Experimental and theoretical investigation of benzyl-N-pyrrolylketene, one- step procedure for preparing of new β-lactams by [2 +2] cycloaddition reaction

Abstract

3-Phenyl-2-(1-H-pyrrol-1-yl) propanoic acid has been used as a ketene source in synthesizing of monocyclic-2-azetidinones. Hindrance in ketene and imines successfully controlled the diastereoselectivity of the reaction. For example, in some cases only one isomer was achieved. By using Mukaiyama reagent, the leaving group in acid was activated and the by-products were separated by simple aqueous work-up. DFT calculation indicated that the benzyl-N-pyrrolylketene has nonconjugated structure and the pyrrolyl ring is perpendicular to the ketene plane in both the twisted and planar structures.

Stereoselective synthesis and characterization of monocyclic cis‐β‐lactams containing 5‐methyl‐1,3,4‐thiadiazole‐2‐thiol moiety

“…The 1 H NMR depicted J = 5.0-5.1 Hz for cisstereoisomers because of coupling constant (J) value of H-3 and H-4, for cis isomer J À3,4 > 4 Hz and trans isomer J À3,4 ≤ 3 Hz. This confirmed the cis geometry of β-lactams synthesized [42][43][44][45]. The 13 C NMR spectra were recorded at a characteristic peak at 161.89-166.35 ppm for β-lactams carbonyl carbon.…”

Designed synthetic pathway of stereoselective novel monocyclic cis‐bis‐β‐lactams including a 1,3,4‐thiadiazole‐2,5‐dithiol constituent: Antimicrobial activity, molecular docking

“…Stereochemical aspects of the synthesized bis-β-lactams were elucidated by 1 H NMR spectra, which showed a coupling constant (J) value, J = 5.3-5.6 Hz, for cis-stereoisomers of H-3 and H-4 in the β-lactams. These values for cis-stereoisomers J 3,4 > 4 Hz and trans isomers J 3,4 ≤ 3 Hz confirmed the cis geometry of the β-lactams [46][47][48][49]. The 13 C NMR spectra revealed characteristic peaks at 161.6-167.1 ppm showing the presence of carbonyl groups in bis-β-lactams.…”

Stereoselective Synthesis of Novel Monocyclic cis‐β‐Lactams Bearing 1,3,4‐Thiadiazole Nucleus: Bioactive Agents and Potential Synthons

“…Stereochemistry of newly synthesized monocyclic β-lactams was conclude using the proton NMR coupling constants of the hydrogens H-3 and H-4 of the βlactam ring, which were calculated to be J = 5.0 to 5.4 Hz for the cis stereoisomers ( J value of H-3 and H-4, for cis isomer J 3, 4 > 4.0 Hz, and for trans isomer J 3, 4 � 3.0 Hz). [43][44][45][46] The most accepted mechanism of Staudinger reaction is completed in two steps, in the first step nucleophilic attack of the imine nitrogen on the electrophilic central carbon of insitu generated ketene from phenoxyacetyl chloride and triethylamine to form a zwitterionic intermediate which in the second step undergo ring closure by conrotatory process to give fourmembered β-lactams, [47][48][49] J-value calculation from 1 HNMR data of synthesized compounds confirmed that the reaction proceeds through the mechanism as depicted in figure 3.…”

“…Their 13 C NMR spectra showed a characteristic peak at 162.3‐165.4 ppm for carbonyl carbon of β‐lactam ring. Stereochemistry of newly synthesized monocyclic β‐lactams was conclude using the proton NMR coupling constants of the hydrogens H‐3 and H‐4 of the β‐lactam ring, which were calculated to be J=5.0 to 5.4 Hz for the cis stereoisomers ( J value of H‐3 and H‐4, for cis isomer J 3, 4 > 4.0 Hz, and for trans isomer J 3, 4 ≤ 3.0 Hz) …”