Facile synthesis of novel [alpha]-methylene-pyrazole-carboxylate substituted imines and trans-[beta]-lactams: Versatile synthons for diverse heterocyclic molecules

• Published in: Synthetic communications Vol. 48; no. 10; p. 1190
• Main Authors: Hundal, Qudrat, Berry, Shiwani, Narula, Dipika, Bari, Shamsher S, Bhalla, Aman
• Format: Journal Article
• Language: English
• Published: Philadelphia Taylor & Francis Ltd 15.05.2018
• Subjects: Alcohols; Amides; Carbon 13; Carboxylates; Coupling (molecular); Cycloaddition; Fourier transforms; Imines; Methylene; Molecular chains; NMR; Nuclear magnetic resonance; Peptides; Pyrazole; Pyrazolones; Refluxing; Synthesis; Toluene
• ISSN: 0039-7911; 1532-2432
• DOI: 10.1080/00397911.2018.1439174

A simple, facile, and high yielding stereoselective approach for the integration of α-methylene-pyrazole-carboxylates at the [beta]-lactam nucleus is described. These monocyclic [beta]-lactams have been synthesized by treatment of 2-phenoxy/benzylthio/phenylthio ethanoic acids or acetoxyacetyl chloride/phthalimidoacetyl chloride 5a-e with novel α-methylene-pyrazole-carboxylate imines 4a-c using Et3N and POCl3 in refluxing toluene. All of the newly synthesized α-methylene-pyrazole carboxylate imines 4a-c and their [beta]-lactam derivatives 6a-h have been fully characterized by spectroscopic techniques such as FTIR, NMR (1H, 13C, and 13C DEPT-135), 2D-NMR (COSY and HSQC), and elemental analyses (CHN). The cycloaddition reaction was found to be highly stereoselective leading to the exclusive formation of trans-[beta]-lactams 6a-h and trans configuration was assigned with respect to coupling constant values of C3-H and C4-H. The novel [beta]-lactams 6a-h bearing α-methylene-pyrazole-carboxylate ring system will serve as useful synthons for highly functionalized acids, acetohydrazides/pyrazolones, alcohols, pyrazole carboxamides, peptides, and promising biologically active agents.