Acids, acid strength electrophilic aromatic

Indolmycin, biosynthesis of, 864 Inductive effect. 37, 562 alcohol acidity and. 604 carboxylic acid strength and. 758 electronegativity and, 37 electrophilic aromatic substitution and, 562... 

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. 

Depending on the strength of the Lewis acid and on the structure of the R substituent, the actual acylating agent may be the acid-base complex 1 or the acyl cation 2. The active reagents 1 or 2 or even a mixture of both undergo the electrophilic aromatic substitution affording the final ketone products [1]. 

Section 10.6), the strength of F-substituted carboxylic acids, the deactivating effect of the CF3 group in electrophilic aromatic substitutions, and the non-basic character of NF3 and (CF3)3N (see end-of-chapter problem 17.4). 

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