Substitution reactions 382 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],... 

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, ... 

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... 

Benzyloxy(cyano)carbene would be expected to be electrophilic by virtue of the calculated selectivity index, Wp -HjOccN 111- This has not yet been experimentally proved as 3-bcnzyloxy-3-cyano-3//-diazirine is rather labile and cannot be isolated if it is synthesized by the substitution of chlorine by a cyano group in 3-benzyloxy-3-chloro-3if-diazirine consequently, this substitution reaction is carried out in the presence of an alkene, hence, preparing 1-benzyloxy-cyclopropane-l-carbonitrile derivatives. However, the cyanide ion present in the system induces the polymerization of electrophilic alkenes, such as acrylonitrile or methyl acrylate. 

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. 

Where Chomo.tce is the HOMO energy of tetracyanoethylene (TCE) taken as a reference molecule because it exhibits the lowest HOMO energy in a large series of molecules previously considered in the framework of polar DA cydoadditions). N is the global nudeophilidty index and is its local counterpart. This nudeophilicity index has been useful to explain the nucleophilic reactivity of some molecules towards electrophiles in cycloaddition as well as substitution reactions. (Domingo, et al, 2008)... 

A second theoretical index, and one for which there appears to be more justification in its application to free-radical reactions, is the atom localization energy. This index is a measure of the energy required to localize one electron of the 7r-electron system in the aromatic molecule at the point of attack of the radical. The formation of the intermediate adduct in a free-radical aromatic substitution may be regarded as the sum of two processes one, the localization of an electron at the point of attack and the other, the pairing of this... 

The susceptibility or mixing coefficients, pj and pj , depend upon the position of the substituent (indicated by the index, /) with respect to the reaction (or detector) center, the nature of the measurement at this center, and the conditions of solvent and temperature. It has been held that the p/scale of polar effects has wide general applicability (4), holding for substituents bonded to an sp or sp carbon atom (5) and, perhaps, to other elements (6). The or scale, however, has been thought to be more narrowly defined (7), holding with precision only for systems of analogous pi electronic frameworks (i.e., having a dependence on reaction type and conditions, as well as on position of substitution). 

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. 

As a result of the nonuniform reaction process, all commercial products within the Alkali Blue series represent mixtures of various products. The respective structure which is listed in the Colour Index only reflects the main component of a differently arylated mixture. Moreover, the aromatic moieties not only represent differently substituted compounds but also mixtures of various degrees of sulfonation. 

Another example of the use of transition state pKa values has been provided by Pollack (1978). From the rate constants for the decarboxylation of substituted a,a-dimethylbenzoylacetic acids ([37] — [38]) and their anions, he calculated pK for reaction of the acids (Table A6.2). The values vary significantly with the phenyl substituent (p = +1.7), much more so than the p/(a values of the substrate acids (p = +0.2). This difference is consistent with the proton being much closer to the phenyl group in the transition state than in the initial state, and it may even denote a relatively late transition state (Pollack, 1978). However, from the pKa values of the reactant acids (approximately 3.4), the transition states (approximately 4.4), and the enol product (11.8) (Pruszynski et al., 1986), the Leffler index... 

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