Nucleophilicity parameter combinations

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. 

Mayr and Patz have recently evaluated 56 reaction series, mostly for reactions as described in this article, and derived Eq. (23), in which carbo-cations are characterized by the electrophilicity parameter E, whereas nucleophiles are characterized by the nucleophilicity parameter N and the slope parameter s [182]. The latter quantity, s, which basically describes the slopes of plots as shown in Figs. 10 and 11, ranges from 0.8 to 1.2 for 91 % of the 7r-nucIeophiles investigated. The mathematical form of Eq. (23) implies that the exact value of s will usually only be of importance when rate constants, which strongly deviate from 1 (e.g., (log > 5), are considered. Some of the characterized nucleophiles and electrophiles are listed in Scheme 53, where the two scales are arranged in such a way that electrophiles and nucleophiles which are located at the same level are predicted to combine with rate constants of lg k = -5 s. With s 1 one expects slow combinations for electrophile-nucleophile pairs at the same level, whereas reactions of nucleophiles with electrophiles located below them are expected to be very slow or not to occur at all at 20° C. 

Nucleophilicity parameters, N and % for electrophile-nucleophile combination based on the Mayr equation ogk = Sj (N+E), were reported for highly nucleophilic pyridines bearing amino groups at carbons 3, 4, and 5, isothioureas," and thiocarboxylates, dithiocarbamate, and dithiocarbonate." Electrophilicity parameters E were reported for triarylmethyl cations with para and meta fluorine substituents," 1,3-diarylallyl cations," and aldehydes, imines, and enones." Nucleofugality parameters Nf and Sf for ionization based upon the Mayr equation logki = Sf(Ef + Nf) were reported for acetate in aqueous methanol" and chloride in aprotic solvents." The latter study also shows that common solvent parameters do not reliably predict ionization rates in aprotic solvents. Electrofugality parameters Ef were reported for triarylmethyl cations with para and meta fluorine substituents." ... 

Nucleophilicity parameters N and % for electrophile-nucleophile combination based on the Mayr equation log k=+E) were reported for fluorides in protic solvents, enamines derived from imidazolidinones, trimethylsilyl enol ethers with perfluori-nated substituents at the a-carbon, O-methylated Breslow intermediates, anions of nucleobases and their subunits, enamides, symmetrical and unsymmetrical hydrazines, and heteroarylboron compounds. Of note, replacement of CH3 with CF3 and C6H5 with CgF5 in the trimethylsilyl enol ethers reduces the nucleophilicity by 8 and 4.5 orders of magnitude, respectively. Hydrazines have very similar nucle-ophilicities to alkyl amines in other words, there is no evidence of an a-effect. With NH2NMC2, there is a fast reversible reaction corresponding to addition of the tertiary amine, followed by a slow irreversible reaction for addition at the primary amine, with a 3000-fold difference in nucleophilicity between the two sites. ... 

Stronger Lewis acids such as SnCLi, TiCLt, and CH3AICI2 yield fast but uncontrolled polymerization with broad PDI. LCP of vinyl ethers can be achieved if the other components and reaction parameters are appropriately adjusted by various combinations of lower reaction temperature, added nucleophile, added common salt, and solvent prolarity. For example, polymerization of isobutyl vinyl ether using HC1 as the initiator (or one can use the preformed adduct of monomer and HC1) with SnCLt or TiCLj in CH2CI2 is non-LCP... 

For the reactivity parameters Y, n, a+ (but not a) andN+ the lack of curvature is not unexpected. This is because these parameters are defined with respect to the rate of some standard reaction (solvolysis of t-butyl chloride, substitution of methyl iodide, solvolysis of cumyl chlorides, combination reaction of nucleophiles with a standard electrophile). Therefore the resultant plot is of the type log k vs. log k, while the curvature shown in a typical Br nsted plot (Figure 5) results from a plot of log k vs. log K. This curvature is due to a gradual change from a reactant-like transition state, which is insensitive to a perturbation in the reactivity parameter, to a product-like transition state in which equilibrium perturbations are largely reflected in the transition state (and hence the rate). A log k — log k plot is not expected to show this effect and hence is not expected to show curvature. 

Equation (33) suggests that the failure to observe a reactivity-selectivity relationship for electrophile-nucleophile combination reactions is due to the counter influence of the solvent. The parameter 0 represents the inherent reactivity of the electrophile and is large for unreactive electrophiles, while for reactive electrophiles P is small. Now, it is the reactive electrophiles which are... 

From the results summarized in Table I, apparently the Brpnsted relationship will hold for all combinations of nucleophiles and electrophiles. Because, as pointed out previously, the Hammett equation is really a special case of the Brpnsted relationship, all the legion of nucleophile-electrophile, rate-equilibrium Hammett correlations that have been studied also fall under the scope of the Brpnsted relationship. For example, nucleophilicities of ArO , ArS , ArC(CN)2 , and the other families listed in footnote c of Table I have generally been correlated by the Hammett equation, where the acidities of benzoic acids in water are used as a model for substituent interactions with the reaction site (a), and the variable parameter p is used to define the sensitivity of the rate constants to these substituent effects. The Brpnsted equation (equation 3) offers a much more precise relationship of the same kind, because this equation does not depend on an arbitrary model and allows rate and equilibrium constants to be measured in the same solvent. Furthermore, the Brpnsted relationship is also applicable to families of aliphatic bases such as carboxylate ions (GCH2C02 ), alkoxide ions (GCH20 ), and amines (GCH2NH2). In addition, other correlations of a kinetic parameter (log fc, AGf, Ea, etc.) can be included with various thermodynamic parameters (pKfl, AG°, Eox, etc.) under the Brpnsted label. 

To test the generality of the Ritchie equation, we reacted the olefins 9-(dinitromethylene)fluorene (FDN), 9-(dicyanomethylene)fluorene (FDCN), and 9-(nitromethylene)fluorene (FN) with a series of nucleophiles (4, 5). The reaction of these three substrates resemble that of anion-cation combination reactions in the absence of leaving group departure at the transition state. Yet, in spite of the fact that these substrates are not positively charged, an excellent correlation was observed with the N+ scale. Similar results were observed for other uncharged substrates such as carbonyl functions (6) and activated aryl halides (7). However, the three systems, FDN, FDCN, and FN, are unique in that the slopes of log k versus N+ are significantly larger than 1. This necessitates the incorporation of a selectivity parameter (S+) into the Ritchie equation. 

Zahradnlk et al.160 have combined a set of parameters which may be regarded as aromaticity indices into the stability index. The approach is more comprehensive than that of Balaban, but as the authors point out it is obviously difficult to assess the relative importance of the selected indices. Those included are the specific delocalization energy DE,P34 (Section II, A,3,a) related to the extent of -electron delocalization, Aq the difference between the maximum and minimum ir-electron density in the molecule (related to the reactivity toward nucleophilic and electrophilic reagents see the preceding section), the free valence F (related to radical reactivity) and the radical super-delocalizability ST (related to radical reactivity, oxidizability, and reducibility). 

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