Bases Versus Nucleophiles

PROBLEMS In each of the foUowing steps, identify the nucleophile and electrophile, 

Students are often unclear about the difference between nucleophiles and bases. Since most mechanisms involve the use of nucleophiles and bases, it will be worth our time to clear up the difference. 

Consider the hydroxide ion (HO ). Sometimes it acts like a base and removes a proton from another compound  

At other times it acts like a nucleophile and attacks another compound (forming a new bond to an atom in that compound)  

The difference between basicity and nucleophilicity is a difference of function. In other words, the hydroxide ion can function in two ways as a base (which means it is pulling off a proton and then running away with that proton) or as a nucleophile (latching onto a compound). In some cases, the hydroxide ion might function mostly as a base while in other situations, the hydroxide ion might function mostly as a nucleophile. To understand mechanisms weU, it is important to be able to distinguish between the two roles. Let s see an example. 

PROBLEMS In each of the reactions below, determine which compound is the nucleophile and which compound is the electrophile. 

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A kinetic smdy of the acylation of ethylenediamine with benzoyl chloride (110) in water-dioxane mixtures at pH 5-7 showed that the reaction involves mainly benzoylation of the monoprotonated form of ethylenediamine. Stopped-flow FT-IR spectroscopy has been used to study the amine-catalysed reactions of benzoyl chloride (110) with either butanol or phenol in dichloromethane at 0 °C. A large isotope effect was observed for butanol versus butanol-O-d, which is consistent with a general-base-catalysed mechanism. An overall reaction order of three and a negligible isotope effect for phenol versus phenol- /6 were observed and are consistent with either a base- or nucleophilic-catalysed mechanism. Mechanistic studies of the aminolysis of substituted phenylacetyl chlorides (111) in acetonitrile at —15 °C have revealed that reactions with anilines point to an associative iSN2 pathway. ... 

Secondary halides are borderline, and substitution or elimination may be favored, depending on the particular base/nucleophile, solvent, and temperature at which the reaction is carried out. Elimination is favored with strong bases/good nucleophiles—for example, hydroxide ion and ethoxide ion. Substitution is favored with weak bases/poor nucleophiles—for example, acetate ion. Table 7.7 summarizes these generalizations about substitution versus elimination reactions of haloalkanes. 

The radical versus electrophilic character of triplet and singlet carbenes also shows up in relative reactivity patterns shown in Table 10.1. The relative reactivity of singlet dibromocarbene toward alkenes is more similar to that of electrophiles (bromination, epoxidation) than to that of radicals ( CC13). Carbene reactivity is strongly affected by substituents.61 Various singlet carbenes have been characterized as nucleophilic, ambi-philic, and electrophilic as shown in Table 10.2. This classification is based on relative reactivity toward a series of different alkenes containing both nucleophilic alkenes, such as tetramethylethylene, and electrophilic ones, such as acrylonitrile. The principal structural feature that determines the reactivity of the carbene is the ability of the substituents to act as electron donors. For example, dimethoxycarbene is devoid of electrophilicity toward... 

NUCLEOPHILIC Versus GENERAL BASE CATALYSIS BY ACETATE ION OF THE HYDROLYSIS OF ARYL ACETATES IN WATER AT pH 5.0 AND IONIC STRENGTH... 

A plot of l/fcobs versus 1/[M2+] is linear of slope 1/kK and intercept 1/fc The pH dependence of the plateau rate constant fcUm can be used to determine if the reaction shows a dependence on the hydroxide ion concentration. A typical situation is shown in Figure 3. In this case there is a positive intercept so that kljm = fc0 + feOH[OH ]. The k0 term normally indicates a solvolytic reaction (nucleophilic attack by water) while fc0H, the slope of the line, relates to base hydrolysis. 

For the reaction of MOH(n 1)+ with propionic anhydride,200 the Bronsted plot of log kMOH versus the pKa of MOH2n+ follows a smooth curve if the values for HzO and OH- are included (Figure 4). However, if the line is drawn to exclude the fcHj0 value, a Bronsted /3 of ca, 0.25 is obtained. Although kMOH for [Co(NH3)5OH]2+ (3 M s 1) is some 103-fold less than k0H, this reaction will compete favourably at neutral pH with base hydrolysis. At pH 7 where the cobalt(III) complex exists almost completely as the MOH2+ species the observed first order rate constant for nucleophilic attack by OH would be ca. 10-4 s 1. AIM solution of [Co(NH3)5OH]2+ would give a value of kobs 2.5 s 1, a rate acceleration of > 104-fold. Since the effective concentration of a nucleophile in the intramolecular reaction could be ca. 102 M, rate accelerations of 10° are possible. The role of the metal ion in such reactions is to provide an effective concentration of an efficient nucleophile at low pH. 

Buckingham and Engelhardt200 have studied the hydrolysis of propionic anhydride in the presence of kinetically inert complexes of the type [M(NH3)5OH]n+. These reactions occur by nucleophilic attack of coordinated hydroxide on the anhydride (Scheme 32). For reactions of M-OHl" l,+ with propionic anhydride, the Bronsted plot of log kMOH versus the p.Ka of M—OH2k+ is a smooth curve if values for reaction with HzO and OH- are included. Although Icmoh for [(NH3)5CoOH]2+ (3 M-1 s-1) is about 103-fold less than fcoH. its reaction will compete favourably at neutral pH with base hydrolysis. Such effects are considered in more detail in Section 61.4.2.2.3. 

On the other hand, it seems less likely that the relative reactivities of n-nucleophiles should be independent of the reactivity of a carbocation. At least when they act as bases, there is little or no evidence that changes in structure of n-nucleophiles lead to changes in intrinsic barrier.301 One might expect therefore that carbocations of different reactivities reacting with a structurally related group of nitrogen or oxygen nucleophiles would show different slopes of plots of log k versus log K. 

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