Thiohydantoins. XI Kinetic Studies of the Alkaline Hydrolysis of 1-Acyl-2-thiohydantoins

Abstract

1-Acyl-2-thiohydantoins ionize in alkaline solution (pK -7). In solutions more alkaline than p H > 11 they are rapidly hydrolyzed to 2-thiohydantoin and a carboxylic acid, by attack of a hydroxide ion on the conjugate base of the 1-acyl-2-thiohydantoin. Possible mechanisms to accord with the entropy of activation, which is less negative than usual for base-catalyzed amide hydrolyses, are discussed. 1-Benzoyl-2-thiohydantoin hydrolyzes more rapidly than 1-acetyl-2-thiohydantoin, possibly because the ground state of the former molecule is destabilized by steric effects.Les acyl-1 thiohydantoi'nes-2 s'ionisent en milieu alcalin (pK -7). En milieu plus alcalin (pH z 11 ) ils s'hydrolisent rapidement aux acides carboxyliques et a thiohydantoi'ne-2, par I'attaque de I'ion hydroxide a la base conjuguee de I'acyl-1 thiohydantoi'ne-2. On riflechit sur les mtcanismes qui peuvent Ctre en accord avec I'entropie de I'activation, qui est moins negative que les entropies de I'activation pour les amides plus ordinaires. Le benzoyl-l thiohydantoi'ne-2 s'hydrolyse plus vite que I'acetyl-1 thiohydantotne-2, peut-etre parce que le premier est destabilise par les effets sttriques.

Determination of Acid Dissociation Constants (pKa) of Bicyclic Thiohydantoin-Pyrrolidine Compounds in 20% Ethanol-Water Hydroorganic Solvent

“…It is assumed that high affinity causes the protonation of the sulfur and oxygen atoms on ligand and increases the mobility of its π -electrons. Consequently, sulfur and oxygen atoms of thiohydantoin begin to be hydrolyzed at appreciable rates in the solutions more alkaline than pH 9 [ 30 , 31 ].…”