In nucleophilic aromatic substitution

A nitro group is a strongly activating substituent in nucleophilic aromatic substitution where it stabilizes the key cyclohexadienyl anion intermediate... 

Cycloalkene (Section 5 1) A cyclic hydrocarbon characterized by a double bond between two of the nng carbons Cycloalkyne (Section 9 4) A cyclic hydrocarbon characterized by a tnple bond between two of the nng carbons Cyclohexadienyl anion (Section 23 6) The key intermediate in nucleophilic aromatic substitution by the addition-elimination mechanism It is represented by the general structure shown where Y is the nucleophile and X is the leaving group... 

I > Br > Cl > F. In nucleophilic aromatic substitution, the formation of the addition intermediate is usually the rate-determining step so the ease of C—X bond breaking does not affeet the rate. When this is the ease, the order of reactivity is often F > Cl > Br > I. This order is the result of the polar effeet of the halogen. The stronger bond dipoles assoeiated with the more eleetronegative halogens favor the addition step and thus inerease the overall rate of reaetion. 

Indeed, the order of leaving-group reactivity in nucleophilic aromatic substitution is the... 

The most common types of aryl halides in nucleophilic aromatic substitutions are those that bear- o- or p-nitro substituents. Among other classes of reactive aryl halides, a few merit special consideration. One class includes highly fluorinated aromatic compounds such as hexafluorobenzene, which undergoes substitution of one of its fluorines on reaction with nucleophiles such as sodium methoxide. 

Nucleophilic aromatic substitution can also occur by an elimination-addition mechanism. This pathway is followed when the nucleophile is an exceptionally strong base such as amide ion in the fonn of sodium amide (NaNH2) or potassium amide (KNH2). Benzyne and related arynes are intennediates in nucleophilic aromatic substitutions that proceed by the elimination-addition mechanism. 

Cyclohexadienyl anion (Section 23.6) The key intermediate in nucleophilic aromatic substitution by the addition-elimination mechanism. It is represented by the general structure shown, where Y is the nucleophile and X is the leaving group. 

A treatise on kinetics is a logical and fitting medium in which to analyze and discuss just such limitations and uncertainties of mechanism. The present chapter will attempt such a treatment for the SN2 mechanism in nucleophilic aromatic substitution. An effort will be made to pinpoint every assumption and highlight every instance where alternate choices are possible. The end result hoped for is a clearer delineation of the known and the probable from the uncertain and the unknown. 

In discussing base catalysis it will prove convenient to adopt, at the outset, a distinction first proposed by Bunnett and Garst22, who noted that the observed cases of catalysis in nucleophilic aromatic substitution could be broadly divided into two categories. The classification was in terms of the relative rates of the catalyzed and uncatalyzed reactions. Since all of the systems could be accommodated empirically by eqn. (4),... 

The available experimental results are completely in accord with this formulation. Both of these limiting conditions have been observed experimentally, and plots of both k versus [B]0 and k versus [R2NH]0 have been shown to have characteristics consistent with this proposed mechanism. These observations thus constitute very convincing evidence for the intermediate complex mechanism in nucleophilic aromatic substitution. 

Bifunctional catalysis in nucleophilic aromatic substitution was first observed by Bitter and Zollinger34, who studied the reaction of cyanuric chloride with aniline in benzene. This reaction was not accelerated by phenols or y-pyridone but was catalyzed by triethylamine and pyridine and by bifunctional catalysts such as a-pyridone and carboxylic acids. The carboxylic acids did not function as purely electrophilic reagents, since there was no relationship between catalytic efficiency and acid strength, acetic acid being more effective than chloracetic acid, which in turn was a more efficient catalyst than trichloroacetic acid. For catalysis by the carboxylic acids Bitter and Zollinger proposed the transition state depicted by H. 

It has also been argued10,40 that the second mechanism (rapid, reversible interconversion of II and IV) cannot be general. The basis for this contention is the fact that electrophilic catalysis is rare in nucleophilic aromatic substitution of non-heterocyclic substrates, an exception being the 2000-fold acceleration by thorium ion of the rate of reaction of 2,4-dinitrofluorobenzene with thiocyanate... 

The difference in reactivity is not as much as is generally observed in nucleophilic aromatic substitution in solution by an addition-elimination mechanism (ref. 25). Substituents with electron withdrawing capabilities enhance the rate of the reaction therefore decabromobiphenyl ether reacts nearly 2 times faster than 1,2,3,4-tetrabromodibenzodioxin. 

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. 

Due to its strong activating effect in nucleophilic aromatic substitutions and to the possibility of its removal by decarbonylation, the aldehyde function has been used for the preparation of [ F]fluoroarenes not bearing electron-withdrawing substituents. Decarbonylations, possible in the presence of Pd/C [ 161 ], are more efficient in terms of time (15 min vs 1 h) and yields (80%) when using Wilkin-... 

Relative Reactivity of Pyridyl Derivatives in Nucleophilic Aromatic Substitutions... 

Problem 11.26 Why do the typical 5 2 and S l mechanisms not occur in nucleophilic aromatic substitution ... 

The absence of nitro groups in these substrates is noteworthy. The observed adducts are exclusively stabilized by the electron-withdrawing capacity of the aza groups present in the fused ring system of purine. Accordingly, all ring protons in the adducts are more shielded than the corresponding protons in the substrates. Adducts 19 and 20 can be taken as models for intermediates in nucleophilic aromatic substitution at the C-6 position of purine. Moreover, their formation support the view that a tetrahedral carbon at C-6 is involved in the mechanism of the adenosine deaminase-catalyzed hydrolysis of 6-substituted purine ribonucleosides.43... 

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