Nucleophilic substitution, aromatic rates

Kinetic studies have shown that the enolate and phosphorus nucleophiles all react at about the same rate. This suggests that the only step directly involving the nucleophile (step 2 of the propagation sequence) occurs at essentially the diffusion-controlled rate so that there is little selectivity among the individual nucleophiles. The synthetic potential of the reaction lies in the fact that other substituents which activate the halide to substitution are not required in this reaction, in contrast to aromatic nucleophilic substitution which proceeds by an addition-elimination mechanism (see Seetion 10.5). 

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. ... 

Specific alterations of the relative reactivity due to hydrogen bonding in the transition state or to a cyclic transition state or to electrostatic attraction in quaternary compounds or protonated azines are included below (cf. also Sections II, B, 3 II, B, 5 II, C and II, F). A-Protonation is often reflected in an increase in JS and therefore the relative reactivity can vary with the significance of JS in controlling the reaction rate. Variation can also result from rate determination by the second stage of the SjjAr2 mechanism or from the intervention of thermodynamic control of product formation. Variation in the rate and in the reactivity pattern of polyazanaph-thalenes will result when nucleophilic substitution [Eq. (10)] occurs only on a covalent adduct (408) of the substrate rather than on its aromatic form (400). This covalent addition is prevented by any 4-... 

Such nucleophilic displacements are likely to be addition-elimination reactions, whether or not radical anions are also interposed as intermediates. The addition of methoxide ion to 2-nitrofuran in methanol or dimethyl sulfoxide affords a deep red salt of the anion 69 PMR shows the 5-proton has the greatest upfield shift, the 3- and 4-protons remaining vinylic in type.18 7 The similar additions in the thiophene series are less complete, presumably because oxygen is relatively electronegative and the furan aromaticity relatively low. Additional electronegative substituents increase the rate of addition and a second nitro group makes it necessary to use stopped flow techniques of rate measurement.141 In contrast, one acyl group (benzoyl or carboxy) does not stabilize an addition product and seldom promotes nucleophilic substitution by weaker nucleophiles such as ammonia. Whereas... 

A diverse group of organic reactions catalyzed by montmorillonite has been described and some reviews on this subject have been published.19 Examples of those transformations include addition reactions, such as Michael addition of thiols to y./bunsatu rated carbonyl compounds 20 electrophilic aromatic substitutions,19c nucleophilic substitution of alcohols,21 acetal synthesis196 22 and deprotection,23 cyclizations,19b c isomerizations, and rearrangements.196 24... 

For a number of reactions in functional micelles and comicelles second-order rate constants are similar in micelles and in water. Except for aromatic nucleophilic substitution they are slightly smaller in the micelles than in water, and the pattern of behavior is exactly that found for reactions of organic nucleophilic anions in non-functional micelles. Some examples of these comparisons are in Table 9. 

Rate constants of bimolecular, micelle-assisted, reactions typically go through maxima with increasing concentration of inert surfactant (Section 3). But a second rate maximum is observed in very dilute cationic surfactant for aromatic nucleophilic substitution on hydrophobic substrates. This maximum seems to be related to interactions between planar aromatic molecules and monomeric surfactant or submicellar aggregates. These second maxima are not observed with nonplanar substrates, even such hydrophobic compounds as p-nitrophenyl diphenyl phosphate (Bacaloglu, R. 1986, unpublished results). 

Unless a more specific reference is given, rate coefficients in Section VI.B have been taken from the volumes of Reference 107c Volume 3, Part 1 (first order nucleophilic substitution) Volume 4, Part 2 (aromatic nucleophilic substitution). 

In contrast with aliphatic nucleophilic substitution, nucleophilic displacement reactions on aromatic rings are relatively slow and require activation at the point of attack by electron-withdrawing substituents or heteroatoms, in the case of heteroaromatic systems. With non-activated aromatic systems, the reaction generally involves an elimination-addition mechanism. The addition of phase-transfer catalysts generally enhances the rate of these reactions. 

The utilization of polar polymers and novel N-alkyl-4-(N, N -dialklamino)pyridinium sedts as stable phase transfer catalysts for nucleophilic aromatic substitution are reported. Polar polymers such as poly (ethylene glycol) or polyvinylpyrrolidone are thermally stable, but provide only slow rates. The dialkylaminopyridininium salts are very active catalysts, and are up to 100 times more stable than tetrabutylammonium bromide, allowing recovery and reuse of catalyst. The utilization of b is-dialkylaminopypridinium salts for phase-transfer catalyzed nucleophilic substitution by bisphenoxides leads to enhanced rates, and the requirement of less catalyst. Experimental details are provided. 

The arene oxide valence tautomer of oxepins in principle should undergo nucleophilic substitution reactions (Sn2) which are characteristic of simple epoxides. In reality oxepin-benzene oxide (7) is resistant to attack by hard nucleophiles such as OH-, H20, NH2- and RNH2. Attempts to obtain quantitative data on the relative rates of attack of nucleophiles on (7) in aqueous solution hqye been thwarted by competition from the dominant aromatization reaction. 

Anilines with strongly electron-withdrawing groups or diarylamines [38] are only weak nucleophiles, and might require deprotonation to react with electrophiles at acceptable rates (Scheme 6.8). These anilines can also be allylated by allyl palladium complexes [34], Electron-deficient anilines are electrophiles themselves, and can transfer the aryl group to other nucleophiles by aromatic nucleophilic substitution [39]. 

---