Swain-Scott nucleophilicity

Finally, we would like to emphasize that, besides obtaining values of ccfrom the Marcus analysis, another great advantage is that one can separate kinetic and thermodynamic contributions to the parameters in linear free-energy relations. In this article we have done this for the Swain-Scott nucleophilicity parameter n, for m describing the change of reaction rate with solvent, and for the Hammett p-values. 

The ease with which a given 8 2 displacement occurs depends on multiple factors, such as the nucleophilicity of the incoming nucleophile (which depends on both its electronic and steric character), steric hindrance at the electrophilic carbon center, the effectiveness of the leaving group, and the solvent and other environmental effects. By defining a standard substrate and standard reaction conditions, the reactivity of different nucleophiles may be quantified. One such measure of nucleophilicity is the Swain-Scott nucleophilicity constant n, for which methyl iodide is chosen as the standard substrate and reaction rates are measured in methanol at 25 °C ... 

TABLE 1.1 Swain-Scott Nucleophilicity Constants and Conjugate Acid pK Values of Some Common Nucleophiles ... 

Halides are nucleophilic. The Swain-Scott nucleophilicity increases down the group (see, e.g.. Table 1.1) ... 

The LFER correlation according to the Swain-Scott equation for nucleophilic attack on /3-propiolactone. Data are from Ref. 13. 

The following overall nucleophilicity order for Sn2 mechanisms (in protic solvents) was given by Edwards and Pearson RS > ArS >1 >CN > OH > Nj > Br > ArO > Cl > pyridine > AcO > H2O. A quantitative relationship (the Swain-Scott equation) has been worked out similar to the linear free energy equations considered in Chapter 9 ... 

A completely empirical LFER can also be constructed with recourse only to kinetic data. This has been the case in the setting up of a scale of nucleophilic power for ligands substituting in square-planar complexes based on the Swain-Scott approach. The second-order rate constants Ay for reactions in MeOH of nucleophiles Y with tra 5-Pt(py)2Cl2, chosen as the standard substrate... 

A point of key importance in study of solvolysis is the nucleophilicity of the solvent. Whereas the Y and other scales have been available for measuring ionizing power for some years, there has been no satisfactory scale for nucleophilicity. Swain, Mosely, and Bown attempted to set up an equation for correlation of solvolysis rates that included both nucleophilicity and ionizing power 112 their system did not prove particularly helpful for understanding mechanism.113 The Swain-Scott equation, discussed in Chapter 4 (p. 185), was not evaluated for solvents. 

Second-order rate constants for the reactions of phenacyl bromide with a number of anionic or neutral nucleophiles in 3 2 (v/v) acetone-water have been measured at several temperatures.141 Correlation analysis with the Bronsted equation or Swain-Scott equation is not satisfactory. Better results were obtained with the two-parameter Edwards equation. 

Solvolysis of the R,R and R,S isomers of 2-bromo-9-(l-X-ethyl)fluorenes, X = Cl, Br, I, or OBs, in 25% (v/v) acetonitrile in water has been studied with respect to rates of formation of elimination products and of substitution products (X = OH or NHCOMe).142 The parent 9-(l-X-ethyl)fluorenes and the 2,2/-dibromo-9-(l-X-ethyl)-fluorenes were also studied. Various effects of leaving group and of the presence of nucleophiles on the competition between the reactions were observed and the Bronsted equation was applied to the results for the elimination reactions. A related study of solvolysis of 9-(X-methyl)fluorenes, X = I, Br, or Bs, was also carried out, in which the Swain-Scott equation was applied to nucleophilic selectivities in the S 2 reactions.143... 

Correlation of nucleophilic rate data for phenyldimethylsulfonium ions with common nucleophiles, with pX e values shows that the slopes of the lines, jS[ e, correlate qualitatively with the Edwards hardness parameter for the nucleophile and not with the Swain-Scott n parameter.144 cw,cw-2,4,6-Trimethyl-l,3,5-triaminocyclohexane is weakly basic in aqueous solution, because of steric inhibition to solvation of the conjugate acid.145 The three NH2 groups are axial and the steric effect also results in reduced reactivity as a nucleophile in, S n2 reactions. Highly stereoselective syntheses of N-. and O-glycosides have been carried out by addition of anionic nucleophiles to glycosyl iodides.146 5 n2 reactions are involved, but some substrates are susceptible to E2 elimination when treated with highly basic anions. 

In principle, these measurements represent an application of the Swain-Scott relationship to two nucleophiles only. This is apparent from Equation (28), in which nAz corresponds to n for the azide ion and the electrophilic parameter s is seen to measure the selectivity of the carbocation between azide... 

Mayr initially defined a set of electrophilic parameters for the benzhydryl cations using a reference nucleophile, which was chosen as 2-methyl-1-pentene.268,269 Values of E were then defined as log k/k0, where k0 refers to a reference electrophile (E= 0), which was taken as the 4,4 -dimethoxybenzhydryl cation. Plots of log k against E for other alkenes are thus analogous to the plots of logk against p fR in Fig. 7 except that the correlation is referenced to kinetic rather than equilibrium measurements. However, they differ from plots based on the Swain-Scott or Ritchie relationships in which log k is normally plotted against a nucleophilic parameter, that is, n or N+, rather than E. 

Note again that 5 here differs from s in the Swain-Scott equation which refers to the slope of a plot of log k versus the nucleophilicity parameter n (or N) rather than electrophilicity parameter (E). 

The simplest linear free energy relation that has been used to describe the attack of a series of nucleophiles in an SN2 reaction is the Swain-Scott relation (Swain and Scott, 1953). In our notation the relation becomes (45), where the nucleophilicity parameter for X, x, is defined by (46) or its equivalent (47)... 

In general this analysis shows that the behaviour which the Swain-Scott relation attempts to describe is governed by both kinetic and thermodynamic contributions. The mix of the two contributions (Table 6 and Fig. 11) is different for different nucleophiles. This is probably the reason why the Swain-Scott relation does not hold for a large number of reactions (Leffler and Grunwald, 1963b Koskikallio, 1972) and why more complicated expressions, such as the Edwards relation (Edwards, 1954), have been proposed. 

In this section we examine the evidence about transition state structure that can be obtained from Hammett op relations. We start by considering substitution in the attacking nucleophile X or in the leaving group, Y. From the general relation (36) we deduce (117). As with the Swain-Scott n and the m Y ... 

Similar SN 2 mechanisms occur in the uncatalyzed ring-opening reactions of ethylene oxide and other epoxides with nucleophiles such as halide ions or amines [151, 154]. The dependence of the rate coefficient kx on the attacking nucleophile is the same as in SN 2 reactions of alkyl halides. It follows the Swain—Scott [155] and Edwards [156] relationships. 

The rate coefficient x is dependent on the nucleophilic power of the halide ion according to the Swain—Scott relationship [155]... 

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