Nucleophile-specific parameters

Equation (31) has an electrophilic ( ) and a nucleophilic (N component and the value, s, is a nucleophile specific parameter. This equation has a close family relationship with the Ritchie and Swain-Scott equations (Chapter 2) and the Edwards equation (29). The equation successfully correlates rate constants for a wide range of disparate structures and... 

Kinetics of the reactions of pyridinium ylides (210) and their isoquinolinium and quinolinium congeners with arylidene malonates (211) and related electrophiles, such as diarylcarbenium ions and quinone methides, have been studied in DMSO by UV-vis spectroscopy. The second-order rate constants thus obtained were used to derive the nucleophile-specific parameters Nand % for these ylides. Pyridinium substitution turned out to have a similar effect as that of alkoxycarbonyl substituents on the reactivity of carbanionic reaction centres. Agreement between the experimental rate constants and those calculated from E, N, and % shows that this correlation can also be employed for predicting the absolute rate constants of step-wise or highly unsymmetrical concerted cycloadditions. On the other hand, deviation by a factor of 10 would indicate a change of reaction mechanism. ... 

Nucleophile-specific parameters N and % of enamides have allowed their rates of reaction with various electrophiles to be predicted and thereby reveal the stepwise nature of iminium-activated reactions of electrophilic a,)0-unsaturated aldehydes with enamides and the inadvisability of using strong acid co-catalysts. ... 

The further behavior of benzo[c]annelated adducts 100 depends on the structure of substituents in the initial cation 30, nature of the nucleophile, thermodynamic parameters of the final products, and conditions of the experiment. The reaction may be stopped at the step of adduct 100 (b, 1 in Scheme 5) or may be continued with the formation of ring-opened intermediate 101 (b,2). However, the latter step has some specific features, in comparison with monocyclic pyrylium salts, as a consequence of the presence of the annelated benzenoid ring in benzo[c]pyrylium cations. 

The scale was developed using a series of benzhydrylium ions having the general structure 54, where the E value was taken to be 0.00 for system with both X and Y = OCH3. This system allowed the study of a wide range of reactivity, because the E value Ifor 54 having X and Y = Cl is 6.0, while that for 54 with X and Y = N(CH3)2 is —7.4. The nucleophiles in the initial study were all 7i-nucleophiles, and the nucleophile-specific slope parameter was chosen to be 1.00 for the case of 2-methyl-l-pentene, which was foimd to have an N value of 0.96. Each nucleophile is identified with both an N and an Sn value, so the listing for 2-methyl-l-pentene is 0.96 (1.00). 

Interestingly, the nucleophilicity parameters were shown to apply fairly well for reactions with the four l-halogeno-2,4-dinitrobenzenes in water and in methanol. An exception was for reaction with the azide ion, which showed lower than expected reactivity in the substitution reaction [20]. Inclusion of an extra parameter increases the applicability of the equation so that Mayr [60] has shown that Equation 6.2, where S is a nucleophile specific slope parameter, allows the reactivities of very many nucleophiles... 

This equation implies that the relative reactivity is independent of the specific nucleophile and that relative reactivity is insensitive to changes in position of the transition state. Table 8.4 lists the B values for some representative ketones. The parameter B indicates relative reactivity on a log scale. Cyclohexanone is seen to be a particularly reactive ketone, being almost as reactive as cyclobutanone and more than 10 times as reactive as acetone. 

Very recent extensions of the formalism of Thiel and Voityuk to AMI have been reported by multiple groups. Voityuk and Rosch (2000) first described an AMl/d parameter set for Mo, and, using the same name for the method, Lopez and York (2003) reported a parameter set for P designed specifically to facilitate the study of nucleophilic substitutions of biological phosphates. Winget et al. (2003) described an alternative model, named AMI, that adds d orbitals to P, S, and Cl. As with MNDO/d, the primary improvement of this model is in its general ability to describe hypervalent molecules more accurately. Subtle differences in the various individual formalisms will not be further delved into here. 

In this context, another empirical solvent parameter called SI should be mentioned. SI stands for Solvent /nfluence (in Russian, BP for Ejmstsae FacTBopHTena). This parameter was introduced by Shmidt et al. in 1967 and was derived from the study of many different extraction equilibria, i.e. of the distribution of organic and inorganic compounds between two immiscible liquid phases [298-301]. It was found that in the extraction of metal salts using various extraction reagents, the distribution coefficients of the extractable compound depend on the specific electrophilic and/or nucleophilic properties of the solvents used as diluent. From a large number of well-studied extraction systems, Eq. (7-12d) has been derived. 

The chemical behaviour of a given species strongly depends on the nature of the other molecules involved in the interaction. For a specific type of reaction, an appropriate model is needed to simulate the chemical environment of the species of interest. In the present work, the interest is focused on the initial response of the molecule to a particular type of chemical situation, independent of the value of those parameters that characterize one specific reaction. In other words, the intrinsic capabilities of the chemical species are studied and modelled as derivatives of the electronic properties with respect to an appropriate independent variable. For example, in those processes where charge transfer is involved (such as Lewis acidity and basicity, electrophile-nucleophile interactions and coordination compounds), the number of electrons must be an independent variable when a small molecule interacts with a very large counterpart (such as enzyme-substrate interaction and adsorption on solid surfaces), the chemical potential of the large partner will be imposed on the small molecule, and its number of electrons will not be independent. 

Koppel-Palm solvent parameters Parameters to measure separately the ability of a solvent to enter into nonspecific solvent-solute interactions (permittivity, , and refractive index, nD) and specific solvent-solute interaction (solvent basicity or NUCLEOPHILICITY B and solvent acidity or ELECTROPHILICITY E) as contributing to overall solvent POLARITY. 

In the kinetic approach, the serine or cysteine peptidase rapidly reacts with a suitable acyl donor ester to form the acylenzyme intermediate, which can be deacylated competitively by the added nucleophilic amine component and water. The ratio between aminolysis and hydrolysis of the acyl donor ester is of great importance for the outcome of the synthesis route.This selectivity is essentially determined by the S subsite specificity of the enzyme as shown above. To establish an optimum synthesis strategy, it is useful to know the basic kinetic parameters for the reaction course, in particular those obtained by S subsite mapping are of great importance for planning and optimization of the enzymatic synthesis. 

The Kramers result for k T) of Eq. (3.41) has been tested by Wilson and co-workers [14] in their MD simulations of model aqueous nucleophilic substitution reactions. Specifically, these authors determined by MD simulation both the exact Kmd(T) and Kramers Kkr(T) transmission coefficients for 12 Sjv2 systems [14a] and for one system [14b]. The coefficients Kmd(T) were determined from ensembles of reactive and nonreactive MD trajectories. The coefficients kkr(T) were found from Eq. (3.41), with the parameters copmf and being computed via an MD implementation of our partial clamping model [21]. Namely, (Opmf and J (S) are computed via constrained MD simulations in which the reaction coordinate X is held fixed at its transition state value x while the remaining degrees of freedom of the solution are allowed to move freely subject to this single constraint. 

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