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

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 pyranopyrazoles5.The extremely large negative Delta S-double dagger values were obtained for all the reactions, particularly in four-component reaction among1,2,3and para electron-withdrawing substituted benzaldehyde4. The high unfavorable Delta S-double dagger value (-188.2 J mol(-1) K-1) is compensated by the favorable Delta H-electron-withdrawing(double dagger) value (lower, 13.47 k J mol(-1)) in comparison with Delta H-double dagger 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 Delta G(electron-withdrawing)(double dagger) = 69.58 k J mol(-1) is faster than other reactions, compared to Delta G(electron-withdrawing)(double dagger) = 72.74 and Delta G(electron-withdrawing)(double dagger) = 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 step(8) with the substituent group near the reaction center could be resonated directly with this center. So, step(8) was identified as RDS.

Automated summary

The full chemical kinetics of a four-component condensation reaction for the synthesis of pyranopyrazoles has been investigated spectrally. The reactions involving ethyl acetoacetate, hydrazine hydrate, malononitrile, and various substituents of benzaldehyde were studied. The reaction with para electron-withdrawing substituted benzaldehyde showed the largest negative Delta S-double dagger value. The unfavorable Delta S-double dagger value was compensated by a favorable Delta H-double dagger value. This correlated with a faster reaction rate and a lower Delta G-double dagger value. The study also revealed the importance of resonance and inductive effects in stabilizing the reaction center with a strong electron-withdrawing group.