Solvation nucleophilicity and

The solvation and nucleophilic reactivity (towards ethyl iodide) of the 1,2,4-triazol-ate ion have been investigated in MeCN-MeOH mixtures. Various correlations of thermodynamic and kinetic functions are presented. 

Any species having an unshared pair of electrons may act as a nucleophile, whether it is neutral like an alcohol or negative like the alkoxide ion. The rate of S l reactions is independent of the structure and charge of the nucleophile. For S 2 reactions, factors like the charge of the nucleophile, its degree of solvation and nucleophilicity determine the rate of the reaction (6A). 

Solvation and nucleophilic reactivity in MeCN-MeOH mixtures has been studied for the conjugate-base anions of 5-methyl Meldrum s acid and 3,3-dimethylbarbituric acid. Their nucleophilic reactivities are comparable, to each other and to those of the anions of 3,5-dinitrobenzoic acid and phthalimide. The pXa values in water vary much more. Thermodynamic data are presented and discussed. 

Rate increases with increasing po larity of solvent as measured by its dielectric constant e (Section 8 12) Polar aprotic solvents give fastest rates of substitution solvation of Nu IS minimal and nucleophilicity IS greatest (Section 8 12)... 

Once in the organic phase, cyanide ion is only weakly solvated and is far more reactive than it is in water or ethanol, where it is strongly solvated by hydrogen bonding. Nucleophilic substitution takes place rapidly. 

The reactivity of a nucleophilic reagent may also depend on stereochemical conformation, degree of solvation and hydrogen-bonding,... 

Besides differences in reactant stability as well as differences in the stability of the intermediate ions, there may also be other reasons, such as differences in solvation and differences in backside nucleophilic assistance, for the large discrepancy in reactivity between alkyl halides and vinyl halides. 

For carbon-carbon bond-formation purposes, S 2 nucleophilic substitutions are frequently used. Simple S 2 nucleophilic substitution reactions are generally slower in aqueous conditions than in aprotic organic solvents. This has been attributed to the solvation of nucleophiles in water. As previously mentioned in Section 5.2, Breslow and co-workers have found that cosolvents such as ethanol increase the solubility of hydrophobic molecules in water and provide interesting results for nucleophilic substitutions (Scheme 6.1). In alkylations of phenoxide ions by benzylic chlorides, S/y2 substitutions can occur both at the phenoxide oxygen and at the ortho and para positions of the ring. In fact, carbon alkylation occurs in water but not in nonpolar organic solvents and it is observed only when the phenoxide has at least one methyl substituent ortho, meta, or para). The effects of phenol substituents and of cosolvents on the rates of the competing alkylation processes... 

In polar aprotic solvents the nucleophile is only very slightly solvated and is, consequently, highly reactive. 

In the solvolysis of secondary alkyl sulfonates, competition between nucleophilic solvation and electron donation by the substituents results in a significantly solvent-dependent p, which varies from — 9 to — 1 on going from the non-nucleophilic hexafluoro-2-propanol to 80% aqueous ethanol (Bentley et al, 1981). In contrast, the p -invariance for alkene bromination in H20, M70, MeOH and AcOH [equations (22)-(25)] seems to imply a perfect balance between the two types of charge stabilization. However, this conclusion is probably risky since the nucleophilicities of the solvents implied in (22)-(25) do not vary markedly. Data in non-nucleophilic fluorinated solvents would therefore help to fill the gap in our knowledge. 

To check this possibility we performed experiments with different concentrations of NaBr in the NaY zeolite. Table 2 presents the results. It can be seen that upon increasing the amount of NaBr impregnated on NaY, there is preference to formation of the cyclobutyl bromide over allylcarbinyl bromide, indicating that the relative position between the bromide ions and bicyclobutonium governs the product distribution. Hence, zeolites may act as solid solvent, favoring ionization of alkyl halides and nucleophilic substitution reactions. In contrast to liquid solvents, where solvation is mostly uniform, the zeolite surface seems to provide unsymmetrical solvation of the cations, leading to product distribution that is different from solution. 

This ambiguity was removed by the results of a comprehensive investigation on the gas-phase acid-induced nucleophilic substitution on several allylic alcohols showing that the concerted 8 2 reaction competes with the classical 8 2 pathway in the absence of solvation and ion-pairing factors. " Assessment of the... 

Rate constants and products have been reported for solvolysis of benzhydryl chloride and /7-methoxybenzyl chloride in 2,2,2-trifluoroethanol (TFE)-water and-ethanol, along with additional kinetic data for solvolysis of r-butyl and other alkyl halides in 97% TFE and 97% hexafluoropropan-2-ol. The results are discussed in terms of solvent ionizing power Y and nucleophilicity N, and contributions from other solvation effects are considered. Comparisons with other 3 nI reactions show that the solvolyses of benzhydryl chloride in TFE mixtures are unexpectedly fast an additional solvation effect influences solvolysis leading to delocalized cations. 

A previous study has shown that the effects of solvating a nucleophile by a protic or a dipolar aprotic solvent differ in degree and not so much in nature the major effect remains a lowering of the nucleophile s HOMO level. It is therefore possible, in order to observe the general trend, to solvate the anion with just one molecule of water. 

As noted in Section 4.2.1, the gas phase has proven to be a useful medium for probing the physical properties of carbanions, specifically, their basicity. In addition, the gas phase allows chemists to study organic reaction mechanisms in the absence of solvation and ion-pairing effects. This environment provides valuable data on the intrinsic, or baseline, reactivity of these systems and gives useful clues as to the roles that solvent and counterions play in the mechanisms. Although a variety of carbanion reactions have been explored in the gas phase, two will be considered here (1) Sn2 substitutions and (2) nucleophilic acyl substitutions. Both of these reactions highlight some of the characteristic features of gas-phase carbanion chemistry. 

Similarly, a lipophilic crown ether is partitioned into the organic phase. Its complexing ability serves to transfer salts with alkali cations into the organic phase. The anions in the organic phase are poorly solvated and highly reactive. The overall reactivity in phase-transfer-catalyzed nucleophilic displacement reactions thus is a function of both the partition coefficient for extraction of the reactive anion into the organic... 

On one hand, they increase the reaction rate due to an electrophilic assistance for the epoxy ring opening and, on the other, lower the reactivity of the alcoxy anion owing to its solvation and the decrease of its nucleophility. Positive, neutral or even negative effects of the alcohol additives on the reaction rate are governed by the relationship between these two factors. The chain propagation reaction mechanism itself remains trimolecular. 

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