Hard nucleophiles, definition

Our approach was outlined in the framework of the Hard-Soft Acid-Base theory (HSAB, Ref. 90). In a short definition, the HSAB theory states that hard nucleophiles prefer to react with hard electrophiles and soft nucleophiles prefer to react with soft electrophiles. 

Although the final products of the amination of 5-bromo-4-R-pyrimidines are the 6-amino-4-R-pyrimidines,106 107 two mechanisms, by which these same products are formed, have been recognized. The substrate is converted in part to the product via C-6 adduct 41, whereas the remaining part follows an ANRORC mechanism requiring attack of the reagent at C-2.105 Evidence for the existence of C-2 adducts as intermediates in nucleophilic substitutions is hard to obtain. However, the formation of an adduct of this kind (34) from 4,6-diphenyIpyrimidine was definitely proved by H-NMR measurements (Table XI).98 C-6 adducts such as 42-44 have also been described (see also Table XI) and shown to be the sole intermediates in the amination of 5-chIoro-4-te/T-butyIpyrimidine and 5-X-2,4-di-tert-butyIpyrimidines (X = Cl, Br), the ANRORC mechanism remaining excluded with the latter substrates.98... 

S, I) are more polarizable (they are further away from the nucleus), and since larger soft species have, in general, lower solvation energies, they are better nucleophiles as compared to smaller hard species. (For definition of the term hard and soft nucleophiles, see Box 13.1.) Thus, we can qualitatively understand why, for example, nucleophilicity increases from F to Cl to Br to V (Table 13.3), and why HS- is a stronger nucleophile than OH". 

Model Definition. The HSAB model classifies Lewis acids (electrophiles) and bases (nucleophiles) as either "hard" or "soft." Hard acids and bases are relatively small, and exhibit low polarizability and a comparatively low tendency to form covalent bonds. Soft acids and bases have the opposite characteristics (24). Stated simply, the model postulates that hard acids react most readily with hard bases, and soft acids react most readily with soft bases (26). 

It soon became clear that these two classes should be called hard and soft electrophiles, respectively. Since the terms nucleophile and electrophile refer to rates of reaction, by definition, the acid-base reaction involved is... 

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. 

In the brief guidelines given above for what makes a good nucleophile and electrophile, we touched on the energy and accessibility of the electrophilic and nucleophilic orbitals. This brings us to another related concept, that of "hard" and "soft" acids and bases. In this definition, the acids and bases are best viewed as being of the Lewis type. Here we examine the "hardness" and "softness" of the acid and base to predict reactivity. In this analysis, the character of a nucleophile or electrophile is most often correlated with the polarizability of the species hard reactants are non-polarizable, whereas soft reactants are polarizable. The... 

Eq. 5.30 is a general relationship for the interactions of electrophiles and nucleophiles, and is not restricted to definitions and discussions of hard and soft acids and bases. It tells us that the relative nucleophilicity of several Lewis bases will depend upon which electrophile is used, because the c s and yS values will change for each different electrophile. Similarly, the relative electrophilicities of several Lewis acids will depend upon what nucleophile is used. We will see exactly such results when we explore quantitative scales for various nucleophiles and electrophiles, where the scales are highly dependent upon the particular reaction that is chosen to analyze relative reactivities (see Chapter 8). Eq. 5.30 nicely explains the reactivity trends for soft acids and bases. It predicts that the Eoveriap will be best for Lewis acids and bases that have electrophilic and nuclephilic orbitals of roughly the same energy, which is the cases for the soft acids and bases of Table 5.8. 

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