5-Ureido hydantoin

Hydrolysis. Although hydantoins can be hydroly2ed under strongly acidic conditions, the most common method consists of heating ia an alkaline medium to give iatermediate ureido acids (the so-called hydantoic acids), which are finally hydroly2ed to a-amino acids. 

This subsection examines the hydrolytic stability of cyclic structures containing a ureido link. Schematically, ring closure can be achieved by N-alkylation or by /V-acylation of the second N-atom of the ureido moiety. The former results in the formation of, e.g., hydantoins and dihydropyrimidines. The latter ring closure leads to, e.g., barbituric acids. Taken together, cyclic ureides can also be regarded as ring structures that contain an imido function with an adjacent N-atom. We begin our discussion with the five-membered hydantoins, to continue with six-membered structures, namely dihydropyrimidines, barbituric acids, and xanthines. 

N -lsopropyl-Ureido] -Acetic Acid Azide (5-Iso-propyl-hydantoin acid azide). (CH3)2CH.NH.CO.NH.CH2.CO.N3 mw 185.22 N 37.82% OB to CO2 -133.89% mp ca 100° (deflagrates quickly when heated). Prepn is by reacting [N-isopropyl-ureido] -acetic acid-hydra-zide with Na nitrite dissolved in aq HCl Ref Beil 4, 1169 ... 

N3-Substituted hydantoins and 2-thiohydantoins (9) are prepared by acid-catalyzed cyclization of the substituted ureido or thioureido acids (8) obtained from a reaction of a-amino acids with alkyl or aryl isocyanates and isothiocyanates.1 3,12 This method has been applied to prepare 2-selenohy-dantoins,13 and also in the stereospecific synthesis of (S)-(+)-l,5-cyclotrimethylene-3-phenyl-2-thiohydantoin.14... 

A similar strategy has been used in the hydrolysis of hydantoins with pendant ureido groups, using the bacterial culture Agrobacterium radiobacterl55 ... 

Treatment of the ureide 129 or its 4-methyl derivative with diazomethane results in the formation of the monomethylated, and then the dimethylated spirohydantoin 131. This also demonstrates the ease of cyclization of these ureido derivatives. Similar reactions occur with 1,2-dihydro-2-oxo-3-ureidopyrido[2,3-h]pyrazine. If the methylated hydantoin 131 is treated with nitrous acid, the 1-nitroso compound 132 is formed. On alkaline hydrolysis this yields the 2-methylamino compound 133. The corresponding reactions with the 2-oxo isomer of 131 failed as... 

An unexpected feature of the chemistry of the above ureido ester analogues was the apparent ease with which they underwent at least partial racemization at the a-carbon during alkaline hydrolysis to ureido acids. Support for the conclusion that racemization was taking place came from a combination of direct polarometric measurements on the ureido diacids (low rotation in comparison with MTX and folic acid) and indirect evidence that hydrolysis was proceeding via a hydantoin intermediate. Thus, when the ester (VI.9) was heated in MeOH or CHCI3 in the presence of the strong organic base l,5-diazabicyclo[3.4.0]non-5-ene, a product formed in 61% yield which was tentatively identified as (VI.15). Alkaline hydrolysis of (VI.15) yielded (VI.8). 

---