The kinetics of hydrolysis at medium acid strength (pH interval 2-5) of a series of phenylsulfamate esters 1 have been studied and they have been found to react by an associative S(N)2(S) mechanism with water acting as a nucleophile attacking at sulfur, cleaving the S-O bond with simultaneous formation of a new S-O bond to the oxygen of a water molecule leading to sulfamic acid and phenol as products. In neutral to moderate alkaline solution (pH ≥ ~ 6-9) a dissociative (E1cB) route is followed that involves i) ionization of the amino group followed by ii) unimolecular expulsion of the leaving group from the ionized ester to give N-sulfonylamine [HN=SO(2)] as an intermediate. In more alkaline solution further ionization of the conjugate base of the ester occurs to give a dianionic species which expels the aryloxide leaving group to yield the novel N-sulfonylamine anion [(-)N=SO(2)]; in a final step, rapid attack of hydroxide ion or a water molecule on it leads again to sulfamic acid. A series of substituted benzyl 4-nitrophenylsulfamate esters 4 were hydrolysed in the pH range 6.4-14, giving rise to a Hammett relationship whose reaction constant is shown to be consistent with the E1cB mechanism.
Many compounds containing a sulfamate moiety, such as NH 2 SO 2 O-are now known to be medicinally important. However, very little is known about their mechanisms of reaction even under non-biological conditions. In this work the various types of elimination mechanisms that may occur have been probed by studying the kinetics of the reactions of model sulfamate substrates with amines (bases) that act as models for the enzymes involved. The principal mechanistic tool employed has been Brönsted plots and both 'normal' rectilinear and two types of biphasic plots have been found for the decomposition of the esters in acetonitrile (ACN). The mechanisms operating are seen as being of the E2 and E1cB types.
The kinetics of the reaction of 4-nitrophenyl sulfamate NH 2 SO 2 OC 6 H 4 NO 2 -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 Brönsted plots were biphasic for the aminolysis (with alicyclic amines) with an initial slope β 1 = 0.53 and a subsequent slope β 2 = 0.19. The change in slope occurs near the first pK a of 1a (17.9) in ACN. Leaving-group effects
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