Kinetic Studies and Mechanism

To a first approximation, electrophilic substitution in five-membered heteroaromatic substrates proceeds through a mechanism which does not differ substantially from that usually accepted for homocyclic aromatic substrates. 

The most widely accepted mechanism for electrophilic aromatic substitution involves a change from sp2 to sps hybridization of the carbon under attack, with formation of a species (the Wheland or a complex) which is a real intermediate, i.e., a minimum in the energy-reaction coordinate diagram. In most of cases the rate-determining step is the formation of the a intermediate in other cases, depending on the structure of the substrate, the nature of the electrophile, and the reaction conditions, the decomposition of such an intermediate is kinetically significant. In such cases a positive primary kinetic isotope effect and a base catalysis are expected (as Melander43 first pointed out). 

Prior to, and perhaps also after, the formation of the a complex, a 77 complex (with the aromatic ring behaving as electron donor) can form, although it has not been proved that its formation is a necessary step in the reaction path.44 It has recently been suggested that the formation of the n complex could in some cases become rate-determining, when the electrophile is a very powerful one.45 This hypothesis, although questioned both from the experimental and theoretical point of view,46-48 is a possibility and could be applicable also when the aromatic substrate is a powerful nucleophile (as is the case with many five-membered heterocyclic rings). 

A number of factors often contributes to making the substitution in heteroaromatic substrates more complicated. 

Whereas some of these complications are also encountered in substitutions of six-membered rings,7, 8 49-51 others are specifically characteristic of the reactions of the five-membered rings. 

---

Electrophilic Attack on Carbon 3.14.2.4.1 Kinetic studies and mechanism... 

Kader, F, Haluk, J, Nicolas, J and Metche, M (1998) Degradation of cyanidin 3-glucoside by blueberry polyphenol oxidase kinetic studies and mechanisms. J. Agric. Food Chem., 46, 3060-3065. 

Kineties and mechanism of the vapor-phase ammoxidation of 3P was reported in mid 1970s by Prasad and Kar [62]. Radheshyam et al. [63] also reported kinetic studies and mechanism of the ammoxidation of 3P over V2O5/ ZrOj catalysts in a differential flow reactor in the temperature range from 300 10°C. They claimed from their kinetics studies that the meehanism of the reaction is of the Redox type and the rate equation dedueed assuming a steady state involves a three-stage oxidation-reduetion proeess dming the conversion of 3-picoline to 3CP. Based on that a tentative mechanism of the process has been proposed. 

Radheshyam, A., Reddy, V. S., Dwivedi, R., and Prasad, R. Kinetic studies and mechanism evolution of the ammoxidation of 3-picohne over NfiJZxO catalyst. Can J Chem Eng 83,274-280 (2005). 

The following mechanism of the Sandmeyer reaction has been proposed as a result of a kinetic study, and incidentally accounts for the formation of the azu compounds as by-products. The catalyst is the CuCl ion produced in the dissolution of cuprous chloride in the chloride solution ... 

Mechanisms. Because of its considerable industrial importance as well as its intrinsic interest, emulsion polymerization of vinyl acetate in the presence of surfactants has been extensively studied (75—77). The Smith-Ewart theory, which describes emulsion polymerization of monomers such as styrene, does not apply to vinyl acetate. Reasons for this are the substantial water solubiUty of vinyl acetate monomer, and the different reactivities of the vinyl acetate and styrene radicals the chain transfer to monomer is much higher for vinyl acetate. The kinetics of the polymerization of vinyl acetate has been studied and mechanisms have been proposed (78—82). 

This variation from the ester hydrolysis mechanism also reflects the poorer leaving ability of amide ions as compared to alkoxide ions. The evidence for the involvement of the dianion comes from kinetic studies and from solvent isotope effects, which suggest that a rate-limiting proton transfer is involved. The reaction is also higher than first-order in hydroxide ion under these circumstances, which is consistent with the dianion mechanism. 

The pioneering work of Bamford and coworkers in 1965 [17] and 1966 [18] has given a detailed kinetics study and a mechanism of the photoinitiation of polymeriza-... 

In this article we critically review most of the literature concerning non-catalyzed, proton-catalyzed and metal-catalyzed polyesterifications. Kinetic data relate both to model esterifications and polyeste-rificatiom. Using our own results we analyze the experimental studies, kinetic results and mechanisms which have been reported until now. In the case of Ti(OBu)f catalyzed reactions we show that most results were obtained under experimental conditions which modify the nature of the catalyst. In fact, the true nature of active sites in the case of metal catalysts remains largely unknown. 

Potassium peroxodisulphate (K2S2Og) also oxidizes sulphoxides to sulphones in high yield, either by catalysis with silver(I) or copper(II) salts at room temperature85 or in pH 8 buffer at 60-80 °c86-88. The latter conditions have been the subject of a kinetic study, and of the five mechanisms suggested, one has been shown to fit the experimental data best. Thus, the reaction involves the heterolytic cleavage of the peroxodisulphate to sulphur... 

Alkoxycarbonylation has been known for a long time, but the rates and selectivities of the new catalysts are outstanding. The mechanism of the alkoxycarbonylation reaction catalysed by palladium has been the topic of research for many years [55], Stepwise reactions had shown the feasibility of two mechanistic pathways, shown in Figure 12.20, but kinetic studies and in situ observations on catalytic systems were lacking. 

A. Matagne, M. F. Ghuysen, J. M. Frere, Interactions between Active-Site-Serine beta-Lactamases and Mechanism-Based Inactivators A Kinetic Study and an Overview , Biochem. J. 1993, 295, 705-711. 

Cyclic voltammetry is probably the most commonly encountered technique for studying dynamic electrochemistry. It is useful for discerning kinetics, rates and mechanisms, in addition to thermodynamic parameters which are usually obtained at equilibrium. 

Kinetic studies can be invaluable in providing detailed information concerning the mechanisms that lead to the final equilibrium state. The design of kinetic experiments, and the analysis of the data obtained from them are frequently complicated. Below we describe only the most elementary kinetic studies and the interested reader should consult specialist texts for more comprehensive descriptions. 

Theoretical evidence [Hartree-Fock (RHF) calculations and density functional theory] has been obtained for a concerted mechanism of oxirane cleavage and A-ring formation in oxidosqualene cyclization. A common concerted mechanistic pathway has been demonstrated for the acid-catalysed cyclization of 5,6-unsaturated oxiranes in chemical and enzymic systems. For example, the conversion of (24) into (26) proceeds via (25) and not via a discrete carbocation (27). Kinetic studies and other evidence are presented for various systems. 

Crabtree and coworkers proposed a catalytic cycle for the reaction outUned in Equation 6.10. The mechanism is based on labeling and kinetic studies, and is outlined in Scheme 6.4 [25]. Adduct 36 was observed in nuclear magnetic resonance (NMR) spectra and appears to be a catalyst resting state. It should be noted that there is no change in the oxidation state of Ir, and that the key step is thought... 

We first consider the Demko and Sharpless article (2001) on the synthesis of substituted tetrazoles from nitriles in water (excerpt 5D). This excerpt is particularly useful because it illustrates several types of content that authors typically discuss in synthesis papers. The authors begin by proposing two possible mechanisms for the tetrazole reaction, a two-step mechanism and a concerted mechanism. The mechanisms are presented in a scheme (Scheme 1). In the accompanying text, the authors cite evidence for both mechanisms, highlight salient features of the mechanisms, mention the results of kinetic studies, and point out that the role of zinc metal is as yet unclear. 

On the basis of kinetic studies, a mechanism for the radical oxidation of thioether with 36 has been proposed and is indicated in Scheme D ". The key step involves the formation of a radical cation-anion pair within the solvent cage. The presence of the pic ligand in the coordination sphere of the metal reduces the electrophilicity of the peroxo complex, thus allowing the competitive radical process to take place. 

---