Reaction mechanisms, SNAr formation

The SNAr reactions of heteroarenes can be realized in a similar manner, as in the series of arenes [71, 82]. These nucleophilic reactions are analogous to electrochemical Sn transformations of arenes [22, 24, 25]. Terrier and co-workers considered an opportunity for electrochemical methoxylation of 4,6-dinitrobenzofuroxan by action of the methoxide ion via the SnAt mechanism [21]. The intermediate o -complex formed was oxidized successfully into the corresponding substitution product. Analogously, the formation of heteroaromatic amines has been suggested to occur via intermediacy of the corresponding amino adducts, as exemplified by the oxidation of the o -complex derived fi om the reaction of pyrimidine with NH2 (Scheme 26) [3, 102-104]. 

Consider an alternative mechanism (Figure 8.70) for the formation of m-tri-fluoromethylaniline by reaction of o-chlorotrifluoromethylbenzene with KNH2 in liquid ammonia in which a phenyl carbanion isomerizes prior to an SNAr reaction. Suggest experiments to determine whether such a mechanism occurs in this case or in other reactions of aryl halides with KNH2 in liquid anunonia. 

On the basis of experiment results and the previous reports, a tentative mechanism of this reaction is depicted in Scheme 7.2. [Cu] is required for the SNAr with azide and the decomposition of the azide takes place after the aryl azide formation. There exist two possibilities for the subsequent C-N bond formation. A step-wise process involving an initial C-N bond formation and subsequent C-H bond cleavage, or a concerted process with simultaneous breaking of the C-H bond and the formation of the C-N bond. The author preferred a concerted process involved in the present reaction, which has Cu-participation in both steps. 

The activation of carboxylic acids by means of 2-chloro-l,3,5-triazines 1 proceeds via triazinyl ammonium salts 2 that are formed in situ in flie presence of flie appropriate tertiary amine. The formation of salts 2 occurs by an addition-elimination SNAr mechanism and the reaction rates strongly depend on the steric hindrance of the substituents in the amine employed. 

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