Novel change in rate-determining step within an E1cB mechanism during aminolysis of a sulfamate ester in acetonitrile

Article abstract of DOI:10.1039/a801505h

The observation of biphasic Bronsted plots (β₁ ca. 0.7 and β₂ ca. 0) in the aminolysis (alicyclic amines, pyridines) of 4-nitrophenyl N-benzylsulfamate 1a in MeCN is interpreted as being due to a mechanistic change from (ElcB)_ir

Full text of DOI:10.1039/a801505h

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Novel change in rate-determining step within an E1cB mechanism during
aminolysis of a sulfamate ester in acetonitrile
William J. Spillane,*† Paul McGrath, Chris Brack and Keith Barry (in part)
Chemistry Department, National University of Ireland, Galway, Ireland
The observation of biphasic Brønsted plots (b1 ca. 0.7 and b2
ca. 0) in the aminolysis (alicyclic amines, pyridines) of
4-nitrophenyl N-benzylsulfamate 1a in MeCN is interpreted
as being due to a mechanistic change from (ElcB)irrev to
(ElcB)rev; the change in rate-determining step occurs at
approximately the pKa of 1a and other more basic substrates
give straight line plots; an entropy study supports the change
from a bimolecular to a unimolecular mechanism.
Further support for this mechanistic change comes from an
activation study using morpholine, 1-(2-aminoethyl)piperazine
and piperazine [Fig. 1(a)] and DMAP and 4-pyrrolylpyridine
[Fig. 1(b)] with the ester 1a in MeCN. The observed entropy
changes (DS±, J K21 mol21) are (temperature range in
parenthesis): morpholine 2262 (17–47 °C), 1-(2-amino-
ethyl)piperazine 259 (17–47 °C), piperazine 211 (17–47 °C),
DMAP 2124 (15–43 °C) and 4-pyrrolylpyridine 232
(15–46 °C). These entropy changes support the onset of a
unimolecular (ElcB)rev mechanism as the basicity of the
catalytic amine is increased, and with piperazine and 4-pyrro-
lylpyridine the reaction should proceed substantially via this
mechanism. Typical values of DS± for the (ElcB)rev mechanism
lie5 in the range of ca. +150 to 2 40 J K21 mol21 and these
authors also report much more negative entropies (255 to 2170
J K21 mol21) for studies on related substrates undergoing
BAC2, SN2 and E2 mechanisms. DS± values of 2163 to 2130
J K21 mol21 have been reported for the (ElcB)irrev mecha-
nism.6
Recently in our laboratory we have been studying the
elimination-addition reactions of sulfamoyl chlorides with
anilines1 and of sulfamate esters with a series of amines2
(pyridines, alicyclic amines and quinuclidines) in CHCl3 and
MeCN. The mechanism was seen as being E2 with ElcB-like
character. UV kinetics fitted the rate law kRR NH[RRANH]-
A
[ester], and good straight line Brønsted type plots were obtained
in this work. In particular, the aminolysis of the 4-nitrophenyl
N-benzyl ester 1a in CHCl3 at 37 °C gave straight line Brønsted
plots.2 However, we have now found that this ester in MeCN at
37 °C gives curved plots with similar series of amines (Fig. 1).
These plots are essentially biphasic with slopes b1 ca. 0.7 at
lower pKas and b2 ca. 0 at higher pKas and are best interpreted
in terms of a mechanistic change within the ElcB mechanism
from (ElcB)irrev (amines of lower pKa) to (ElcB)rev (amines of
higher pKa). The change from general to specific base catalysis
expected for such a mechanistic change3 is clearly evident in
Fig. 1. The situation may be represented by Scheme 1. At lower
amine pKas the rate-determining step is the bimolecular
formation of the conjugate base of the substrate 2 and the second
step is relatively rapid departure of the leaving groups and
formation of products p-nitrophenol and sulfamide
When the substrate was 1b using the same set of alicyclic
amines in MeCN, surprisingly a straight line Brønsted plot was
obtained (b = 0.19) [Fig. 2(b)]. Again with a slightly less basic
ester 1c no curvature was seen in the Brønsted plot (b = 0.35)
using a set of pyridine bases [Fig. 2(a)]. The reason for
this behaviour became apparent when we measured7 and
calculated8 pKas in MeCN for the esters 1. The values obtained
(calculated in parenthesis) were: 1a 17.68 ± 0.5 ( ~ 16.5 ± 0.5),9
1b 19.1 ± 0.1 (19.5 ± 0.5) and 1c 18.56 ± 0.3 ( ~ 18.87 ± 0.5).9
The ester 1a showed curvature because the catalytic bases used
are sufficiently strong to remove the substrate proton, the k1 step
becomes unimportant kinetically and k2 dominates giving the
observed (ElcB)rev mechanism. A referee has pointed out that
the plots in Fig.1 are analogous to classical Eigen plots, and in
keeping with this the changeover in rate-determining step
occurs at about the pKa of 1a, i.e. DpK = 0; in the case of the
other two esters studied the available amines are all less basic
than the substrate, and the NH proton is not extensively
removed and a change in rate determining step is therefore not
observed with these esters.
+
(k2 > > k21[RRANH2 ]). The reaction path from 2 to products
may involve an N-sulfonylamine (BnNNSO2)1,2,4
(b)
0.0
–0.5
–1.0
–1.5
–2.0
–1.0
–1.5
–2.0
–2.5
–3.0
–3.5
(a)
k1
k –1
–
+
ArNHSO2ONp
+
RR′NH
ArNSO2ONp
+
RR′NH2
1
2
k
k
k2
ArNHSO2NRR′
+
HONp
–2.5
a Ar = Bn
b Ar = Ph
c Ar = 2-MeO-5-MeC6H3
d Ar = H
14
15
16
17
pK
18
19
20
a
Fig. 1 Biphasic Brønsted plots for the aminolysis of 1a in MeCN 37 °C: (a)
alicyclic amines from left to right: morpholine, 1-formylpiperazine,
1-(2-hydroxyethyl)piperazine, 1-(2-aminoethyl)piperazine and piperazine;
(b) pyridines from left to right: 2-aminopyridine, 2-amino-4-methylpyr-
idine, 4-aminopyridine, DMAP and 4-pyrrolylpyridine
Np =
NO2
Scheme 1
Chem. Commun., 1998
1017

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Notes and References
–2.0
–2.5
† E-mail: William.Spillane@UCG.ie
1 W. J. Spillane, F. A. McHugh and P. O. Burke, J. Chem. Soc., Perkin
Trans. 2, 1998, 13.
(a)
2 W. J. Spillane, G. Hogan, P. McGrath, J. King and C. Brack, J. Chem.
Soc., Perkin Trans. 2, 1996, 2099.
3 A. F. Cockerill and R. G. Harrison, Mechanisms of elimination and
addition reactions involving the X = Y groups, in Chemistry of double-
bonded functional groups, ed. S. Patai, Part 1, Supplement A, Wiley,
London, 1977.
(b)
–3.0
–3.5
–4.0
k
4 A. Williams and K. T. Douglas, J. Chem. Soc., Perkin Trans. 2, 1974,
1727.
5 A. Vigroux, M. Bergon, C. Bergonzi and P. Tisnes, J. Am. Chem. Soc.,
1994, 116, 11787 and earlier papers; M. Mowafak Al Sabbagh,
M. Calman and J.-P. Calman, J. Chem. Soc., Perkin Trans. 2, 1984,
1233 and earlier papers; G. Cevasco and S. Thea, J. Org. Chem., 1995,
60, 70 and earlier papers; F. Nome, W. Erbs and V. R. Correia, J. Org.
Chem., 1981, 46, 3802; T. J. Broxton, Aust. J. Chem., 1985, 38, 77;
K. T. Leffek and G. Schroeder, Can. J. Chem., 1982, 60, 3077.
6 A. Jarczewski and G. Schroeder, Polish J. Chem., 1978, 52, 1985.
7 B. R. Cho, S. J. Lee and Y. K. Kim, J. Org. Chem., 1995, 60, 2072. The
method described was employed to measure the pKas of some of the
amines used and was adapted to measure the substrate pKas.
8 Using the Advanced Chemistry Development (ACD) Inc., Canada, pKa
program, which calculates pKa in water, 8.0 was added to the values
obtained since this was the approximate difference between calculated
(for H2O) and experimental values (in MeCN) for the various series of
amines studied.
9 These are approximate values since the calculations had to be performed
without the p-nitro group. The program cannot calculate pKa for
compounds with > 20 atoms other than hydrogen.
10 C. Reichardt, in Solvents and Solvent Effects in Organic Chemistry, 2nd
edn., VCH, Weinheim, 1988, section 4.2.
11 J. C. Fishbein and W. P. Jencks, J. Am. Chem. Soc., 1988, 110, 5075 and
earlier papers.
12 C. K. M. Heo and J. W. Bunting, J. Org. Chem., 1992, 57, 3570 and
earlier papers.
14
15
16
17
pK
18
19
20
a
Fig. 2 Brønsted plots for the aminolysis of sulfamate esters in MeCN at
37 °C: (a) pyridines from left to right: 2-aminopyridine, 2,4,6-trimethylpyr-
idine, 2-amino-4-methylpyridine, 4-aminopyridine, DMAP and
4-pyrrolylpyridine using 1c; (b) alicyclic amines from left to right:
morpholine,
thiomorpholine,
1-(2-hydroxyethyl)piperazine,
1-(2-aminoethyl)piperazine and piperazine using 1b
In CHCl3 we have never observed curvature in Brønsted plots
with 1a, 1b or with 4-nitrophenylsulfamate 1d and various
series of amines. This may be due to a more substantial
difference in basicity between the substrates and the catalytic
amines in this medium compared to MeCN. This view can be at
least qualitatively supported by considering the Gibbs energy
differences (DDG) for the ionization of the substrates and the
+
conjugate bases RRANH2 in solvents of differing relative
permittivity.10
Change in rate-determining step within an ElcB reaction path
involving carbanions has been demonstrated by a number of
groups.11–15 However such a change involving nitrogen acids
has not been clearly demonstrated previously; Caplow16 has
obtained a very similar plot (b1 ca. 0.77 and b2 ca. 0) to those
in Fig.1 for the decomposition of carbamates in water in the
presence of various amines, but has interpreted it differently.
Hence the present work is the first clear-cut example of this
ElcB mechanistic change not involving a carbon acid.
13 S. Thea, N. Kashefi-Naini and A. Williams, J. Chem. Soc., Perkin
Trans. 2, 1981, 65 and earlier papers.
14 J. F. King and R. P. Beatson, Tetrahedron Lett., 1975, 973.
15 J. L. Kice and L. Weclas, J. Org. Chem., 1985, 50, 32.
16 M. Caplow, J. Am. Chem. Soc., 1968, 90, 6795.
Received in Cambridge, UK, 23 February 1998; 8/01505H
1018
Chem. Commun., 1998