A Practical and Efficient Synthesis of 2,5-Disubstituted-3,5-dihydro-imidazol-4-ones from Oxazolones

Abstract

An alternative procedure for the synthesis of 2,5-disubstituted-3,5-dihydro-imidazol-4-ones from substituted oxazolones was evaluated. The initial oxazolone ring-opening reaction was examined with a variety of ammonia source compounds followed by the subsequent 3,5-dihydro-imidazol-4-one cyclization reaction, which was carried out with either an organic or inorganic base in aprotic solvents. In this article, we report the results of an efficient and straightforward procedure for the synthesis of 2,5-disubstituted-3,5-dihydro-imidazol-4-ones that gives satisfactory yield and quality.

GRAPHICAL ABSTRACT

Keywords:

• Azlactone
• DBU
• Erlenmeyer reaction
• imidazolone
• oxazolone
• potassium carbonate

ACKNOWLEDGMENTS

We express sincere thanks to Stephan Chan for the valuable HPLC/MS data and Dr. Jodie Brice for her useful comments.

Notes

^a Ammonia source = 2 equiv.

^b Conversion by HPLC.

^a Ammonium source used for carbamoyl intermediate 2a.

^b Conversion by HPLC.

^a 0.8 mol% of ammonium carbamate.

^b DBU as base (0.35 equiv except when noted).

^c K₂CO₃ as base (0.5 equiv).

^d Scale up run (20 g).