toxic metals, ensuring safer handling and minimizing environmental impact. A plausible mechanism for tosyloxylation of N-arylbenzamides involving iodonium ylide has been proposed.