Comprehensive Kinetics and a Mechanistic Investigation on the Biological Active Pyrano[2,3-C]Pyrazole Core in the Presence of Both Eco-Friendly Catalyst and Solvent: Experimental Green Protocol

Abstract

Full chemical-kinetics of the green one-pot four-component condensation among ethyl acetoacetate 1, hydrazine hydrate 2, malononitrile 3 and various substituents of benzaldehyde 4 has been spectrally investigated for the generation of pyranopyrazoles 5. The extremely large negative ΔS^‡ values were obtained for all the reactions, particularly in four-component reaction among 1, 2, 3 and para electron-withdrawing substituted benzaldehyde 4. The high unfavorable ΔS^‡ value (-188.2 J mol⁻¹ K⁻¹) is compensated by the favorable ${\mathrm{ }\Delta H}_{\mathrm{ }\mathit{electron}-\mathit{withdrawing}}^{‡}$ value (lower, 13.47 k J mol⁻¹) in comparison with ΔH^‡ values of unsubstituted benzaldehyde 4 (19.1 k J mol⁻¹) and electron-donating substituted benzaldehyde 4 (37.4 k J mol⁻¹), herein, the reaction rate with lesser value of ${\mathrm{ }\Delta G}_{\mathrm{ }\mathit{electron}-\mathit{withdrawing}}^{‡}=69.58$ k J mol⁻¹ is faster than other reactions, compared to ${\Delta G}_{\mathrm{ }\mathit{unsubstituted}}^{‡}=72.74$and ${\Delta G}_{\mathit{electron}-\mathit{donating}}^{‡}=76.63$ k J mol⁻¹. A reliable correlation of log k and ${\sigma }_{R^{+}}$ with an excellent DPF (r = 0.990) and positive value of reaction constant ($\rho =+1.1003)$ demonstrated that both resonance and inductive effects “altogether” contributed on the reaction center with a strong electron-withdrawing group, accompanied by high positive charges, which can be stabilized by electron-donating compound. The substituent effects on the reaction kinetics generally obey the same kinetics role for the series of compounds used in this work (Hammett, Exner and isokinetic relationship studies). Among ten steps inside the reaction mechanism, only step₈ with the substituent group near the reaction center could be resonated directly with this center. So, step₈ was identified as RDS.

Keywords:

• kinetic and mechanism
• pyranopyrazoles
• water
• sodium benzoate
• Hammett
• equation

Additional information

Funding

We gratefully acknowledge financial support from the Research Council of the University of Sistan and Baluchestan.