In an alternative method, condensation of semicarbazide hydrochloride (I) with cyclohexanone (II) yields the semicarbazone (III). Subsequent reaction of (III) with ethyl chloroacetate (IV) in the presence of NaOMe gives rise to the cyclohexylidene aminohydantoin (V). Treatment of (V) with 5-(p-nitrophenyl)furfural (VI) under acidic conditions affords the furfurylidene aminohydantoin (VII). This is finally converted into the corresponding sodium salt employing methanolic NaOMe (3).
The title compound has also been obtained by solid phase synthesis. Bromoacetic acid (I) is coupled to hydroxymethyl polystyrene resin by means of DIC/DMAP to produce the bromoacetyl resin (II). Bromide displacement with tert-butyl carbazate (III) leads to the N-Boc hydrazino ester (IV), which is further deprotected to (V) employing trifluoroacetic acid. The hydrazinoacetic acid-bound resin (V) is then condensed with 5-(p-nitrophenyl)furfural (VI) to furnish hydrazone (VII). Acylation of resin (VII) with p-nitrophenyl chloroformate (VIII) produces the p-nitrophenyl carbamate (IX), which upon treatment with ammonia gives rise to the semicarbazone (X). Finally, concomitant intramolecular ring closure and resin cleavage of (X) produces the target aminohydantoin derivative (XI) (4, 5).
Diazotization of 4-nitroaniline (I), followed by copper-catalyzed coupling of the resultant diazonium salt (II) with 2-furaldehyde (III) leads to 5-(p-nitrophenyl)-2-furancarboxaldehyde (IV) (1). Cyclization of semicarbazideacetic acid (V) by heating in aqueous sulfuric acid leads to 1-aminohydantoin (VI) (2). This is then condensed with aldehyde (IV) to furnish the furfurylidene aminohydantoin (VII) (1, 2). Treatment of (VII) with sodium methoxide gives rise to the corresponding sodium salt (1).