Electrophilic substitution INDEX

Evaluation of the only appropriate Fukui function is required for investigating an intramolecular reaction, as local softness is merely scaling of Fukui function (as shown in Equation 12.7), and does not alter the intramolecular reactivity trend. For this type, one needs to evaluate the proper Fukui functions (/+ or / ) for the different potential sites of the substrate. For example, the Fukui function values for the C and O atoms of H2CO, shown above, predicts that O atom should be the preferred site for an electrophilic attack, whereas C atom will be open to a nucleophilic attack. Atomic Fukui function for electrophilic attack (fc ) for the ring carbon atoms has been used to study the directing ability of substituents in electrophilic substitution reaction of monosubstituted benzene [23]. In some cases, it was shown that relative electrophilicity (f+/f ) or nucleophilicity (/ /f+) indices provide better intramolecular reactivity trend [23]. For example, basicity of substituted anilines could be explained successfully using relative nucleophilicity index ( / /f 1) [23]. Note however that these parameters are not able to differentiate the preferred site of protonation in benzene derivatives, determined from the absolute proton affinities [24],... 

Brown83 proposed a similar index Zr for electrophilic substitution given by... 

An attempt has been made to analyse whether the electrophilicity index is a reliable descriptor of the kinetic behaviour. Relative experimental rates of Friedel-Crafts benzylation, acetylation, and benzoylation reactions were found to correlate well with the corresponding calculated electrophilicity values. In the case of chlorination of various substituted ethylenes and nitration of toluene and chlorobenzene, the correlation was generally poor but somewhat better in the case of the experimental and the calculated activation energies for selected Markovnikov and anti-Markovnikov addition reactions. Reaction electrophilicity, local electrophilicity, and activation hardness were used together to provide a transparent picture of reaction rates and also the orientation of aromatic electrophilic substitution reactions. Ambiguity in the definition of the electrophilicity was highlighted.15... 

There are principally two different approaches of correlating experimental rate data of electrophilic substitution with reactivity indices (1) Correlating the index with the rate data of a given reaction, e.g. bromination. For example, a satisfying correlation of Dewar reactivity numbers with the log of rate constants of the bromination of benzene, naphthalene (1- and 2-position), biphenyl (4-position), phenanthrene (9-position), and anthracene (9-position) has been observed [55]. In correlations of this type the reactivity index corresponds to the reactivity constant in the Hammett equation while the slope of the linear correlation corresponds to the reaction constant (see also Sect. 3) (2) correlating the index with experimental a values. 

Samsoniya, S. A., Chikvaidze. 1. S., Kerese-lidze, D. A., and Suvorov,, N. N., Bis indoles. II. Electrophilic substitution in the bis(5-in-dolyl) sultbne scries and data on reactivity indexes of some bisindoles, Khim. Geterosikl. Soedin.. 1653, 1982 C7iew. Ahstr., 98, 125033, 1983. 

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. 

In order to get some insight on how ELF works, we will analyse a number of parent molecules CeHsX (X = H, OH, F, Cl, Br and I). Their localization domains are displayed in Figure 14. Except for the substituent itself, all these molecules have 6 V(C, C), 5 V(C, H) and one V(C, X) basins. The differences are to be found in the hierarchy of the V(C, C) basins which is ruled by the nature of the substituent. In benzene, all the V(C, C) basins are equivalent and therefore the six critical points of index 1 between these basins have the same value, i.e. rj(rc) = 0.659. In the phenyl halides where the molecular symmetry is lowered from D h to C2v, the former critical points are then distributed in four sets according to the common carbon position ipso, ortho, meta and para. In phenol with a Cj symmetry, the two ortho and the two meta positions are not totally equivalent. In all studied molecules, the r) rc) values are enhanced in the ipso, ortho and para positions and decreased in the meta position. It has been remarked that the electrophilic substitution sites correspond to the carbon for which r) rc) is enhanced. Moreover, it is worthwhile to introduce electrophilic substitution positional indices defined by equation 26,... 

Langenaeker W, Demel K, Geerlings P. Quantum-chemical study of the Fukui function as a reactivity index. Part 2. Electrophilic substitution on mono-substituted benzenes. J Mol Struct Theochem 1991 234 329-342. 

Using their CNDO results Helland and Skancke calculated indices of reactivity (frontier electron density, FED, for electrophilic substitution frontier orbital density, FOD, for nucleophilic substitution frontier radical density, FRD, for radical substitution) for the thienopyridines. It was indicated that the FED index has its highest value for C-3 in the [2,3-]- and 3,2- -fused systems and for C-2 in the [3,4-1-fused isomers. As far as the former group is concerned, the predictions are in agreement with experimental observations (see Section IV,A.). Little experimental evidence is available for the [3,4-]-fused systems, but it seems highly probable that they would have a considerable tendency to undergo addition reactions at the 1,3-positions, since the product would contain a normal rather than a quinoid pyridine ring [Eq. (23)]. 

In this chapter Chemical Abstracts have been covered by indexes to mid-1980 and by a computer on-line search to September 1981. A few more recent references have been included directly from journals. This review covers 2H- and 3/f-pyrroles that have been isolated or characterized spectroscopically, but protonated pyrroles (which have been reviewed elsewhere ) and transient isopyrrole intermediates in the electrophilic substitution of 1 //-pyrroles are considered to be outside its scope. Pyrroles protonated at the 2-position have been isolated as stable salts. 8 Also excluded are the numerous pyrrolic compounds with exocyclic double bonds and benz-fused compounds (the 2H- and 3//-indoles). 

The perturbational MO method of Longuet-Higgins (11) and Dewar (12), which was thoroughly reviewed by Dewar and Dougherty (6), has been the pencil-and-paper method of choice in numerous applications. More recently, a modified free-electron (MFE) MO approach (13-15) and a valence-bond structure-resonance theory (VBSRT) (7, 16, 17) have been applied to several PAH structure and reactivity problems. A new perturbational variant of the free-electron MO method (PMO F) has also been derived and reported (8, 18). Both PMO F and VBSRT qualify as simple pencil-and-paper procedures. When applied to a compilation of electrophilic substitution parameters (ct+) (19-23), the correlation coefficients of calculated reactivity indexes with cr+ for alternant hydrocarbons are 0.973 and 0.959, respectively (8). In this case, the performance of the PMO F method rivals that of the best available SCF calculations for systems of this size, and that of VBSRT is sufficient for most purposes. 

The reactivity and the orientation effects in aromatic electrophilic substitutions are usually estimated from the relative facility of formation of o-complexes (arenium ions) by comparing such calculation parameters as the index of free valence, the it-electron density, the localization energy of a pair of electrons etc. S. Nagakura and J. Tanaka 27-679) judependraitly, R. Brown have emphasized the role... 

Abstract. The development of theories for interpreting the course of chemical reactions is one of the most important achievements of theoretical chemistry in the twentieth century. I selected the paper by Fukui et al. from 1952, proposing the frontier electron density as the reactivity index for the orientation of electrophilic substitution reactions. This paper may be regarded as a bridge between an older reactivity theory, the electronic theory of organic chemistry, and new ones predicting the stereochemical courses of reactions such as frontier orbital theory and the Woodward-Hoffmann rule. 

Can nrr be a successful index for nucleophilic and electrophilic substitution if these are observed to occur at different sites ... 

Besides the applications of the electrophilicity index mentioned in the review article [40], following recent applications and developments have been observed, including relationship between basicity and nucleophilicity [64], 3D-quantitative structure activity analysis [65], Quantitative Structure-Toxicity Relationship (QSTR) [66], redox potential [67,68], Woodward-Hoffmann rules [69], Michael-type reactions [70], Sn2 reactions [71], multiphilic descriptions [72], etc. Molecular systems include silylenes [73], heterocyclohexanones [74], pyrido-di-indoles [65], bipyridine [75], aromatic and heterocyclic sulfonamides [76], substituted nitrenes and phosphi-nidenes [77], first-row transition metal ions [67], triruthenium ring core structures [78], benzhydryl derivatives [79], multivalent superatoms [80], nitrobenzodifuroxan [70], dialkylpyridinium ions [81], dioxins [82], arsenosugars and thioarsenicals [83], dynamic properties of clusters and nanostructures [84], porphyrin compounds [85-87], and so on. 

Aromatic substitution reactions are often complicated and multistep processes. A correlation, however, in many cases can be found between the charged attacking species and the electron density distribution in the molecule attacked during electrophilic and nucleoph c substitution. No such correlation is expected in radical substitution where the attacking particles are neutral, rather a correlation between the reactivities of separate bonds and a free valency index of the bond order. This allows the prediction of the most reactive bonds. Such an approach has been used by researchers who applied quantum calculations to estimate the reactivities of the isomeric thienothiophenes and to compare them with thiophene or naphthalene. " Until recently quantum methods for studying reactivities of aromatics and heteroaromatics were developed mainly in the r-electron approximation (see, for example, Streitwieser and Zahradnik ). The M orbitals of a sulfur atom were shown not to contribute substantially to calculations of dipole moments, polarographic reduction potentials, spin-density distribution, ... 

The reliability and usefulness of a new empirical nucleofugality index, which is defined as the group electrophilicity of the leaving group embedded in the substrate that undergoes the nucleophilic attack, were tested against experimental kinetic data recorded for aminolysis reactions of variously substituted phenoxy- and thiophenoxy-carbonyl and the corresponding thiocarbonyl derivatives.50... 

The wide scope of application of the electrophilicity index of Parr, Szentpaly, and Liu has been reviewed.1 Applications to electrophilic aromatic substitutions discussed are few. However, some alkylation and acylation reactions do correlate well with electrophilicity values. In the case of the nitration of toluene and chlorobenzene, correlation is not very good and it is suggested2 that electrophilicity is a kinetic quantity with inherent thermodynamic information. 

Reference should also be made to a superdelocalizability index Sp derived within the frame of the simple FEMO model [35], Goodness of fit of correlations of SfE values with relative rate constants for electrophilic aromatic substitution was found to be comparable with those based on CNDO/2 calculations. 

A global electrophilicity index of common benzylating and acylating agents has been established from MO calculations and it shows a quantitative linear correlation with the experimental substrate selectivity index from a series of benzylation and acylation reactions.21 The values of relative rate coefficients predicted from the index may be accurate to within 10%. The reaction of /-butyl chloride with anisole catalysed by /Moluenesulfonic acid in supercritical difluoromethane has been subject to kinetic analysis.22 The proportions of substitution at the ortho -position and disubstitution increase at lower pressures, attributed to the decrease in the hydrogen-bonding ability of the solvent. 

Electrophilic aromatic substitution is a typical reaction for BHs. In the MO treatment, some indices such as free valence [40], localization energy [41], and other quantities [42,43] have been introduced to predict the orientation of electrophilic aromatic substitution. Within the VB framework, several indices have also been formulated [44]. Here we introduce an alternative index, which is available from accurate VB wave functions, and demonstrate its applicability in accounting for the electrophilic aromatic substitution. 

---