Four-Component Synthesis of 3-Amino-1-Aryl-5,10-Dioxo-1H-Pyrazolo[1,2-b] Phthalazine-2-Carbonitrile Derivatives Promoted by Potassium Carbonate

Abstract

The one-pot, four-component reaction of phthalic anhydride, hydrazine hydrate, aromatic aldehydes and malononitrile afford 3-amino-1aryl-5,10-dioxo-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile derivatives in the presence of potassium carbonate in ethanol under reflux conditions. These conditions offer simplified operation, easy purification, excellent yields and environmentally benign reaction conditions. Also, this method avoids the use of expensive catalysts, toxic solvents and chromatographic separation.

One-Pot Synthesis of Substituted Phthalazine-5,10-dione Derivatives in the Presence of Triflate Catalyst

“…Under optimized conditions compounds 4a-f were synthesized with different aldehydes with high yields and short reaction time as shown in the Table 2. The structures of known compounds (4a-f) were in accordance with their spectral data (Ghorbani-Vaghei et al, 2014;Abdesheikhi and Karimi-Jaberi, 2015;Ghorbani-Vaghei et al, 2016;Kerayati et al, 2016;Mohamadpour et al, 2016;Wang et al, 2016;Arora and Rajput, 2017;Eswararao et al, 2017;Tayade and Dalal, 2017;Sabour et al, 2018;Shaikh et al, 2018). To investigate the catalyst activity, the catalyst was reused six times in the one-pot multi-component condensation of phthalhydrazide, benzaldehyde and malononitrile at 80 0 C. In this procedure, after the completion of each reaction, Cu(OTf) 2 was washed with hot water and filtered.…”

Phthalic anhydride (PA): a valuable substrate in organic transformations

“…220 (G) 3-Amino-1-aryl-5,10dioxo-1H-pyrazolo[1,2-b]phthalazine-2-carbonitriles (252) were also obtained by Abdesheikhi and Karimi-Jaberi in 2015 though the domino reaction of PA, hydrazine hydrate, benzaldehydes, and malononitrile in the presence of K 2 CO 3 (0.1 g) in reuxing ethanol within 50-80 min by 86-96%. 221 (H) Kalhor's group in 2022 obtained novel multifunctional nanocatalyst (Mn/4-MePy-IL@ZY), namely, 4-methylpyridinium chloride ionic liquid graed on Mn@zeolite-Y, and scanned its catalytic performance (10 mol%) in the four-component synthesis of pyrazolo [1,2-b] phthalazines (252) under mild reaction conditions (H 2 O/EtOH, 1 : 1, 80 °C) within 8-12 min with 88-98% yields. 222 Jonnalagadda et al in 2020 utilized eggshell powder (ESP, 20 mg) as a biodegradable and recyclable catalyst for the synthesis of pyrazolo-phthalazine derivatives (252) in aqueous media within 28-45 min by 93-98% at 60 °C.…”

“…The neat condensation between (215, 219) and selected phenols (135) resulted in the decomposition of the reaction mixtures. Indeed, three series of new phthalazine derivatives were obtained in reuxing xylene (220,221). All compounds were isolated simply by direct crystallization (Scheme 82).…”