Synthesis of n-phenyl and n-benzylanthranilic acids by Ullmann reaction and evaluation of its antioxidant and inhibitory activity acetylcholinesterase

Abstract

The reaction of 2-halogen benzoic acids with amines using copper salts or metal as catalyst in
order to obtain N-phenylanthranilic acids is known as the Ullmann condensation. Several alcohols have been satisfactorily
used as solvents in this reaction of which the most commonly used is isoamyl alcohol. Other solvents
of higher boiling points like dimethylformamide are usually employed when high temperatures are required.
However, the harsh reaction conditions and the use of contaminant solvents, led to severe limitations in the general
use of this reaction, especially in the synthesis of bioactive products on a large scale. Although the use of
water as a solvent in the reaction, was a step forward, this procedure sometimes leads to long heating times due
to the high heat capacity of water. In the present work, N-phenyl and N-benzylantranilic acids were synthesized
by modified Ullmann reaction. Modifications consisted in use of PEG 400 as innocuous solvent. Furthermore, the
antioxidant and AChE inhibition activities of the panel of molecules obtained were evaluated, showing a potential
antioxidant capacity relative to Trolox® with TEAC values between 0,81 and 2,0 and a moderated AChE inhibition
with IC50 between 12.26 and 28.62 μg/mL .