87962-89-8Relevant academic research and scientific papers
Kinetics and mechanism of formation and decomposition of substituted 1-phenylpyrrolidin-2-ones in basic medium
Sedlak, Milos,Hejtmankova, Ludmila,Kasparova, Pavla,Kavalek, Jaromir
, p. 165 - 173 (2007/10/03)
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 1-1, 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 1-1], 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 1 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
Kinetics and Equilibria of Ring Closure through an Amide Linkage. Part 2. 1-Aryl-2-pyrrolidones
Abdallah, Jassim M.,Moodie, Roy B.
, p. 1243 - 1250 (2007/10/02)
Equilibrium constants, and rate constants for forward and reverse reactions, for ring closure of several 4-(arylamino)butanoic acids to 1-aryl-2-pyrrolidones in aqueous acid, together with ionisation constants of the former group of compounds, are reported.The equilibrium constants K at 50 deg C between neutral protonic forms of open-chain and ring compounds are related to the ionisation constants of the nitrogen-protonated 4-(arylamino)butanoic acids, K1, by the equation: log K=0.70 (pK1)+1.53.The value of K for pyrrolidone itself was measured for comparison.Studies of 18O exchange reveal that (except in the case of the substrate which bears the most electron-withdrawing substituents in the aryl ring, namely 2,4-dinitro) the rate-determining step lies between the tetrahedral intermediate and the ring compound.Substituent effects and solvent deuterium isotope effects on the hydronium-ion catalysed reaction are consisitent with a transition state close to the neutral tetrahedral intermediate.The effects of methyl substituents in the heterocyclic ring on rate and equilibrium constants have also been studied.The variation of K with temperature, and derived thermodynamic parameters, are reported in two cases.
