Synthesis of 3‐Ω‐aminohydantoins

Abstract

Several 3-Ω-amino monosubstituted hydantoins have been obtained in the reaction of isocyanate of glycine ethyl ester with the appropriate aliphatic or aromatic diamine. It was found, that the 3-(aminoaryl) monosubstituted hydantoins may be diazotized and their diazonium salts may be coupled and hydrolysed without changes in the hydantoin ring. [6]. 3-Monosubstituted hydantoins with the free amine group with the substituent at the 3 position are even more scarce and their syntheses have low yield [7] or is protected by patents [8,9].Results and Discussion.In this paper 3-monosubstituted amino and dialkylamino alkyl and aryl hydantoins were synthesized according to the known method [10] and its applications [11]. It involves the reaction between the appropriate diamine and the isocyanate of glycine ethyl ester (Scheme 1). The reaction was carried out at room temperature or alternatively at 0°C. Chloroform or anhydrous ethanol was used as solvents due to the solubility of the substrates. After the reaction, the unisolated intermediate, i.e., a derivative of ethyl ester of hydantoic acid, was cyclised under acidic (HCl) conditions to the appropriate hydantoin in water-e t h a n o l solution. The raw product obtained was purified as a hydrochloride or, after transformation, as a free base. For the synthesis of derivatives with a free amino group a monoacetyl derivative of the diamine was used as substrate. It was found that when a monoalkyldiamine, i . e. N-methyl-1,3-propanediamine, was used the reaction did not follow the proposed scheme (Scheme 1). Immediately after mixing of reagents a mixture of various products was obtained, evidenced by monitoring the reaction in CDCl 3 solution by 1 H NMR spectroscopy. After careful evaporation of the solvent and drying under reduced pressure at 40°C the intermediate was hydrolysed in HCl medium. A mixture of different products was obtained and among them c a. 10% of N-methyl-1,3-propanediamine hydrochloride, the presence of which (confirmed by 1 H NMR, 13 C NMR and MS) may mean that during the mentioned reaction a partial amidation of the ester group of the isocyanate occured. To obtain the indole derivative of 3-monosubstituted hydantoin, 5-aminoindole and isocyanate of glycine ethyl ester were used (Scheme 1). The indole derivative of the ester of hydantoic acid 9 w a s obtained with satisfactory yield but attempts to cyclise it to the hydantoin derivative proved unsuccessful although HCl, CH 3 COOH and heating without a solvent were tried. In each case the final result was a mixture of diff e r e n t , unidentified substances.One of the major aims of this work was to determine whether the free amine group in the 3-monoaminoaryl substituent reacts without simultaneous changes in the hydantoin ring. The reactions were carried out with 3-(4'-aminophenyl)hydantoin 8, which was transformed in the non-isolated diazonium salt (8a) (Scheme 2) at 0 °C without a change of the NH group of the hydantoin ring in the nitroso group [12]. This salt was remarkably stable and could be heat...

Synthesis of 3‐Ω‐amino‐2‐thiohydantoins

“…1%) in comparison to analogous reaction of the hydantoin derivative [17] (ca 45%). The coupling reaction of 16a with 2-naphthol was run in alkaline solution and yielded azo dye 17 with indicator properties.…”

Acyclic and Cyclic Ureas (Update 2013)

“…[236][237][238][239][240] In addition, modifications have been developed involving the intramolecular reaction between a carbonyl group and a urea moiety to give rise to a 5-hydroxyhydantoin, [241] the cyclization of N-terminal amino acids in peptides to produce 2-iminohydantoins, [242] or the replacement of the ester group by a nitrile group. [243] Scheme 87 Hydantoin Synthesis from a-Amino Acid Esters and Isocyanates [236][237][238][239][240] Cyclization of carbamate-protected a-amino acid amides yields hydantoins, as shown in Scheme 88. This reaction can be conveniently mediated by a weakly basic aqueous solution (NaHCO 3 ) if a (4-nitrophenoxy)carbonyl group is used for the protection of the amino group.…”

Synthesis of 3‐Ω‐Amino‐2‐thiohydantoins.

“…Compound 1 6 a was hydrolyzed to 3-(4-hydroxyphenyl)-2-thiohydantoin 14 (identical with that obtained by synthesis) but in very low yield (ca. 1%) in comparison to analogous reaction of the hydantoin derivative [17] (ca 45%). The coupling reaction of 16a with 2-naphthol was run in alkaline solution and yielded azo dye 17 with indicator properties.…”