Peer-Reviewed Journal Details
Mandatory Fields
Spillane, W.J.,O'Byrne, A.,McCaw, C.J.A.
2008
May
European Journal Of Organic Chemistry
Elimination mechanisms in the aminolysis of sulfamate esters of the type NH2SO2OC6H2X - Models of enzyme inhibitors
Published
()
Optional Fields
elimination enzyme models kinetics inhibitors STEROID SULFATASE INHIBITORS EVIDENCE CONSISTENT POTENT INHIBITORS E1CB MECHANISM HYDROLYSIS
24
4200
4205
The kinetics of the reaction of 4-nitrophenyl sulfamate NH2SO2OC6H4NO2-4 (1a) in acetonitrile (ACN) with a series of pyridines (pK(a) range ca. 8 units) and alicyclic amines (pK(a) range ca, 3.6 units) has been studied in the presence of excess amine at various temperatures. The compounds 1a-1f are important as model substrates for the medicinally important sulfamate esters 667-coumate and emate and analogues. Pseudo-first-order rate constants (k(obsd)) have been obtained mainly by the release of 4-nitrophenol/4-nitrophenoxide. Slopes of plots of k(obsd). vs. [amine] gave second-order rate constants (k(2)), and Bronsted plots were biphasic for the aminolysis (with alicyclic amines) with an initial slope beta(1) = 0.53 and a subsequent slope beta(2) = 0.19. The change in slope occurs near the first pK(a) of 1a (17.9) in ACN, Leaving-group effects were probed by using the same series of phenyl sulfamates, i.e. 1a-f and the alicyclic amines N-formylpiperazine and pyrrolidine. The reactions were considered to be dissociative in nature involving E2- and E1cB- type mechanisms with the phenyl sulfamate anion 2 being involved in pyridine and in the weaker alicyclic amines (beta(1) segment) and a phenyl sulfamate dianion 3 being involved with the stronger alicyclic bases (beta(2) segment). The calculation of Leffler indices (a) for bond-forming (base center dot center dot center dot H+) and bond-breaking (S-OAr) steps allows fuller interpretation of the mechanisms occurring, which are seen as having the N-sulfonylamines, HN=SO2 and -N=SO2 on the reaction pathways leading to products. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008).
1434193X
DOI 10.1002/ejoc.200800366
Grant Details
Publication Themes