Solvent effects aromatic substitution

Bromination has been shown not to exhibit a primary kinetic isotope effect in the case of benzene, bromobenzene, toluene, or methoxybenzene. There are several examples of substrates which do show significant isotope effects, including substituted anisoles, JV,iV-dimethylanilines, and 1,3,5-trialkylbenzenes. The observation of isotope effects in highly substituted systems seems to be the result of steric factors that can operate in two ways. There may be resistance to the bromine taking up a position coplanar with adjacent substituents in the aromatization step. This would favor return of the ff-complex to reactants. In addition, the steric bulk of several substituents may hinder solvent or other base from assisting in the proton removal. Either factor would allow deprotonation to become rate-controlling. 

The range of nueleophiles whieh have been observed to partieipate in nueleophilie aromatie substitution is similar to that for S[, 2 reactions and includes alkoxides, phenoxides, sulftdes, fluoride ion, and amines. Substitutions by earbanions are somewhat less common. This may be because there are frequently complications resulting from eleetron-transfer proeesses with nitroaromatics. Solvent effects on nucleophilic aromatic substitutions are similar to those discussed for S 2 reactions. Dipolar... 

Resonance energies and tautomerism of substituted aromatic heterocycles and their benzo derivatives Reaction-field-supermolecule approach to calculation of solvent effects... 

If one limits the consideration to only that limited number of reactions which clearly belong to the category of nucleophilic aromatic substitutions presently under discussion, only a few experimental observations are pertinent. Bunnett and Bernasconi30 and Hart and Bourns40 have studied the deuterium solvent isotope effect and its dependence on hydroxide ion concentration for the reaction of 2,4-dinitrophenyl phenyl ether with piperidine in dioxan-water. In both studies it was found that the solvent isotope effect decreased with increasing concentration of hydroxide ion, and Hart and Bourns were able to estimate that fc 1/ for conversion of intermediate to product was approximately 1.8. Also, Pietra and Vitali41 have reported that in the reaction of piperidine with cyclohexyl 2,4-dinitrophenyl ether in benzene, the reaction becomes 1.5 times slower on substitution of the N-deuteriated amine at the highest amine concentration studied. 

It is clear from the results that there is no kinetic isotope effect when deuterium is substituted for hydrogen in various positions in hydrazobenzene and 1,1 -hydrazonaphthalene. This means that the final removal of hydrogen ions from the aromatic rings (which is assisted either by the solvent or anionic base) in a positively charged intermediate or in a concerted process, is not rate-determining (cf. most electrophilic aromatic substitution reactions47). The product distribution... 

It is more difficult to interpret micellar effects upon reactions of azide ion. The behavior is normal , in the sense that k /kw 1, for deacylation, an Sn2 reaction, and addition to a carbocation (Table 4) (Cuenca, 1985). But the micellar reaction is much faster for nucleophilic aromatic substitution. Values of k /kw depend upon the substrate and are slightly larger when both N 3 and an inert counterion are present, but the trends are the same. We have no explanation for these results, although there seems to be a relation between the anomalous behavior of the azide ion in micellar reactions of aromatic substrates and its nucleophilicity in water and similar polar, hydroxylic solvents. Azide is a very powerful nucleophile towards carboca-tions, based on Ritchie s N+ scale, but in water it is much less reactive towards 2,4-dinitrohalobenzenes than predicted, whereas the reactivity of other nucleophiles fits the N+ scale (Ritchie and Sawada, 1977). Therefore the large values of k /kw may reflect the fact that azide ion is unusually unreactive in aromatic nucleophilic substitution in water, rather than that it is abnormally reactive in micelles. 

An unusual solvent effect was observed in cycloadditions of aromatic nitrile N-oxides with alkyl-substituted p-benzoquinones in ethanol-water (60 40) the reaction rates were 14-fold greater than those in chloroform (148). The use of ion pairs to control nitrile oxide cycloadditions was demonstrated. A chiral auxiliary bearing an ionic group and an associated counterion provides enhanced selectivity in the cycloaddition the intramolecular salt effect controls the orientation of the... 

The polymers used in this study were prepared by a nucleophilic activated aromatic substitution reaction of a bisphenate and dihalo diphenyl sulfone ( ). The reaction was carried out in an aprotic dipolar solvent (NMP) at 170°C in the presence of potassium carbonate (Scheme 1) (5,6). The polymers were purified by repeated precipitation into methanol/water, followed by drying to constant weight. The bisphenols used were bisphenol-A (Bis-A), hydroquinone (Hq) and biphenol (Bp). Thus, the aliphatic character of Bis-A could be removed while retaining a similar aromatic content and structure. The use of biphenol allows an investigation of the possible effect of extended conjugation on the radiation degradation. 

Lipophilicity in particular, as reflected in partition coefficients between aqueous and non-aqueous media most commonly water (or aqueous buffer) and Z-octanol,has received much attention [105,141,152,153,176,199,232,233]. Logic )W for the octanol-water system has been shown to be approximately additive and constitutive, and hence, schemes for its a priori calculation from molecular structure have been devised using either substituent tt values or substructural fragment constants [289, 299]. The approximate nature of any partition coefficient has been frequently emphasized and, indeed, some of the structural features that cause unreliability have been identified and accommodated. Other complications such as steric effects, conformational effects, and substitution at the active positions of hetero-aromatic rings have been observed but cannot as yet be accounted for completely and systematically. Theoretical statistical and topological methods to approach some of these problems have been reported [116-119,175,289,300]. The observations of linear relationships among partition coefficients between water and various organic solvents have been extended and qualified to include other dose-response relationships [120-122,160,161,299-302]. 

Spurred by our desire to avoid use of expensive dipolau aprotic solvents in nucleophilic aromatic substitution reactions, we have developed two alternative phase transfer systems, which operate in non-polar solvents such as toluene, chlorobenzene, or dichlorobenzene. Poleu polymers such as PEG are Inexpensive and stable, albeit somewhat inefficient PTC agents for these reactions. N-Alkyl-N, N -Dialkylaminopyridinium salts have been identified as very efficient PTC agents, which are about 100 times more stable to nucleophiles than Bu NBr. The bis-pyridinium salts of this family of catalysts are extremely effective for phase transfer of dianions such as bis-phenolates. 

Ab initio SCRF/MO methods have been applied to the hydrolysis and methanol-ysis of methanesulfonyl chloride (334). ° The aminolysis by aromatic amines of sulfonyl and acyl chlorides has been examined in terms of solvent parameters, the former being the more solvent-dependent process.Solvent effects on the reactions of dansyl chloride (335) with substituted pyridines in MeOH-MeCN were studied using two parameters of Taft s solvatochromatic correlation and four parameters of the Kirkwood-Onsager, Parker, Marcus and Hildebrand equations. MeCN solvent molecules accelerate charge separation of the reactants and stabilize the transition... 

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