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TCI Practical Example: β-Lactamization through Condensation Reaction

We are proud to present the condensation reaction using 2,2'-dipyridyl disulfide for the formation of β-lactamizations.

Used Chemicals

• 3-Amino-3-phenylpropionic Acid [A2480]
• 2,2'-Dipyridyl Disulfide [D1114]
• Triphenylphosphine [T0519]
• Acetonitrile

Procedure

To a solution of 3-amino-3-phenylpropionic acid (463 mg, 2.80 mmol) and triphenylphosphine (881 mg, 3.36 mmol) in acetonitrile (28 mL) was added 2,2'-dipyridyl disulfide (740 mg, 3.36 mmol) and the mixture was stirred at reflux for 3 hours. The solvent was removed under reduced pressure and the residue was purified by column chromatography (diethyl ether : dichloromethane = 1:1, on silica gel), giving white solid (250 mg, 56%).

Experimenter's Comments

(1) The reaction mixture was monitored by TLC (Et₂O : CH₂Cl₂ = 1 : 1, Rf = 0.35).

(2) This condition is also utilized in the Corey-Nicolaou macrolactonization.

• Synthesis of novel macrocyclic lactones in the prostaglandin and polyether antibiotic series
  • E. J. Corey, K. C. Nicolaou, L. S. Melvin Jr., J. Am. Chem. Soc. 1975, 97, 653.

Analytical Data

4-Phenyl-2-azetidinone

¹H NMR (400 MHz, CDCl₃); δ 7.27 – 7.38 (m, 5H), 6.47 (br s, 1H), 4.70 (dd, 1H, J = 2.4, 5.2 Hz), 3.41 (ddd, 1H, J = 2.4, 5.2, 14.8 Hz), 2.84 (dd, 1H, J = 2.0, 14.8 Hz).

¹³C NMR (101 MHz, CDCl₃); δ 168.2, 140.1, 128.8, 128.2, 125.6, 50.3, 47.9.

Lead Reference

• Ph₃P-(PyS)₂-CH₃CN as an excellent condensing system for β-lactam formation from β-amino acids
  • S. Kobayashi, T. Iimori, T. Izawa, M. Ohno, J. Am. Chem. Soc. 1981, 103, 2406.

Other References

• Synthesis of (S)- and (R)-4[(methoxycarbonyl)methyl]-2-azetidinone by chemicoenzymic approach
  • M. Ohno, S. Kobayashi, T. Iimori, Y.-F. Wang, T. Izawa, J. Am. Chem. Soc. 1981, 103, 2405.