Facile synthesis of novel α-methylene-pyrazole-carboxylate substituted imines and trans-β-lactams: Versatile synthons for diverse heterocyclic molecules

ABSTRACT

A simple, facile, and high yielding stereoselective approach for the integration of α-methylene-pyrazole-carboxylates at the β-lactam nucleus is described. These monocyclic β-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 β-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-β-lactams 6a–h and trans configuration was assigned with respect to coupling constant values of C3-H and C4-H. The novel β-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.

GRAPHICAL ABSTRACT

KEYWORDS:

• β-Lactams
• cycloaddition
• heterocyclic β-lactams
• imines
• pyrazole-ester
• stereoselective

Additional information

Funding

AB gratefully acknowledges the financial support for this work from Department of Science and Technology (DST), New Delhi, Government of India, Project No. SR/FT/CS-037/2010 dated 28-10-2010, FIST-II/PURSE-II (DST) and UGC-CAS, Panjab University, Chandigarh. Qudrat Hundal and Shiwani Berry acknowledges the financial support from Council of Scientific and Industrial Research (CSIR) and University Grants Commission (UGC), New Delhi vides Award No. F.No.10-2(5)/2007(ii)-vE.U.II and F1-17.1/2011-12/RGNF-ST-HIM-9284, respectively.