Hughes-Ingold rules

Table 8-1 shows the application of the Hughes-lngold hypothesis to aliphatic nucleophilic reactions of various charge types. These predictions are borne out by observations on many reactions. It should be noted - that the Hughes—Ingold rule... 

The direction and extent of the effect of solvent polarity on reaction rates of nucleophilic substitution reactions are summarized by the Hughes-Ingold rules, shown in Table 1.9 [26], These rules do not account for the entropic effects or any specific solvent-solute interactions such as H-bonding, which may lead to extra stabilization of reactants or transition states [27],... 

The rates for the Sn2 reactions of seven different anionic nucleophiles (Cl-, Br-, I-, OAc-, CN-, SCN- and trifluoromethylacetate-) with methyl / -nitrobenzenesulfonate have been determined in CH2CI2, MeOH, DMSO, and three ionic liquid solvents.122 The reactivity was not correlated with the dielectric constant for the solvents as predicted by the Hughes-Ingold rules and a different nucleophilic order was found in... 

It is tacitly assumed in the Hughes-Ingold rules that the entropy of activation is small relative to the enthalpy of activation, i.e., AG AH, and that the temperature effect on the rate follows Eq. (2.22) with an assumed temperature independent value of AH. If the number of solvent molecules solvating the activated complex is very different from that solvating the reactants, then this assumption is no longer valid. This is the case in the solvolysis of t-butyl chloride in water (AH = 97 kJ mol 1, TAS = 15 kJ mol 1) compared to, say, ethanol (AH = 109 kJ mol 1, TAS = -4 kJ mol 1). 

When there is no change in the charge distribution in the reaction, as in free radical or isopolar reactions, the Hughes-Ingold rules are inoperative. The solvent polarity may play a minor role only, compared with other effects, such as differences in the volume requirements for cavity formation in highly structured solvents or of the hydrogen bonding abilities of the reactants and the activated... 

This helped to derive the Hughes-Ingold rules for predicting the effect of solvent polarity on the reaction rate.1 We have used the combined QM-MOVB/MM method to study three nucleophilic substitution reactions in aqueous solution, which are summarized below. 

Table 1.9 Hughes-Ingold rules for solvent effects in nucleophilic substitution reactions [27, 28]...

These Hughes-Ingold rules can be used for making qualitative predictions about the effect of solvent polarity on the rates of all heterolytic reactions of known mechanisms. For nucleophilic substitution reactions of types (5-11) and (5-12)... 

According to the Hughes-Ingold rules, in E2 and Sn2 reactions the dispersal of charge is spread over more atoms than in Ei and SnI reactions, so increase in solvent... 

Although the solvent effects are small, the alkene formation diminishes as predicted with increasing water content (corresponding to increased solvent polarity). The Sn2/E2 reaction of 2-phenylpropyl tosylate with sodium cyanide (in hexamethyl-phosphoric triamide and in A,A-dimethylformamide as solvents at 100 °C) gives a-methylstyrene (elimination product) and l-cyano-2-phenylpropane (substitution product) [75]. It has been found, in accordance with the predictions of the Hughes-Ingold rules, that the elimination/substitution ratio decreases as the polarity of the solvents (measured by the relative permittivity) increases [75]. Theoretical investigations of the... 

This failure can be explained as follows application of the Hughes-Ingold rules (1,27) for solvent effects on S 2 reactions does not lead to a clear statement in this case (see Scheme in the next page). 

This set of sinple rules has stood the test of time well and are still the basis of most organic chemists approach to solvent effects on the rates of reactions. The Hughes-Ingold rules do not consider specific interactions, such as hydrogen bonds, but it is easy to see how these can be incorporated into the analysis. 

The S]vj2 and E2 reactions are mechanistically closely related and have similar activated complexes with delocalised charges. However, in the E2 activated complex, the charge is delocalised over more atoms than in that of the 8 2 reaction (see Fig. 10.RT The Hughes-Ingold rules would, therefore, lead us to expect a preference for S]v 2 over E2 reactions. Is there any evidence for this ... 

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