Indian Journal of Chemistry Vol. 46B, April 2007, pp. 643-648 One - pot Reformatsky-Imine addition reaction-leading to the synthesis of structurally diverse β-lactams Jaspreet Rajput a, *, Baldev Singh b & Kewal Krishan Singal b a Department of Chemistry, G.H.G. Khalsa College, Gurusar Sadhar, Ludhiana 141 104, Punjab, India E-mail: drjaspreet@hotmail.com b Department of Chemistry, Punjabi University, Patiala 147 001, Punjab, India Received 31 May 2005; accepted (revised) 29 December 2006 The Reformatsky-imine addition reaction of α-bromoethylacetate with aldimines derived from 3,4-methylenedioxy benzaldehyde and α-methylcinnamaldehyde has provided an efficient and practical access to structurally diverse β-lactams. All the new β-lactams have been identified as 1,4-diaryl-2-azetidinones through their detailed spectral studies. Further it also reveals that the styryl bond of α-methylcinnamylideneanilines does not participate in the reaction and gives β-lactams contrary to their analogues cinnamylideneanilines 15 and o-nitrocinnamylideneanilines 16 which gave δ-lactams. Keywords: Reformatsky reaction, β-lactams, Imines, α-bromoethylacetate, α-methylcinnamaldehyde IPC: Int.Cl. 8 C07D β-Lactams and their derivatives have potential biological activity as antibiotics 1 . Reformatsky reaction is the part of the large and rapidly expanding field of enolate chemistry, where specific mode of metal-enolate formation is from halo carbonyl compounds 2,3 . Improvements in the yields of Reformatsky reaction have been achieved when freshly prepared zinc powder 4 , a heated column of zinc dust 5 , a trimethylborate-THF solvent system 6 , a zinc-copper couple 7 , acid washed zinc 8 , trimethyl- chlorosilane 9 , ultrasonic irradiation 10-13 , microwave irradiation 14 were utilized. In continuation to this research a convenient one- pot thermal method for the preparation of β-lactams 2 from the Reformatsky-Imine addition reaction of 1 equiv. of aldimines 1 with 1.8 equiv. of zinc dust and 1.5 equiv of α-bromoethylacetate (Scheme I) is described. The aldimines (eighteen in number) have been obtained by condensation of 3,4-methylene- dioxybenzaldehyde and α-methylcinnamaldehyde with a series of nine aromatic amines having various substituents at o, m, p-positions. These aldimines are evaluated as potential electrophiles for the Reformatsky-Imine addition reactions. The products obtained by Reformatsky-Imine addition reaction were identified as 1,4-diaryl-2- azetidinones 2 on the basis of their IR, 1 H NMR and mass spectra. The infrared spectrum of these azetidinones (β-lactams) displayed sharp and strong absorption bands in the region 1731-1748 cm -1 , which have been assigned to amidocarbonyl group of the β- lactams. 1 H NMR spectrum of these azetidinones exhibited that the two geminal protons H 3a and H 3b appear as separate signals. The H 3b appears at δ 2.83-2.92 as double doublet having coupling constant JH 3b -H 4 ≈ 2.5 and JH 3b -H 3a ≈ 15.2 Hz. Whereas the proton H 3a appears downfield at δ 3.28-3.52 as double doublet having coupling constant JH 3a -H 4 ≈ 5.5 and JH 3a -H 3b ≈ 15.2 Hz. Out of the two geminal protons H 3a and H 3b , the proton H 3a shows downfield shift as compared to proton H 3b because of orientation of carbonyl group 1 . As a result proton H 3a comes in the deshielding zone of the π-bond electron cloud of the carbonyl group attached to it. Therefore in all the β- lactams the H 3a proton appears (δ 3.28-3.52) down- field as compared to proton H 3b (δ 2.85-2.92). The H 4 proton appears at δ 4.58-4.82 as quartet having coupling constant JH 4 -H 3b ≈ 5.4 Hz and JH 4 -H 3a ≈ 2.4 Hz. The same proton in aldimines appeared downfield at δ 8.5-8.6 due to its association with a double bond.