Nucleophilicity parameters

CH3Br -I- Y CH3Y -H Br A nucleophilic parameter WMcBr is defined... 

It was soon learned that the nucleophilic parameter WMcBr is not a universal measure of reagent nucleophilicity, and Edwards took a more fundamental approach, writing a two-term LFER, Eq. (7-70),... 

E° is the standard potential of the reaction 2Y = Y, -I- 2e . The additive constants set Hu and n equal to zero for H2O. The quantities a and b are parameters measuring susceptibility to the corresponding nucleophilic parameters. Evidently /7n describes... 

Table 7-14. Nucleophile Parameters for Correlation of Nucleophilic Substitutions...

Table 7-16. Nucleophile Parameters for Cation-Anion Recombinations ...

For substituted anilines (Thompson and Williams, 1977) and for 1-naphthylamine and a series of derivatives thereof (Castro et al., 1986a), k2 and the ratio Ar 2/Ar3 have been determined for nucleophilic catalysis with Cl-, Br-, SCN-, and SC(NH2)2. The values of k2 correspond fairly well to those found for the diazotization of aniline, but those of Ar 2/Ar3 increase markedly in the above sequence (Table 3-1). As k3 is expected to be independent of the presence of Cl- or Br- and to show little dependence on that of SCN- or thiourea, the increase in k 2/k3 for this series must be due mainly to 2. Indeed, the value of log(Ar 2/Ar3) shows a linear correlation with Pearson s nucleophilicity parameter n (Pearson et al., 1968). This parameter is based on nucleophilic substitution of iodine (as I-) in methyl iodide by various nucleophiles. The three investigations on nucleophilic catalysis of diazotization demonstrate that Pearson s criteria for bimolecular nucleophilic substitution at sp3 carbon atoms are also applicable to substitution at nitrogen atoms. 

On the basis of the nucleophilicity parameters B, NBs, and fi (see Table 8-2) one expects less of the homolytic product in water than in methanol. This is, however, not the case. It has been known for many decades that a very complex mixture of products is formed in the decomposition of diazonium ions, including polymeric products, the so-called diazo tars. In alcohols this is quite different. The number of products exceeds three or four only in exceptional cases, diazo tars are hardly formed. For dediazoniation in weakly alkaline aqueous solutions, there has, to the best of our knowledge, been only one detailed study (Besse et al., 1981) on the products of decomposition of 4-chlorobenzenediazonium fluoroborate in aqueous HCOf/ CO]- buffers at pH 9.00-10.30. Depending on reaction conditions, up to ten compounds of low molecular mass were identified besides the diazo tar. 

In Eq. (10-17), parameters a and b measure the sensitivity of the reaction to these nucleophilic parameters. Since H measures proton basicity and En the electron-donation ability, this treatment models nucleophilicity as a combination of electron loss and electron pair donation. The Edwards equation is thus an oxibase scale of nucleophilic reactivity. Table 10-5 summarizes the nucleophilic parameters. 

Nucleophilic reactivity toward Pt(II) complexes may be conveniently systematized via linear free energy relationships established between reactions of trans Ptpy2Cl2 (py = pyridine) with various nucleophiles and reactions of other Pt(II) complexes with the same nucleophiles. First, each nucleophile is characterized by a nucleophilicity parameter, derived from its reactivity toward the common substrate, trans Ptpy2Cl2. Reactivity toward other Pt(II) substrates is then quite satisfactorily represented by an equation of the form (21), wherein ky is the value of in the reaction with nucleophile Y... 

Mayr has reviewed the nucleophilicity parameters of allylstannanes and related compounds.276 The allyl-tin bond is easily cleaved, and this has been exploited in the preparation of pentafluorophenyltin chlorides and bromides (Equation (98)).277... 

Correlation analysis of solvent effects on the heterolysis of p-methoxyneophyl tosyl-ate has been performed by using the Koppel-Palm and Kamlet-Taft equations. The reaction rate is satisfactorily described by the electrophilicity and polarity parameters of solvents, but a possible role for polarizability or nucleophilicity parameters was also examined. 

It is accepted that the acmal nucleophile in the reactions of oximes with OPs is the oximate anion, Pyr+-CH=N-0 , and the availability of the unshared electrons on the a-N neighboring atom enhances reactions that involve nucleophilic displacements at tetravalent OP compounds (known also as the a-effect). In view of the fact that the concentration of the oximate ion depends on the oxime s pATa and on the reaction pH, and since the pKs also reflects the affinity of the oximate ion for the electrophile, such as tetra valent OP, the theoretical relationship between the pATa and the nucleophilicity parameter was analyzed by Wilson and Froede . They proposed that for each type of OP, at a given pH, there is an optimum pK value of an oxime nucleophile that will provide a maximal reaction rate. The dissociation constants of potent reactivators, such as 38-43 (with pA a values of 7.0-8.5), are close to this optimum pK, and can be calculated, at pH = 7.4, from pKg = — log[l//3 — 1] -h 7.4, where is the OP electrophile susceptibility factor, known as the Brpnsted coefficient. If the above relationship holds also for the reactivation kinetics of the tetravalent OP-AChE conjugate (see equation 20), it would be important to estimate the magnitude of the effect of changes in oxime pX a on the rate of reactivation, and to address two questions (a) How do changes in the dissociation constants of oximes affect the rate of reactivation (b) What is the impact of the /3 value, that ranges from 0.1 to 0.9 for the various OPs, on the relationship between the pKg, and the rate of reactivation To this end, Table 3 summarizes some theoretical calculations for the pK. ... 

The development of these various solvent parameters and scales has been accompanied by the realization that there are uncertainties in the physical property of the solvent that is correlated by a particular parameter in cases where systematic changes in solvent structure affect several solvent properties. Consider a reaction that shows no rate dependence on the basicity of hydroxylic solvents, and a second reaction that proceeds through a transition state in which there is a small transition state stabilization from a nucleophilic interaction with the hydroxyl group. The rate constants for the latter reaction will increase more sharply with changing solvent nucleophilicity than those for the former, and they should show a correlation with some solvent nucleophilicity parameter. This trend was observed in a comparison of the effects of solvent on the rate constants for solvolysis of 1-adamantyl and ferf-butyl halides, and is consistent with a greater stabilization of the transition state for reaction of the latter by interaction with nucleophilic solvents. ... 

Far from confirming a dependence of nucleophilic selectivity on the reactivity of the carbocations, Ritchie observed that selectivities were unchanged over a 106-fold change in reactivity.15 He enshrined this result in an equation (29) analogous to that of Swain and Scott, but with the nucleophilic parameter n modified to N+ to indicate its reference (initially) to reactions of cations, and with the selectivity parameter s taken as 1.0, that is, with no dependence of the selectivity of the cation on its reactivity (as measured by the rate constant for the reference nucleophile, kn2o for water). 

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). 

Dinitrobenzofuroxan (DNBF) is known as a superelectrophile due to its high reactivity both as an electrophile and in its pericyclic addition reactions. NMR studies show that reaction with 2-aminothiazole and its 4-methyl derivative yield anionic carbon-bonded adducts such as (11) by reaction at the 5-position, whereas the 4,5-dimethyl derivative reacts via the exocyclic amino group. Kinetic studies of the first two compounds, both in acetonitrile and in 70 30 (v/v) water-DMSO, have been used to assess their carbon nucleophilicities and place them on the Mayr nucleophilicity scale.55 In a related study, the nucleophilic reactivity, in acetonitrile, of a series of indoles with both DNBF and with benzhydryl cations have been compared and used to determine nucleophilicity parameters for the indoles.56... 

The kinetics of reaction of four indoles with a number of benzhydryl cations has allowed the determination of the nucleophilicity parameters N and S for these reactions.49 Kinetic data from the reaction of a number of indoles with 4,6-dinitroben-zofuroxan then allow determination of their N values. Correlation of these data with those for protonation at C(3) of 5-substituted indoles and 5-substituted 2-methylindoles... 

The nucleophilicity parameters for carbanions of nitronates and malonic acid derivatives have been investigated.143 The nucleophilic reactivities do not correlate with the acidity constants of the conjugate CH acids, and from the poor correlation of the reactivities of the substituted a-nitrobenzyl anions with Hammett s ex-constants it can be inferred that the nucleophilic reactivities are strongly controlled by solvation. 

Figure 1. Estimated reaction rates, Scaled, using nucleophilicity parameter N and elec-trophilicity 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)... 

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. 

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