Facile synthesis of novel halogenated 4-pyrazolylspirocyclic-β-lactams: versatile heterocyclic synthons

Abstract

A mild approach for the synthesis of halogenated 4-pyrazolylspirocyclic-β-lactams via halogen (I2, Br2, ICl) mediated intrasulfenyl cyclisation of cis-3-(prop-2′-ynyloxy)-4-pyrazolyl-β-lactams is described. The behaviour of the substrate towards the nature and variable amount of halogen was investigated. The structural and stereochemical analysis of novel β-lactams were carried out using FT-IR, NMR (1H and 13C), 2D-NMR (COSY and HSQC), elemental analysis (CHNS), mass spectrometry (EIMS) and single crystal X-ray crystallographic studies (3a, 6a, 7a). NMR experiments were also performed on cis-3-chloro-4-pyrazolyl-β-lactams to establish the relationship between isomeric ratio of rotamers and nature of solvents. The cis or trans configuration of the hydrogen/chloro/nucleophile substituent at C-3 was assigned with respect to C4-H.