Solvent-free, catalyst-free aza-Michael addition of cyclohexylamine to diethyl maleate: Reaction mechanism and kinetics

• Published in: Tetrahedron Vol. 74; no. 1; pp. 58 - 67
• Main Authors: Bláha, Michal, Trhlíková, Olga, Podešva, Jiří, Abbrent, Sabina, Steinhart, Miloš, Dybal, Jiří, Dušková-Smrčková, Miroslava
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 04.01.2018
• Subjects: Amine-assisted transition state; Aza-Michael addition; Catalyst-free; DFT calculations; Fitting a set of coupled differential equations; Gas chromatography/mass spectrometry; NMR spectroscopy; Raman spectroscopy; Solvent-free; Catalyst-free; Gas chromatography/mass spectrometry; Amine-assisted transition state; Aza-Michael addition; Fitting a set of coupled differential equations; Raman spectroscopy; NMR spectroscopy; Solvent-free; DFT calculations
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2017.11.033

The aza-Michael reaction is the addition of an amine to an electron deficient C=C double bond. This reaction is also used in the synthesis of precursors of polymeric networks. In this study, we paid attention to the kinetics and mechanism of the aza-Michael addition of cyclohexylamine (CHXA) to diethyl maleate (DEM) performed as a solvent-free, catalyst-free reaction and to concurrent reactions. In situ Raman spectroscopy, NMR spectroscopy and gas chromatography/mass spectrometry have shown the occurrence of three simultaneous reactions: (i) the aza-Michael addition of CHXA to DEM leading to diethyl 2-(cyclohexylamino)succinate, (ii) isomerization of DEM to diethyl fumarate (DEF), and (iii) the aza-Michael addition of CHXA to DEF formed by the reaction (ii). All of these reactions proceed with third order kinetics, first order in DEM or DEF and second order in CHXA. We propose a kinetic model that allows kinetic constants to be estimated. Furthermore, a numerical solution of the set of differential equations confirms the expected kinetic equations of reactions (i) and (ii) and gives values of rate constants comparable to the estimated ones. A DFT mechanistic study illustrates the structure of the reaction intermediates and transition states of all reactions and explains the contribution of the second amine molecule in the reaction mechanism. [Display omitted]