Nucleophilicity ranking

Table 1.6 shows nucleophiles ranked by one measure of nucleophilicity. These nucleophilicities are based on the relative reactivities of the nucleophile and water with methyl bromide at 25°C. The nucleophilicity n is calculated according to the Swain-Scott equation ... 

For nucleophiles, rank first by softest as best then within the same atom, by most basic. 

The two major differences between these two equations are as follows (1) Unlike the Swain-Scott equation, the Ritchie equation lacks a selectivity parameter. Thus, a plot of log k versus N+ always gives a unity slope. (2) Nucleophilicity ranking by the two scales is different. This difference is especially noticeable for the three nucleophiles, CN-, CH30-, and N3-. According to the N+ scale, the nucleophilicity order is N3- > CH30- > CN-, whereas the reverse is true for the Swain-Scott n scale. 

Nucleophilicity and Ionization Potentials. Previously, the suggestion that the differences in the nucleophilic ranking between the n and the N+ scale may stem from a relatively large amount of electron transfer present in the transition state described by the N+ scale was made. If this statement is true, then some correlation between the N+ scale and the solution ionization potentials of the nucleophiles should exist. Because these data are not available, we have calculated (5) the energy associated with K3 using the thermodynamic cycle shown in Scheme I. 

Examine the eleetrostatic potential map of eaeh nueleophile (enamine, silyl enol ether, lithium enolate and enol) with emphasis on the face of the nucleophilic alkene carbon. Rank the nucleophiles from most electron rich to least electron rich. What factors are responsible for this order (Hint For each molecule, consider an alternative Lewis structure to that given above that places a negative charge on the nucleophilic carbon.)... 

Nucleophilicity is determined by HOMO energy the higher the energy the more reactive the nucleophile. HOMO energies (in au) for these nucleophiles are -0.275 (enamine), -0.266 (lidiium enolate), -0.337 (silyl enol ether), and -0.339 (enol). Rank the nucleophiles from most reactive to least reactive. How does this ranking compare to that based on electrostatic potential ... 

Rank the compounds in each of the following sets in order of their expected reactivity toward nucleophilic acvl substitution ... 

Sites susceptible to nucleophilic attack can also be identified and ranked by means of positive electrostatic potential regions, but it is necessary to analyze the latter at distances at least 1 to 2 A away from the nuclei, e.g., in planes removed from the molecular framework (Murray, Lane, and Politzer 1990 Politzer, Abrahmsen, and Sjoberg 1984 Politzer et al. 1984) or on molecular surfaces (Murray et al. 1991b Murray and Politzer 1991 Murray and Politzer 1992 Pullman, Perahia, and Cauchy 1979 Sjoberg and Politzer 1990). This is because the electrostatic potentials of atoms and molecules have local maxima only at the nuclei (Pathak and Gadre 1990). To identify sites for nucleophilic attack, it is necessary, accordingly, to look for the most positive values in planes or on surfaces that are at some distance from the nuclei. (These are, of course, not true local minima.)... 

Each such region must have one or more local minima, Vmin, at which the potential reaches its most negative values. These have often been used, with some success, to identify and rank sites with regard to reactivity toward electrophiles [5-8]. The converse - taking local maxima as indicative of susceptibility to nucleophilic attack - is not, however, valid. Pathak and Gadre have shown that the only maxima of V(r) are those associated with the nuclei [9] these do not correlate with reactivity. 

Rank the following nucleophiles in order of increasing nucleophilicity with respect to nucleophilic substitution reactions at a saturated carbon atom. Comment on your choice. 

Indolizines rank among the class of 7r-excessive heterocycles, i.e. they readily undergo electrophilic substitution and are inert to nucleophilic attack. Many of them are easily oxidized and therefore unstable in the presence of air. 

B-8. Rank the following species in order of decreasing nucleophilicity in a polar protic solvent (most — least nucleophilic) ... 

B-2. Rank the following in order of decreasing rate of reaction with ethoxide ion (CH3CH2CT) in a nucleophilic aromatic substitution reaction ... 

The site-specific quantities derived from the electrostatic potential are the spatial minima, Fmin, and the surface extrema, FSmin and Fs>max. Molecular sites reactive toward electrophiles can be identified and ranked by means of either Fmin or Fs min74,75, while the maxima of V(r) on the molecular surface, Vs max, serve the analogous purpose for nucleophilic attack75. 

Electron-catalyzed (or electron-stimulated) processes constitute a relatively new class of reactions of great potential synthetic interest (Zelenin and Khidekel, 1970 Linck, 1971). Foremost among these ranks the SRN1 mechanism, which is an electron-initiated radical-chain mechanism of nucleophilic substitution (21-24 X- = halide ion) (for reviews, see Kornblum, 1975 Bunnett, 1978, 1982). The initiation step (21) can be performed photochemically, electrochemically, or by adding alkali metal (Pinson and Saveant, 1978 Amatore et al., 1979 van Tilborg et al., 1977, 1978 Saveant, 1980). 

Hydroiodic acid (HI) reacts with ethers the same way HBr does. Aqueous iodide is a stronger nucleophile than aqueous bromide, and iodide reacts at a faster rate. We can rank the hydrohalic acids in order of their reactivity toward the cleavage of ethers ... 

Just as there is no single measure of acidity and basicity, there is no single measure of nucleophilicity and electrophilicity—the rank order of nucleophiles changes when the reference electrophile changes. A hard nucleophile like a fluoride ion reacts fast with a silyl ether in an SN2 reaction at the silicon atom, which is relatively hard, but a soft nucleophile like triethylamine does not. In contrast, triethylamine reacts with methyl iodide in an SN2 reaction at a carbon atom, but fluoride ion does not. These examples, which are all equilibria, are governed by... 

Problem 7.16 Rank the nucleophiles in each group in order of increasing nucleophilicity. 

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