New Access to Pyrano[2,3-c]pyrazole-3-carboxylates via Domino Four-Component Reaction and Their Antimicrobial Activity

Muhammad Siddiq Maarop (Department of Chemistry, Faculty of Applied Sciences, Universiti Teknologi MARA, UiTM Shah Alam, 40450 Shah Alam, Selangor, Malaysia)
Fatin Nur Ain Abdul Rashid (Department of Chemistry, Faculty of Applied Sciences, Universiti Teknologi MARA, UiTM Shah Alam, 40450 Shah Alam, Selangor, Malaysia)
Mohd Fazli Mohammat (Organic Chemistry Laboratory, Institute of Science, Universiti Teknologi MARA, Kampus Puncak Alam, 42300 Bandar Puncak Alam, Selangor, Malaysia)
Zurina Shaameri (Organic Chemistry Laboratory, Institute of Science, Universiti Teknologi MARA, Kampus Puncak Alam, 42300 Bandar Puncak Alam, Selangor, Malaysia)
Saiful Azmi Johari (Antimicrobial Laboratory, Anti-Infective Branch, Bioactivity Programme, Natural Products Division, Forest Research Institute Malaysia (FRIM), 52109 Kepong, Selangor, Malaysia)
Mazurah Mohamed Isa (Antimicrobial Laboratory, Anti-Infective Branch, Bioactivity Programme, Natural Products Division, Forest Research Institute Malaysia (FRIM), 52109 Kepong, Selangor, Malaysia)
Anis Low Muhammad Low (Atta-ur-Rahman Institute (AURINS), Universiti Teknologi MARA, Kampus Puncak Alam, 42300 Bandar Puncak Alam, Selangor, Malaysia)

Indonesian Journal of Chemistry
Vol 20, No 1 (2020)

A library of some novel classes of pyrano[2,3-c]pyrazole-3-carboxylates was synthesized by employing uncatalyzed domino four-component reaction using diethyloxaloacetate, hydrazine hydrate, aldehydes and malononitrile in refluxing of ethanol-acetic acid solvent systems. Series of domino reactions involving of pyrazolone formation, Michael addition, and Thorpe-Ziegler cyclization reaction managed to produce the cyclized products from moderate to excellent yield. This protocol provides a reliable, general and salient procedure for the title compound using a one-pot approach. Preliminary biological screening unveiled limited potentials of this class of compounds for antimicrobial lead compound due to its limited solubility properties.