Aim and Objective: The objective of our work was to study the peculiarities of transformations of
fluorine-containing flavone-3-carboxylates with N-nucleophiles, including biogenic amines and amino acids.
Materials and Methods:
6,7,8-Trifluoro and 5,6,7,8-tetrafluoroflavone-3-carboxylates were involved in interactions
with a number of N-nucleophiles, such as pyrrolidine, morpholine, proline, arginine, gammaaminobutyric
acid, beta-alanine, histamine, dopamine and amantadine under different reaction conditions. All
synthesized compounds were characterized by NMR 1H, 19F, (NMR 13C for some compounds) and IR spectroscopic
data, and elemental analysis.
Results:
3-(Ethoxycarbonyl)polyfluoroflavones react with morpholine, pyrrolidine and L-proline to form 7-
monosubstituted flavone-3-carboxylates. For the reactions of tetrafluoroflavone with pyrrolidine and morpholine,
the formation of 5,7-disubstituted products is also possible. Interaction with gamma-aminobutyric acid
leads to the 4-{[3-ethoxy-2-(2-hydroxypolyfluorobenzoyl)-3-oxo-1-phenylprop-1-enyl]amino}butanoic acids
as a result of the pyrone ring opening. In reactions with dopamine, histamine, L-arginine and β-alanine,
polyfluoroflavone-3-carboxylates underwent a chromone-coumarin rearrangement. 3-(Ethoxycarbonyl)tetrafluoroflavone
forms with amantadine the nucleophilic aromatic substitution product, while trifluoro-substituted
analog gives the chromone-coumarin rearrangement product.
Conclusion:
This work showed possibilities of chemical modification of polyfluorinated flavones in the reactions
with amines depending on the structure of the nucleophilic reagent. Synthesized compounds are of interest
for biological testing.
Nucleophilic Aromatic Substitution Reactions under Aqueous, Mild Conditions Using Polymeric Additive HPMC
