Substitution rates between bases

Figure 7.3 Relationship between elimination and substitution rates of cyclohexyl tosylates with soft bases. From A. J. Parker, M. Ruane, G. Biale, and S. Winstein, Tetrahedron Lett., 2113 (1968). Reprinted by permission of Pergamon Press.

The subsequent reactivity of substituted epoxides with respect to ethanol (Table 2) for ionic mechanisms has been reported50). Table 2 shows that the relative reaction rates between epoxide and ethanol are in the reverse order for acid- and base-catalyzed... 

Quantitative data on the rate of consumption of pfa are few and somewhat variable. Those based on differences between the CH contents of pure Portland and pfa cements are suspect, because the calculation involves the effects of pfa substitution both on the rate of consumption of the clinker phases and on the compositions of the products, which are not fully understood. Unreacted pfa has been directly determined by dissolution of the other phases with HCl (C43) or with salicylic acid in methanol followed by HCl (T44), chemical separation of the residual pfa followed by QXDA determination of its content of crystalline phases (D12) and a trimethylsily-lation method (U19). A method based on EDTA extraction was found unsatisfactory (L46). 

Figure 14.6. Simplified substitution rate matrix used in ML and distance phylogenetic analysis. The off-diagonal values a represent a product of an instantaneous rate of change, a relative rate between the different substitutions, and the frequency of the target base. In practice, the forward rates (upper triangular values) are presumed to equal the reverse rates (corresponding lower triangular values). The diagonal elements are nonzero, which effectively accounts for the possibility that more divergent sequences are more likely to share the same base by chance. In the simplest model of sequence evolution (the Jukes-Cantor model), all values of a are the same all substitution types and base frequencies are presumed equal.

Kinetic, steric, and thermodynamic results have been reviewed to argue that the rate-determining step in some aliphatic nucleophilic substitutions is the transfer of an electron. The same group carried out a systematic ranking of different nucleophiles with respect to their ability to stabilize the transition states of substitution reactions, acetonitrile and dimethyl sulfoxide being the solvents involved. The nucleophiles included enolates, phenolates, thiophenolates, hydroxide, and cyanide. The method is based on a comparison of the rate coefficient, ksm, for the substitution reaction between a given nucleophile and benzyl chloride with the rate coefficient, A et for the corresponding electron transfer from an aromatic radical anion to benzyl chloride. The ratio ksuB/ ET expresses the rate enhancement due to electronic interaction in the transition state of the substitution reaction. 

Papers have considered the carbon monoxide exchange of metal carbonyls themselves 54) and of metal carbonyl halides (55) as well as of base-substituted complexes. In the series [Ni(CO)4], [Ni(CO)3P(CfiHs)3], Ni(CO)2[P(C5H5)3]2, the rate of CO exchange (SnI) decreases in the ratio 420 70 1 54). This order clearly shows the strengthening effect of phosphine substitution on the remaining metal-carbon bond. The rate of the SnI reaction between P(C6Hs)3 and [Ni(CO)4] is the same as the rate of CO exchange of [Ni(CO)4] 66). 

The term nucleophilicity refers to the effect of a Lewis base on the rate of a nucleophilic substitution reaction and may be contrasted with basicity, which is defined in terms of the position of an equilibrium reaction with a proton or some other acid. Nucleophilicity is used to describe trends in the kinetic aspects of substitution reactions. The relative nucleophilicity of a given species may be different toward various reactants, and it has not been possible to devise an absolute scale of nucleophilicity. We need to gain some impression of the structural features that govern nucleophilicity and to understand the relationship between nucleophilicity and basicity. ... 

It is well known that the rates of all azo coupling reactions in aqueous or partly aqueous solutions are highly dependent on acidity. Conant and Peterson (1930) made the first quantitative investigation of this problem. They demonstrated that the rate of coupling of a series of naphtholsulfonic acids is proportional to [OH-] in the range pH 4.50-9.15. They concluded that the substitution proper is preceded by an acid-base equilibrium in one of the two reactants, which was assumed to be the equilibrium between the diazohydroxide and the diazonium ion, in other words, that the reacting equilibrium forms are the undissociated naphthol and the diazohydroxide. 

The log rate versus acid strength curve for the latter compound is of the exact form expected for reactions of the free base, whilst that of the former compound is intermediate between this form and that obtained for the nitration of aniline and phenyltrimethylammonium ion, i.e. compounds which react as positive species. That these compounds react mainly or entirely via the free base is also indicated by the comparison of the rate coefficients in Table 8 with those in Table 5, from which it can be seen that the nitro substituent here only deactivates weakly, whilst the chloro substitutent appears to activate. In addition, both compounds show a solvent isotope effect (Table 9), the rate coefficients being lower for the deuterium-containing media, as expected since the free base concentration will be lower in these. 

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