Aim and Objective: Because of the low abundance of 3,4-unsubstituted coumarins in plants combined
with the complex purification process required, synthetic routes towards 3,4-unsubstituted coumarins are
especially valuable. In the present work, we explore the possibilities of a solvent-free Green Knoevenagel condensation
on various 2-hydroxybenzaldehyde derivatives and malonic acid without the use of toxic organocatalysts
like pyridine and piperidine but only use ammonium bicarbonate as the catalyst.
Materials and Methods:
To investigate the scope of the Green Knoevenagel condensation for the synthesis of
3,4-unsubstituted coumarins, various 2-hydroxybenzaldehyde derivatives were screened as starting material in
the optimized two-step procedure developed for 2-hydroxybenzaldehyde.
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Results: This study shows that the intramolecular esterification and the decarboxylation are in competition, but
show different temperature optima. In order to suppress premature decarboxylation and maximize the yield of
coumarin, a two-step procedure was adopted. The reaction mixture containing ammonium bicarbonate is initially
kept at 90ºC for 1 hour. After completion of the cyclization, the temperature of the reaction mixture is
increased to 140ºC for 2 hours. Following this protocol, coumarin could be isolated with a yield of 95%.
Conclusion:
A two-step procedure for the solvent-free synthesis of several 3,4-unsubstituted coumarins was
developed using ammonium bicarbonate, resulting in high yields of the desired products. Moreover, this procedure
has a low E-factor and is, therefore an environmental friendly reaction in line with the principles of
Green Chemistry. It was shown that by initially capping the temperature at 90ºC, premature decarboxylation
can be suppressed. After full conversion to the intermediate 3-carboxycoumarin, the temperature can be increased
to 140ºC finalizing the reaction. Ammonium bicarbonate was shown to catalyze both the Green
Knoevenagel condensation and the decarboxylation step.
Ball milling for the quantitative and specific solvent-free Knoevenagel condensation + Michael addition cascade in the synthesis of various 2-amino-4-aryl-3-cyano-4H-chromenes without heating