The synthesis of
kynurenic acid derivatives with potential
biological
effect was investigated and optimized for one-batch, two-step microwave-assisted
reactions. Utilizing both chemically and biologically representative
non-, methyl-, methoxy-, and chlorosubstituted aniline derivatives,
in catalyst-free conditions, syntheses of seven kynurenic acid derivatives
were achieved in a time frame of 2–3.5 h. In place of halogenated
reaction media, tuneable green solvents were introduced for each analogue.
The potential of green solvent mixtures to replace traditional solvents
and to alter the regioisomeric ratio regarding the Conrad–Limpach
method was highlighted. The advantages of the fast, eco-friendly,
inexpensive analytic technique of TLC densitometry were emphasized
for reaction monitoring and conversion determination in comparison
to quantitative NMR. Moreover, the developed 2–3.5 h syntheses
were scaled-up to achieve gram-scale products of KYNA derivatives,
without altering the reaction time in the halogenated solvent DCB
and more importantly in its green substitutes.