Nucleophilic substitution reactions nucleophilicity, factors affecting

Both the initial addition step and the subsequent elimination step can affect the overall rate of a nucleophilic acyl substitution reaction, but the addition step is generally the rate-limiting one. Thus, any factor that makes the carbonyl group more reactive toward nucleophiles favors the substitution process. 

The kinetics and mechanisms of substitution reactions of metal complexes are discussed with emphasis on factors affecting the reactions of chelates and multidentate ligands. Evidence for associative mechanisms is reviewed. The substitution behavior of copper(III) and nickel(III) complexes is presented. Factors affecting the formation and dissociation rates of chelates are considered along with proton-transfer and nucleophilic substitution reactions of metal peptide complexes. The rate constants for the replacement of tripeptides from copper(II) by triethylene-... 

It is often possible to predict the reactivity of a chlorosulfonyloxy group by a consideration of the steric and polar factors affecting the formation of the transition state,27-28 as indicated in Section 11,1 (see p. 227) for nucleophilic-replacement reactions of sulfonic esters of carbohydrate derivatives. Thus, it has been found that the presence of a vicinal, axial substituent or of a (3-trans-axial substituent on a pyranoid ring inhibits replacement of a chlorosulfonyloxy group also, a chlorosulfate group at C-2 has been observed to be deactivated to nucleophilic substitution by chloride ion. 

The purpose of this chapter is to explore the properties and reactions of various Pt-nucleobase complexes. After a short description of various binding modes, attention will be paid on the effects of coordinated platinum. Topics include, e.g., isomerization, thermodynamic stability, and solvolyt-ic reactions of Pt-nucleobase complexes. Finally, factors affecting the mechanism and kinetics of substitution reactions by various nucleophiles will be discussed. 

The rate of nucleophilic addition to cyclopropyl-substituted cations is little affected by the cyclopropyP Thus there was little difference in the rate of reaction of Ph l HR and PhCR2 (R = Ph or c-Pr) with NH3, w-Pr3N, and n-Bu N in methylene chloride solvent except for Ph3C which was less reactive by factors of 10-20. Steric factors were evidently responsible for the latter effect ... 

So far, we have considered the rate of SN2 substitution and factors that affect it. In so doing we have, however, already noted one of the most important points that affects the stereochemical consequences of this type of substitution reaction, namely that the incoming nucleophile approaches the substrate from the opposite side to which the leaving group departs. Suggest what will be the stereochemical consequence of this. 

Radicals have an unpaired electron and are usually electrically neutral. Accordingly, radical substitution reactions tend not to be affected by those factors, such as solvent polarity, that affect mechanisms involving charged species, such as nucleophilic or electrophilic substitution. 

Aliphatic and aromatic nucleophilic substitution reactions are also subject to micellar effects, with results consistent with those in other reactions. In the reaction of alkyl halides with CN and S Oj in aqueous media, sodium dodecyl sulfate micelles decreased the second-order rate constants and dodecyltrimethylammonium bromide increased them (Winters, 1965 Bunton, 1968). The reactivity of methyl bromide in the cationic micellar phase was 30 to 50 times that in the bulk phase and was negligible in the anionic micellar phase a nonionic surfactant did not significantly affect the rate constant for n-pentyl bromide with S2O3-. Micellar effects on nucleophilic aromatic substitution reactions follow similar patterns. The reaction of 2, 4-dinitrochlorobenzene or 2, 4-dinitrofluorobenzene with hydroxide ion in aqueous media is catalyzed by cationic surfactants and retarded by sodium dodecyl sulfate (Bunton, 1968, 1969). Cetyltrimethylammonium bromide micelles increased the reactivity of dinitrofluorobenzene 59 times, whereas sodium dodecyl sulfate decreased it by a factor of 2.5 for dinitrochlorobenzene, the figures are 82 and 13 times, respectively. A POE nonionic surfactant had no effect. 

The evidence available suggests that, in a general way, steric factors affect the course of the reaction. Increase in the size of substituents at positions 5 or 7 or in the size of the nucleophile appears to favor protode-bromination over nucleophilic substitution, Furthermore it appears that 6-iododihydrodiazepines undergo protodeiodination rather than nucleophilic substitution irrespective of the size of the nucleophile or of 5(7)-substituents, whereas 6-chlorodihydrodiazepines are less susceptible to protodchalogenation.64 Thus with thiourea 6-bromodihydrodiazepines undergo protodebromination, whereas 6-chlorodihydrodiazepines form 6-isothiouronium salts, in contrast to the normally more ready formation of isothiouronium salts from bromo compounds than from chloro compounds. It is not unreasonable that protodehalogenation should be favored for more bulky dihydrodiazepines or nucleophiles since this reaction has less steric demands than nucleophilic substitution. Similarly, both for... 

In solution, all participants in a chemical reaction are solvated the reactants and the products—and the transition state. Our examination of these must include any solvent molecules that help make up the structures and help determine their stabilities. And so, in Chapter 7, using as our examples the nucleophilic substitution reactions the students have just studied, we show how reactivity— and, with it, the course of reaction—is affected by the solvent. We show just how enormous solvent effects can be that the presence of a solvent can speed up—or slow down—a reaction by a factor of l(P that a change from one solvent to another can bring about a miUionfold change in reaction rate. 

The sensitivity of the internal carbon to reaction would be a significant complicating factor for carbaporphyrins in protein active sites. Dioxygen binding and activation, for example, would readily result in oxidation at the core carbon position. In addition, the susceptibility of the internal carbon to nucleophiles could affect the coordination chemistry of the side chains of cysteine and histidine, frequently bound at the axial positions of heme sites. While novel inorganic structures do result from adducts formed upon substitution at the internal carbon, directly analogous chemistry to that seen in normal porphyrins is much less likely due to its susceptibility. 

Classes of organic pollutants that hydrolyze via nucleophilic substitution reactions include the halogenated hydrocarbons, epoxides, and phosphorus esters. Further discussion of the factors affecting the reactivity of nucleophilic substitution reactions will be made as the hydrolysis mechanisms of these chemicals are examined in greater detail. 

There are various factors that affect the rate of a nucleophilic substitution reaction involving a halogenoalkane ... 

Since we know the relative stabilities of acyl derivatives, we can predict the position of a nucleophilic acyl substitution reaction. The same factors that affect the relative reactivity of acyl derivatives also control their stabilities. The identity of the groups bonded to the tetrahedral carbon atom affects the stabilities of the reactants and products. Thus, destabilizing the reactant and stabilizing the product increase the equihbrium constant. We conclude that the less stable acyl derivative is more reactive and can be converted into a more stable, less reactive acyl derivative. The relative stabihties of acyl derivatives enable us to understand most of the chemical reactions discussed in this chapter. 

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