Abstract
Experimental studies on the Kolbe–Schmitt reaction and its side reactions have made great progresses; however, the relative theoretical studies fall behind. In order to study the mechanism of the Kolbe–Schmitt reaction with 2,6-di-tert-butylphenol and 2,4-di-tert-butylphenol as reactants, we carried out theoretical calculation studies at the M06-2X/Def2-SVP/SMD level of theory using the Gaussian 09 D.01 software package. For the reactant 2,6-di-tert-butylphenol, there is a dynamic equilibrium between the main product and side product, which can rapidly transform into each other at 160 °C by crossing the Gibbs free energy barrier of 14.1 kcal/mol. Moreover, the relative Gibbs free energy of the main product and side product is close; both of them may be observed in the experimental system. However, for 2,4-di-tert-butylphenol, the main product is thermodynamically favorable due to its lower Gibbs free energy, while the side product is kinetically favorable due to the lower activation energy barrier; the main product and the side product compete with each other. We hope the study can shed light on the Kolbe–Schmitt reaction.
Highlights
Aspirin the most widely used drug, can be synthesized by acetylation reaction of salicylic acid[1]
In order to study the mechanism of Kolbe-Schmitt reaction with 2,6-di-tert-butylphenol and 2,4-di-tert-butylphenol as reactants, we carried out theoretical calculation studies at M06-2X/Def2-SVP/Solvation Model Based on Density (SMD) level of theory using Gaussian 09 D.01 software package
A binds with CO2 through a O-K coordination bond to form the complex A-CO2 with the Gibbs free energy increase of 1.7 kcal/mol
Summary
Aspirin the most widely used drug, can be synthesized by acetylation reaction of salicylic acid[1]. In 1859, Kolbe and his assistant Schmitt developed the synthesis method of salicylic acid by means of sodium phenoxide and CO2 at 125 °C and 100 atm, named as Kolbe-Schmitt reaction[1,2,3,4,5]. Experimental studies on Kolbe-Schmitt reactions have made great progress, the reaction substrates and catalysts were fully extended, and the reaction conditions were studied and optimized[6, 7]. Thermodynamics and kinetics of Kolbe-Schmitt reaction were investigated[14, 21]
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