Nucleophile-substrate interaction

Hayami, J., Koyanagi, T., Kaji, A. Sn2 reactions in dipolar aprotic solvents. VIII. Chlorine isotopic exchange reaction of (arylsulfonyl)chloromethanes, (arylsulfinyl)chloromethanes, and 2-chloro-1-arylethanones in acetonitrile. A role of the nucleophile-substrate interaction in the Finkelstein reaction. Bull. Chem. Soc. Jpn. 1979, 52, 1441-1446. 

Weak nucleophile-electrophile interactions (and the donor-acceptor complexes) are considered precursors in aromatic electrophilic substitutions133 and in additions of electrophiles to C=C double bond of olefins the first step (the addition of the electrophile to an electron-rich substrate) is probably the same for both reactions. 

Note how the key interaction boosting the catalytic effect is the protonation of the carbonyl group on the TG. Such catalyst-substrate interaction increases the electrophilicity of the adjacent carbonyl carbon atom, making it more susceptible to nucleophilic attack. Compare this to the base-catalyzed mechanism where the base catalyst takes on a more direct route to activate the reaction, creating first an alkoxide ion that directly acts as a strong nucleophile (Figure 4). Ultimately, it is this crucial difference, i.e., the formation of a more electrophilic species (acid catalysis) v.s. that of a stronger nucleophile (base catalysis), that is responsible for the differences in catalytic activity. 

The stereochemical behavior of Ph2CHLi, i.e., cleavage of the Si—H bond with predominant inversion, can be explained as follows. We are faced with a very soft nucleophile of low level (Scheme 10). The substrate superjacent MO-nucleophile HOMO interaction prevails. The big lobe of the Si hybrid orbital points to the rear in the superjacent MO (Scheme 11), and the inversion is therefore favored. However, this reaction is quite slow (10). 

Carbon dioxide (C02) can interact easily with several N-nucleophiles. Such interaction results in an activation of the heterocumulene, and has a great synthetic relevance as it is a key step towards the carboxylation or, more generally, the car-bonylation of the N-donor substrate and the synthesis of a variety of N-carbonyl compounds. 

A systematic and in-depth study involving bio-imprinted subtilisin using nucleophilic substrates as the templates has been reported by Rich and Dordrick [19]. They allowed subtilisin Carlsberg to interact with thymidine (the template) in an aqueous buffer solution and the resulting complex was lyophilised. After removing the template, catalytic activity of the imprinted enzyme was studied by the acylation reaction of thymidine. Compared to the control (enzyme lyophilised from the aqueous solution in the absenee of the nucleotide template), the imprinted enzyme... 

As a mechanistic criterion we introduce the cross-interaction constant (CIC) p,7, defined in equations la and lb based on the adoption of a convention denoting substituents on the nucleophile, substrate and leaving groups, respectively, as X, Y and Z15. 

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. 

Figure 72.5-77. Schematic representation of subsite-substrate interactions in the course of the acyl transfer from the acylenzyme to the nucleophilic amine component catalyzed by a serine peptidase.

Figure 17-9 One possible model for substrate interactions with the dinuclear metal cluster. In this model, substrate binds to the Fe site, positioning the phosphate ester for in-line nucleophilic attack by a hydroxide ion coordinated to the Fe + ion.

The electrochemical conditions, the electrode material, the solvent, the coimterion and the monomer all influence the nature of the processes occurring. For example, if the applied potential is too low (imder certain conditions), the rate of polymerization will be such that no precipitate eventuates. If the solvent is nucleophilic (or contains dissolved oxygen), it will react with the free radical intermediates. If the electrode material is extremely polar, at the potential required for polymerization, deposition may be discouraged. In addition the solvent, monomer, counterion and substrate interactions are all important since they dictate the solubility and/or deposition of the resultant polymer. 

Covalent activations of substrates can be achieved through different methods. One such method includes the formation of intermediates between an otherwise relatively inert substrate and the catalyst. This is comparable with the formation of an enzyme-substrate complex in an enzymatic reaction. In organocatalytic reactions, the substrates can be classified as nucleophilic and electrophiUc partners. Each of these substrates can be activated by interactions with the catalyst The catalyst-substrate interaction can either be covalent or non-covalent While the non-covalent activations are described elsewhere in other chapters of these volumes, the focus herein is on covalent activations. In covalent activation, the substrate forms a bond with the catalyst and thereby becomes activated. For instance, in the following example of the formation of the prohne enamine of acetone the substrate (acetone) reacts with proline to generate the activated nucleophile (enamine) (Scheme 17.1). 

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