Facile One-Pot Multi-Component Synthesis, Characterization, Molecular Docking Studies, Biological Evaluation of 1,2,4-Triazolo Isoindoline-1,3-Diones and Their DFT Calculations

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

“…Shaabani's research group in 2012 developed the synthesis of structurally diverse 1H-pyrazolo[1,2-b]phthalazine-1,2dicarboxylates ( 257) via a four-component reaction of PA (1), hydrazine hydrate (56), dialkyl acetylenedicarboxylates (17), and isocyanides (196) in ethanol/acetone (1 : 1) at room temperature in good to moderate yields (Scheme 97). 228 Kumar's research group in 2013 presented one-pot fourcomponent protocol for the synthesis of structurally diverse spirooxindoles, spiroannulated with chromenopyrazolophthalazines/pyranopyrazolophthalazines/ indazolophthalazine (262,263,264) from the reaction of PA (1), hydrazine hydrate (56), isatins (258), and cyclic ketones [4hydroxy-2H-chromen-2-one (259), 4-hydroxy-6-methylpyran-2one (260), dimedone (261)] in aqueous alcoholic medium (H 2 O/C 2 H 5 OH, 5 : 1) using catalytic amounts of sulphamic acid (SA) (Scheme 98). 229 The reaction mechanism is considered to involve acid-catalyzed Knoevenagel condensation, Michael-type addition reaction, and consequent intramolecular dehydrative cyclization to obtain the pure products via recrystallization from ethanol.…”

“…A novel catalyst obtained via the stabilization of methylene dipyridine nanoparticles on Fe 3 O 4 (Fe 3 O 4 /SiO 2 / propyltriethoxysilane/methylene dipyridine nanoparticles) was prepared by Sadeghzadeh and Nasseri in 2013, which was utilized to prepare pyrazolophthalazinyl spirooxindoles ( 269) via a four-component solvent-free reaction at room temperature (Scheme 100). 232 Maleki and Sedigh Ashra in 2014 reported the synthesis of 1H-pyrazolo [ phthalazine-triones (272) via a four-component reaction of PA (1), different aldehydes (19), hydrazine hydrate (56), and dimedone (261). (A) The Javidi and Esmaeilpour group in 2016 synthesized dendrimer-encapsulated phosphotungstic acid nanoparticles immobilized on nanosilica with surface amino groups (dendrimer-PWA n ) and utilized it as a reusable catalyst to accelerate the green synthesis of ( 272) via a one-pot, one-step, and four-component condensation reaction of PA (1), aldehydes (19), hydrazinium hydroxide (56), and dimedone (261) in a 1.2 : 1 : 1 : 1 molar ratio at both under solvent-free conditions at 80 °Scheme 99 Construction of indenopyrazolophthalazines and pyrazolopyrimidophthalazines.…”

“…via the reaction of PA (1), aldehydes (19) (which are 4-chloro-3nitrobenzaldehyde and pentanal), aminonitriles/ethyl cyanoacetate (112), and hydrazine hydrate (56) in a 1 : 1 : 1 : 1.2 molar ratio in the same reaction conditions within 20-25 min with 92-97%. 257 Zaheer et al in 2016 exploited Pr x CoFe 2−x O 4 (x = 0.1) nanoparticles to catalyze the efficient one-pot four-component reaction of PA (1), hydrazine hydrate (56), dimedone (261), and various quinoline aldehydes (278, 279) to achieve phthalazine quinoline derivatives (280, 281) (Scheme 106). 258 The synthesized adducts were evaluated for antibiolm activity against P. aeruginosa and C. albicans.…”

“…They also prepared phthalazine-diones (271) by the reaction of PA (1), aromatic aldehydes (19), hydrazine hydrate (56), and alkyl cyanoacetates (112) (methyl and ethyl) successfully in the same reaction conditions within 22-37 min with 80-95%. (R) Tigote's group in 2017 used ZnFe 2 O 4 nanoparticles (1.5 mol%) as a catalyst for this transformation via the one-pot and two-step reaction of aromatic aldehyde (19) and the dimedone (261), which was added into the mixture of PA (1) and hydrazine hydrate (56) in a 1 : 1 : 1 : 1.2 molar ratio at room temperature within 30-90 min with 76-89% yield. 254 (S) Mahmoodi's group in 2020 used tetrabutyl phosphonium sulfate ([TBP] 2 SO 4 , 5 mol%) as a novel room-temperature ionic liquid (RTIL) to prepare (272) via the domino reaction of the mentioned four substrates at room temperature within 10-20 min with 89-92% yield.…”