Nucleophiles substitution affected

When a molecule that is a substrate for nucleophilic substitution also contains a group that can act as a nucleophile, it is often observed that the kinetics and stereochemistiy of nucleophilic substitution are strongly affected. The involvement of nearby nucleophilic substituents in a substitution process is called neighboring-group participation ... 

The rate at which reactions occur can be important in the laboratory, and understanding how solvents affect rate is of practical value. As we proceed through the text, however, and see how nucleophilic substitution is applied to a variety of functional group transfonnations, be aware that it is the nature of the substrate and the nucleophile that, more than anything else, determines what product is formed. 

Experimental observations indicate that acid strength significantly affects the reaction rate. For example, sulfuric acid promotes nucleophilic substitution of alcohols by bromide, but acetic acid does not. How would a change in acid strength affect your calculated reaction energies ... 

The nucleophilic substitution of quinoline as affected by cationiza-tion and hydrogen bonding is discussed in Section II, C, by the leaving group and other substituents in Sections II, D and II, E, respectively, and in Section III, A, 2, and by the nucleophile in Section II, F. 

Ejfect ofSolvent. In addition to the solvent effects on certain SeI reactions, mentioned earlier (p. 764), solvents can influence the mechanism that is preferred. As with nucleophilic substitution (p. 448), an increase in solvent polarity increases the possibility of an ionizing mechanism, in this case SeI, in comparison with the second-order mechanisms, which do not involve ions. As previously mentioned (p. 763), the solvent can also exert an influence between the Se2 (front or back) and SeI mechanisms in that the rates of Se2 mechanisms should be increased by an increase in solvent polarity, while Sni mechanisms are much less affected. 

In halogenated solvents the results indicate that return can occur, even for the uncongested stilbenes. Unfortunately, its importance, as measured by the k i/kN ratio (Fig. 10), cannot be estimated. It must be noted that Bellucci s experiments prove only that return is possible, but do not demonstrate conclusively that it occurs in bromination, since reversibility is controlled by the relative energy levels of TS and TSN which can be affected by the reaction conditions. Now, these conditions are not the same for nucleophilic substitution on bromohydrins and for bromine addition in particular, the counter-ions, Br and Br3 respectively, can alter the lifetime of the intermediate and thus control its partitioning between return and nucleophilic attack. 

Here we have a c = c group attached to a carbon atom which is adjacent to be carbon atom where nucleophilic substitution can occur and during the course of the reaction becomes bonded of partially bonded to the reaction centre to form a non-classical or bridged ion (Fig. 1 to 1(c)). Thus the rate and/or the stereochemistry may be affected. This explains why the acetolysis of 5 is 1011 times faster than that of 5(a), because it involves the formation of a non-classical carbocation... 

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-... 

Example 34 bis(iV,iSr-diisopropylamino)trimethylsiloxyphosphine was prepared from readily available chlorobis(diisopropylamino)phosphine in almost quantitative yield [67]. Michalski et al. have observed that this trimethylsilyloxy-bis-(diisopropylamino)phosphine has the ability to undergo highly selective nucleophilic substitution at the atom without affecting the silicon centre. A number of 3, 5 -dinucleoside trimethylsilylphos-phites have been prepared in this way in very high yield without isolation of the mononucleotide intermediate. 

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. 

Salt Effects. Dissolved salts may also affect the rates of nucleophilic substitution and elimination in aqueous solution through their influence on the relative stabilities of the reactants, transition states, and other reactive intermediates. The nonspecific effects of increasing ionic strength are therefore analogous to those arising from increasing solvent polarity (281. and are sometimes referred to as "salt effects."... 

Under these conditions, the order of reactivity to nucleophilic substitution changes dramatically from that observed in the Sn2 reaction, such that tertiary alkyl halides are more reactive then secondary alkyl halides, with primary alkyl halides not reacting at all. Thus a different mechanism must be involved. For example, consider the reaction of 2-iodo-2-methylpropane with water. (Following fig.). In it, the rate of reaction depends on the concentration of the alkyl halide alone and the concentration of the attacking nucleophile has no effect. Thus, the nucleophile must present if the reaction is to occur, but it does not matter whether there is one equivalent of the nucleophile or an excess. Since the reaction rate depends only on the alkyl halide, the mechanism is called the SN1 reaction, where SN stands for substitution nucleophilic and the 1 shows that the reaction is first order or unimolecular, i.e. only one of the reactants affects the reaction rate. 

Because the reactions we consider in this section are single-step and therefore elementary reactions, the rate law specified in Section 2.3 as Equation 2.1 is obtained for the rate of formation of the substitution product Nu—R in Figure 2.4. It says that these reactions are bimolecular substitutions. They are consequently referred to as SN2 reactions. The bimolecu-larity makes it possible to distinguish between this type of substitution and SN1 reactions, which we will examine in Section 2.5 nucleophile concentration affects the rate of an SN2 reaction, but not an SN1 reaction. 

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