Energy, electrophilic localization

Relative electrophilic localization energies vs. logarithms of partial rate factors for nitration (a) Hiickel, (6) PPP with fixed /3. (From Dewar Thompson. ) (iv) Plot of log K vs. AB c. (From Dewar. )... 

Nitration of isoquinoline with nitric and sulfuric acids occurs preferentially at positions 5 and 8, the former predominating, in the approximate ratio of 9 1 at 0 °C. The amount of 8-nitro isomer is slightly increased at higher temperatures. Electrophilic localization energies predict the reactivity order 5>8>others. Over the range 71—85% sulfuric acid it has been shown that the reaction proceeds via the isoquinolinium cations (Scheme 6) (63CI(L)1283, 60T(8)23, 57JCS2521). 

An attempt has been made to analyse whether the electrophilicity index is a reliable descriptor of the kinetic behaviour. Relative experimental rates of Friedel-Crafts benzylation, acetylation, and benzoylation reactions were found to correlate well with the corresponding calculated electrophilicity values. In the case of chlorination of various substituted ethylenes and nitration of toluene and chlorobenzene, the correlation was generally poor but somewhat better in the case of the experimental and the calculated activation energies for selected Markovnikov and anti-Markovnikov addition reactions. Reaction electrophilicity, local electrophilicity, and activation hardness were used together to provide a transparent picture of reaction rates and also the orientation of aromatic electrophilic substitution reactions. Ambiguity in the definition of the electrophilicity was highlighted.15... 

Fig. 7.1. Nitration of polynuclear hydrocarbons by nitric acid in acetic anhydride, (i) Plot of logio (KJKo) against N. , 9-Anthryl positions A,a-napthyl positions V, 4-phenanthryi positions O, other positions. (From Dewar et a/.286) (ii) and (iii) Relative electrophilic localization energies vs. logarithms of partial rate factors for nitration (a) Hiickel, (6) PPP with fixed p. (From Dewar Thompson.83 ) (iv) Plot of log K vs. AEiac- (From Dewar.23 )...

Orientation in electrophilic and nucleophilic reactions of aromatic compounds can be predicted with the aid of the reactivity index of MO theory. Electrophiles will attack positions of higher electron densities, larger superdelocalizability (electrophile), and the lower localization energy (electrophile). On the other hand, nucleophilic attack is preferred at positions of lower electron densities, larger superdelocalizability (nucleophile), and lower localization energy (nucleophile). Table XXIII shows reactivity indexes of some aromatic nitrogen cations. 

Pyridinium, quinolinium, and isoquinolinium cations are the major species undergoing electrophile substitution reactions under acidic conditions [90AHC(47)1]. As expected from Table XXIII, the electrophilic reaction of pyridinium ion occurs at the 3-position, and an electrophile attacks at the 5- and 8-positions of quinolinium and isoquinolinium cations. Electrophile reactivity of 1 is rather low because of its electron accepting character. Molecular orbital calculations of its orientation did not give a consistent conclusion. Electron density and superdelocalizability (electrophile) predict that position 1 will be the most reactive towards an electrophile, while inspection of the localization energy (electrophile) predicts that electrophilic reaction takes place at position 4. 

Within an aromatic substitution transform the terms RLENERGY, NLENERGY, and ELENERGY refer to the radical, nucleophilic, and electrophilic localization energies respectively. Several types of statements use these terms, e.g. ... 

Statement 5 shows comparison of electrophilic localization energy (LE) on 2 atoms, whereas in statement 6 the LE of atom 4 is compared to the LE s of each atom in the set of atoms (1). The compound statement 7 selects nucleophilic conditions if possible, otherwise electrophilic conditions. In statement 8, "CORRECT"... 

As stated already, the observed orientations of electrophilic substitution can be accounted for, in the pyrrole molecule, in terms of electrophilic localization energies, without invoking an auxiliary inductive parameter, for positive values of A. However, pyrrole is very reactive, and for this reason orientation would be expected to follow 7r-electron densities. These fall into line (when the acceptable value A = + 2 is used) if A >0 19. The orientation of electrophilic substitution is satisfactorily accounted foi s when A = 2 and A = 0 25. 

Electronic effects in conjugated systems may be computed with the Hiickel HMO method. Electron densities are used to predict aromatic substitution reactions, and it is possible to refer to radical, nucleophilic, and electrophilic localization energies.For the latter, the term ELENERGY is used in a transform, for example IF ELENERGY ON ATOM 1 BETTER THAN ATOM 2 THEN ADD 20. 

Table 1-4 gives some calculated reactivity indices free valence or Wheland atomic localization energies for radical, electrophilic, or nucleophilic substitution. For each set of data the order of decreasing reactivity is indicated. In practice this order is more reliable than the absolute values of the reactivity indices themselves. 

The localization energies for electrophilic substitution in benzimidazole predict that all three reactive forms should undergo substitution in the 4-position. This does not explain the formation of the 5-nitro compound or that of the 2-deutero compound. It is doubtful whether any electrophilic substitution occurs preferentially in the 4-position. 

As discussed in the theoretical section (4.04.1.2.1), electrophilic attack on pyrazoles takes place at C-4 in accordance with localization energies and tt-electron densities. Attack in other positions is extremely rare. This fact, added to the deactivating effect of the substituent introduced in the 4-position, explains why further electrophilic substitution is generally never observed. Indazole reacts at C-3, and reactions taking place on the fused ring will be discussed in Section 4.04.2.3.2(i). Reaction on the phenyl ring of C- and A-phenyl-pyrazoles will be discussed in Sections 4.04.2.3.3(ii) and 4.04.2.3.10(i), respectively. The behaviour of pyrazolones is quite different owing to the existence of a non-aromatic tautomer. 

Both HMO calculations and more elaborate MO methods can be applied to the issue of the position of electrophilic substitution in aromatic molecules. The most direct approach is to calculate the localization energy. This is the energy difference between the aromatic molecule and the n-complex intermediate. In simple Hiickel calculations, the localization energy is just the difference between the energy calculated for the initial n system and that remaining after two electrons and the carbon atom at the site of substitution have been removed from the conjugated system ... 

In a study of quantum chemical calculations of reactivity, it was found that charge densities give only qualitative agreement with experimental reactivities in electrophilic substitution, whereas semiquantitative agreement is obtained with the localization energies.7... 

The next consideration is the HSAB principle formulated at a local level. Let us consider the interaction energy between two chemical species A and B, in which one is electrophilic and the other nucleophilic. From a global point of view and neglecting the effect of change in external potential of A and B, the change in grand canonical potential can be expressed as [7a]... 

FIGURE 23.5 Profiles of different local reactivity descriptors (electrophilic attack) along the path of the gas phase SN2 substitution F + CH3—Fb —> Fa—CH3 + Fb. Profiles of energy and bond order are also shown. (Reprinted from Chattaraj, P.K. and Roy, D.R., J. Phys. Chem. A, 110, 11401, 2006. With permission.)... 

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