Isoquinoline localization energies

It is difficult to treat the effect of a heteroatom on the localization energies of aromatic systems, but Brown has derived molecular orbital parameters from which he has shown that the rates of attack of the phenyl radical at the three positions of pyridine relatively to benzene agree within 10% with the experimental results. He and his co-workers have shown that the formation of 1-bromoisoquinoline on free-radical bromination of isoquinoline is in agreement with predictions from localization energies for physically reasonable values of the Coulomb parameters, but the observed orientation of the phcnylation of quinoline cannot be correlated with localization ener-... 

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). 

A well understood case is that of quinoline reaction at position 2 is kinetically favored as compared with reaction at position 4, but the adduct from the latter is thermodynamically more stable. This situation, where the site of attack leading to the more stable adduct is the y position, is analogous with those regarding the formation of Meisenheimer adducts from benzene and pyridine derivatives and RCT nucleophiles. Presumably, with quinoline kinetic control favors the position that is more strongly influenced by the inductive effect of the heteroatom. The fact that position 2 of quinoline is the most reactive toward nucleophilic reagents is probably related to the lower 71-electron density at that position.123 However, the predominance of the C-4 adduct at equilibrium can be better justified by the atom localization energies for nucleophilic attachment at the different positions of quinoline. Moreover, both 7t-electron densities and atom localization energies indicate position 1 of isoquinoline to be the most favored one for nucleophilic addition. 

A systematic and intensive theoretical study of reactivity has been reported by Brown and his colleagues,8,115,139-142 who discussed the reactivity of pyridine, quinoline, and isoquinoline in terms of localization energies. They investigated the values of these indices, first of all for electrophilic substitution, with regard to the value of the Coulomb integral of the heteroatom orbital and the orbitals adjacent to it (auxiliary inductive parameters). They demonstrated that the course of electrophilic substitution can be estimated from theoretical reactivity indices if 77-electron densities are used for reactions that occur readily and localization energies for those occurring only reluctantly. 

Scheme 11.8. n Densities and localization energies (-8) for quinoline and isoquinoline. 

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