Rate-product correlations

An added nucleophile may contribute a medium ejfectwhich could complicate interpretations of rate-product correlations (Equation 2.15) to avoid this, onlylow concentrations of nucleophiles should be used ( 10 2 M). Allowances can be made (at least partially) for the medium effect of added electrolytes by conducting reactions at a constant ionic strength (I) as the concentration of a reactive anionic nucleophile such as chloride or bromide 

Entry no. Salt Salt cone (mol dm 3) 105fciOlv (s 1) % Azide product 

Addition of non-nucleophilic electrolytes (e.g. nitrates, Table 2.5, entry 3) shows that the consequent increased rate is due to the increase in the ionic strength of the medium, further supporting the trapping mechanism. A comparison of the effects of added bromide and chloride (entries 2 and 5) illustrates the common ion effect, i.e. trapping Ar2CH+ by chloride to regenerate starting material retards solvolyses of A CHCl. 

In general, mechanistic evidence for a reactive intermediate from trapping experiments needs to be linked to arguments against the introduction of an alternative pathway from the reactant, i.e. to show that an intermediate really has been trapped, not the reactant. A classic case is the hydrolysis of 4-nitrophenyl acetate catalysed by imidazole. The mechanism is nucleophile catalysis and the intermediate (N-acetylimidazolium cation) was trapped by aniline (to give acetanilide) with no kinetic effect, i.e. the aniline does not react directly with the substrate [51]. 

Sternell, S. and Raima, J.R. (2002) Organic Structures from Spectra (3rd edn). Wiley, New York. 

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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). 

Combinations of product studies with kinetic data provide particularly powerful indications of reaction mechanisms. Either the presence or absence of a rate-product correlation may be of mechanistic significance. First, we have an explanation of rate-product correlations using the example of competing methanolysis (second-order rate constant, IcMeOH) and aminolysis (second-order rate constant, kam) of benzoyl chloride (59) in Scheme 2.21. The mechanism is initially assumed to involve independent competing pathways, as shown, so that the equations of correlation can be derived. 

The left-hand side of Equation 2.15 refers to a ratio of experimental rate constants kQ K and ksoiv are obtained entirely from kinetic data (Equation 2.12) and the ratio k0 K/k0 v is the rate enhancement for a particular concentration of amine for example, if the ratio is 2.0, addition of the amine has doubled the rate, corresponding to a rate enhancement of 100%. The right-hand side refers to the observed product ratio, which is obtained by independent measurements (e.g. by HPLC). A fit to Equation 2.15, as observed for m-nitroaniline in methanol at 25°C, exemplifies a rate-product correlation (Table 2.4) [44]. From the agreement between calculated and observed yields of amide shown in Table 2.4, we conclude that there are indeed competing second-order reactions, as assumed in Scheme 2.21. If the mechanism proceeded via an intermediate formed in a slow step, which was trapped by the amine in a subsequent rapid step, then more amide product would be formed than predicted by Equation 2.15. 

Supporting evidence was later obtained from rate-product correlations for solvolyses of 2-propyl and 2-octyl sulfonates in the presence of added azide ion (Nj ). The observed rate-product correlation [47] is consistent with competing SN2 reactions ofthe covalent substrates (Scheme 2.23), rather than the trapping of a cationic intermediate by azide ion (Scheme 2.24). Although the medium effect of the added electrolyte complicates the interpretation of... 

The reaction of azide ions with carbocations is the basis of the azide clock method for estimating carbocation lifetimes in hydroxylic solvents (lifetime = 1 lkiy where lq, is the first-order rate constant for attack of water on the carbocation) this is analogous to the radical clock technique discussed in Chapter 10. In the present case, a rate-product correlation is assumed for the very rapid competing product-forming steps of SN1 reactions (Scheme 2.24). Because the slow step of an SN1 reaction is formation of a carbocation, typical kinetic data do not provide information about this step. Furthermore, the rate constant for the reaction of azide ion with a carbocation (kaz) is assumed to be diffusion controlled (ca. 5 x 109 M 1 s 1). The rate constant for attack by water can then be obtained from the mole ratio of azide product/solvolysis product, and the molar concentrations of azide (Equation 2.18, equivalent to Equation 2.14) [48]. The reliability of the estimated lifetimes was later... 

Scheme 9.9 adapts our basic reaction scheme to take account of the effect of a substantial excess of a trapping reagent (T) on the conversion of the reactant (R) to the product (P) via the intermediate, I. The new and characteristic product (Q) may be formed by the reaction of I with T and, to be effective, the trapping reaction must compete efficiently with the main reaction channel, i.e. k [T] ss fc in Scheme 9.9. Competing processes are included as dashed lines in Scheme 9.9 whereby the product P is also formed by a pathway not involving the intermediate with rate constant kD, and the trapping product Q is formed by the direct bimolecular reaction of R with the trap (T) with second-order rate constant k. These considerably complicate interpretations of experimental data, but may be recognised and their contributions quantified under some circumstances by analysis of rate-product correlations (see Chapter 2).

Compound mb) aq. EtOH (fcEtOH/ AcOH)Yb) fcOTs/feBr c) 80 % EtOH CH3/fcH d) Bromides 80 % EtOH Retention e) Inversion Ratios Azide Rate-Product Correlation 0... 

M NaN3, McLennan (1974) found a rate-product correlation in agreement with the classical SN2 mechanism. Similar rate/product correlations were obtained when thiourea was used as nucleophile instead of azide thiourea has the advantage that salt effects can be ignored because, by control experiments, it was established that the non-nucleophilic urea had a negligible effect on the reaction rate (McLennan, 1975). 

Table 10. Rate-product correlation for the acetolysis of 2-arylethyl tosylates (315) at 115 ...

Solvent Effects on Competing Nucleophilically Solvent Assisted (ks) and Anchimerically Assisted (JtA) Processes. Schleyer et al.s work (8) on solvolyses of 2-adamantyl (II) arose from earlier studies (71) of the competition between ks and fcA processes in (3-arylalkyl systems (XII and XIII). Apparently, no crossover occurred between the two processes, because rate-product correlations were observed. Hence, any cationic intermediates in the ks process must be sufficiently strongly solvated to prevent attack by... 

Bentley TW, RatecUff J, Renfrew A, Taylor J (1996) Rate-product correlations for concurrent nucleophilic displacements of halotriazines by hydroxide and alkoxides in water. J Chem Soc Perkin Trans 2 2377-2381... 

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