Lino Reyes

The mechanism of the Baeyer–Villiger rearrangement: quantum chemistry and TST study supported by experimental kinetic data

The mechanism of the Baeyer-Villiger rearrangement is modelled for the reaction of propanone with trifluoroperacetic acid, catalyzed by trifluoroacetic acid in dichloromethane, using three DFT methods (B3LYP, BH&HLYP and MPWB1K) and MP2. These results are refined and used to calculate the overall reaction rate coefficient using conventional Transition State Theory. The excellent agreement between the calculated (1.00 x 10(-3) L mol(-1) s(-1)) and the experimental (1.8 x 10(-3) L mol(-1) s(-1)) rate coefficients at the MPWB1K level strongly supports the mechanism recently proposed by our group. This DFT method is then used to study the mechanism of a larger system: cyclohexanone + trifluoroperacetic acid, for which a very good agreement between the calculated and the experimental rate coefficients is also found (1.37 and 0.32 L mol(-1) s(-1), respectively). The modelled mechanism is not ionic but neutral, and consists of two concerted steps. The first one is strongly catalyzed while the second one, the migration step, seems not to be catalyzed for the systems under study. The results of this work could be of interest for understanding other reactions in non-polar solvents for which ionic mechanisms have been assumed.

Semiempirical studies on the transition structure of the Baeyer and Villiger rearrangement. The reaction of acetone with alkyl and aryl peracids

Abstract The mechanism of Baeyer–Villiger reaction with substituted peracids is analyzed by determining with semiempirical (AM1 and PM3) methods, the Mulliken charges, structures, energies, and the evolution of bond orders. A significant correlation was found between the bond order and the activation energy as well as with the charge and the activation energy. Elliptical coordinates were extensively used, finding correlation between the energy of activation and the parallel, antisymmetric coordinates, and eccentricity. The latter was also correlated with the shift of bond order. The geometries of the Criegee intermediate, the methyl group migration transition state structure (TSs), and the product were found and optimized. As in our previous work, we find that the topology of the TSs is invariant. By using elliptic coordinates we can also observe that the atoms constituting three reactive circuits are found on ellipsoidal surfaces where the reactive centers are the foci. The relationship between the energy of activation and the Hammett electronic constant of each of the substituents is presented.

Acid-Catalyzed Nucleophilic Additions to Carbonyl Groups: Is the Accepted Mechanism the Rule or an Exception?

The transesterification reaction, and in particular the methanolysis of ethyl acetate with sulfuric acid as catalyst, is used as a model reaction to study the acid-catalyzed nucleophilic addition to a carbonyl group. Continuum solvation methods (SMD and IEF-PCM) and the MPWB1K functional are used. The reaction mechanism is studied in methanol and in acetonitrile as solvents. Our results indicate that the acid-catalyzed addition mechanism is stepwise, and the transition state (TS) is a contact ion-pair. The counteranion of the acid catalyst remains in the reaction site playing an important role in the TS of this reaction. Changes in the reaction kinetics and the ionic/nonionic nature of the TS with the ionizing ability of the solvent and the strength of the acid catalyst are explored. Additional calculations at the CBS-Q3 level of theory reinforce the conclusions of this paper. The results obtained allow the generalization of important ideas regarding the mechanism of the nucleophilic addition to carbonyl groups.

Effects of Alkyl Groups in the Rate Determining Step of the Baeyer–Villiger Reaction of Phenyl Alkyl Ketones: A Quantum Chemistry Study

In this work, we have studied the substituent effect of several alkyl groups in the rate-determining step of the catalyzed Baeyer-Villiger (BV) reaction of phenyl alkyl ketones with performic (PFA) and trifluoroperacetic (TFPAA) acids, using quantum chemistry methods. Our results reveal that the substituent effect is more pronounced in the migration step barriers than in the corresponding addition step; that could change the rate-determining step (RDS) of the reaction, as observed in the oxidation of phenyl tert-butyl ketone with both peracids. In addition, the effect of the acid/peracid pairs used is also analyzed. We have demonstrated that the addition step is less susceptible to the acid/peracid nature since the acid strength and the nucleophilicity of the peracid have opposite effects. The effect of the acid/peracid pair is much more pronounced in the migration step because it only depends on the leaving ability of the acid, which in turn depends on its strength. These observations are relevant for understanding the effects of the substrate, the peracid, and the catalyst on the switching of the RDS in the BV reaction.

Molecular Disorder in (‒)-Encecanescin

(‒)-Encecanescin (1) has been isolated from the leaves of Eupatorium aschembornianum. Two conformers are present in the crystal structure as a result of molecular disorder. The structure of 1 was established by 1H- and 13C-NMR spectroscopy in CDCl3 solution using 2D NMR techniques (gHSQC, gHMBC and NOESY). A Monte Carlo random search using molecular mechanics followed by the geometry optimization of each minimum energy structure using density functional theory (DFT) calculations at the B3LYP/6–31G* level and a Boltzmann analysis of the total energies generated accurate molecular models describing the conformational behavior of 1. The three most stable conformers 2–4 of compound 1 were reoptimized at the B3LYP/6-311++G(d,p) level of theory using CHCl3 as a solvent. Correlations between the experimental 1H- and 13C-NMR chemical shifts (δexp) have been found, and the GIAO/B3LYP/6-311++G(d,p) calculated magnetic isotropic shielding tensors (σcalc) for conformers 2 and 3, δexp = a + b σcalc, are reported. A good linear relationship between the experimental and calculated NMR data has been obtained for protons and carbon atoms.