Solvolytic reactions rate determination

As with solvolysis reactions of octahedral complexes, the rate-determining step may be solvolytic or dissociative in any case, it is independent of the concentration of Y ... 

One of the first differences to be noted about the Rhm acido-amine complexes is that the chloro complexes are frequently much more stable with respect to solvolysis than their Co111 and Cr111 analogues and solvolytic equilibrium is reached when very little of the chloro complex has aquated, even in dilute solution and in the absence of added chloride ions. This is, to some extent, the consequence of the move away from class a character already mentioned above. As a result, the rate constants for aquation are obtained from ligand substitution reactions (including chloride exchange) which first have to be shown to be mediated by a rate determining aquation. More recently, data have been obtained from a study of the solvolysis in basic solution. This serves to... 

These aquation reactions follow the same general mechanism as for non-cyclic amines, even though the rates can be many orders of magnitude less.35 The rate expression can show acid independent (solvolytic) and/or acid dependent pathways. For secondary amine/imine macrocycles with less than 16 members, reactions with Ni2+ are usually first order in [H+] (cleavage of first M—N bond rate-determining), while for Cu2+ they are second order in [H+] (cleavage of second... 

A plot of l/fcobs versus 1/[M2+] is linear of slope 1/kK and intercept 1/fc The pH dependence of the plateau rate constant fcUm can be used to determine if the reaction shows a dependence on the hydroxide ion concentration. A typical situation is shown in Figure 3. In this case there is a positive intercept so that kljm = fc0 + feOH[OH ]. The k0 term normally indicates a solvolytic reaction (nucleophilic attack by water) while fc0H, the slope of the line, relates to base hydrolysis. 

In these later sections, interpretations of quantitative data for product mixtures are emphasised, and the relationship between kinetics and product analysis will be developed. Mechanistic applications of kinetic data are limited to steps of reactions prior to and including the rate-determining step. As separate later steps often determine the reaction products, detailed product studies and investigations of reactive intermediates are important supplements to kinetic studies. Examples of solvolytic and related (SN) reactions have been chosen first because they provide a consistent theme, and second because SN reactions provide an opportunity to assess critically many of the mechanistic concepts of organic chemistry. Product composition in solvolytic reactions will be discussed next followed by product selectivities (Section 2.7.2) and rate-product correlations (Section 2.7.3). 

The chemistry of dihalocyclopropanes has been reviewed in several places the most recent being in 1983 in an earlier volume of this series. The principles involved in explaining the rate and product behaviors observed with the dihalocyclopropanes follow from those described previously for the reactions of monohalo- or sulfonate ester-substituted cyclopropanes and thus will not be repeated here. In most of these studies the solvolytic reactions were silver ion assisted and only qualitative rate data were presented. The major emphasis was on determining by means of product studies whether the endo or exo halogen was the most reactive in the various systems and thus whether the product was a CIS- or trans-cycloalkene derivative. 

Primary and secondary kinetic isotope effects are of general importance in the study of neighboring group participation. Isotopic substitution a to the incipient carbo-cation produces a secondary isotope effect whereas 0 and y substituents may give rise to both primary and secondary effects. For example, if the rate determining step of a solvolytic reaction involves a hydrogen shift or elimination, primary deuterium isotope effects are clearly implicated. 

Rates and products of solvolytic reactions (equation 1) were obtained by standard NMR or high-performance liquid chromatographic (HPLC) methods. Rates of reactions were also monitored from the appearance of acid (HX, equation 1), determined by the change in conductance of the solution or by titrimetric methods. For anions X- containing a suitable chromophore, reaction rates were monitored by the change in UV spectrum of the solution. The chemicals required for this study were either... 

First derivative spectra of levomepromazine (LV) and its sulphoxide were employed for investigation of LV photodegradation [11]. The degradation process of biapenem was monitored by measurement of first-derivative amplitude at 312 nm [12]. The determined rate constants for studied process were in good agreement with those obtained by HPLC method [12]. The second-order derivative spectrophotometric method was used for investigation of solvolytic reaction 2-phenoxypropionate ester of fluocinolone acetonide [45]. The run of process was observed by measurement the second-order amplitude at 274.96 nm corresponded to fluocinolone acetonide. The solvolysis rate constant was calculated using derivative method and compare with those obtained by HPLC methods [45]. 

Since the rates of the replacement reactions studied are independent of the nucleophilic ligands they must proceed via a rate-determining step to a reactive intermediate. This may be the five-coordinate [Rhen Xp dissociative mechanism) or the six-coordinate [Rhen XH O] (Sj 2 solvolytic mechanism). Since the reactions are reversible, they can be written as in 2 where k +Y... 

In solvolytic reactions hydride transfer is an important process. If hydride transfer occurs during the rate-determining step, a deuterium... 

The partial rate factors af and /3f for the a- and /3-positions of thiophene have been calculated for a wide range of electrophilic reactions these have been tabulated (71 AHC(13)235, 72IJS(C)(7)6l). Some side-chain reactions in which resonance-stabilized car-benium ions are formed in the transition states have also been included in this study. A correspondence between solvolytic reactivity and reactivity in electrophilic aromatic substitution is expected because of the similar electron-deficiency developed in the aromatic system in the two types of reactions. The plot of log a or log /3f against the p-values of the respective reaction determined for benzene derivatives, under the same reaction conditions, has shown a linear relationship. Only two major deviations are observed mercuration and protodemercuration. This is understandable since the mechanism of these two reactions might differ in the thiophene series from the benzene case. 

The extension of equilibrium measurements to normally reactive carbocations in solution followed two experimental developments. One was the stoichiometric generation of cations by flash photolysis or radiolysis under conditions that their subsequent reactions could be monitored by rapid recording spectroscopic techniques.3,4,18 20 The second was the identification of nucleophiles reacting with carbocations under diffusion control, which could be used as clocks for competing reactions in analogy with similar measurements of the lifetimes of radicals.21,22 The combination of rate constants for reactions of carbocations determined by these methods with rate constants for their formation in the reverse solvolytic (or other) reactions furnished the desired equilibrium constants. 

These methods are not always applicable or convenient. A more general method used by Richard and Jencks utilizes HPLC analysis of carbocation formation in alcohol-water mixtures.22 As shown in Scheme 2 for an a-aryl ethyl cation, formation of the ether product from reaction of the carbocation with the alcohol depends on the rate constant for carbocation formation kll and the partition ratio between product formation and the back reaction to form the alcohol kROiiAii2o- This ratio may be determined from the ratio of products formed from reaction of the carbocation generated from a suitable solvolytic precursor such as an alkyl halide. 

The investigations carried out in this area were done primarily to determine the magnitudes of steric and electronic effects on the solvolytic rates and products of reaction in the cyclopropylcarbinyl cation system. The goal of most of these studies was to learn more about the nature of the charge delocalization in the cyclopropylcarbinyl system and of the stereochemistry of the cyclopropylcarbinyl-cyclobutyl and cyclopropyl-carbinyl-allylcarbinyl cation rearrangements. Key papers in these studies were those in 1966 by Schleyer and Van Dine, in 1971 by Majerski and Schleyer and in 1974 by Poulter and Spillner which demonstrated that in the simple cyclopropylcarbinyl system... 

Four different probes gave short reactivity orders toward vinyl cations (1) common ion rate depression in solvolysis (2) competitive capture of solvolytically generated ions (3) direct reaction of a vinyl cation with nucleophiles and (4) competition between intra- and intermolecular nucleophilic capture. A short reactivity order is obtained in each case, but because of the different solvents and conditions the orders cannot be combined to a single series. However, a selectivity rule that governs the relative reactivities toward different vinyl cations in terms of a constant selectivity or a reactivity-selectivity relationship can be determined. 

The solvent may also drastically affect the anchimerically assisted fraction in nucleophilically assisted ionization reactions. As the solvent becomes more nucleophilic, there is greater solvent participation, if possible, at the expense of neighboring group assistance. The data in Table 4 are illustrative of this effect. It is obvious that in both formic acid and acetic acid there is considerable MeO-5 and MeO-6 nucleophilic participation. In ethanol, however, the ratio kjk is diminished as solvent attack (fcj becomes more effective. These effects may be quantitatively assessed. Winstein et alP used a Taft treatment for the system RCH2OBS in estimating the kj portion of the solvolytic rate constant [Eq. (14)]. Values for K/K where /c, is the titrimetrically observed rate constant, were determined. 

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