Anion nucleophiles relative reactivities

Polar aprotic solvents can solvate cations very well, but they solvate anions (nucleophiles) relatively poorly, because they cannot donate a hydrogen bond to an anion, as can a protic solvent. For this reason, nucleophiles are freer and more reactive in polar aprotic solvents than in protic solvents so the rates of Sj 2 reactions are dramatically accelerated, often by several orders of magnitude compared to the same reaction in protic solvents. 

In fee absence of fee solvation typical of protic solvents, fee relative nucleophilicity of anions changes. Hard nucleophiles increase in reactivity more than do soft nucleophiles. As a result, fee relative reactivity order changes. In methanol, for example, fee relative reactivity order is N3 > 1 > CN > Br > CP, whereas in DMSO fee order becomes CN > N3 > CP > Br > P. In mefeanol, fee reactivity order is dominated by solvent effects, and fee more weakly solvated N3 and P ions are fee most reactive nucleophiles. The iodide ion is large and very polarizable. The anionic charge on fee azide ion is dispersed by delocalization. When fee effect of solvation is diminished in DMSO, other factors become more important. These include fee strength of fee bond being formed, which would account for fee reversed order of fee halides in fee two series. There is also evidence fiiat S( 2 transition states are better solvated in protic dipolar solvents than in protic solvents. 

Sn2 reactions with anionic nucleophiles fall into this class, and observations are generally in accord with the qualitative prediction. Unusual effects may be seen in solvents of low dielectric constant where ion pairing is extensive, and we have already commented on the enhanced nucleophilic reactivity of anionic nucleophiles in dipolar aprotic solvents owing to their relative desolvation in these solvents. Another important class of ion-molecule reaction is the hydroxide-catalyzed hydrolysis of neutral esters and amides. Because these reactions are carried out in hydroxy lie solvents, the general medium effect is confounded with the acid-base equilibria of the mixed solvent lyate species. (This same problem occurs with Sn2 reactions in hydroxylic solvents.) This equilibrium is established in alcohol-water mixtures ... 

Irreversible cationization of the azine-nitrogen will increase the reactivity of anionic nucleophiles at the position adjacent to the azinium moiety (71 relative to 70), in the absence of substantial... 

The drastic change in the reactivity of oxygen nucleophiles is also found in several other examples. Thiolate anions are classified as stronger nucleophiles than their oxyanionic counterparts (DeTar and Coates, 1974 Williams and Donahue, 1978). It was found, however, that towards PNPA in dimethyl-formamide the nucleophilic reactivity of thiophenoxide ion exceeds that of phenoxide ion when [H20] = ca. 1000 mM but the relative reactivity was sharply reversed below [H20] = 300 mM (Shinkai et al., 1979a). Therefore, phenoxide ion can be a much stronger nucleophile than thiophenoxide ion in very dry aprotic solvents. 

Table 5.4 Relative reactivities (normalized to iodide) for a series of nucleophiles under phase transfer, homogeneous dipolar aprotic, and homogeneous protic conditions, and the hydration number of the quaternary onium-anion ion pair [43]...

The addition of strong nucleophile to reactive electrophile gives a relatively stable anionic addition intermediate with a lifetime long enough to diffuse through the solution and abstract a proton before it reverts to reactants (k > k i) (Scheme 2.2). 

Aryl radical additions to anions are generally very fast, with many reactions occurring at or near the diffusion limit. For example, competition studies involving mixtures of nucleophiles competing for the phenyl radical showed that the relative reactivities were within a factor of 10, suggesting encounter control,and absolute rate constants for additions of cyanophenyl and 1-naphthyl radicals to thiophenox-ide, diethyl phosphite anion, and the enolate of acetone are within an order of magnitude of the diffusional rate constant. ... 

New catalysts have been described,646 and ab initio MO calculations have shown that the transformation takes place through a four-center transition state.647 In addition, the anomalous relative reactivities of substrates, specifically, the higher reactivity of alkynes compared to those of alkenes, can be explained by considering the reaction to essentially be a nucleophilic attack by an alkyl anion, rather than an electrophilic one. 

For both nucleophiles, 2,5-dinitrofuran is the most active substrate, the thiophene derivative follows. On the other hand, the relative reactivity of 1-methyl-2,5-dinitropyrrole and 1,4-dinitrobenzene depends on the nature of the nucleophile. For the 4-MeC6H4S anion, the former is more active by about two powers of ten, but in the piperidinolysis reaction the 1,4-benzene is superior. These phenomena appear to be caused by differences in the polarizability of both substrate and nucleophiles. p-Tolylthiolate anion is a softer nucleophile in comparison with piperidine and the pyrrole system is certainly more polarizable than the benzene molecule. Therefore soft-soft interaction of 1-methyl-2,5-dinitropyrrole with 4-MeC6H4S and hard-hard interaction of 1,4-dinitrobenzene with piperidine should occur easier than interactions between reagents with opposite types of softness and hardness. 

In this connection, it is helpful to look first at the reactivity of the anions. There is no generally acceptable measure of nucleophilic reactivity since both the scale and order of relative reactivities depend on the electrophilic centre being attacked (Ritchie, 1972). However, in the present reaction, the similarity in the reactivity of the different anions is remarkable. Thus, the Swain and Scott n-values (cf. Hine, 1962) indicate that the iodide ion should be 100 times more reactive than the chloride ion in nucleophilic attack on methyl bromide in aqueous acetone. In the present reaction, the ratio of the rate coefficients for iodide ions and chloride ions is 1.4. This similarity led to the suggestion that these reactions are near the diffusion-controlled limit (Ridd, 1961). If, from the results in Table 5, we take this limit to correspond to a rate coefficient (eqn 19) of 2500 mol-2 s 1 dm6 then, from the value of ken for aqueous solutions at 0° (3.4 x 109 mol-1 s 1 dm3 Table 1), it follows that the equilibrium constant for the formation of the electrophile must be ca. 7.3 x 10 7 mol-1 dm3. This is very similar to the equilibrium constant reported for the formation of the nitrosonium ion (p. 19). The agreement is improved if allowance is made for the electrostatic enhancement of the diffusion-controlled reaction by a factor of ca. 3 (p. 8) the equilibrium constant for the electrophile then comes to be ca. 2.4 x 10-7. 

Anion 29 was found to be 2.2 times more reactive than 27b, and nucleophile 27b was 7.5 times more reactive than enolate ion 27a. Based on these relative reactivities, carbanion 29 is 16.5 times more reactive than 27a169. 

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