Nucleophilicity local hardness

The pair of electrophilicity and nucleophilicity comes together in chemistry textbooks. Just as the former is formally defined in Equation 13.11, is there a similar, straightforward formalization for the latter It turns out that it is not the case. One of the reasons may lie in the theoretical difficulty in dealing with local hardness [41,42], a quantity that is intrinsically related to nucleophilicity. Another reason stems from... 

The alkali metals share many common features, yet differences in size, atomic number, ionization potential, and solvation energy leads to each element maintaining individual chemical characteristics. Among K, Na, and Li compounds, potassium compounds are more ionic and more nucleophilic. Potassium ions form loose or solvent-separated ion pairs with counteranions in polar solvents. Large potassium cations tend to stabilize delocalized (soft) anions in transition states. In contrast, lithium compounds are more covalent, more soluble in nonpolar solvents, usually existing as aggregates (tetramers and hexamers) in the form of tight ion pairs. Small lithium cations stabilize localized (hard) counteranions (see Lithium and lithium compounds). Sodium chemistry is intermediate between that of potassium and lithium (see Sodium and sodium alloys). 

To predict which of the two alkyne carbons, C1 or C2, HNC will preferentially attack, one now invokes the local hard-soft acid-base (HSAB) principle (cf. [157]), which says that interaction is favored between electrophile/nucleophile (or radical/radical) of most nearly equal softness. The HNC carbon softness of 1.215 is closer to the softness of C1 (1.102) than that of C2 (0.453) of the alkyne, so this method predicts that in the reaction scheme above the HNC attacks C1 in preference to C2, i.e. that reaction should occur mainly by the zwitterion A. This kind of analysis worked for -CH3 and -NH2 substituents on the alkyne, but not for -F. 

Pertrifluoroacetic acid, produced in situ from HP and trifluoroacetic anhydride, is an efficient reagent for B V oxidation of butanone to yield ethyl acetate. The possible mechanism of the oxidation of aliphatic ketones by pertrifluoroacetic acid is discussed. Several organic reactions, including BV oxidations, have been studied by using reactivity and selectivity indexes proposed in the DFT. The concepts of electrophilicity and nucleophilicity have been applied as reactivity descriptors. The local hardness has been applied as well as a selectivity descriptor. The reactivity and selectivity patterns have been studied for the reactants involved in these organic reactions. They have been ranked in theoretical scales, which are comparable with experimental results obtained from... 

Electrophilic additions, Baeyer-Villiger oxidations, and the nucleophilic substitutions have been studied using the density functional theory (DFT), applying the concepts of electrophilicity, nucleophilicity, and the local hardness as reactivity and selectivity descriptors. The reactants have then been ranked in theoretical scales, which proved to be comparable with those obtained experimentally from kinetic data. ... 

Since biological systems are rich in nucleophiles (DNA, proteins, etc.) the possibility that electrophilic metabolites may become irreversibly bound to cellular macromolecules exists. Electrophiles and nucleophiles are classified as hard or soft depending on the electron density, with hard electrophiles generally having more intense charge localization than soft electrophiles in which the charge is more diffuse. Hard electrophiles tend to react preferentially with hard nucleophiles and soft electrophiles with soft nucleophiles. 

Figure 1.12 suggests that for carbonyl complexes the HOMO is localized primarily on the metal centre, with only a modest contribution from oxygen orbitals. Thus by far the majority of reactions of metal carbonyls with electrophiles involve direct attack at the metal, with the carbonyl serving as a spectator ligand. If, however, the metal centre is (i) particularly electron rich and (ii) sterically shielded and the electrophile is hard (in the HSAB sense) and also sterically encumbered, then attack may occur at the oxygen. Thiocarbonyls (LM-CS) are stronger 71-acids than CO and the sulfur is both softer and more nucleophilic. Thus electrophilic attack at the sulfur of thiocarbonyls is more common if the metal centre is electron rich (vcs < 1200 cm-1). Similarly, coordinated isocyanides (CNR) are more prone to attack by electrophiles at nitrogen. This is noteworthy in the sense that free isocyanides are attacked by electrophiles at carbon (Figure 3.19). The resulting carbyne ligands will be discussed in Chapter 5.

The electronic chemical potential /x, chemical hardness 17, and global electrophilicity 10 for the dipoles 83-86 are displayed in Table 11. Also included in Table 11 are the values of local electrophilicity and the values of the Fukui function for an electrophilic attack and for a nucleophilic attack fk at sites k for these dipoles. The two dipo-larophiles present similar electrophilicity values, 1.52 eV (14) and 1.49 eV (15) (see Table 1). According to the absolute scale of electrophilicity based on the co index,39 these compounds may be classified as strong electrophiles. 

Geerlings De Proft, 2008 Cardenas et al., 2009 Senet, 1996). One may obtain a condensed-to-atom variant and also for the electrophilic, nucleophilic and radical attacks in the usual way. Moreover, the inverse of tu(r,r ) may generate a hierarchy of nucleophilicity kernel. Unlike the previous formulations, the overall treatment here is general and analytic with hardly any bearing on the explicit form of E(N). The traditional operational definition of local softness and hardness contain the same potential information and they should be interpreted as the local abundance or concentration of their corresponding global properties. 

As noted earlier, the solvent parameters are not independent. Clearly, if a reaction gives rise as a product or as an activated complex to a species that is cationic or has a site with localized positive charge, the reaction will be favored by solvent properties including polarity, polarizability, basicity (whether hard or soft), and by tendencies to covalent or electrostatic interaction with vacant orbitals (i.e., nucleophilicity). Similarly, if the product or activated complex bears a locahzed negative charge, the reaction will still be favored by solvent polarity and polarizabihty, but also by acidity and by the presence in solvent molecules of vacant orbitals capable of receiving electron donation (electrophilicity). 

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