Hammond postulate, applications

The SnI mechanism Carbocation stability The Hammond postulate Application SnI reactions, nitrosamines, and cancer... 

Many programs allow the user to input a weighting factor (i.e., to give a structure that is 70% of the way from reactants to products). This allows the application of the Hammond postulate that the transition structure will look more like the reactants for an exothermic reaction and more like the products for an endothermic reaction. 

A most useful application of the Hammond postulate involves reactions which proceed by the formation of unstable intermediates, such as die carbocations,... 

In this section, solvolysis reactions are described which are thought to proceed via silyl-substituted carbocations. The reader should be aware of the fact that nearly all effects which are described here are of purely kinetic origin and therefore refer to energy differences between ground states and transition states. Hence they are not strictly applicable to the intermediate silyl-substituted carbocations, although the Hammond postulate suggests a close structural resemblance between the transition state for the ionization and the formed carbocation. 

In spite of these uncertainties, however, the utility of the reactivity-selectivity principle has been illustrated for a number of diverse areas of mechanistic interest. Such applications are being extended to other areas as well. For example, Olah has recently studied the mechanism of electrophilic addition to multiple bonds using selectivity data and concluded that the transition states of the bromine addition to alkenes are of a 7r-complex nature (Olah and Hockswender, 1974). Finally the large number of reactivity-selectivity relationships which have been discovered offer considerable experimental support for the various expressions and formulations of the Hammond postulate whose profound effect on modem mechanistic chemistry is now beyond question. 

When the electrophilic atom is H+ and the alkene is unsymmetrical, H+ adds to the alkene so that the more stable carbocation (almost always the more substituted one) is formed. The nucleophile then adds to the carbocation to give the product. The observation that the nucleophile adds to the more substituted C of the double bond is known as Markovnikov s rule. Markovnikov s rule is simply an application of the Hammond postulate the faster reaction is the one that leads to the intermediate lower in energy. 

Careful application of the Hammond postulate allows us to ascertain the structure of the transition state under certain conditions if we know something about the structure and energy of the next prior or later consecutive species, which could bean unstable intermediate, reactant, or product. Proposed originally by George Hammond,41 the postulate declares, "if two states, as for example, a transition state and an unstable intermediate, occur consecutively during a reaction process and have nearly the same energy content, their interconversion will involve only a small reorganization of molecular structure."... 

A general definition of the Quantum Molecular Similarity Measure is reported. Particular cases of this definition are discussed, drawing special attention to the new definition of Gravitational-like Quantum Molecular Similarity Measures. Applications to the study of fluoromethanes and chloro-methanes, the Carbonic Anhydrase enzyme, and the Hammond postulate are presented. Our calculations fully support the use of Quantum Molecular Similarity Measums as an efficient molecular engineering tool in order to predict physical properties, lMok>gical and pbarraacdogical activities, as well as to interpret complex chemical problems. 

In the most well-known example of the application of Hammond postulate, we consider the comparison of structures of the various carbocations in SN1 reaction. The relative stabilities of the carbocations decrease in the order 3° > 2° > 1° > Me+. According to the Hammond postulate, and as shown in Fig. 6, the transition state shifts toward the product cation as the stability of the cation decreases. Also, coupled with this, the transition state energy is lowered with the increase in the stability of the resultant cation [78-81]. 

The applicability of the Hammond postulate and the Curtin-Hammett principle was discussed in the review of Manuilov and Barkhash (1990) on the mechanism of deamination. This principle allows evaluation of the effect of conformational changes on the reactivity of compounds A and A forming B and B in the kinetic system (7-40), in which the steps with rate constants k and k, may be monomolecular or bimolecular (with a reagent R) A and A are conformers of the starting material. 

The nitrous acid deamination will be discussed in comparative terms with the solvolysis of the corresponding halide or sulfonate in the same solvent. Application of the Hammond Postulate to the... 

The ortho-para- versus meta-directing and activating versus deactivating effects of substituents can also be described in terms of PMO theory. The discussion can focus either on the structure of the cr complex or on the aromatic substrate. According to the Hammond postulate, it would be most appropriate to focus on the intermediate in the case of reactions which are relatively endothermic. The transition state should then resemble the a complex in reactions when the initial step has an appreciable activation energy. For more highly reactive electrophiles the transition state may be more reactant-like, in which case consideration of the reactant and application of frontier orbital theory would be more appropriate. Let us examine the effect of substituents from both perspectives. 

Fig. 4.3. Some typical potential energy diagrams that illustrate the application of Hammond s postulate.

Application of Hammond s postulate indicates that the transition state should resemble the product of the first step, the carbocation intermediate. Ionization is facilitated by factors that either lower the energy of the carbocation or raise the energy of the reactant. The rate of ionization depends primarily on how reactant structure and solvent ionizing power affect these energies. 

Many reactions exhibit effects of thermodynamics on reaction rates. Embodied in the Bell-Evans-Polanyi principle and extended and modified by many critical chemists in a variety of interesting ways, the idea can be expressed quantitatively in its simplest form as the Marcus theory (15-18). Murdoch (19) showed some time ago how the Marcus equation can be derived from simple concepts based on the Hammond-Leffler postulate (20-22). Further, in this context, the equation is expected to be applicable to a wide range of reactions rather than only the electron-transfer processes for which it was originally developed and is generally used. Other more elaborate theories may be more correct (for instance, in terms of the physical aspects of the assumptions involving continuity). For the present, our discussion is in terms of Marcus theory, in part because of its simplicity and clear presentation of concepts and in part because our data are not sufficiently reliable to choose anything else. We do have sufficient data to show that Marcus theory cannot explain all of the results, but we view these deviations as fairly minor. 

This effect illustrates another application of the Hammond—Leffler postulate (Section 6.13A). The arenium ion is a high-energy intermediate, and the step that leads to it is a highly endothermic step. Thus, according to the Hammond—Leffler postulate, there should be a strong resemblance between the arenium ion itself and the transition state leading to it. 

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