US EPA

7419098 

Journal Article 

The aminobarbituric acid-hydantoin rearrangement 

Meusel, M; Ambrozak, A; Hecker, TK; Gütschow, M; , 

2003 

Yes 

Journal of Organic Chemistry
ISSN: 0022-3263
EISSN: 1520-6904 

AMER CHEMICAL SOC 

WASHINGTON 

68 

12 

4684-4692 

English 

12790571 

10.1021/jo020761f 

WOS:000183360000009 

https://pubs.acs.org/doi/10.1021/jo020761f
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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. 

Alkylation; Amines; Catalysis; Synthesis (chemical); Bromination; Organic acids; 1 benzyl 5 ethylcarbamoyl 5 methylhydantoin; 1 benzyl 5 methyl 5 methylcarbamoylhydantoin; 1 cyclohexyl 5 ethylcarbamoyl 5 methylhydantoin; 1 cyclohexyl 5 methyl 5 methylcarbamoylhydantoin; 1 ethyl 5 isopropylamino 5 methylbarbituric acid; 1 ethyl 5 methyl 5 propylaminobarbituric acid; 1 ethyl 5 phenyl 5 propylaminobarbituric acid; 1 isopropyl 5 methyl 5 methylcarbamoylhydantoin; 1 methyl 5 phenyl 5 propylaminobarbituric acid; 1,5 dimethy 5 isopropylaminobarbituric acid; 1,5 diphenyl 5 isopropylaminobarbituric acid; 1,5 diphenyl 5 propylaminobarbituric acid; 5 aminobarbituric acid derivative; 5 benzylamino 1 ethyl 5 methylbarbituric acid; 5 benzylamino 1 ethyl 5 phenylbarbituric acid; 5 benzylamino 1 methyl 5 phenylbarbituric acid; 5 benzylamino 1,5 dimethylbarbituric acid; 5 benzylamino 1,5 diphenylbarbituric acid; 5 benzylamino 5 methyl 1 phenylbarbituric acid; 5 benzylamino 5 phenyl 1 propylbarbituric acid; 5 carbamoylhydantoin; 5 cyclohexylamino 1 ethyl 5 methylbarbituric acid; 5 cyclohexylamino 1,5 dimethylbarbituric acid; 5 cyclohexylamino 5 methyl 1 phenylbarbituric acid; 5 ethylcarbamoyl 1 isopropyl 5 methylhydantoin; 5 ethylcarbamoyl 5 methyl 1 propylhydantoin; aminobarbituric acid; barbituric acid derivative; hydantoin; unclassified drug; unindexed drug; alkylation; article; bromination; carbon nuclear magnetic resonance; chemical reaction; chemical structure; proton nuclear magnetic resonance; reaction analysis; synthesis; Alkylation; Amines; Barbiturates; Chromatography, Thin Layer; Combinatorial Chemistry Techniques; Cyclization; Hydantoins; Magnetic Resonance Spectroscopy; Molecular Structure