Gas phase reactivity of heteroaromatic

Gas-phase proton affinities (PAs) (of. The reactivity of heteroaromatic compounds in the gas phase , Speranza, M., Adv. Heterocycl. Chem., 1986, 40, 25) are rather similar for all bases such measurements, though of considerable theoretical interest, are of limited value in considerations of solution chemistry. 

Compounds with a high HOMO and LUMO (Figure 5.5c) tend to be stable to selfreaction but are chemically reactive as Lewis bases and nucleophiles. The higher the HOMO, the more reactive. Carbanions, with HOMO near a, are the most powerful bases and nucleophiles, followed by amides and alkoxides. The neutral nitrogen (amines, heteroaromatics) and oxygen bases (water, alcohols, ethers, and carbonyls) will only react with relatively strong Lewis acids. Extensive tabulations of gas-phase basicities or proton affinities (i.e., —AG° of protonation) exist [109, 110]. These will be discussed in subsequent chapters. 

Reactivity of 5-membered heteroaromatics toward electrophiles in the gas phase 91PAC243. 

The experimental program at the University of Sussex (1970-present) of reactivity in the gas phase (involving formation of side-chain car-bocations) has, in addition to the points already mentioned, demonstrated the need to take hydrogen bonding into account for both ir-deficient and TT-excessive heteroaromatics, showing that this can in some cases markedly alter the 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. 

Theoretical calculations share with gas-phase kinetic and thermodynamic measurements the common aim of the understanding of the intrinsic reactivity properties of heteroaromatic compounds. The purpose of this subsection is to consider the predictive value of theoretical methods insofar as ionic substitution reactions on simple heteroaromatics are concerned. The topic under discussion is inherently limited by the wide range of interest in the understanding of the principles of these processes in solution. It is exactly in this field that an appropriate amount of data concerning gas-phase structural and reactivity properties of heteroaromatic compounds is at present available from modern experimental techniques that can be tested against theoretical predictions. 

On the other hand, five-membered heteroaromatic molecules are the model structures first employed for kinetic investigation of the reaction mechanism in gas-phase heteroaromatic substitutions. While comparison of the relevant kinetic data with most common ion-neutral body collision theories and with theoretical predictions appears quite promising, nevertheless, accurate modeling of intrinsic reactivity properties of heteroaromatic compounds demands a more complete research effort, mainly directed to comparing the kinetic behavior of heteroaromatic compounds toward electrophilic and nucleophilic species (83IJM225 84JOC764) in the gas phase and in solution. 

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