HSAB principle reactions

The concept of hard and soft acids and bases can be used to interpret many trends in chemical reactivity. These trends are summarized in the hard-soft acid-base principle (HSAB principle), an empirical summary of results collected from many chemical reactions studied through decades of research. 

We have already used the HSAB principle as it applies to linkage isomers in metal complexes. This application to bonding site preference can also be used to show the behavior of other systems. For example, the reactions of organic compounds also obey the principles when reacting with nucleophiles such as SCN- or N02 ... 

The pathway characterized with the lower energy barrier is expected to be the preferred reaction channel, especially when the addition leads to the same product. Following the local HSAB principle, one has to look at the softness matching criteria, and the minimum of sAi —. BJ and sAj —. B will determine the preferred site of attack. 

It is clear from the A.v values in Table 12.2 that the site associated with the lower A.v value, implying a better satisfaction of the local HSAB principle, is the preferred site of attack for this type of reaction [26]. 

These descriptors have been widely used for the past 25 years to study chemical reactivity, i.e., the propensity of atoms, molecules, surfaces to interact with one or more reaction partners with formation or rupture of one or more covalent bonds. Kinetic and/or thermodynamic aspects, depending on the (not always obvious and even not univoque) choice of the descriptors were hereby considered. In these studies, the reactivity descriptors were used as such or within the context of some principles of which Sanderson s electronegativity equalization principle [16], Pearson s hard and soft acids and bases (HSAB) principle [17], and the maximum hardness principle [17,18] are the three best known and popular examples. 

Thus, local softness contains the same information as the Fukui function fir) plus additional information about the total molecular softness, which is related to the global reactivity with respect to a reaction partner, as stated in HSAB principle. Thus, the Fukui function may be thought of as a normalized local softness. Atomic softness values can easily be calculated by using Equation 32.4, namely... 

Mendez, F., Tamariz, J., and Geerlings, P. 1998. 1,3-Dipolar cycloaddition reactions A DFT and HSAB principle theoretical model. J. Phys. Chem. A 102 6292-6296. 

The major disadvantage of the HSAB principle is its qualitative nature. Several models of acid-base reactions have been developed on a quantitative basis and have application to solvent extraction. Once such model uses donor numbers [8], which were proposed to correlate the effect of an adduct on an acidic solute with the basicity of the adduct (i.e., its ability to donate an electron pair to the acidic solute). The reference scale of donor numbers of the adduct bases is based on the enthalpy of reaction. A//, of the donor (designated as B) with SbCb when they are dissolved in 1,2-dichloroethane solvent. The donor numbers, designated DN, are a measure of the strength of the B—SbCb bond. It is further assumed that the order of DN values for the SbCb interaction remains constant for the interaction of the donor bases with all other solute acids. Thus, for any donor base B and any acceptor acid A, the enthalpy of reaction to form B A is ... 

To summarize, the HSAB principle is a very good first approximation but is usually inadequate for detailed analysis of reaction mechanisms. This is not really surprising. After all, this principle is nothing else than a two parameters relationship each reactant is characterized by its acidic or basic strength and by its hardness (softness). And obviously, we cannot expect to describe the complexity of chemistry with only two parameters. On the other hand, one should not underestimate its utility. Simple Hiickel calculations are also a two parameters treatment where the initial choice of the coulombic and resonance integrals a and )3 is critical. There is no doubt however that, handled with care, these calculations may give valuable insights. The same may be said for the HSAB principle. 

The hydrogenation reaction can take place at any place in the layer where favorably polarized hydrogen molecules are available. That is, the hard and soft acids and bases (HSAB) principle must be applied to hydrogenations on the surfaces of heterogeneous catalysts. 

Part of the difficulties encountered in comparing these two approaches results from the different ways in which they are used. The E-C approach treats the interaction of only two species ala time to the extent that the nonpolar solvents used in these studies minimize solvation effects, the results are comparable to gas-phase proton affinities. In contrast, the HSAB principle is usually applied to exchange or competition reactions of the sort ... 

According the HSAB principles, the carbon centre is more basic and more nucleophilic. When protic solvents are used, the resulting greater solvation of this carbon centre is thought to favour the competing reaction at the weaker nitrogen centre. A similar rationale explains why the more covalent cyanide salts such as silver cyanides and cuprous cyanides also give isonitriles as main product. 

HSAB is particularly useful for assessing the reactivity of ambident nucleophiles or electrophiles, and numerous examples of chemoselective reactions given throughout this book can be explained with the HSAB principle. Hard electrophiles, for example alkyl triflates, alkyl sulfates, trialkyloxonium salts, electron-poor car-benes, or the intermediate alkoxyphosphonium salts formed from alcohols during the Mitsunobu reaction, tend to alkylate ambident nucleophiles at the hardest atom. Amides, enolates, or phenolates, for example, will often be alkylated at oxygen by hard electrophiles whereas softer electrophiles, such as alkyl iodides or electron-poor alkenes, will preferentially attack amides at nitrogen and enolates at carbon. 

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. 

The reaction of cyanide ion with substituted benzhydryl carbenium ions to form nitriles and isocyanides is controlled by the rates of reaction at carbon and nitrogen.124 In slow reactions, far from the diffusion limit, the attack is completely at the cyanide carbon. Very fast reactions, with little or no reaction barrier reacting at the diffusion-controlled limit, occur at both the N and the C of the cyanide ion. XN2 reactions occur almost exclusively at carbon regardless of the substrate or source of the cyanide ion. The HSAB principle cannot predict the products of these reactions. 

The HSAB principle itself is the following the acid-base reactions take place in such a way that hard acids (HA) prefer to be connected with hard bases (HB), meanwhile soft acids (SA) react with soft bases (SB). 

The HSAB principle very clearly explains the competitive reactions of organo-sulfoxides, amongst which DMSO is the most commonly used as ligand [1,2,19]. The coordination compounds of these ligands are described in monographs [62,63] and also in Sec. 3.1.1 [Eqs. (3.21)—(3.24)]. The main reaction of these syntheses is represented by a simple equation (4.11) ... 

The tribochemical reactions based on the hard and soft acids and bases (HSAB) principle linked to the friction coefficient (p) are summarized above. The effect of tribological processes consists of the formation of mixed short-chain phosphate glasses containing sulfide precipitates. 

A Cameron-Plint friction machine generated tribofilms with two-layer structure a zinc polyphosphate thermal film overlying a mixed short-chain phosphate glass, containing iron sulfide precipitates. A tribochemical reaction between the zinc polyphosphate and the iron oxides species is proposed on the basis of the hard and soft acid and base HSAB principle (Martin, 1999 Martin et al., 2001). 

The adsorption of organic compounds on nascent surfaces can be considered as an acid-base reaction. According to the hard-soft acid and bases HSAB principle (Ho, 1977), polar compounds such as carboxylic acid and amine (with lone pair electrons on oxygen or nitrogen) are classified as "hard bases". A hard base reacts more easily with a hard acid than with a soft acid. Metals are classified as soft acids which react much more easily with soft bases than hard bases. The results in Table 5.1 can be explained with this concept. The soft bases (benzene, 1-hexene, diethyl disulfide) react easily with the nascent surface as a soft acid. On the other hand, the hard bases such as propionic acid, stearic acid, propyl amine and trimethyl phosphate exhibit a very low activity (Fischer et al., 1997a and 1997b Mori and Imazumi, 1988). 

Based on this process, which is sometimes referred to as the Blaise reaction ,20,21 a straightforward entry into the saxitoxin and gonyautoxin series has been devised (Scheme 14.4) which relies upon the selective alkylation of the ambident zinc enamide 9 initially formed at its soft or hard site according to the HSAB principle.22 Specifically, a terminal halide group in substrate 8 (X = Br) affords the carbocyclic product 10 via C-alkylation, whereas a terminal sulfonate entity (X = 0S02Me) leads to the pyrrolidine derivative 11 via the N-alkylation pathway. 

The HSAB Principle at a Local Level Regioselectivity of Diels-Alder Reactions... 

The Local HSAB Principle Importance of Equal Softness Between Reaction Sites... 

Two proofs for the HSAB principle were provided under the restriction of a common chemical potential of the reaction partners [83, 84]. Later on, a local HSAB principle was provided by Gazqu z and Mendez [85], They showed that the interaction between two chemical species will not necessarily occur through their softest atoms, but through those whose softnesses are approximately equal. In Section 4.2, an intuitive application of the HSAB concept is provided, followed by an application of the local HSAB principle in the interpretation of regioselectivity in Diels Alder reactions. 

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