Gilles Desmet

Computational Study and Kinetic Analysis of the Aminolysis of Thiolactones

The aminolysis of three differently α-substituted γ-thiolactones (C4H5OSX, X = H, NH2, and NH(CO)CH3) is modeled based on CBS-QB3 calculated free energies corrected for solvation using COSMO-RS. For the first time, quantitative kinetic and thermodynamic data are provided for the concerted path and the stepwise path over a neutral tetrahedral intermediate. These paths can take place via an unassisted, an amine-assisted, or a thiol-assisted mechanism. Amine assistance lowers the free energy barriers along both paths, while thiol assistance only lowers the formation of the neutral tetrahedral intermediate. Based on the ab initio calculated rate coefficients, a kinetic model is constructed that is able to reliably describe experimental observations for the aminolysis of N-acetyl-dl-homocysteine thiolactone with n-butylamine in THF and CHCl3. Reaction path analysis shows that for all conditions relevant for applications in polymer synthesis and postpolymer modification, an assisted stepwise mechanism is operative in which the formation of the neutral tetrahedral intermediate is rate-determining and which is mainly amine-assisted at low conversions and thiol-assisted at high conversions.

Ab initio based kinetic Monte Carlo analysis to unravel the propagation kinetics in vinyl acetate pulsed laser polymerization

The radical propagation kinetics of vinyl acetate (VAc) in pulsed laser polymerization (PLP) is studied by combining ab initio calculated rate coefficients for propagation of head, tail and mid-chain radicals, and backbiting reactions with kinetic Monte Carlo modeling of PLP spectra. The intriguing laser pulse frequency dependency of the propagation kinetics is shown to be mainly caused by the formation of stabilized mid-chain radicals via backbiting of tail radicals, originating from head-to-head propagation. These mid-chain radicals are approximately 35 times less reactive towards propagation at 323 K which, in agreement with experimental observations, results in a 15% increase of the observed propagation rate coefficient if the laser pulse frequency is increased from low (25–100 s−1) to high (300–500 s−1) values. Under typical PLP conditions, only tail radicals are reactive towards backbiting while this reaction is energetically unfavorable for head radicals. Tail-to-tail propagation of the radicals formed by head-to-head propagation is not sufficiently slow to fully explain the observed frequency dependence. The effect of chain length dependent propagation remains limited but can no longer be neglected at frequencies above 500 s−1.

Thiol-Michael addition in polar aprotic solvents: nucleophilic initiation or base catalysis?

The thiol-Michael addition of ethanethiol to ethyl acrylate, methyl vinylsulfone and maleimide initiated by ethyl-, diethyl-, triethylamine and triethylphosphine in tetrahydrofuran (THF) is investigated at room temperature for concentrations ranging from 0.5 to 2 mol L−1 for the reactants and 0.03 to 0.3 mol L−1 for the initiators. Rate coefficients for all elementary steps in a reaction scheme consisting of both the base catalyzed and the nucleophile initiated mechanism are calculated using CBS-QB3 corrected for solvation with COSMO-RS. Diffusional limitations are taken into account using the coupled encounter pair model. The ab initio apparent kinetic parameters are used in a microkinetic model and simulated conversions agree well with experimental data. Competition with the aza-Michael addition is shown to be insignificant. Regardless of the choice of ene or catalyst, conversion is governed by an anionic cycle in which first an addition from the thiolate to the ene occurs, followed by a rate-controlling proton transfer to the obtained Michael adduct anion from another thiol. For acrylates and vinylsulfones, the addition of the thiolate to the ene is quasi-equilibrated, while for maleimides this elementary reaction has a positive affinity, explaining their large reactivity. The choice of catalyst or ene strongly affects the initiation mechanism. Using tertiary phosphines only nucleophilic initiation takes place while with tertiary amines, only base catalysis occurs. For primary and secondary amines both initiation mechanisms contribute. The presented kinetic parameters and the insights on diffusional limitations are critical for the further optimization of thiol-Michael additions for polymer conjugation.

Ab‐Initio‐Based Kinetic Modeling to Understand RAFT Exchange: The Case of 2‐Cyano‐2‐Propyl Dodecyl Trithiocarbonate and Styrene

Ab-initio-calculated rate coefficients for addition and fragmentation in reversible-addition fragmentation chain transfer (RAFT) polymerization of styrene with 2-cyano-2-propyl dodecyl trithiocarbonate initiated by azobisisobutyronitrile allow the reliable simulation of the experimentally observed conversion, number average chain length, and dispersity. The rate coefficient for addition of a macroradical Ri to the macroRAFT agent Ri X at 333 K (6.8 104 L mol-1 s-1 ) is significantly lower than to the initial RAFT agent R0 X (3.2 106 L mol-1 s-1 ), mainly due to a difference in activation energy (15.4 vs 3.0 kJ mol-1 ), which causes the dispersity to spike in the beginning of the polymerization.