HETEROAROMATIC REACTIVITY

The usual order found with halogenonitrobenzenes is F > Cl Br I, the order of Cl and Br being variable, just as in heteroaromatic reactivity. The position of fluorine is of interest the available data indicate that it is usually the same as for nitrobenzene derivatives. Thus, in acid hydrolysis the order F > Cl for 2-halogeno-quinolines can be deduced beyond doubt since the fluoro derivative appears to react in the non-protonated form and the chloro derivative to resist hydrolytic attack even in the protonated form under appropriate conditions (Section II,D, l,d). Furthermore, in the benzo-thiazole ring, fluorine is displaced by the CHgO reagent at a rate 10 times that for chlorine. ... 

Heteroaromatic Reactivity , J. Ridd, in Physical Methods in Heterocyclic Chemistry , ed. A. R. Katritzky, Academic Press, New York, 1963, vol. 1, pp. 109-160. 

The recognition of the species which is undergoing reaction, of the quantitative effects of heteroatoms, of interactions between heteroatoms and substituents, and of the importance of hydrogen bonding have made possible, for the first time, a rational, quantitative, overall treatment of heteroaromatic reactivity patterns. 

Part I commences with hydrogen exchange, both because this is the simplest electrophilic substitution, and because the studies can be and have been extended over a far wider range of experimental conditions, and substrates, than any other electrophilic substitution. Chapter 3 deals with nitration, and Chapter 4 with other electrophilic substitutions. Chapter 5 is devoted to a study of the formation of side-chain carbocations, the results of which are of great importance in the interpretation of heteroaromatic reactivity. 

A radical solution to all of the above-mentioned difficulties is to eliminate the solvent medium entirely and to measure structural effects on heteroaromatic reactivity in the gas phase. During the last decade, a revolution has occurred in the experimental and theoretical approaches to understanding gas-phase ion chemistry. This has occurred as the result of the simultaneous development of several experimental methods for studying organic ion-molecule kinetics and equilibria in the gas phase with precision and range of effects equivalent to or even better than that normally obtained in solution and by very sophisticated molecular orbital calculations. The importance of reactivity studies in the gas phase is twofold. Direct comparison of rates and equilibria in gaseous and condensed media reveals previously inaccessible effects of ion solvation. In addition, reactivity data in the gas phase provide a direct evaluation of the fundamental, intrinsic properties of molecules and represent a unique yardstick against which the validity of theoretical estimates of such properties can be adequately assayed. 

Two distinct approaches are generally employed in the theoretical analysis of heteroaromatic reactivity the method of reactivity indices and potential surfaces. 

The geometry and the electron properties of such charged intermediates are expected to be profoundly different from those of neutral precursors (Fig. 7) (68JA4232). Therefore, the already ambiguous scenario offered by theoretical predictions of heteroaromatic reactivity appears further complicated by the concomitant presence of these conjugate species in the reaction medium (67T2513). 

Ridd, j. H. Heteroaromatic Reactivity. Phys. Methods Heterocyclic Chem. 1, 109-160 (1963). 

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