Of heteroaromatic compounds in the gas phase

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. 

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. 

Benzylic oxidation of aromatic side-chains is also a well established technology in the bulk chemicals arena, e. g. toluene to benzoic acid and p-xylene to ter-ephthalic acid [1,2]. These processes involve homogeneous catalysis by, e. g., cobalt compounds, however, and also fall outside the scope of this book. Ammoxi-dation of methyl-substituted aromatic and heteroaromatic compounds is performed over heterogeneous catalysts in the gas phase but this reaction is treated elsewhere (Section 9.5). Transition metal-substituted molecular sieves have been widely studied as heterogeneous catalysts for oxidation of aromatic side-chains in the liquid phase, but there are serious doubts about their heterogeneity [5,6]. Here again, a cursory examination of the literature reveals that supported palladium seems to be the only heterogeneous catalyst with synthetic utility [4]. 

In Ref [6] the macroscopic proton association constants (PAC) of many of these compounds have been determined in solution. Kj and K2 are the PAC of the side chain and heteroaromatic nucleus, respectively. Our PA s are calculated in the gas phase, however, as both PA and PAC values are for a series of molecules, their relative values should correlate. Therefore, we have related PA s of l-A, and 9-12, calculated with the PAC s depending on the protonated centres and the type of T/C s (for instance, 1A+ with logK2, or iB with logKi). The best correlation has been found for iA+ and logK2 (Fig. 6), with the PA values obtained from the 6-31G //6-31G wave functions and the direct reactions (I) with a good linear relationship ... 

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. 

A group of Italian workers from Modena, led by Professor Taddei, has reviewed published work on the conformations of acyl groups in heterocyclic compounds, including both C-acyl and N-acyl derivatives. The first recent review of the basicity and acidity of azoles, covering both gas-phase and solution measurements, is presented by a group of Spanish workers (Catalan et al.). H. Weber has summarized the considerable recent progress in oxidative transformations of heteroaromatic iminium salts. 

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. 

In solution, resonance stabilization (R) is commonly the predominant structural driving force of a reaction. Gas-phase proton-transfer equilibria offer a striking contrast, in which the R effects are frequently found to be secondary to a predominant combination of I and P effects. However, it is recognized that for aromatic compounds, such as, for instance, imidazole, resonance stabilization of the protonated form is the predominant contribution determining the relatively high basicity of imidazole and its congeners in the class of five-membered heteroaromatic compounds. 

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