For nucleophilic aromatic substitution

As we ve seen, aromatic substitution reactions usually occur by an electrophilic mechanism. Aryl halides that have electron-withdrawing substituents, however, can also undergo nucleophilic aromatic substitution. For example. 2,4,6-trinitrochlorobenzene reacts with aqueous NaOH at room temperature to give 2,4,6-trinitrophenol. The nucleophile OH- has substituted for Cl-. 

Nucleophilic aromatic substitution for heteroatom nucleophiles through electrochemical oxidation of intermediate a-complexes (Meisenheimer complexes) in simple nitroaromatic compounds has been reported, see Gallardo, 1. Guirado, G. Marquet, J. J. Org. Chem. 2002, 67, 2548. 

Semmelhack, M. F., Bargar, T., Photostimulated Nucleophilic Aromatic Substitution for Halides with Carbon Nucleophiles. Preparative and Mechanistic Aspects, J. Am. Chem. Soc. 1980, 102, 7765 7774. 

Nucleophilic Aromatic Substitution For Hydrogen Oxidation of a-Complex Intermediates... 

Figure 11. Amination of nitrobenzene via nucleophilic aromatic substitution for hydrogen.

Figure 2. Nucleophilic aromatic substitution for hydrogen reaction.

The formation of substituted anilides from the reaction of amides with nitrobenzene is the first example of the direct formation of aromatic amide bonds via nucleophilic aromatic substitution for hydrogen. This reaction proceeds in high yield and regioselectivity, and does not require the use of halogenated materials or auxiliary leaving groups. Furthermore, these studies have demonstrated that the use of O2 as the terminal oxidant in NASH reactions can result in a highly selective and environmentally favorable route for the production of PNA and PPD. 

Two examples of nucleophilic aromatic substitution for hydrogen reactions were described from which we have proposed two new atomically efficient processes for the manufacturing of commercially relevant aromatic amines. Our mechanistic studies have revealed that the direct oxidation of a-complex intermediates by either nitro groups or O2 can eliminate the need for chlorination of benzene as a starting point for the manufacturing of aromatic amines. Accordingly, these reactions demonstrate the key objective of alternate chemical design which is not to make the waste in the first place. 

Each of the two new chapters offers the advantage of a timely treatment of core material along with efficiency in its delivery. Nucleophilic aromatic substitution, for example, becomes a first-semester or second-quarter topic along with both nucleophilic aliphatic and electrophilic aromatic substitution. 

Elimination of Chlorine in the Synthesis of 4-Aminodiphenylamine A New Process That Utilizes Nucleophilic Aromatic Substitution for Hydrogen... 

One example of feedstock replacement that has been applied commercially is the work of Stem and co-workers (19-21) at the Monsanto Corporation in the synthesis of a variety of aromatic amines. By using nucleophilic aromatic substitution for hydrogen. Stem was able to obviate the need for the use of a chlorinated aromatic in the synthetic pathway. Certain chlorinated aromatics are known to be persistent bioaccumulators and to possess other environmental concerns this research in feedstock replacement resulted in the removal of that concern. 

In addition to the SNAr mechanism, several other mechanisms are known for nucleophilic aromatic substitutions. For example, an SnI mechanism is relevant for nucleophilic substitution reactions which encounter aromatic diazonium salts. Radical-nucleophilic aromatic substitutions (SrnI) are known in reactions where no electron-withdrawing group is available, whereas a mechanism via a benzyne intermediate is of relevance for substitutions employing NHJ as a nucleophile. 

This type of nucleophilic aromatic substitution for halogen has been studied extensively, and it has been determined that reaction occurs in two steps nucleophilic addition followed by elimination. For the majority of reactions of this type, addition of the nucleophile in Step 1 is the slow, rate-determining step. Elimination of halide ion in Step 2 gives the product. This reaction thus resembles reactions of carboxylic acid derivatives in that it proceeds by an addition-elimination mechanism rather than by direct substitution. 

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