A new efficient domino approach for the synthesis of pyrazolyl-phthalazine-diones. Antiradical activity of novel phenolic products

Abstract

Pyrazolyl-phthalazine-dione derivatives (PPDs) were synthetized in the ionic liquid catalyzed one-pot multicomponent reaction of acetylacetone, 2,3-dihydrophthalazine-1,4-dione, and different aldehydes in moderate to good yields. Six new PPDs were obtained, and the crystal structure of 2-acetyl-1-(4-fluorophenyl)-3-methyl-1H-pyrazolo[1,2-b]phthalazine-5,10-dione (PPD-4) was determined. The most interesting structural features of the novel PPD-4 is the formation of a rather short intermolecular distance between the F atom of one molecule and the midpoint of the neighbouring six-membered heterocyclic ring. This interaction arranges all molecules into parallel supramolecular chains. UV-Vis spectra of all PPDs were acquired and compared to the simulated ones obtained with TD-DFT. All synthetized compounds were subjected to evaluation of their in vitro antioxidative activity using a stable DPPH radical. It was shown that PPD-7, with a catechol motive, is the most active antioxidant, while PPD-9, with two neighbouring methoxy groups to the phenolic OH, exerted a somewhat lower, but significant antioxidative potential. The results of DFT thermodynamical study are in agreement with experimental findings that PPD-7 and PPD-9 should be considered as powerful radical scavengers. In addition, the obtained theoretical results (bond dissociation and proton abstraction energies) specify SPLET as a prevailing radical scavenging mechanism in polar solvents, and HAT in solvents with lower polarity. On the other hand, the obtained reaction enthalpies for inactivation of free radicals suggest competition between HAT and SPLET mechanisms, except in the case of the cOH radical in polar solvents, where HAT is labeled as prefered.

Green One-Pot Synthesis of Coumarin-Hydroxybenzohydrazide Hybrids and Their Antioxidant Potency

“…This is in agreement with the fact that the pronounced antioxidative capacity of compounds with catechol moiety stems from resonance and electron-donating effects of these groups, which increase the stability of the formed phenoxy radical. In these compounds, the hydroxy group supports the homolytic cleavage of the neighboring O-H bond and enables the formation of a hydrogen bond with formed phenoxy radical [40][41][42].…”

Recent Achievements in the Synthesis of Heterocyclic Compounds by Phthalhydrazide-Based Multicomponent Reactions

“…73 . 75 This reaction was also reported in the presence of other catalysts such as wet 2,4,6-trichlorotriazine (TCT) under solvent-free condition, 76 [SBA-Im]HSO4, 77 Fe3O4@silica sulfuric acid nanoparticles, 78 (S)-camphorsulfonic acid, 79 ionic liquid [HDEA][ClAc], 80 and RHA@DABCO. 81 This reaction was also accomplished under various conditions via different catalysts as shown in Table 2.…”

Acetophenone Mannich bases: study of ionic liquid catalysed synthesis and antioxidative potential of products

“…For estimation of the mechanism in the absence of free radicals, bond dissociation enthalpy (BDE), ionization potential (IP) and proton abstraction (PA) energies were calculated [13,54–60], while in the presence of free radicals, the reaction enthalpies (Δr H ) were calculated for the reactions of MB8 and MB10 with each of the eight selected free radicals. Details on terms upon which radical selection was made (hydroxy ( • OH), hydroperoxy ( • OOH), methylperoxy (CH 3 –O–O • ), superoxide radical anion (O 2 •− ), methoxy ( • OCH 3 ), tert -butoxy ( • OC(CH 3 ) 3 ), vinyl peroxy (CH 2 =CH–O–O • ) and DPPH), as well as details on the calculation of thermodynamic parameters in the absence and in the presence of free radicals are provided in our previous studies, and for the sake of clarity presented in the electronic supplementary material [13,61]. Nevertheless, thermodynamical parameters and reaction enthalpies indicate which of HAT, SET-PT and SPLET mechanism prevails.…”

“…), methoxy ( † OCH 3 ), tert-butoxy ( † OC(CH 3 ) 3 ), vinyl peroxy (CH 2 ¼CH-O-O † ) and DPPH), as well as details on the calculation of thermodynamic parameters in the absence and in the presence of free radicals are provided in our previous studies, and for the sake of clarity presented in the electronic supplementary material [13,61]. Nevertheless, thermodynamical parameters and reaction enthalpies indicate which of HAT, SET-PT and SPLET mechanism prevails.…”