HSAB theory

The Hard-Soft-Add-Base (HSAB) theory was developed by Pearson in 1963. According to this theory, Lewis acids and Lewis bases are divided into two groups on one hand hard acids and bases, which are usually small, weakly polarizable species with highly localised charges, and on the other hand soft acids and bases which are large, polarizable species with delocalised charges. A selection of Lewis acids, ordered according to their hardness in aqueous solution is presented in Table 1.3. 

The theory predicts high stabilities for hard acid - hard base complexes, mainly resulting from electrostatic interactions and for soft acid - soft base complexes, where covalent bonding is also important Hard acid - soft base and hard base - soft acid complexes usually have low stability. Unfortunately, in a quantitative sense, the predictive value of the HSAB theory is limited. Thermodynamic analysis clearly shows a difference between hard-hard interactions and soft-soft interactions. In water hard-hard interactions are usually endothermic and occur only as a result of a gain in entropy, originating from a liberation of water molecules from the hydration shells of the... 

Table 1,3, Cla,ssification of the hardness in aqueous solution of some selected Lewis-acids according to the HSAB theory . ...

Several alternative attempts have been made to quantify Lewis-acid Lewis-base interaction. In view of the HSAB theory, the applicability of a scale which describes Lewis acidity with only one parameter will be unavoidably restricted to a narrow range of struchirally related Lewis bases. The use of more than one parameter results in relationships with a more general validity ". However, a quantitative prediction of the gas-phase stabilities of Lewis-acid Lewis-base complexes is still difficult. Hence the interpretation, not to mention the prediction, of solvent effects on Lewis-add Lewis-base interactions remains largely speculative. 

More complete interpretations of Diels-Alder regioselectivity have been developed. MO results can be analyzed from an electrostatic perspective by calculating potentials at the various atoms in the diene and dienophile. These results give a more quantitatively accurate estimate of the substituent effects. Diels-Alder regioselectivity can also be accounted for in terms of HSAB theory (see Section 1.2.3). The expectation would be that the most polarizable (softest) atoms would lead to bond formation and that regioselectivity would reflect the best mateh between the diene and dienophile termini. These ideas have been applied using 3-2IG computations. The results are in agreement with the ortho rule for normal-electron-demand Diels-Alder reactions. ... 

Calculations at several levels of theory (AMI, 6-31G, and MP2/6-31G ) find lower activation energies for the transition state leading to the observed product. The transition-state calculations presumably reflect the same structural features as the frontier orbital approach. The greatest transition-state stabilization should arise from the most favorable orbital interactions. As discussed earlier for Diels-Alder reactions, the-HSAB theory can also be applied to interpretation of the regiochemistry of 1,3-dipolar cycloaddi-... 

These concepts play an important role in the Hard and Soft Acid and Base (HSAB) principle, which states that hard acids prefer to react with hard bases, and vice versa. By means of Koopmann s theorem (Section 3.4) the hardness is related to the HOMO-LUMO energy difference, i.e. a small gap indicates a soft molecule. From second-order perturbation theory it also follows that a small gap between occupied and unoccupied orbitals will give a large contribution to the polarizability (Section 10.6), i.e. softness is a measure of how easily the electron density can be distorted by external fields, for example those generated by another molecule. In terms of the perturbation equation (15.1), a hard-hard interaction is primarily charge controlled, while a soft-soft interaction is orbital controlled. Both FMO and HSAB theories may be considered as being limiting cases of chemical reactivity described by the Fukui ftinction. 

Heterocyclic sulphoxides 65 mass spectra of 130-132 Hexahydronaphthalenols, synthesis of 310 Hofmann elimination 953 HOMO energies 1048, 1049 Homolytic substitution 1109 intramolecular 846 Horner-Wittig reaction 333 Hot electrons 892, 893 HSAB theory 282, 549 Hydrides, as reducing agents 934-941, 959 Hydrogen abstraction, photochemical 874, 876, 877, 879, 880... 

Yatsimirskii (1970) attempted to quantify HSAB theory and produced hardness indices for adds and bases. These indices were obtained by plotting the logarithms of the equilibrium constants for the reactions of bases with the proton (the hardest add) against similar values for the reactions with CHjHg (one of the softest adds). For adds, the hydroxyl ion (the hardest base) and the chloride ion (a soft base) were chosen. 

According to Yatsimirskii, group (2) and (3) species are equivalent to Pearson s hard acids and bases, and group (4), (5) and (6) species correspond to Pearson s soft acids and bases. This classification is of more value than HSAB theory to our subject. It can be seen that all cementforming anions come from group (3) and cations from groups (3), (4) and (5). Thus, the bonding in cement matrices formed from cation-anion combinations is not purely a but contains some n character. 

An observation regarding HSAB theory here is that metal ions that are soft in aqueous solution must not only be able to form covalent M-L bonds, but also must have a loose enough coordination sphere to tolerate potentially adverse steric effects such as bulky donor atoms or substituents on a ligand. For a soft Zn(II) ion to be produced in zinc metalloenzymes, its coordination number must drop from six in the... 

The differences in reactivity between the nitrogen and the sulfur atom in OZTs reveal that most reactions can be interpreted with reference to Pearson s HSAB theory.56 In the case of l,3-oxazolidine-2-thiones, one may consider the nitrogen atom as a harder basic center than the softer sulfur atom. 

In order to clarify the different behavior of anion 2 and 3 (Scheme 4.10) toward DMC, various anions with different soft/hard character (aliphatic and aromatic amines, alcohoxydes, phenoxides, thiolates) were compared with regard to nucleophilic substitutions on DMC, using different reaction conditions. Results were in good agreement with the hard-soft acid-base (HSAB) theory. Accordingly, the high selectivity of monomethylation of CH2 acidic compounds and primary aromatic amines with DMC can be explained by two different subsequent reactions, which are due to the double electrophilic character of DMC. The first... 

This pronounced double selectivity has been explained in terms of Pearson s HSAB theory. According to this procedure, A-methylcarbamates have been prepared from primary aliphatic and aromatic amines, either at reflux temperature of... 

Further examination of the results indicated that by invocation of Pearson s Hard-Soft Acid-Base (HSAB) theory (57), the results are consistent with experimental observation. According to Pearson s theory, which has been generalized to include nucleophiles (bases) and electrophiles (acids), interactions between hard reactants are proposed to be dependent on coulombic attraction. The combination of soft reactants, however, is thought to be due to overlap of the lowest unoccupied molecular orbital (LUMO) of the electrophile and the highest occupied molecular orbital (HOMO) of the nucleophile, the so-called frontier molecular orbitals. It was found that, compared to all other positions in the quinone methide, the alpha carbon had the greatest LUMO electron density. It appears, therefore, that the frontier molecular orbital interactions are overriding the unfavorable coulombic conditions. This interpretation also supports the preferential reaction of the sulfhydryl ion over the hydroxide ion in kraft pulping. In comparison to the hydroxide ion, the sulfhydryl is relatively soft, and in Pearson s theory, soft reactants will bond preferentially to soft reactants, while hard acids will favorably combine with hard bases. Since the alpha position is the softest in the entire molecule, as evidenced by the LUMO density, the softer sulfhydryl ion would be more likely to attack this position than the hydroxide. 

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