THE INTERMEDIATE COMPLEX MECHANISM

On both experimental and theoretical grounds there is little doubt of the importance of polarizability as a major factor in determining the commonly encountered, though variable, high RS /RO ratios. Were thermodynamic carbon affinities mainly responsible for the usual reactivity order RS > RO, the peculiar behavior of chloroquinolines would be very difficult to understand. There is some indication, however, that carbon affinities roughly parallel basicities (hydrogen affinities), In the latter case, lower RS /RO ratios could be explained in terms of the intermediate complex mechanism, ... 

Sn2 nucleophilic aromatic substitution 2. The intermediate complex mechanism... 

In early rate studies the nucleophile was frequently an anion, and the intermediate complex mechanism was formulated as... 

The available experimental results are completely in accord with this formulation. Both of these limiting conditions have been observed experimentally, and plots of both k versus [B]0 and k versus [R2NH]0 have been shown to have characteristics consistent with this proposed mechanism. These observations thus constitute very convincing evidence for the intermediate complex mechanism in nucleophilic aromatic substitution. 

The mechanism has also been called by other names, including the Sn2At, the addition-elimination, and the intermediate complex mechanism. 

The relative orders in which the halogens are displaced in nucleophilic aromatic substitution reactions has been advanced as an u-ment both for and against the intermediate complex mechanism. In particular Fierens and Halleux (91), who found the order, F < Cl < Br < I, for the reactions of the l-halo-2,4-dinitrobenzenes and the l-halo-2,4-dinitro-6-methylbenzenes with potassium iodide in dry acetone, and Hammond and Parks (92), who obtained the same order for the reactions of the l-halo-2,4-dinitrobenzenes with N-methylaniline in both nitrobenzene and 99.8% ethanol, have offered these results as support for a one-step mechanism, since this is the sequence observed in non-activated nucleophilic aromatic substitution reactions and in typical aliphatic displacements. Hammond has, however, pointed out that these experiments do not permit a distinction between a one-step mechanism and a two-step mechanism in which the second step is rate-determining (90). 

Both of these reported kinetic hydrogen-deuterium isotope effects are disturbingly small, yet they are probably too large to be considered secondary isotope effects. These results lend support to the intermediate complex hypothesis, but they can be accommodated equally well by all three of the mechanisms that have been considered. These results, therefore, afford no basis for discrimination among the possible mechanisms. 

From the fundamental knowledge concerning the interfacial complexation mechanism obtained from the kinetic studies on chelate extraction, ion-association extraction, and synergistic extraction, one can design the interfacial catalysis. The main strategy is to raise the concentration of the reactant or intermediate at the interface. 

For either of the ternary complex mechanisms described above, titration of one substrate at several fixed concentrations of the second substrate yields a pattern of intersecting lines when presented as a double reciprocal plot. Hence, without knowing the mechanism from prior studies, one can not distinguish between the two ternary complex mechanisms presented here on the basis of substrate titrations alone. In contrast, the data for a double-displacement reaction yields a series of parallel lines in the double reciprocal plot (Figure 2.15). Hence it is often easy to distinguish a double-displacement mechanism from a ternary complex mechanism in this way. Also it is often possible to run the first half of the reaction in the absence of the second substrate. Formation of the first product is then evidence in favor of a doubledisplacement mechanism (however, some caution must be exercised here, because other mechanistic explanations for such data can be invoked see Segel, 1975, for more information). For some double-displacement mechanisms the intermediate E-X complex is sufficiently stable to be isolated and identified by chemical and/or mass spectroscopic methods. In these favorable cases the identification of such a covalent E-X intermediate is verification of the reaction mechanism. 

The reactions of the bare sodium ion with all neutrals were determined to proceed via a three-body association mechanism and the rate constants measured cover a large range from a slow association reaction with NH3 to a near-collision rate with CH3OC2H4OCH3 (DMOE). The lifetimes of the intermediate complexes obtained using parameterized trajectory results and the experimental rates compare fairly well with predictions based on RRKM theory. The calculations also accounted for the large isotope effect observed for the more rapid clustering of ND3 than NH3 to Na+. 

Such a mechanism would have to involve the nitrosyl ligand acting in a non-innocent manner, changing from a three-electron donor to a one-electron donor in the intermediate complex. Such participation of the nitrosyl ligand has precedent in related systems (108). 

Most catalysts are based on chromium that has been studied for this purpose since the mid-seventies, probably started by Union Carbide Corporation. Chromium is the metal of the Phillips ethene polymensation catalysts and presumably it was discovered accidentally that under certain conditions 1-hexene was obtained as a substantial by-product. Neither the precise catalytic cycle nor the intermediate complexes or precursors are known. It is generally accepted that an alkyl aluminium compound first reduces the chromium source and that coordination of two molecules of ethene is followed by cyclometallation, giving a chromocyclopentane. During the cyclometallation the valence of chromium goes up by two and thus a starting valence of either one or zero seems reasonable. This cyclic mechanism explains why such high selectivity is obtained [5],... 

Recently, some attempts were nndertaken to uncover the intimate mechanism of cation-radical deprotonation. Thns, the reaction of the 9-methyl-lO-phenylanthracene cation-radical with 2,6-Intidine (a base) was stndied (Ln et al. 2001). The reaction proceeds through two steps that involve the intermediary formation of a cation-radical/base complex before unimolecular proton transfer and separation of prodncts. Based on the value of the kinetic isotope effect observed, it was concluded that extensive proton tnnneling is involved in the proton-transfer reaction. The assumed structure of the intermediate complex involves n bonding between the unshared electron pair on nitrogen of the Intidine base with the electron-deficient n system of the cation-radical. Nonclassical cation-radicals wonld also be interesting reactants for snch a reaction. The cation-radical of the nonclassical natnre are known see Ikeda et al. (2005) and references cited therein. 

The mechanism of an enzymatic reaction is ultimately defined when all the intermediates, complexes, and conformational states of the enzyme are characterized and the rate constants for their interconversion are determined. The task of the kineticist in this elucidation is to detect the number and sequence of these intermediates and processes, define their approximate nature (that is, whether covalent intermediates are formed or conformational changes occur), measure the rate constants, and, from studying pH dependence, search for the participation of acidic and basic groups. The chemist seeks to identify the chemical nature of the intermediates, by what chemical paths they form and decay, and the types of catalysis that are involved. These results can then be combined with those from x-ray diffraction and NMR studies and calculations by theoretical chemists to give a complete description of the mechanism. 

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