Of aromatic systems

Calculations for electrophilic substitution in the quinolinium ion can be compared with experiment, and for a range of values of h the predicted order of positional reactivities, s 8>6>3>7, agrees moderately well in a qualitative sense with the observed order of s 8>6>7>3 (table 10.3). Further evaluation of the method must await the results of more extensive calculations for a range of aromatic systems. 

The meaning of the word aromaticity has evolved as understanding of the special properties of benzene and other aromatic molecules has deepened. Originally, aromaticity was associated with a special chemical reactivity. The aromatic hydrocarbons were considered to be those unsaturated systems that underwent substitution reactions in preference to addition. Later, the idea of special stability became more important. Benzene can be shown to be much lower in enthalpy than predicted by summation of the normal bond energies for the C=C, C—C, and C—H bonds in the Kekule representation of benzene. Aromaticity is now generally associated with this property of special stability of certain completely conjugated cyclic molecules. A major contribution to the stability of aromatic systems results from the delocalization of electrons in these molecules. 

Partial fluorination [50] and perfluorination [5/] of aromatic systems can be accomplished electrochemically. A number of other reagents add fluorine to benzene and its derivatives, as elaborated in equation 5 [52, 53, 54, 551... 

Strained pertrifluoromethyl-substituted valence tautomers of aromatic systems, such as tetrakis(trifiuoromethyl)Dewar thiophene [87] and hexalas(tnfluorQ-methyl)benzvalene [Diels-Alder reactions with various cyclic and acyclic dienes (equations 76 and 77). 

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-... 

The mechanisms of the electrophilic substitutions in the isoxazole nucleus have not yet been studied. They should not differ fundamentally from those usually accepted for the substitution of aromatic systems but the structural specificity of the isoxazole ring might give rise to some peculiarities, as recently specially discussed.One important point is that isoxazole shows a clearcut tendency to form coordination compounds. Just as pyridine and other azoles, isoxazoles coordinate with halogens and the salts of heavy metals, for example of cadmium,mercury,zinc. Such coordination... 

Huorine is an especially powerful ortho director in lithiation of aromatic systems Gilday, J.P. Negri, J.T. Widdowson, D.A. Tetrahedron, 1989, 45, 4605. 

The complex that is formed can dissociate to form a cation (n-tr-complex) and an iodide anion, with the iodide ion reacting with the excess iodine molecules that are present. In addition the decomposition of the n-cr-complex can lead to the formation of highly reactive iodine cations, which can initiate further reactions — e.g. oxidations or electrophilic substitutions of aromatic systems [11, 13]. 

As noted previously, a wide variety of aromatic systems serve as nuclei for arylacetic acid antiinflammatory agents. It is thus to be expected that fused heterocycles can also serve the same function. Synthesis of one such agent (64) begins with condensation of indole-3-ethanol (60) with ethyl 3-oxo-caproate (61) in the presence of tosic acid, leading directly to the pyranoindole 63. The reaction may be rationalized by assuming formation of hemiketal 62, as the first step. Cyclization of the carbonium ion... 

The second mechanism, due to the permutational properties of the electronic wave function is referred to as the permutational mechanism. It was introduced in Section I for the H4 system, and above for pericyclic reactions and is closely related to the aromaticity of the reaction. Following Evans principle, an aromatic transition state is defined in analogy with the hybrid of the two Kekule structures of benzene. A cyclic transition state in pericyclic reactions is defined as aromatic or antiaromatic according to whether it is more stable or less stable than the open chain analogue, respectively. In [32], it was assumed that the in-phase combination in Eq. (14) lies always the on the ground state potential. As discussed above, it can be shown that the ground state of aromatic systems is always represented by the in-phase combination of Eq. (14), and antiaromatic ones—by the out-of-phase combination. 

A brief overview of the historical developments that led to the dichotomy between aliphatic and aromatic compounds delineates that the former are characterized by additivity for heats of formation and practically all other properties, whereas the situation for aromatic systems is less straightforward. Definitions, criteria, and properties of aromatic systems will be discussed. Notwithstanding controversies over aro-... 

In biological systems, H-bond donors and acceptors are predominantly nitrogen and oxygen atoms. However, the n electrons of aromatic systems can also act as acceptors, and H-bonds involving sulfur groups or metallic cofactors are also known. The presence of individual H-bonds in biomacromolecular structures is usually derived from the spatial arrangement of the donor and acceptor groups once the structure of a molecule has been solved by diffractive or NMR techniques. More detailed information about H-bonds... 

The discovery of the metal-like properties of conducting polymers has once again focused attention on the oxidation and reduction characteristics of aromatic systems. It turns out that most of these conducting materials consist of chainlike connected carbocyclic or heterocyclic aromatics [94-97]. 

Briegleb (1961) gives an extensive summary of the stability constants of EDA-complexes in connection with the donor strength of aromatic systems. 

In addition to these kinetic investigations, which were in part carried out with a view to the basicity of the aromatic substances, numerous investigations have also been carried out on the subject of electrophilic substitution of aromatic systems, and all of these ultimately show, directly or indirectly, a dependence on the basicity of the aromatic substance (cf. Mason, 1958, 1959 Gould, 1962 Brown and Stock, 1962). 

We have recently reported ( ) several synthetic studies of weak nucleophile SnAr reactions. In the latter cases (26f-1), new synthetic methodology was reported for the direct introduction of fluoroalkoxy groups into a variety of aromatic systems. These reports represent synthetically useful procedures for obtaining some otherwise inaccessible fluoroalkoxy materials but, unfortunately, they require the use of a dipolar, aprotic solvent (usually hexamethylphosphoramide, HMPA) and, in some cases, elevated temperatures. However, because of their diverse and important applications ( ), the syntheses of these and other organofluoro compounds continue to be of interest. For example, two recent reports of useful fluoroalkoxy materials include the insecticide activity exhibited by fluoroalkoxy substituted 1,3,4-oxadiazoles... 

Examples of other cases of prediction of complex organic reactions have been given elsewhere ( ). Functions applicable to the reactivity of multiple bonds and of aromatic systems have been developed in an analogous manner. 

Carbon and nitrogen are the most common elements from the first row of the periodic table to form aromatic compounds, characterized by cyclic electron delocalization. The bonding of these elements in the conjugated systems shows a large variety. Carbon can be a divalent (carbene), sp carbon with one jT-electron, but also sp carbon can be part of hyperconjugate aromatic systems, provided that it is properly substituted. The pyrrole- and pyridine-type nitrogens also allow the formation of cyclic electron delocalization in a large variety of aromatic systems. 

In eukaryotes, such as mammals and fungi, epoxide hydrolases play a key role in the metabolism of xenobiotics, in particular of aromatic systems [30,31 ]. On the other hand, in prokaryotes (e.g. bacteria) these enzymes are essential for the utilization of alkenes as carbon-source. In general, aromatics can be metabolized via two different pathways (Scheme 5) (i) dioxetane formation via dioxyge-... 

Reduction of arenediazoninm salts provides the basis for a substantial number of chemical reactions. A notable application is the Sandmeyer reaction, which utilizes the diazo moiety to facilitate functionalization of aromatic systems and remains one of the most reliable transformations in organic chemistry. The general reaction involves the addition of the cuprate salt of the desired moiety to the diazonium species—ArN2 + CuX — ArX. 

Epoxide metabolites can be generated from a variety of aromatic systems. Anticonvulsants are a class of drug whose side-effects, such as hepatic necrosis and aplastic anaemia, are thought to be mediated by chemically reactive epoxide metabolites formed by cytochrome P450 oxidation. For instance phenytoin (Figure 8.6) toxicity is correlated with oxidation and the inhibition of epoxide hydrolase [8]. 

A number of reagents derived from nitrate salts and acid anhydrides have been reported for the V-nitration of amides and related compounds. Crivello first reported the use of metal nitrates in trifluoroacetic anhydride (TFAA) for the nitration of aromatic systems. Chapman... 

The molecular orbital picture of benzene proposes that the six jt electrons are no longer associated with particular bonds, but are effectively delocalized over the whole molecule, spread out via orbitals that span all six carbons. This picture allows us to appreciate the enhanced stability of an aromatic ring, and also, in due course, to understand the reactivity of aromatic systems. There is an alternative approach based on Lewis structures that is also of particular value in helping us to understand chemical behaviour. Because this method is simple and easy to apply, it is an approach we shall use frequently. This approach is based on what we term resonance structures. 

A very active elemental rhodium is obtained by reduction of rhodium chloride with sodium borohydride [27]. Supported rhodium catalysts, usually 5% on carbon or alumina, are especially suited for hydrogenation of aromatic systems [iTj. A mixture of rhodium oxide and platinum oxide was also used for this purpose and proved better than platinum oxide alone [i5, 39]. Unsaturated halides containing vinylic halogens are reduced at the double bond without hydrogenolysis of the halogen [40]. 

Ultraviolet spectra of aromatic systems are often used to probe strain-induced perturbations in the K-system. Out-of-plane deformations of the benzene ring shift the 260 nm band to the red and increase its intensity. Classical examples are [2.2]paracyclophane (286 nm) and Pascal s twisted benzenes. The for a given transition reveals changes in the energy of the filled/unfilled gap, whereas the extinction coefficient reveals the efficiency of the transition. 

---