A collection of novel curcumin-based 2-amino-4H-pyran-3-carbonitrile was synthesized, characterized by 1H- NMR, MS, FT-IR, and tested for antimicrobial activity. The literature review realized that many synthetic methods exist however, most of these are associated with difficulties like harsh reaction conditions and longer reaction times. This fact motivated us to prepare a novel nano-catalyst i.e., Cobalt doped polyaniline (Co-PANI) and subsequently used as a catalyst for the preparation of curcumin-based pyrans through a one-pot reaction at room condition. The polyaniline and Co-PANI were prepared and confirmed by FTIR, FEG-SEM, TEM, and XRD.