Imidazolidin-4-ones, hydrolysis

Butandisaure 2-Amino- -1-nitril E21a, 825 (l-Acyl-imidazolidin-4-one Hydrolysis)... 

Fig. 6.38. Imidazolidin-4-one derivatives of j Mel5 fenkephalin and their nonenzymatic hydrolysis to liberate the neuropeptide [202]...

Some cyclic AT-Mannich bases have also been reported, for example, the imidazolidin-4-ones (11.116) that were investigated as potential prodrugs of peptides (11.117) [141], The imidazolidin-4-ones, prepared by allowing the peptide to react with acetone under dehydrating conditions, are bases with pKa values of 3 - 4. For most of the derivatives, hydrolysis is spontaneous the protonated form (i.e., at pH < 2) reacts ca. 10 - 30 times slower than does the neutral form (pH > 6). Very large differences in reactivity were noted,... 

The imidazolidine-4-one 29, obtained by heating the methanol solution of an a-aminoamide and a 4-substituted benzaldehyde, is a mixture of two diastereomers which can be separated by chromatography. They are oxidized by MCPBA, separately or as a mixture, into the two diastereomeric l-hydroxyimidazolidine-4-ones 30. Hydrolysis of 30 by ethanolic HC1 and hydroxylamine hydrochloride gives the optically pure TV-hydroxyamino acid amide 31 (Scheme 9).[12]... 

Butansaure (S )-2-Amino-2-isopro-pyl-4-methylthio- E21a, 827 (1-Acyl-imidazolidine-2-one-Der.-Hydrolysis)... 

Removal of the mercapto (or thione) function is most commonly achieved using Raney nickel, although concentrated HCl at high temperatures or nickel boride have been employed. Thiohydantoins are transformed into imidazolidin-4-ones by sodium in amyl alcohol (70JHC439). Oxidative desulfurization procedures too are often used the reactions probably proceed through the unstable sulfinic acid species which very readily eliminates sulfur dioxide. The high resistance of sulfonic acids to acid hydrolysis renders unlikely the possibility that they are reaction intermediates. 

A sequence of hydrobenzamide-amarine-isoamarine (8) is one of the useful synthetic routes for C2-symmetric 1,2-diamines through cyclic amidines (Scheme 3.8). The reaction course is proposed as follows (i) formation of hydrobenzamide from benzaldehyde and ammonia, (ii) trimeric condensation to amarine, and (iii) isomerization to isoamarine (8) under basic condition [20] (path A). Corey and Kuhnle [21] proposed an alternative path for the reaction course (path B) based on characterization of each intermediate. This amidine is found to be rather stable to acid-catalysed hydrolysis. Thus, reduction of isoamarine (8) to imidazolidine with aluminum amalgam in wet tetrahydrofuran (THE) followed by acid hydrolysis yields the corresponding 1,2-diamine. 

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