A Sustainable, Semi-Continuous Flow Synthesis of Hydantoins

• Published in: Chemistry : a European journal Vol. 22; no. 38; pp. 13451 - 13454
• Main Authors: Vukelić, Stella, Koksch, Beate, Seeberger, Peter H., Gilmore, Kerry
• Format: Journal Article
• Language: English
• Published: WEINHEIM Blackwell Publishing Ltd 12.09.2016; Wiley; Wiley Subscription Services, Inc
• Subjects: Aliphatic compounds; Amines; Carbon dioxide; Chemistry; Chemistry, Multidisciplinary; flow chemistry; Hydantoin; hydantoins; multiphase chemistry; Physical Sciences; Reagents; Science & Technology; Sustainability; sustainable chemistry; Synthesis; Transformations; carbon dioxide; MAIN-CHAIN; ONE-POT SYNTHESIS; MOIETIES; REARRANGEMENT; multiphase chemistry; MICROREACTORS; CHEMISTRY; SINGLET OXYGEN; PHOTOCHEMISTRY; sustainable chemistry; SECONDARY-AMINES; DERIVATIVES; flow chemistry; hydantoins
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201602609

Hydantoins are an important class of heterocycles with applications in pharmacy, agriculture, and as intermediates in organic synthesis. Traditional synthetic procedures to access hydantoins are target oriented with multiple synthetic steps and often use reagents that are not commercially available or sustainable. Herein, an efficient process is described for accessing hydantoins starting from commercially available amines using consecutive gas–liquid transformations (oxygen, carbon dioxide). This semi‐continuous process produced ten benzylic/aliphatic hydantoins in good overall yields (52–84 %). Let it flow! A new process for the synthesis of hydantoins, starting from commercially available amines using consecutive gas–liquid transformations, has been described. The semi‐continuous process uses highly atom economical and traceless reagents (O2, CO2, light) in environmentally friendly solvents (MeOH and MeTHF) and produces ten benzylic/aliphatic hydantoins in good overall yields (52–84 %) without need for further chromatographic purifications.