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Elimination Mechanisms in the Aminolysis of Sulfamate Esters of the Type NH 2 SO 2 OC 6 H 4 X – Models of Enzyme Inhibitors
Author(s) -
Spillane William J.,
O'Byrne Andrew,
McCaw Cheryl J. A.
Publication year - 2008
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200800366
Subject(s) - alicyclic compound , aminolysis , chemistry , amine gas treating , pyridine , reaction rate constant , medicinal chemistry , acetonitrile , piperidine , base (topology) , stereochemistry , kinetics , organic chemistry , catalysis , mathematical analysis , physics , mathematics , quantum mechanics
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 (p K a range ca. 8 units) and alicyclic amines (p K 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 p K 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 ( β 1 segment) and a phenyl sulfamate dianion 3 being involved with the stronger alicyclic bases ( β 2 segment). The calculation of Leffler indices ( α ) for bond‐forming (base ··· H + ) and bond‐breaking (S–OAr) steps allows fuller interpretation of the mechanisms occurring, which are seen as having the N ‐sulfonylamines, HN=SO 2 and – N=SO 2 on the reaction pathways leading to products. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)