Linear free-energy relationships studies

As a rule, the presence of a high dielectric constant medium leads to the rise of the dipole moment of the compound. However, the relative increase of the dipole moment varies substantially from one structure to another. For instance, the calculated dipole moment of 2(H)-3-pyrazolone (7) increases by 72% when transferred from the medium with e = 1 to the medium with s = 80, whereas the corresponding change in the dipole moment of pyrazole (3) is only 15%. Therefore, it is questionable to assume constant dipole moment values for a series of congeneric compounds in different dielectric media and derive correlations of the chemical reactivity or physical properties of such series of compounds with some fixed function of the dielectric constant of the solvent (a common approach in the linear free energy relationship studies of solvent effects, cf. [65-67]). 

Linear free energy relationship studies have demonstrated that OMO is an... 

Solvents exert their influence on organic reactions through a complicated mixture of all possible types of noncovalent interactions. Chemists have tried to unravel this entanglement and, ideally, want to assess the relative importance of all interactions separately. In a typical approach, a property of a reaction (e.g. its rate or selectivity) is measured in a laige number of different solvents. All these solvents have unique characteristics, quantified by their physical properties (i.e. refractive index, dielectric constant) or empirical parameters (e.g. ET(30)-value, AN). Linear correlations between a reaction property and one or more of these solvent properties (Linear Free Energy Relationships - LFER) reveal which noncovalent interactions are of major importance. The major drawback of this approach lies in the fact that the solvent parameters are often not independent. Alternatively, theoretical models and computer simulations can provide valuable information. Both methods have been applied successfully in studies of the solvent effects on Diels-Alder reactions. 

Another method for studying solvent effects is the extrathermodynamic approach that we described in Chapter 7 for the study of structure-reactivity relationships. For example, we might seek a correlation between og(,kA/l ) for a reaction A carried out in a series of solvents and log(/ R/A R) for a reference or model reaction carried out in the same series of solvents. A linear plot of og(k/iJk ) against log(/ R/ linear free energy relationship (LFER). Such plots have in fact been made. As with structure-reactivity relationships, these solvent-reactivity relationships can be useful to us, but they have limitations. 

In this chapter it is clearly impossible to do more than sample the extensive literature on the carbon acidity of sulfinyl and sulfonyl compounds, as it illuminates the electronic effects of these groups, particularly in connection with linear free-energy relationships. There are three main areas to cover first, as already indicated, equilibrium acidities (pKa values) second, the kinetics of ionization, usually studied through hydrogen isotopic exchange and finally, the kinetics of other reactions proceeding via carbanionic intermediates. 

Servis, K. L. and Domenick, R. L. (1987). J. Am. Chem. Soc. 107, 7186 Shorter, J. (1972). Advances in Linear Free Energy Relationships (ed. N. B. Chapman and J. Shorter), Chap. 2. Plenum Press, London Shorter, J. (1982). Correlation Analysis of Organic Reactivity. Research Studies Press Wiley, New York... 

Significance of the Br nsted Slope in Electron Transfer. Linear free energy relationships have been extensively studied for electron transfer and related reactions in both inorganic and organic systems. For highly endergonic reactions, the Br0nsted slope a is close to unity. In many cases, however, the more or... 

Quite recently, the same research group compared the electrophilicity of 6-nitro-tetrazolo[l,5- ]pyridine and 6,8-dini-trotetrazolo[l,5- ]pyridine 11 with a series of electron-deficient aromatic and heteroaromatic compounds <2005JOC6242>. As reference nucleophiles, fV-methylpyrrole, indole, fV-methylindole, and some morpholino enamines were used. The reactivity of the electrophiles studied followed the linear-free energy relationship defined by Mayr et al. <2003ACR66>. 

Lokajova, J., Tesrfova, E., and Armstrong, D.W., Comparative study of three teicoplanin-based chiral stationary phases using the linear free energy relationship model, J. Chromatogr. A, 1088, 57, 2005. 

Computational chemistry methodology is finding increasing application to the design of new flavoring agents. This chapter surveys several useful techniques linear free energy relationships, quantitative structure-activity relationships, conformational analysis, electronic structure calculations, and statistical methods. Applications to the study of artificial sweeteners are described. 

Laser flash photolysis (LFP) studies have been carried out on the generation of N,C-diaryl nitrile imines from sydnones and from tetrazoles in solution at 77 K. They were found to have lifetimes of milliseconds and were quenched by dimethyl acetylenedicarboxylate (DMAD) ( q = 5-9 x 103A7 s-1) and by carboxylic acids (kq = 104—109 M l s I) (13). The strong dependence of vmax on the nature of the aromatic substituents in N,C-diaryl nitrile imines was interpreted by a linear free energy relationship as due to intramolecular charge transfer (14). 

Structural modification of a molecule usually has profound and complex influence on its crystal s packing and mechanical properties. This type of behavior is so pervasive that one usually despairs of being able to apply the kind of linear free energy relationships that are so useful in solution chemistry to studies of solid-state mechanisms. When structural modification is sufficiently subtle, however, analogous techniques can be helpful. 

The hydrolysis of alkoxysilane esters has been extensively studied. The influences of the silane ester structure and acids, bases, solvent, and temperature on the reaction rates and kinetics have been investigated. Linear free energy relationships, such as Taft equations and Brensted plots, were used to gain... 

The kinetics of the acid catalyzed hydrolysis of ethoxysilanes has been studied. Each of the silanes that were used had a phenyl or para-substituted phenyl group attached to the silicon atom. This permitted a study of the linear free energy relationships of this reaction. The reaction is of interest because of its role in silane coupling agent chemistry, in the preparation of zinc-rich silicate coatings, in the sol-gel process and in the preparation of silicones in general. 

The Hammett cr—p correlation has proved useful in studying substituent effects of aryl-substituted systems.55 In Section 6.1 we consider applications of this linear free-energy relationship to solvolysis with rearrangement. 

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