Patent GB-844277-A (GB)
Title: Improvements in or relating to the preparation of hydantoins
IPC: C07D233/72
Filed: 1958-09-11
Abstract: Hydantoins are prepared by reacting a hydrazone, as hereinafter defined, with ammonium, carbonate and cyanide ions in solution in an inert polar liquid solvent.  The hydrazones utilisable are those in which the second nitrogen bears one hydrogen atom and one substituent R which is attached to the nitrogen atom by carbon and is unchanged under the reaction conditions though it appears not in the hyantoin product but in the also formed hydrazino compound R.NH.NH2, such as a carbamyl, thiocarbamyl, oxamyl, lower acyl or alkyl, aralkyl or aryl hydrocarbon radical.  The hydrazone reagents are preferably aldehyde or ketone alkyl hydrazones, aryl hydrazones, semicarbazones and thio semi carbazones derived from aldehydes and ketones R1R11CO wherein R1 and R11 may represent hydrogen, hydrocarbon radicals, substituted hydrocarbon radicals containing hydrolytically stable halogen, oxygen, nitrogen or sulphur substituents such as lower alkoxy or acyl or hydroxyl groups, and hetero cyclic groups containing a single oxygen, nitrogen or sulphur atom, or R1 and R11 together with the shared alkylidene carbon may form a 5 or 6-membered carbocyclic ring. The term "lower" denotes a carbon content of up to 4.  The polar solvent may be water or a lower alcohol.  The necessary ions may be supplied as ammonium carbonate or carbon dioxide and ammonia or another ammonium salt and hydrogen cyanide or a metal cyanide.  Solid carbon dioxide may be added.  The yields are increased by operating in the presence of a small amount of sodium or other bisulphite and by including oxygen.  Temperatures of from 40 DEG -220 DEG C. are utilisable.  The resulting hydantoins may be hydrolysed to amino-acids.  In Examples: (1) n-butyraldehyde semicarbazone, ammonium carbonate, HCN and water are heated in an autoclave at 100 DEG C. yielding 5-n-propyl hydantoin; (2) 3-indole acetaldehyde semicarbazone is similarly reacted to yield 5-(3-indolyl methyl)-hydantoin; (3) a mixture of benzaldehyde semi carbazone, ammonium carbonate, HCN, sodium hydrogen sulphite and aqueous methanol similarly heated yields 5-phenyl hydantoin isolated as its monohydrate; (4) cyclo pentanone thio semi carbazone treated similarly yields spiro (cyclo pentane-1:51-hydantoin); (5) n-butyraldehyde phenyl hydrazone reacted as in (3) yields 5-n-propyl hydantoin; (6) 3-indole acetaldehyde phenyl hydrazone is similarly reacted; (7) 1-acetyl-3-indole acetaldehyde phenyl hydrazone is reacted as in (3) or (8) as in (1) yielding 5-(3-indolyl methyl)-hydantoin. Reference is also made to the similar reactions of semi-carbazones of n-propionaldehyde, acetone, methyl ethyl ketone, 3-indolealdehyde, furfural, aceto phenone and cyclohexanone, and of butyraldehyde phenyl hydrazone, benzaldehyde propyl hydrazone, benzaldehyde acetyl hydrazone and indole acetaldehyde semi oxamizide. The hydantoin obtained in (2) above is heated with aqueous NaOH under pressure to give DL-trytophan.  In similar manner, the semicarbazones of formaldehyde, acetaldehyde, 2-hydroxy propion aldehyde (as the acetic ester), iso-valeraldehyde, 2-methyl butyraldehyde, valeraldehyde, iso-butyraldehyde, a -tolualdehyde, p-hydroxy-a -tolualdehyde, 2-hydroxy acetaldehyde, 3-methyl mercapto propionaldehyde, 4-amino butyraldehyde and 5-amino valeraldehyde are converted into the corresponding hydantoins and then hydrolysed to amino acids.  n-Butyraldehyde semi carbazone is prepared by heating butyro nitrile, semicarbazide hydrochloride, sodium acetate, Raney nickel catalyst and water under hydrogen in an autoclave. 3-indole acetaldehyde phenyl hydrazone is prepared from the aldehyde and phenyl hydrazine; the 1-acetyl derivative is similarly prepared.