Nucleophiles relative reactivity

Common ion rate depression for solvolysis of RX with the same R but with different leaving groups X was followed only for a single system. From the a values obtained in the solvolysis of ( )- and (Z)-l,2-dianisyl-2-phen-ylvinyl-X, 16, in AcOH-AcO- (equation 9), relative reactivities toward the derived ion 17 were measured (74) (nucleophile, relative reactivity) OMs-, 0.16 OAc, 1.0 Cl , 15.2 Br 45.5 and AcOH, 0.0024. From other data, I will probably be at the top of a similar order (75) and 2,4,6-trinitrobenzene-sulfonate at the bottom (76). 

RELATIVE REACTIVITIES OF SOME HALO-AZA-ACTIVATED AROMATIC SUBSTRATES WITH NUCLEOPHILES ... 

Relative reactivity is A (nucleophile)/A (methanol) for typical Sn2 reactions and is approximate Data pertain to methanol as the solvent... 

I itro-DisplacementPolymerization. The facile nucleophilic displacement of a nitro group on a phthalimide by an oxyanion has been used to prepare polyetherimides by heating bisphenoxides with bisnitrophthalimides (91). For example with 4,4 -dinitro monomers, a polymer with the Ultem backbone is prepared as follows (92). Because of the high reactivity of the nitro phthalimides, the polymerkation can be carried out at temperatures below 75°C. Relative reactivities are nitro compounds over halogens, Ai-aryl imides over A/-alkyl imides, and 3-substituents over 4-substituents. Solvents are usually dipolar aprotic Hquids such as dimethyl sulfoxide, and sometimes an aromatic Hquid is used, in addition. 

Although different reaction types exhibit large quantitative differences, and there are exceptions, the order 5>6>3>7>4> 8-10 is a rough guide of relative reactivity for many systems. Some quantitative data on typical reactions involving nucleophilic substitution or participation are shown in Scheme 3.4. 

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. 

Reductions by NaBKt are characterized by low enthalpies of activation (8-13kcal/mol) and large negative entropies of activation (—28 to —40eu). Aldehydes are substantially more reactive than ketones, as can be seen by comparison of the rate data for benzaldehyde and acetophenone. This relative reactivity is characteristic of nearly all carbonyl addition reactions. The reduced reactivity of ketones is attributed primarily to steric effects. Not only does the additional substituent increase the steric restrictions to approach of the nucleophile, but it also causes larger steric interaction in the tetrahedral product as the hybridization changes from trigonal to tetrahedral. 

This equation implies that the relative reactivity is independent of the specific nucleophile and that relative reactivity is insensitive to changes in position of the transition state. Table 8.4 lists the B values for some representative ketones. The parameter B indicates relative reactivity on a log scale. Cyclohexanone is seen to be a particularly reactive ketone, being almost as reactive as cyclobutanone and more than 10 times as reactive as acetone. 

Table 8.4. Relative Reactivity of Some Ketones toward Addition of Nucleophiles...

As we have seen, the nucleophile attacks the substrate in the rate-detennining step of the Sn2 mechanism, it therefore follows that the rate of substitution may vary from nucleophile to nucleophile. Just as some alkyl halides are more reactive than others, some nucleophiles are more reactive than others. Nucleophilic strength, or nucleophilicity, is a measure of how fast a Lewis base displaces a leaving group from a suitable substrate. By measuring the rate at which various Lewis bases react with methyl iodide in methanol, a list of their- nucleophilicities relative to methanol as the standard nucleophile has been compiled. It is presented in Table 8.4. 

The relative reactivity of different positions in azines towards nucleophiles is an interesting problem which has not been solved although there is agreement on certain general features. We endeavor... 

All these methods demonstrate that the 2-positions of pyridine, pyrimidine, and other azines are the most electron deficient in the ground state. However, considerably greater chemical reactivity toward nucleophiles at the 4-position is often observed in syntheses and is supported by kinetic studies. Electron deficiency in the ground state is related to the ability to stabilize the pair of electrons donated by the nucleophile in the transition state. However, it is not so directly related that it can explain the relative reactivity at different ring-positions. Certain factors which appear to affect positional selectivity are discussed in Section II, B. 

The lack of a uniform order of relative reactivity of the halogens in reactions of certain nucleophiles with nitro- and polynitro-phenyl halides led Parker and Read to propose a one-stage mechanism for some aromatic nucleophilic substitutions. An alternative explanation within the framework of the two-stage S Ar2 mechanism had been proposed earlier. A range of mechanisms has been considered in the past by Chapman, who properly points out that only in a limited number of examples is the evidence for the two-stage mechanism compelling even though the balance of evidence favors it. 

The relative reactivity of azine rings and their ring-positions is determined by a number of factors that are considered in this section. Data and examples are taken up in Sections III and IV on the comparative reactivity of mono- and bi-cyclic azines. It is of interest to note that nucleophilic substitution comprises a sizeable section in the heterocyclic chemistry textbooks by Albert and by Katritzky and Lagowski. ... 

There are conflicting generalizations in the heterocyclic literature as to the relative reactivity of a- and y-positions in azines toward nucleophiles. Variations in the relative reactivity are attributed in this and subsequent sections to specific factors operating in addition to activation by azine-nitrogen. Another possible source of variation may be a decrease in selectivity with increasing reactivity of one or both reagents, an effect established in electrophilic aromatic... 

The effects of the nucleophile on aromatic substitution which are pertinent to our main theme of relative reactivity of azine rings and of ring-positions are brought together here. The influence of a nucleophile on relative positional reactivity can arise from its characteristics alone or from its interaction with the ring or with ring-substituents. The effect of different nucleophiles on the rates of reaction of a single substrate has been discussed in terms of polarizability, basicity, alpha effect (lone-pair on the atom adjacent to the nucleophilic atom), and solvation in several reviews and papers. ... 

In many cases, the effects of the nucleophile observed with carbo-aromatics can be expected to carry over to heteroaromatics, e.g., changing the relative reactivity of leaving groups (Section II, D, 2, b) deceleration by charge-transfer complexing with the substrate... 

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