Carl LeBlond

Reaction calorimetry as an in-situ kinetic tool for characterizing complex reactions☆

Abstract Due to its ability to provide directly reaction rate data and its in-situ nature, reaction calorimetry has become one of the most powerful probes of reaction pathways and mechanisms of chemical reactions by virtue of providing high-quality kinetic data. In this paper, examples of enantioselective hydrogenation and selective consecutive hydrogenation reactions are presented to demonstrate the high quality of kinetic data obtainable from the reaction calorimetry. They are also used to illustrate the use of reaction calorimetry for elucidating reaction pathways and mechanisms from detailed kinetic and thermodynamic information about individual step involved in multi-step reactions that is otherwise difficult to obtain without calorimetry.

KINETIC INFLUENCES ON ENANTIOSELECTIVITY IN ASYMMETRIC CATALYTIC HYDROGENATION

Abstract The influence of reaction conditions on enantioselectivity in the Ru II -(binap)-catalyzed asymmetric hydrogenation of allylic alcohols is discussed. This work highlights the importance of considering kinetic influences in addition to the stereochemical aspects of the chiral catalytic environment in interpreting catalytic behavior in asymmetric hydrogenation reactions.

Diffusion, adsorption, and desorption of molecular hydrogen on graphene and in graphite.

The diffusion of molecular hydrogen (H2) on a layer of graphene and in the interlayer space between the layers of graphite is studied using molecular dynamics computer simulations. The interatomic interactions were modeled by an Adaptive Intermolecular Reactive Empirical Bond Order (AIREBO) potential. Molecular statics calculations of H2 on graphene indicate binding energies ranging from 41 meV to 54 meV and migration barriers ranging from 3 meV to 12 meV. The potential energy surface of an H2 molecule on graphene, with the full relaxations of molecular hydrogen and carbon atoms is calculated. Barriers for the formation of H2 through the Langmuir-Hinshelwood mechanism are calculated. Molecular dynamics calculations of mean square displacements and average surface lifetimes of H2 on graphene at various temperatures indicate a diffusion barrier of 9.8 meV and a desorption barrier of 28.7 meV. Similar calculations for the diffusion of H2 in the interlayer space between the graphite sheets indicate high and low temperature regimes for the diffusion with barriers of 51.2 meV and 11.5 meV. Our results are compared with those of first principles.

Establishment and maintenance of an optimal chiral surface in cinchona-modified 1% Pt/Al2O3 for enantioselective hydrogenation of α-keto esters

An optimal chiral surface in the cinchona-modified Pt/Al2O3 catalytic system is established for fast enantioselective hydrogenation of ethyl pyruvate. A makeup protocol is used to compensate for the destructive hydrogenation of the chiral modifier, thus maintaining the optimal chiral surface over the course of the hydrogenation reaction. Hydrogenation over the optimal surface (Ptsurface/modifier = 5–12) results in high enantioselectivity (94% ee) under mild conditions (5.8 bar and 17°C) with high turnover frequency (4 s-1) and turnover numbers (pyruvate/modifier>28,000, pyruvate/Ptsurface>5,500).

Kinetic influences on enantioselectivity in asymmetric catalytic hydrogenation

Examples from both homogeneous and heterogeneous catalytic systems are presented which demonstrate the role that reaction dynamics may play in dictating the ultimate enantioselectivity observed in asymmetric hydrogenation reactions. The hydrogenation of allylic alcohols using Ru(S)-binap and the hydrogenation of α-keto esters using cinchona-modified supported Pt are discussed. This work highlights the importance of considering reaction kinetics in addition to the stereochemical aspects of the chiral catalytic environment in interpreting catalytic behavior in asymmetric hydrogenation reactions.

A combined approach to characterization of catalytic reactions using in situ kinetic probes

Several in situ probes for continuously monitoring rate of catalytic reactions under reaction conditions are described. They are reaction calorimetry, measurements of hydrogen uptake in the case of hydrogenation, and infrared spectroscopy. In studying catalytic hydrogenation reactions, for example, these in situ probes provide kinetic details of the reactions from different perspectives over the entire course of the reaction. The reaction calorimetry and the hydrogen uptake measure directly, continuously, and in a non-invasive manner the rate of reaction, while the in situ infrared spectroscopy provides time-resolved compositional information in the liquid phase. A combination of the information thus obtained leads to a clear and coherent kinetic picture of the reaction under study which can greatly facilitate pathway analysis and mechanistic description of the catalytic reaction. In this report, the usefulness of the combination of these in situ probes is illustrated with two examples of heterogeneously-catalyzed hydrogenation reactions.

Harvesting short-lived hypoiodous acid for efficient diastereoselective iodohydroxylation in Crixivan® synthesis

Abstract The evasive hypoiodous acid is generated in situ from NaOCl and NaI and used efficiently for clean iodohydroxylation of 1 , producing the Crixivan ® intermediate 2 in high yield with highly efficient 1,3-asymmetric induction. This pH-tunable process allows HOI generation at a pH optimal for supressing byproduct formation in pH-sensitive iodohydroxylation reactions.

Palladium on Carbon-Catalyzed Cross-Coupling of Aryl Halides with Potassium p-Tolyltrifluoroborate in Air

Abstract Palladium supported on carbon (Pd/C) has been shown to be an effective catalyst for the cross-coupling of potassium p-tolyltrifluoroborate with a variety of aryl bromides and iodides. Yields ranging from moderate to good were obtained using Pd/C in ethanol/water mixtures with potassium carbonate as base at 50 °C under an air atmosphere.

Modeling of kinetically coupled selective hydrogenation reactions: Kinetic rationalization of pressure effects on enantioselectivity

Abstract A two-site, two-step kinetic model is proposed to rationalize the observed effects of solution hydrogen concentration on enantioselectivity in the asymmetric hydrogenation of ethyl pyruvate using a dihydrocinchonidine-modified heterogeneous Pt catalyst. The model successfully predicted enantioselectivity at a hydrogen concentration outside the range used in the kinetic fit. This work demonstrates how the perturbation from equilibrium adsorption of the organic substrate on a heterogeneous catalyst may account for the observed effects of pressure on enant ioselectivity. Both positive and negative hydrogen dependences on enantioselectivity may be rationalized using the same model.

Kinetics and pathways of selective hydrogenation of 1-(4-nitrobenzyl)-1,2,4-triazole

The nitro group in 1-(4-nitrobenzyl)-1,2,4-triazole (4NBT) was selectively hydrogenated to the amine using a Pd/C catalyst. Kinetics and reaction pathways were studied using in-situ kinetic tools, i.e. , measurements of heat flow by reaction calorimetry and rate of hydrogen uptake, in addition to analysis of samples taken from the reactor. The hydrogenation reaction follows predominantly a two-step monomeric pathway from 4NBT to the hydroxylamine intermediate and then to the aniline. The first step, hydrogenation of 4NBT to the hydroxylamine, follows nearly zero-order kinetics. Activation energies and heats of hydrogenation associated with each step in the consecutive hydrogenation were determined. The heat of hydrogenation of the second step, hydrogenation of the hydroxylamine (−58 kcal/mol), is slightly less than that of the first step (−65 kcal/mol). However, the activation energy associated with the second step is higher than that associated with the first step. Consequcently, the rate of hydrogenation of the hydroxylamine increases with increasing temperature at a faster pace than that of hydrogenation of the 4NBT does. Hydrogenation via the dimeric pathway, as evidenced by presence of a trace amount of the azoxy intermediate (formed from a coupling reaction of the nitroso and the hydroxylamine intermediates) contributes only ∼0.1% to the overall hydrogenation reaction. The low probability of the reaction following the dimeric pathway may be attributed to the high rate of hydrogenation of the nitroso on the catalyst.