Electrophilic Aromatic Substitution SEAr

The mechanisms of the Gattermann and Gattermann-Koch formylation belong to the category of electrophilic aromatic substitution (SEAr) but are not known in detail, since they have a tendency to vary from one substrate to another, and the reaction conditions may also play a role. When carbon monoxide is used, the electrophilic species is believed to be the formyl cation, which is attacked by the aromatic ring to form a -complex. This -complex is then converted to the aromatic aldehyde upon losing a proton. When HCN is used, the initial product after the SEAr reaction is an imine hydrochloride, which is subsequently hydrolyzed to the product aldehyde. 

The preceding explanation would seem to explain most of the data in Table 8.21, but there is one apparent discrepancy. We might have expected the methoxy substituent to be electron-donating, but it gives the same product orientation as does trifluoromethyl. This intuitive expectation of the substituent effect of methoxy is based primarily on its influence on electrophilic aromatic substitution (SeAr) and on nucleophilic aromatic substitution (SwAr) reactions, both of which involve attachment of a species to an aromatic ring to form a cr complex. In contrast, the carbanionic intermediates presumed to be formed in the benzyne reaction have the nonbonded pair of electrons in... 

In 2010, Zhu and coworkers first reported the direct intramolecular C(sp )-H amination of Af-arylpyridine-2-ammes using a combination of Cu(OAc)2 and Fe(N03)3 as a bimetalUc catalytic system to furnish pyrido[l,2-a]benzimidazoles in satisfactory yields [13]. The authors believe that a Cu(lll)-catalyzed electrophilic aromatic substitution (SEAr) pathway is operating in this process according to the results of mechanistic studies, wherein iron(lll) acts a unique role to facilitate the formation of the more electrophilic Cu(III) species because in the absence of iron(III), a much less efficient and reversible Cu(II)-mediated SEAr process takes place. 

The reaction is believed to begin with the metalation of the substrate via aromatic electrophilic substitution (SEAr) followed by CO insertion and nucleophilic displacement by water or another protic nucleophile such as tri-fluoroacetic acid (TFFA) to give, respectively, the aromatic carboxylic acid or its mixed anhydride derivative, from which the acid is freed by hydrolysis (Scheme 24). 

Notes-. Most used reactions are SEAr (iododemetallation) and SNAr (halogen exchange, copper assisted). SeI, unimolecular electrophilic substitution Se2, bimolecular electrophilic substitution SeAp aromatic electrophilic substitution SeI, intramolecular electrophilic substitution S l, unimolecular nucleophilic substitution 3 2, bimolecular nucleophilic substitution S Ar, aromatic nucleophilic substitution. 

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