Molecular orbital electrophilic aromatic

Electrophilic Aromatic Substitution. The Tt-excessive character of the pyrrole ring makes the indole ring susceptible to electrophilic attack. The reactivity is greater at the 3-position than at the 2-position. This reactivity pattern is suggested both by electron density distributions calculated by molecular orbital methods and by the relative energies of the intermediates for electrophilic substitution, as represented by the protonated stmctures (7a) and (7b). Stmcture (7b) is more favorable than (7a) because it retains the ben2enoid character of the carbocycHc ring (12). 

Certain groups attached to an aromatic ring can donate electrons into its delocalized molecular orbitals. Examples of these electron-donating substituents include —NH2 and —OH. Electrophilic substitution of benzene is much faster when an electron-donating substituent is present. For example, the nitration of phenol, C6H5OH, proceeds so quickly that it requires no catalyst. Moreover, when the products are analyzed, the only products are found to be 2-nitrophenol (ortho-nitrophenol, 37) and 4-nitrophenol (pnra-mtrophcnol, 38 . 

The first paper of the frontier-electron theory pointed out that the electrophilic aromatic substitution in aromatic hydrocarbons should take place at the position of the greatest density of electrons in the highest occupied (HO) molecular orbital (MO). The second paper disclosed that the nucleophilic replacement should occur at the carbon atom where the lowest unoccupied (LU) MO exhibited the maximum density of extension. These particular MO s were called "frontier MO s . In homolytic replacements, both HO and LU.were shown to serve as the frontier MO s. In these papers the "partial" density of 2 pn electron, in the HO (or LU) MO, at a certain carbon atom was simply interpreted by the square of the atomic orbital (AO) coefficient in these particular MO s which were represented by a linear combination (LC) of 2 pn AO s in the frame of the Huckel approximation. These partial densities were named frontier-electron densities . 

In addition to the above prescriptions, many other quantities such as solution phase ionization potentials (IPs) [15], nuclear magnetic resonance (NMR) chemical shifts and IR absorption frequencies [16-18], charge decompositions [19], lowest unoccupied molecular orbital (LUMO) energies [20-23], IPs [24], redox potentials [25], high-performance liquid chromatography (HPLC) [26], solid-state syntheses [27], Ke values [28], isoelectrophilic windows [29], and the harmonic oscillator models of the aromaticity (HOMA) index [30], have been proposed in the literature to understand the electrophilic and nucleophilic characteristics of chemical systems. 

Aromatic substrates are by far the most commonly used substrates in the rapidly expanding area of photoinduced electron transfer [1,2]. This is obviously due to the favourable location of the frontier molecular orbitals in such compounds. The same factor facilitates the formation of electron transfer donor-acceptor (EDA) complexes both in the ground state (these possibly are intermediates in some thermal reactions, e.g. selected electrophilic substitutions), and in the excited state (exciplexes). 

Pyrrole, furan, and thiophene give electrophilic substitution products because they re aromatic (Section 15.7). Each has six -ir electrons in a cyclic conjugated system of overlapping p orbitals. Taking pyrrole as an example, each of the four carbon atoms of pyrrole contributes one n electron, and the sp -hybridized nitrogen atom contributes two (its lone pair). The six ir electrons occupy p orbitals, with lobes above and below the plane of the ring, as shown in Figure 28.1. Overlap of the five p orbitals forms aromatic molecular orbitals just as in benzene. 

If only the electron density of the highest occupied molecular orbital (HOMO) is taken into account, an electrophilic attack is said to be regulated by the frontier electron density index (54JCP1433 79FCF1). In nucleophilic substitutions, the aromatic substrate tends to accept an electron pair in the transition state, and so the frontier orbital is taken as the lowest unoccupied molecular orbital (LUMO). In this case, the frontier electron density is assumed to be as the electron distribution that would be present in the LUMO if it were occupied by two electrons. In contrast to arguments based on the charge or 7c-electron densities, both nucleophilic and electrophilic substitution occur preferentially at the atom with the highest electron density within the appropriate frontier orbital, i.e., LUMO or HOMO, respectively. 

Considerable advances have been made in recent years in the understanding of the aromatic substitution reactions of oxazoles. Molecular orbital calculations (Section III, B) predict that electrophilic attack should occur preferentially at position 5, and indeed this is observed. The relative order of reactivity calculated theoretically is not in complete accord with the experimentally observed order (5 > 4 > 2) therefore it is evident that the electrophilic substitution reactions are rather more complex than the present theoretical calculations would predict. 

Abbreviations PAH, polycyclic aromatic hydrocarbon DE, diol epoxide PAHDE, polycyclic aromatic hydrocarbon diol epoxide PAHTC, polycyclic aromatic hydrocarbon triol carbocation TC, triol carbocation BaP, benzo[a]pyrene BeP, benzo[e]pyrene BA, benz[a]anthracene DBA, dibenz[a,h]anthracene BcPh, benzo[c)phenanthrene Ch, chrysene MCh, methylchrysene MBA, 7-methyl benz[a]anthracene DMBA, 7,12-dimethyl benz[a]anthracene EBA, 7-ethyl benz[a]anthracene DB(a,l)P, dibenzo[a,l]pyrene MSCR, mechanism-based structure-carcinogenicity relationship PMO, Perturbational molecular orbital method dA, deoxyadenosine dC, deoxycytosine dG, deoxyguanosine MOS, monoxygenase enzyme system EH, epoxide hydrolase enzyme system N2(G), exocyclic nitrogen of guanine C, electrophilic centre of PAHTC K, intercalation constant CD, circular dichroism LD, linear dichroism. 

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