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In the six-membered heterocyclic compound piperazine, two nitrogen atoms are positioned within the ring at 1 and 4 positions. Numerous studies have shown that piperazine has the potential to be a useful pharmacophore in many harmful pharmacological conditions such as microbiocidal, anti-inflammatory, anticancer, antioxidant, etc. In this present review, we highlighted the synthetic protocols for piperazine and its analogs, as well as the synthetic protocol for piperazine via rearrangement reaction, which have been adopted in recent years. The study also involved a listing of several patents (granted), which comprised important work on piperazine and its derivatives. Among all the methods, the most commonly adopted synthetic methods included the synthesis of piperazine analogs by diza-cope, hydrolytic, mumm, multi-component, ugi-smiles, [2+3]-stevens, aza-Wittig, Curtius, Schmidt rearrangement reactions, etc. These synthetic protocols have also been compared based on different reaction conditions, feasibility, and economy to help the researchers in designing their work.
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