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Steric and electronic substituent effects in hydrolysis and aminolysis of 4‐alkyl‐4‐methyl‐2‐aryl‐4,5‐dihydro‐1,3‐oxazol‐5‐ones
Author(s) -
Sedlák Miloš,
Keder Roman,
Skála Pavel,
Hanusek Jiří
Publication year - 2005
Publication title -
journal of physical organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.325
H-Index - 66
eISSN - 1099-1395
pISSN - 0894-3230
DOI - 10.1002/poc.928
Subject(s) - chemistry , aminolysis , substituent , medicinal chemistry , isopropyl , nucleophile , steric effects , aryl , alkyl , propylamine , electronic effect , alkoxy group , hydrolysis , protonation , stereochemistry , organic chemistry , amine gas treating , catalysis , ion
The kinetics and mechanism of the acid‐catalysed hydrolysis of substituted 4‐alkyl‐4‐methyl‐2‐aryl‐4,5‐dihydro‐1,3‐oxazol‐5‐ones to the corresponding 2‐alkyl‐2‐benzoylaminopropanoic acids were studied. The Taft correlation of rate constants of the acid‐catalysed hydrolysis with alkyl substitution at the 4‐position of the 1,3‐oxazol‐5‐one ring is non‐linear. In the Hammett correlation, the value of ρ decreases with increasing steric demand of the alkyl substituent. With the 4‐isopropyl and tert ‐butyl derivatives, ρ = − 0.63 and − 0.32, respectively. The protonated 4‐isopropyl and tert ‐butyl derivatives undergo nucleophilic attack by water at the carbonyl carbon atom at the 5‐position of the 1,3‐oxazol‐5‐one ring to the extents of ca 70% and 60%, respectively. Another reaction path consists in nucleophilic attack by water at the 2‐position of the 1,3‐oxazol‐5‐one ring. The reaction kinetics of aminolyses of substituted 4‐isopropyl‐4‐methyl‐2‐phenyl‐1,3‐oxazol‐5(4 H )‐ones ( 1a , 1b , 1f ) giving substituted N ‐{1,2‐dimethyl‐1‐[(propylamino)carbonyl]‐propyl}benzamides ( 3a , 3b , 3f , 4a ) was studied in aqueous propylamine buffers. In the case of the aminolysis of 1a and 1b with propylamine, the rate‐limiting step consists in the decomposition of the intermediate In ± catalysed by both the acidic and the basic buffer components. The base‐catalysed route is four times faster in both cases. In the case of the aminolysis of 1f with propylamine and that of 1a with ethylenediamine, the rate‐limiting step is the formation of the intermediate In ± , the subsequent reaction step being accelerated by substitution and/or intramolecular catalysis. Copyright © 2005 John Wiley & Sons, Ltd.