Synlett 2017; 28(12): 1453-1456
DOI: 10.1055/s-0036-1558974
letter
© Georg Thieme Verlag Stuttgart · New York

Stereoselective Synthesis of 3-(5-Benzoyl-1-methyl-1H-pyrrol-2-yl)-2-azetidinone Derivatives via an in Situ Generated Ketene

Behjat Bananezhad, Mohammad Reza Islami*
  • Department of Chemistry, Shahid Bahonar University of Kerman, 76169 Kerman, Iran   Email: mrislami@uk.ac.ir
Further Information

Publication History

Received: 24 December 2016

Accepted after revision: 27 February 2017

Publication Date:
06 April 2017 (eFirst)

Abstract

A short route toward β-lactams from tolmetin has been developed. In the key step, a ketene was generated on the C-2 of pyrrole ring and reacted with aromatic imines to form trans-β-lactams as the only observed products. The identification of the ketene was confirmed by reaction with the stable free radical TEMPO (TO·).

Supporting Information

 
  • References and Notes

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  • 43 Reaction of Tolmetin Ketene with TEMPO: [1-Methyl-5-(4-methylbenzoyl)-1H-pyrrol-2-yl]acetic acid (2; 0.25 g, 1 mmol) and Mukaiyama’s reagent (3; 0.31 g, 1.2 mmol) were stirred in anhyd CH2Cl2 (15 mL) at r.t. under nitrogen for 5 min. Then Et3N (0.50 mL, 3.6 mmol) was added. A solution of TEMPO (6; 0.47 g, 3.0 mmol) in CH2Cl2 (5 mL) was added and the suspension was stirred for 17 h. The solvent was evaporated and the excess of TEMPO removed by sublimation. Then the residue was washed with 5% aq HCl followed by H2O. The organic layer was separated and dried over Na2SO4 and the solvent was filtered and removed under reduced pressure. The product was purified by column chromatography (silica gel, n-hexane–EtOAc, 10:2) to furnish 7 as a yellow oil; yield: 193 mg (35%). IR (νmax): 1766, 1657 (C=O) cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.71 (2 H, Ar), 7.25 (2 H, Ar), 6.69 (d, 3 J H–H = 4.0 Hz, 1 H), 6.17 (d, 3 J H–H = 4.0 Hz, 1 H), 4.42 (s, 3 H, Me), 3.77 (s, 1 H, CH), 4.02 (s, 3 H, Me), 1.21–1.72 (m, 12 H, 6 × CH2), 1.27 (s, 6 H, 2 × Me), 1.09 (s, 9 H, 3 × Me), 1.02 (s, 9 H, 3 × Me). 13C NMR (100 MHz, CDCl3): δ = 185.94, 168.81, 141.92, 137.33, 134.37, 131.30, 129.45, 128.88, 128.70, 128.11, 122.27, 109.58, 60.25, 39.01, 33.30, 31.82, 31.73, 29.71, 21.56, 20.48, 16.86. Anal. Calcd for C33H49N3O4 (551.76): C, 71.83; H, 8.95; N, 7.62. Found: C, 71.4; H, 8.6; N, 7.8.Typical Procedure for the Preparation of Compounds 5a–m: [1-Methyl-5-(4-methylbenzoyl)-1H-pyrrol-2-yl]acetic acid (2; 0.51 g, 2 mmol) was mixed with Mukaiyama’s reagent (3; 0.53 g, 2.1 mmol) and Et3N (0.20 mL, 2 mmol) in anhyd CH2Cl2 (25 mL) under nitrogen and heated to reflux for 10 h. A solution of the N-benzylideneaniline (4; 0.37 g, 2 mmol) in anhyd CH2Cl2 (10 mL) and Et3N (0.20 mL, 2.0 mmol) was then added and refluxing was continued for an additional 10 h. The solution was washed with H2O, 5% HCl and again with H2O. The organic layer was separated and dried over Na2SO4 and the solvent was filtered and removed under reduced pressure. The products were purified by column chromatography (silica gel, n-hexane–EtOAc, 10:2). Analytical data for trans-3-[1-methyl-5-(4-methylbenzoyl)-1H-pyrrol-2-yl]-1,4-diphenylazetidin-2-one (5a): white solid; yield: 253 mg (60%); mp 152–154 °C. IR (KBr): 1744, 1624 (C=O) cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.00–7.65 (14 H, Ar), 6.64 (d, 3 J H–H = 4.0 Hz, 1 H), 6.25 (d, 3 J H–H = 4.0 Hz, 1 H), 4.34 (d, 3 J H–H = 2.8 Hz, 1 H), 4.94 (d, 3 J H–H = 2.8 Hz, 1 H) 3.77 (s, 3 H, Me), 2.35 (s, 3 H, Me). 13C NMR (100 MHz, CDCl3): δ = 186.19, 163.32 (C=O), 142.21, 137.32, 137.04, 136.76, 135.17, 132.08, 129.54, 129.49, 129.19, 128.79, 126.04, 124.39, 122.29, 117.20, 107.62, 62.10, 57.84, 33.78, 21.58.