Enhanced reactivity in the ammonolysis of phenyl thiolacetates in aqueous medium

Abstract

The ammonolysis of several substituted phenyl thiolacetates is kinetically studied in aqueous medium, 18 • C, ionic strength 0.1 M (KCl). By following the leaving groups spectrophotometrically (λ max = 260-410 nm), under excess free ammonia, pseudo-first-order rate coefficients (k obs ) are obtained. The plots of (k obs − k H ) against free ammonia concentration are linear at constant pH. The macroscopic nucleophilic substitution rate coefficients (k N ) are obtained as the slopes of these plots and found to be pH-independent for all the thiolesters. The Brönsted-type plot (log k N against pK a of leaving groups) and the Hammett plot (log k N against σ values of substituents) obtained for the title reactions of thiolesters are linear with slope values of β lg = −0.34 and ρ = 0.74 respectively. From the magnitude of these values, experimental data, the kinetic law, and the analysis of products, it is deduced that the ammonolysis of thiolesters proceeds through a simple bimolecular nucleophilic substitution pathway with a zwitterionic tetrahedral addition intermediate (T ± ), whereby its formation is rate-determining (k 1 step). Comparison of this reaction of thiolesters with a similar reaction of analogue oxyesters shows a mechanistic difference. Further, for thiolesters there is a rate enhancement with larger k N values. The change in mechanism and enhanced reactivity observed by substitution of the oxygen atom by sulphur atom on the phenyl moiety are discussed in detail.

Mechanistic change in the reactivity of substituted phenyl acetates over phenyl thiolacetates toward imidazole in aqueous phase

“…Thus in the imidazolysis of phenyl acetates with poor nucleofuges, the dissemination of various pathways leading to product is possible whereas for phenyl thiolacetates with poor nucleofuges for similar reaction k N and k ga were prominent with no kinetic significance of k gb 12. This observation is again in contradiction that the ammonolysis of phenyl thiolacetates in aqueous medium irrespective of the nature of the substituents proceeds only through the simple bimolecular nucleophilic substitution path with assisted paths as has been kinetically evident for analogue oxyesters 13.…”

“…Our earlier studies on the imidazolysis 12 and ammonolysis 13 of several substituted phenyl thiolacetates in aqueous phase showed contradictory results; the reactions of which for the former proceeding through a general‐acid assisted path ( k ga ), while the latter through simple bi‐molecular nucleophilic attack ( k N ) lacking any such assisted paths. Further, a comparison of ammonolysis of thiol esters with substituted phenyl acetates showed a mechanistic change with enhanced reactivity 13.…”

“…Our earlier studies on the imidazolysis 12 and ammonolysis 13 of several substituted phenyl thiolacetates in aqueous phase showed contradictory results; the reactions of which for the former proceeding through a general‐acid assisted path ( k ga ), while the latter through simple bi‐molecular nucleophilic attack ( k N ) lacking any such assisted paths. Further, a comparison of ammonolysis of thiol esters with substituted phenyl acetates showed a mechanistic change with enhanced reactivity 13. In a similar pattern, keeping in view of the catalytic cycle of the cysteine proteases—a large group of proteolytic enzymes containing cysteine thiol and histidine imidazole units at their active sites, which is known to proceed through acyl‐thiol intermediate 14–21, it is of special interest to investigate further and reevaluate the available data to shed light on the mechanism of imidazolysis of phenyl thiolacetates.…”

Nulceophilic Displacements at Carbonyl Compounds

“…Nadar et al [6] reported enhanced reactivity in the ammonolysis of phenyl thiolacetates in aqueous medium the ammonolysis of thiolesters proceeds through a simple bimolecular nucleophilic substitution pathway with a zwitterionic tetrahedral addition intermediate (T ± ), whereby its formation is rate-determining (k1 step). Comparison of this reaction of thiolesters with a similar reaction of analogue oxyesters shows a mechanistic difference.…”

“…Brønsted -type plot obtained in the ammonolysis of substituted phenyl thiolacetates in aqueous medium, 18 °C , ionic strength 0.1 M (KCl)[6].…”