A study of chemical behaviour of substituted 4‐chloro‐N‐phenylbutanamides in aqueous solutions of sodium hydroxide showed that the substrate first undergoes ring closure to give substituted 1‐phenylpyrrolidin‐2‐ones, which are subsequently hydrolysed to substitution derivatives of sodium 4‐amino‐N‐phenylbutanoates. Kinetic measurements provided the values of dissociation constants pKa and cyclization rate constants kc in water at 25 °C for 2‐bromo‐4‐chloro‐N‐(4‐nitrophenyl)butanamide [pKa = 11.64 ± 0.01; kc = (1.94 ± 0.03) × 10−2 s−1], 4‐chloro‐N‐(4‐nitrophenyl)butanamide [pKa = 13.35 ± 0.02; kc = (1.60 ± 0.02) × 10−2 s−1] and 4‐chloro‐2‐methyl‐N‐(4‐nitrophenyl)butanamide [pKa = 13.55 ± 0.03; kc = (7.61 ± 0.11) × 10−2 s−1]. The pKa and kc values of individual derivatives differ depending on the substitution at the α‐position of the butanamide skeleton. In methanolic sodium methoxide solutions, the course of ring closure of 2‐bromo‐4‐chloro‐N‐(4‐nitrophenyl)butanamide is of similar nature but slower [K = 60.10 ± 0.08 and kc = (6.52 ± 0.05) × 10−3 s−1]. The subsequent hydrolyses of substituted 1‐phenylpyrrolidin‐2‐ones to substituted 4‐aminobutanoic acids also have different courses with different derivatives and depend on the substituents in the aromatic and/or heterocyclic moiety. The rate‐limiting step of hydrolysis of 1‐(4‐nitrophenyl)pyrrolidin‐2‐one consists of the non‐catalysed decomposition of the tetrahedral intermediate. In the case of 3‐bromo‐1‐(4‐nitrophenyl)pyrrolidin‐2‐one at sodium hydroxide concentrations below 0.1 mol l−1, the rate‐limiting step is the second reaction pathway, i.e. the hydroxide ion‐catalysed decomposition of the tetrahedral intermediate. At sodium hydroxide concentrations above 0.1 mol l−1, the rate‐limiting step shifts to formation of the tetrahedral intermediate. This formation of the intermediate is 140 times slower than its hydroxide ion‐catalysed decomposition [k3/k−1 = (1.40 ± 0.04) × 102 l mol−1]. Introduction of a 3‐bromo substituent into 1‐(4‐nitrophenyl)pyrrolidin‐2‐one results in acceleration of all the reaction steps of hydrolysis and increases the acidity of the intermediate. Copyright © 2002 John Wiley & Sons, Ltd.
