REACTIVITY OF NON-AROMATIC COMPOUNDS

Before turning to the dihydro and tetrahydro derivatives of the fundamental ring systems, we deal with two special classes. The pyrrolenines and the thiophene sulfones both contain two double bonds in the heterocyclic ring, but in each case the conjugation does not include all the ring atoms. Finally we consider hydroxy derivatives, most of which exist predominantly as the non-aromatic carbonyl tautomers. 

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The discrepancy between physicochemical and reactivity criteria for aromaticity was known long ago. Yet the data procured by the studies of compounds like 186 or 189 shed a new light on this problem. The observed deviation from planarity did not cause any substantial changes in the spectral parameters of these compounds. Thus they still should be considered aromatic from the point of view of physical chemists. At the same time, this distortion of geometry so dramatically affected their reactivity pattern that, in accordance with this criterion, cyclophanes 186 or 189 should best be referred to as non-aromatic compounds, derivatives of 1,3,5-cyclohexatriene. ... 

A9.6.4.7 The Nordic Council of Ministers issued a report (Pederson et al, 1995) entitled Environmental Hazard Classification, that includes information on data collection and interpretation, as well as a section (5.2.8) entitled QSAR estimates of water solubility and acute aquatic toxicity . This section also discusses the estimation of physicochemical properties, including log Kow For the sake of classification purposes, estimation methods are recommended for prediction of minimum acute aquatic toxicity, for ...neutral, organic, non-reactive and non-ionizable compounds such as alcohols, ketones, ethers, alkyl, and aryl halides, and can also be used for aromatic hydrocarbons, halogenated aromatic and aliphatic hydrocarbons as well as sulphides and disulphides, as cited in an earlier OECD Guidance Document (OECD, 1995). The Nordic document also includes diskettes for a computerized application of some of these methods. 

The application of KGCM is recommended for accomplishing the following tasks (1) identification of sample compounds (2) quantitative analysis of compounds (usually isomers) differing widely in reactivity (3) enhancing the sensitivity of analytical determinations and (4) extending the area of analysis (analysis of non-volatile compounds that form volatile compounds as a result of a reaction). It should be pointed out that the theory of typical organic reactions is now fairly well developed and a wealth of experimental data have been accumulated, which permits sufficiently reliable determinations of relative rates of chemical reactions, for example, with compounds that differ in the nature and position of the aromatic substituents [8—13]. 

As discussed in Section 4.01.5.2, hydroxyl derivatives of azoles (e.g. 463, 465, 467) are tautomeric with either or both of (i) aromatic carbonyl forms (e.g. 464,468) (as in pyridones), and (ii) alternative non-aromatic carbonyl forms (e.g. 466, 469). In the hydroxy enolic form (e.g. 463, 465, 467) the reactivity of these compounds toward electrophilic reagents is greater than that of the parent heterocycles these are analogs of phenol. 

The term aromatic will be used in a strict non-historical sense to mean possessing a cyclic 7r-electron system (6 and 10 electrons for the mono- and bi-cyclic rings discussed in this review). Heteroaromatic compounds, like carboaromatics, have widely different degrees and types of electronic dissymmetry and polarizabihty. Consequently, their reactivity varies tremendously with any one reagent and their relative reactivity changes drastically with the type of reagent. In this sense, aromatic compounds show differences in reactivity but not in aromaticity. The virtues of this qiuilitative concept of aromaticity and the pitfalls of trying to use it as a quantitative concept in modern context have been ably presented by Peters and by Balaban and Simon. ... 

The effect of cryptands on the reduction of ketones and aldehydes by metal hydrides has also been studied by Loupy et al. (1976). Their results showed that, whereas cryptating the lithium cation in LiAlH4 completely inhibited the reduction of isobutyraldehyde, it merely reduced the rate of reduction of aromatic aldehydes and ketones. The authors rationalized the difference between the results obtained with aliphatic and aromatic compounds in terms of frontier orbital theory, which gave the following reactivity sequence Li+-co-ordinated aliphatic C=0 x Li+-co-ordinated aromatic C=0 > non-co-ordinated aromatic C=0 > non-co-ordinated aliphatic C=0. By increasing the reaction time, Loupy and Seyden-Penne (1978) showed that cyclohexenone [197] was reduced by LiAlH4 and LiBH4, even in the presence of [2.1.1]-cryptand, albeit much more slowly. In diethyl ether in the absence of... 

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