Effect of changing the nucleophile

The effect of changing the nucleophile in an SN reaction continues to attract considerable interest. A study of the rates of the XN2 reactions between S-methyldibenzo-thiophenium ion or methyl iodide and many nucleophiles93 has shown that the... 

Table 6.1 Effects of changing the nucleophile and leaving group...

The rates of 5 2 and 2 reactions of several fluorinated alkyl bromides and iodides have been measured in methanol and in DMSO using azide ion and methoxide ion as the nucleophile (base). The results demonstrate the effect of changing the nucleophile, the solvent, the leaving group, and a- and -fluorine substituents on the rates of these reactions. MP2/6-3 l-l-G(d,p)-LANL2DZ level calculated AG and transition states found for both the 5 2 and the 2 reactions are consistent with the experimental results. The azide ion reactions are almost exclusively 5 2 processes, whereas the methoxide ion reactions... 

In addition to investigating the effect of changing the voltage sweep rate and of addition of nucleophiles/bases (oxidation) or electrophiles/acids (reductions), the preliminary work often also includes investigation of how the voltammograms are affected by changes in the substrate concentration. 

When styrene oxide was reacted in alcohols in the presence of an Al(OTf)3 catalyst, the nucleophile attacked at the benzyl carbon.28 The effect of catalyst loading and the effect of changing the structure of the reacting alcohols was investigated. The reactions of oxiranes with alkyl substituents were not regiospecific. More catalyst was needed when bulkier alcohols were used. 

Attack on Halogen. The effect of changing the phosphorus nucleophile used on the reactions with a-halogenosulphones that give the dehalogenated sulphone (52) has... 

In such a mechanism, what is the effect of increasing the nucleophilicity of the nucleophile and the basicity of the catalyst For a constant nucleophile changing the basicity of the catalyst would affect the rate as shown in the Eigen curve of Fig. 2a. When proton transfer from to B is thermodynamically favourable the rate of proton transfer is diffusion controlled and hence independent of the basicity of the catalyst B. When it is thermodynamically unfavourable the rate decreases proportionally to the decreased basicity of the catalyst, and is given by Kk K] /, where ATj and AT are the acid dissociation constants of T- and BH", respectively. 

It is often difficult to understand at an intuitive level the explanation for the effect of changing substituents on the rate constant ratio kjkp for partitioning of carbocations between nucleophilic addition of solvent and deprotonation. In these cases, insight into the origins of the changes in this rate constant ratio requires a systematic evaluation of substituent effects on the following ... 

The extent to which the effect of changing substituents on the values of ks and kp is the result of a change in the thermodynamic driving force for the reaction (AG°), a change in the relative intrinsic activation barriers A for ks and kp, or whether changes in both of these quantities contribute to the overall substituent effect. This requires at least a crude Marcus analysis of the substituent effect on the rate and equilibrium constants for the nucleophile addition and proton transfer reactions (equation 2).71-72... 

The next consideration is the HSAB principle formulated at a local level. Let us consider the interaction energy between two chemical species A and B, in which one is electrophilic and the other nucleophilic. From a global point of view and neglecting the effect of change in external potential of A and B, the change in grand canonical potential can be expressed as [7a]... 

It is accepted that the acmal nucleophile in the reactions of oximes with OPs is the oximate anion, Pyr+-CH=N-0 , and the availability of the unshared electrons on the a-N neighboring atom enhances reactions that involve nucleophilic displacements at tetravalent OP compounds (known also as the a-effect). In view of the fact that the concentration of the oximate ion depends on the oxime s pATa and on the reaction pH, and since the pKs also reflects the affinity of the oximate ion for the electrophile, such as tetra valent OP, the theoretical relationship between the pATa and the nucleophilicity parameter was analyzed by Wilson and Froede . They proposed that for each type of OP, at a given pH, there is an optimum pK value of an oxime nucleophile that will provide a maximal reaction rate. The dissociation constants of potent reactivators, such as 38-43 (with pA a values of 7.0-8.5), are close to this optimum pK, and can be calculated, at pH = 7.4, from pKg = — log[l//3 — 1] -h 7.4, where is the OP electrophile susceptibility factor, known as the Brpnsted coefficient. If the above relationship holds also for the reactivation kinetics of the tetravalent OP-AChE conjugate (see equation 20), it would be important to estimate the magnitude of the effect of changes in oxime pX a on the rate of reactivation, and to address two questions (a) How do changes in the dissociation constants of oximes affect the rate of reactivation (b) What is the impact of the /3 value, that ranges from 0.1 to 0.9 for the various OPs, on the relationship between the pKg, and the rate of reactivation To this end, Table 3 summarizes some theoretical calculations for the pK. ... 

There is an ongoing controversy about whether there is any stabilization of the transition state for nucleophilic substitution at tertiary aliphatic carbon from interaction with nucleophilic solvent." ° This controversy has developed with the increasing sophistication of experiments to characterize solvent effects on the rate constants for solvolysis reactions. Grunwald and Winstein determined rate constants for solvolysis of tert-butyl chloride in a wide variety of solvents and used these data to define the solvent ionizing parameter T (Eq. 3). They next found that rate constants for solvolysis of primary and secondary aliphatic carbon show a smaller sensitivity (m) to changes in Y than those for the parent solvolysis reaction of tert-butyl chloride (for which m = 1 by definition). A second term was added ( N) to account for the effect of changes in solvent nucleophilicity on obsd that result from transition state stabilization by a nucleophilic interaction between solvent and substrate. It was first assumed that there is no significant stabilization of the transition state for solvolysis of tert-butyl chloride from such a nucleophilic interaction. However, a close examination of extensive rate data revealed, in some cases, a correlation between rate constants for solvolysis of fert-butyl derivatives and solvent nucleophicity. " ... 

We know relatively little about the effect of change in positive ion in the system, but we think that the rate would probably be fairly sensitive to this. The only definite information we have involves recent studies of the substitution of water by pyridine, a netftral nucleophile, and a rather efficient one. Here there is perhaps a 20 or 30% difference in rate depending on whether we are working in IM sodium ion or 1M pyridinium ion. The rate is faster in the pyridinium ion solution. 

It is of interest to observe that the kinetic behaviour (and the effect of changes of temperature on the rate of reactions) of brominations of olefins and of electrophilic aromatic brominations confirms the presence of pre-associative processes77,130,131 on the reaction pathway, as well as that observed for some nucleophilic aromatic substitutions132. 

In the case of an SN1 reaction, the nucleophile does not become involved until after the rate-determining step. Therefore, changing the nucleophile has no effect on the rate of an SN1 reaction, although it may change the product of the reaction. In contrast, changing the nucleophile in an SN2 reaction has a dramatic effect on the reaction rate because the nucleophile attacks in the rate-determining step. 

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