Hydantoins with electrophiles

Hydantoins can react with electrophiles at both nitrogen atoms and at C-5. The electrophilic carbonyl groups can be attacked by nucleophiles, leading to hydrolysis of the ring or to partial or total reduction of the carbonyl system. Other reactions are possible, including photochemical cleavage of the ring. 

The imide proton N-3—H is more acidic than N-1—H and hence this position is more reactive toward electrophiles in a basic medium. Thus hydantoins can be selectively monoalkylated at N-3 by treatment with alkyl haUdes in the presence of alkoxides (2,4). The mono-A/-substituted derivatives (5) can be alkylated at N-1 under harsher conditions, involving the use of sodium hydride in dimethylform amide (35) to yield derivatives (6). Preparation of N-1 monoalkylated derivatives requires previous protection of the imide nitrogen as an aminomethyl derivative (36). Hydantoins with an increased acidity at N-1—H, such as 5-arylmethylene derivatives, can be easily monoalkylated at N-3, but dialkylation is also possible under mild conditions. 

The amino acid ester forms the hydantoin 33 with the isocyanate 41. The free amine 32 attacks the isocyanate carbon and the nucleophilic isocyanate nitrogen in 42 then reacts with the electrophilic ester moiety. The carbonate base prevents protonation of the amine. 

As would be expected, hydantoins and thiohydantoins can react with nucleophilic and electrophilic as well as with other types of reagents. 

Lithium phosphanylidene carbenoid can react with a number of electrophiles, and an example is described in Scheme 14. The -configured phos-phanyhdene carbenoid -la was allowed to react with phenyl isocyanate to afford the corresponding amide -26 but the yield was low. The major product was a hydantoin compound possessing an exo P=C bond ( -34). Compound -34 isomerized to an ElZ mixture by irradiation or heating, and Z-34 was analyzed by X-ray crystallography to establish the hydantoin skeleton [11,34]. 

The electrophilic bromination of alkenes, for example, with l,3-dibromo-5,5-dimethyl-hydantoin in the presence ofconcentrated hydrogen peroxide, leads to P-bromo hydroperoxides. These are cyclized with bases or with silver acetate to give 1,2-dioxetanes, for... 

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