Sustainable Synthetic Approach for (Pyrazol-4-ylidene)pyridines By Metal Catalyst-Free Aerobic C(sp²)–C(sp³) Coupling Reactions between 1-Amino-2-imino-pyridines and 1-Aryl-5-pyrazolones

Abstract

A novel, metal catalyst-free, and efficient method has been developed for the synthesis of (pyrazol-4-ylidene)pyridine derivatives. The process involves dehydrogenative coupling of 1-amino-2-imino-pyridines with 1-aryl-5-pyrazolone derivatives utilizing O 2 as the sole oxidant. The new method benefits from a high atom economy, efficiency, and substrate scope, as well as the simplicity of reaction and product purification procedures.

The first Q-Tube based high-pressure synthesis of anti-cancer active thiazolo[4,5-c]pyridazines via the [4 + 2] cyclocondensation of 3-oxo-2-arylhydrazonopropanals with 4-thiazolidinones

“…Observations made in this effort serve as a basis for further investigations into the design and preparation of new anti-cancer drugs.Thiazolopyridazine derivatives comprise a broad range of structurally interesting substances that display a variety of medicinally interesting properties including activities against cancers 1,2 , microbes 3,4 , viruses 5 and bacteria 6 , as well as antioxidant 7 , analgesic and pesticidal activities 8,9 . As a result of these important properties, thiazolopyridazines remain the focus of our continuing investigations aimed at developing new and green routes for the synthesis of novel fused nitrogen containing heterocycles [10][11][12][13][14][15][16][17][18] . Until now, several methods have been developed for the synthesis of fused thiazolopyridazines, most of which are targeted at the synthesis of thiazolo[4,5-d] pyridazines 1-3,5 , thiazolo[3,2-b]pyridazine 19 and thiazolo[5,4-c]pyridazine 6 .…”

A facile, practical and metal-free microwave-assisted protocol for mono- and bis-[1,2,4]triazolo[1,5-a]pyridines synthesis utilizing 1-amino-2-imino-pyridine derivatives as versatile precursors

“…Enaminonitrile derivatives (2a-e) could then be converted to their corresponding targets 3a-e through thermally mediated reaction with hydrazine hydrate in EtOH (Scheme 1). 33 Our initial investigation commenced by the reaction of 1amino-2-imino-pyridine derivative (3a) with acetic acid (as a solvent and reactant) at reux for 3 h. Interestingly, the formation of the required product (5a) has been detected, albeit in a good yield of 74%, as a preliminary endeavor ( Table 1, entry 1). Encouraged by the obtained results, the reaction conditions such as solvents, energy sources, and temperature have been evaluated to improve both reaction rate and yield (Table 1).…”

“…A reasonable reaction mechanism for the synthesis of 1,2,4-triazole derivative (5a) was described in Table 1, based on experimental evidences and our reported studies. [31][32][33] As outlined in Table 1, the transformation of the non-isolable intermediate (A) to the target compound (5a) occurred under metal-free conditions. Now, the limitations and scope of the aforesaid reaction have then investigated.…”

“…The N-amino-2-iminopyridines 3a-e were prepared according to the literature procedure. 33 General procedure for the preparation of 1-amino-2-imino-4aryl-1,2-dihydropyridine-3-carbonitrile 3a-e. 33 A mixture of the enaminonitriles 2a-e (20.0 mmol) and hydrazine hydrate (1.5 mL, 30.0 mmol) in 60.0 mL of EtOH was stirred at reux for 1 h. The mixture was concentrated in vacuo giving a solid that was crystallized from the appropriate solvent to give 3 as pure product.…”

Synthetic Strategy for Pyrazolo[1,5-a]pyridine and Pyrido[1,2-b]indazole Derivatives through AcOH and O2-Promoted Cross-dehydrogenative Coupling Reactions between 1,3-Dicarbonyl Compounds and N-Amino-2-iminopyridines

“…A plausible mechanistic pathway for the CDC coupling reactions 80 described above is illustrated in Scheme 4. In one possible route, proton transfer from acetic acid activates N -amino-2-iminopyridine 1 for nucleophilic addition of the enol form of the β-dicarbonyl substrates 2 or 5 .…”