Synthesis, Kinetics and a Full Mechanistic Investigation of Four-Component Reaction for Preparation of 2-Amino-3-Cyanopyridine Derivatives in the Presence of Green Catalysts

Abstract

2-Amino-3-cyanopyridine derivatives have been synthesized via a four-component reaction of malononitrile (1), aromatic aldehyde (2), cyclohexanone (3), and amines (4) in the presence of fructose and maltose catalysts with good to excellent yields. In addition, for the first time we describe the experimental kinetics study and a full mechanistic investigation of title reaction. To determine the right position of each component in the reaction path, kinetic study of the reaction was carried out using UV–vis spectrophotometry technique. Based on temperature effects on the reaction rate, activation energy (E_a= 28.97 ± 0.21 kJ mol⁻¹) and its parameters (ΔH^‡ = 26.49 ± 0.23 kJ mol⁻¹, ΔS^‡ = −122.88 ± 0.67 J mol⁻¹ K⁻¹ and ΔG^‡ = 63.12 ± 0.46 kJ mol⁻¹) were determined, so the reaction was enthalpy and chemically controlled and also its mechanism was associative. By the change in the solvent polarity, it was found that polar solvents increase the reaction rate and the mixture of water/ethanol (50/50) was the best choice. Changing the structure of aniline (4) and benzaldehyde (2) by the substituent groups exhibited that the reaction proceeds faster in a poor electronic ring, regarding benzaldehyde (2), which is the result of the electron-withdrawing groups and a rich electronic ring for aniline, which is because of the electron donating groups. Further investigations on the partial orders of reactants approved the independency of the rate law to the concentrations of components (3) and (4), so the reaction was second-order kinetics corresponding to compounds (1) and (2) with the right rate law = $\raisebox{1ex}{${\mathit{k}}_7{\mathit{k}}_2{\mathit{k}}_1\left[1\right]\left[2\right]\left[\mathit{Cat}\right]$}\!\left/ \!\raisebox{-1ex}{${\mathit{k}}_{-6}$}\right.$. Step₇ was recognized as the RDS.

Keywords:

• 2-Amino-3-cyanopyridine
• Aldehyde
• Amines
• Chemically-Controlled
• Cyclohexanone
• Fructose
• Kinetics
• Malononitrile

Acknowledgment

The authors gratefully acknowledge support from the Research Council of the University of Sistan and Baluchestan.