The aminobarbituric acid-hydantoin rearrangement.
A general synthesis protocol for the generation of tri- and tetrasubstituted 5-carbamoylhydantoins is described. Starting from barbituric acids and following bromination and reaction with primary amines, 5-aminobarbituric acids 3a-s and 8 were prepared. Compounds 3 and 8 were subjected to different conditions of a base-catalyzed rearrangement reaction to yield the 1,5,5-trisubstituted hydantoins 4a-s and the 1,3,5,5-tetrasubstituted hydantoin 5c, respectively. Alkylation of 4a-s afforded 1,3,5,5-tetrasubstituted hydantoins 5a-h. Mechanisms that explain the transformation of corresponding aminobarbituric acids to hydantoins 4a-s and 5c were discussed in terms of the formation of ring-opened intermediates. Aminobarbituric acids 3a-s unsubstituted at position 3 underwent a ring contraction via intermediate isocyanates which were trapped by the amino function. A different mechanism involving a carbamate intermediate was concluded for conversion of the 1,3,5,5-tetrasubstituted aminobarbituric acid 8.
Meusel
Manuela
M
Pharmaceutical Institute, Poppelsdorf, University of Bonn, D-53115 Bonn, Germany.
Ambrozak
Agnieszka
A
Hecker
Thomas K
TK
Gütschow
Michael
M
D000478:Alkylation; D000588:Amines / Q000138:chemical synthesis* / Q000737:chemistry*; D001463:Barbiturates / Q000138:chemical synthesis* / Q000737:chemistry*; D002855:Chromatography, Thin Layer; D020650:Combinatorial Chemistry Techniques; D003500:Cyclization; D006827:Hydantoins / Q000138:chemical synthesis* / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure
D000588:Amines; D001463:Barbiturates; D006827:Hydantoins; C032232:barbituric acid