Change in rate-determining step in an E1cB mechanism during aminolysis of sulfamate esters in acetonitrile

Article abstract of DOI:10.1021/jo015691b

The kinetics of the reactions of the nitrogen-sulfur(VI) esters 4-nitrophenyl N-methylsulfamate (NPMS) with a series of pyridines and a series of alicyclic amines and of 4-nitrophenyl N-benzylsulfamate (NPBS) with pyridines, alicyclic amines, and a series of quinuclidines have been investigated in acetonitrile (ACN) in the presence of excess amine at various temperatures. Pseudo-first-order rate constants (k_obsd) have been obtained by monitoring the release of 4-nitrophenol/4-nitrophenoxide. From the slope of a plot of k_obsd vs [amine], second-order rate constants (k′₂) have been obtained for the pyridinolysis of NPMS, and a Bronsted plot of log k′₂ vs pK_a of pyridine gave a straight line with β = 0.45. However, aminolysis with alicyclic amines of NPMS gave a biphasic Bronsted plot (β₁ = 0.6, β₂ ? 0). Pyridinolysis and aminolysis with alicyclic amines and quinuclidines of NPBS also gave similar biphasic Bronsted plots. This biphasic behavior has been explained in terms of a mechanistic change within the E1cB mechanism from an (E1cB)_irrev (less basic amines) to an (E1cB)_rev (more basic amines), and the change occurs at approximately the pK_a's (in ACN) of NPMS (17.94) and NPBS (17.68). The straight line Bronsted plot for NPMS with pyridines occurs because the later bases are not strong enough to substantially remove the substrate proton and initiate the mechanistic change observed in the reaction of NPMS with the strong alicyclic amines and quinuclidines. An entropy study supports the change from a bimolecular to a unimolecular mechanism. This is the first clear demonstration of this E1cB mechanistic changeover involving a nitrogen acid substrate.

Full text of DOI:10.1021/jo015691b

J . Org. Chem. 2001, 66, 6313-6316
6313
Ch a n ge in Ra te-Deter m in in g Step in a n E1cB Mech a n ism d u r in g
Am in olysis of Su lfa m a te Ester s in Aceton itr ile
William J . Spillane,* Paul McGrath, Chris Brack, and Andrew B. O’Byrne
Chemistry Department, National University of Ireland, Galway, Ireland
william.spillane@nuigalway.ie
Received April 17, 2001
The kinetics of the reactions of the nitrogen-sulfur(VI) esters 4-nitrophenyl N-methylsulfamate
(NPMS) with a series of pyridines and a series of alicyclic amines and of 4-nitrophenyl
N-benzylsulfamate (NPBS) with pyridines, alicyclic amines, and a series of quinuclidines have been
investigated in acetonitrile (ACN) in the presence of excess amine at various temperatures. Pseudo-
first-order rate constants (kobsd) have been obtained by monitoring the release of 4-nitrophenol/4-
nitrophenoxide. From the slope of a plot of kobsd vs [amine], second-order rate constants (k′2) have
been obtained for the pyridinolysis of NPMS, and a Brønsted plot of log k′2 vs pKa of pyridine gave
a straight line with â ) 0.45. However, aminolysis with alicyclic amines of NPMS gave a biphasic
Brønsted plot (â1 ) 0.6, â2 ≈ 0). Pyridinolysis and aminolysis with alicyclic amines and quinuclidines
of NPBS also gave similar biphasic Brønsted plots. This biphasic behavior has been explained in
terms of a mechanistic change within the E1cB mechanism from an (E1cB)irrev (less basic amines)
to an (E1cB)rev (more basic amines), and the change occurs at approximately the pKa’s (in ACN) of
NPMS (17.94) and NPBS (17.68). The straight line Brønsted plot for NPMS with pyridines occurs
because the later bases are not strong enough to substantially remove the substrate proton and
initiate the mechanistic change observed in the reaction of NPMS with the strong alicyclic amines
and quinuclidines. An entropy study supports the change from a bimolecular to a unimolecular
mechanism. This is the first clear demonstration of this E1cB mechanistic changeover involving a
nitrogen acid substrate.
In tr od u ction
of the established propensity of sulfamate esters to
undergo elimination reactions rather than nucleophilic
additions,7,8 an elimination pathway is more likely. This
probable link between the mechanism of action of these
steroidal sulfamates, H2NSO2OR, and our present study
gives added importance to this work.
Sulfamate esters, RNHSO2ORI, have been prepared
and tested for a wide range of properties including uses
as herbicides, pharmaceutical agents, and artificial sweet-
eners.1 In the 1990s, interest has heightened because of
further discoveries with regard to the efficacy of these
esters, for example, in the inhibition of carbonic anhy-
drase2 (an enzyme linked to abnormally high intraocular
pressure causing glaucoma and leading to blindness), in
the use of the clinically important sulfamate anticonvul-
sant topiramate,3 in the inhibition of ACAT4 (lowering
of cholesterol levels), and most importantly in the use of
certain steroidal sulfamates to inhibit estrone sulfatase5
(the enzyme associated with the development of breast
cancer). The inactivation of this enzyme by the sulfamate
occurs as a result of irreversible sulfamoylation of an
essential amino acid residue, and this may involve direct
nucleophilic attack at the sulfur atom by the enzyme, or
instead, an E1cB mechanism may be occurring.6 In view
Exp er im en ta l Section
Ma ter ia ls. The substrates 4-nitrophenyl N-methylsulfa-
mate (NPMS)7,9 and 4-nitrophenyl N-benzylsulfamate (NPBS)10
have been reported previously. All liquid amines were distilled
under reduced pressure, and solid amines were either recrys-
tallized from the appropriate solvent or distilled under reduced
pressure on a Kugelrohr distillation unit. The acetonitrile
(ACN) used in our work was HPLC grade, claimed to be 99.9%
pure, and shown by Karl Fischer analysis of the separate
batches used (three analyses each) to have a mean water
content of 0.200%, 0.142%, 0.106%, and 0.120%.
Det er m in a t ion of p Ka ’s of Am in es a n d Su lfa m a t e
Ester s. The spectrophotometric procedure of Bordwell and co-
workers,11 as modified by Cho et al.,12 was used. As a check
on the method, the pKa’s in ACN of three secondary amines
(1) For some examples, see: Benson, G. A.; Spillane, W. J . Sulpha-
mic acid and derivatives. In The Chemistry of Sulphonic Acids, Esters
and their Derivatives; Patai, S., Rappoport, Z., Eds.; Wiley: New York,
1991; p 987 ff.
(6) Purohit, A.; Williams, G. J .; Howarth, N. M.; Potter, B. V. L.;
Reed, M. J . Biochemistry 1995, 34, 11508.
(2) Lo, Y. S.; Nolan, J . C.; Maren, T. H.; Welstead, W. J .; Gripshover,
D. F.; Shamblee, D. A. J . Med. Chem. 1992, 35, 4790.
(3) Maryanoff, B. E.; Costanzo, M. J .; Nortey, S. O.; Greco, M. N.;
Shank, R. P.; Schupsky, J . J .; Ortegon, M. P.; Vaught, J . L. J . Med.
Chem. 1998, 41, 1315.
(4) Lee, H. T.; Sliskovic, D. R.; Picard, J . A.; Roth, B. D.; Wierenga,
W.; Hicks, J . L.; Bourley, R. F.; Hamelehle, K. L.; Homan, R.; Speyer,
C.; Stanfield, R. L.; Krause, B. R. J . Med. Chem. 1996, 39, 5031.
(5) Reed, M. J .; Purohit, A.; Woo, W. L.; Potter, B. V. L. Endocr.-
Relat. Cancer 1996, 3, 9. Poirier, D.; Ciobanu, L. C.; Maltais, R. Expert
Opin. Ther. Pat. 1998, 9, 1083.
(7) Williams, A.; Douglas, K. T. J . Chem. Soc., Perkin Trans. 2 1974,
1727.
(8) Spillane, W. J .; Hogan, G.; McGrath, P.; King, J .; Brack, C. J .
Chem. Soc., Perkin Trans. 2 1996, 2099.
(9) Spillane, W. J .; Hogan, G.; McGrath, P.; King, J . J . Chem. Soc.,
Perkin Trans. 2 1998, 309.
(10) Spillane, W. J .; Hogan, G.; McGrath, P. J Phys. Org. Chem.
1995, 8, 610.
(11) Olmstead, W. N.; Margolia, Z.; Bordwell, F. G. J . Org. Chem.
1979, 45, 3295.
(12) Cho, B. R.; Lee, S. L.; Kim, Y. K. J . Org. Chem. 1995, 60, 2072.
10.1021/jo015691b CCC: $20.00 © 2001 American Chemical Society
Published on Web 08/18/2001

6314 J . Org. Chem., Vol. 66, No. 19, 2001
Spillane et al.
Sch em e 1a
a
Key: Np ) -C6H4NO2-4; R1 ) Me (NPMS), Bn (NPBS), Ph
(NPPS), 2-MeO, 5-MeC6H3 (NPMMS).
previously determined12 were remeasured at 25 °C with the
following results (previous values in parentheses): (iBu)2NH,
17.95 ( 0.2 (18.3); (iPr)2NH, 18.4 ( 0.2 (18.5); and 2,4-
dimethylpiperidine, 18.7 ( 0.2 (18.9). The pKa values obtained
for the amines used in this work are presented in Tables
S1-S5 of the Supporting Information. The pKa values were
determined for NPMS and NPBS and previously pre-
pared substrates 4-nitrophenyl N-phenylsulfamate10 (NPPS)
and 4-nitrophenyl N-2-methoxy-5-methylphenylsulfamate13
(NPMMS).
Kin etic Mea su r em en ts. Rates of aminolysis of substrates
were measured on Cary 1/3 UV/Vis or Shimadzu UV-260
spectrophotometers fitted with thermostated cell holders. All
reactions were carried out under pseudo-first-order conditions,
i.e., in excess amine (at least 10-fold and usually 20-2000-
fold). The initial substrate concentrations were 1 × 10-4 to 5
× 10-5 M, and the reaction was followed by monitoring the
appearance of 4-nitrophenol (∼335 nm) or 4-nitrophenoxide
(∼410 nm). From plots of kobsd vs [amine], straight lines were
obtained, and the slopes of these plots gave k′2, the second-
order rate constant for the aminolysis reactions. Some kinetic
runs were followed by the disappearance of sulfamate ester,
and the agreement between the rates obtained this way and
those obtained by following the appearance of 4-nitrophenol
or 4-nitrophenoxide was good. The initial concentration of
substrate ester used did not affect the rates obtained, showing
that these reactions are first-order in substrate. The precise
details of the kinetic runs have been given previously.8,10 The
rate data obtained are recorded in Tables S1-S5 in the
Supporting Information.
F igu r e 1. Brønsted-type plots for the aminolysis (pyridinoly-
sis) of NPMS (9, Table S1 data, Supporting Information), the
bases left to right being pyridine, 2-NH2-pyridine, 2-NH2-4-
CH3-pyridine, 4-NH2-pyridine, 4-(CH3)2N-pyridine, and 4-pyr-
rolodinopyridine, and of NPBS (O, Table S2 data, Supporting
Information), the bases left to right being pyridine, 4-MeO-
pyridine, 2-NH2-pyridine, 2-NH2-4-CH3-pyridine, 4-NH2-pyri-
dine, 4-(CH3)2N-pyridine, and 4-pyrrolidinopyridine in ACN
at 42 and 37 °C, respectively.
P r od u ct Stu d ies. Partial product analysis was carried out
by comparing the absorbances of spent (reacted g10 half-lives)
kinetic solutions with spiked solutions of 4-nitrophenol in the
corresponding amine solution. In previously described product
studies8,10 in ACN, CHCl3, and 50% aqueous ACN, the sulfa-
mide product has been monitored by reverse phase HPLC.
F igu r e 2. Brønsted-type plots for the aminolysis (alicyclic
amines) of NPMS (9, Table S3 data, Supporting Information),
the bases left to right being morpholine, thiomorpholine,
N-formylpiperazine, N-(2-hydroxyethyl)piperazine, N-(2-ami-
noethyl)piperazine, piperazine, and piperidine, for the ami-
nolysis (alicyclic amines) of NPBS (O, Table S4 data, Support-
ing Information), using the same bases excluding piperidine,
and for the aminolysis (quinuclidines) of NPBS (4, Table S5
data, Supporting Information), the bases left to right being
quinuclidinone, 3-chloroquinuclidine, quinuclidinol, and qui-
nuclidine. All plots represent reactions in ACN at 37 °C.
Resu lts a n d Discu ssion
The general rate law followed for the aminolysis
reactions studied in this work has the following form:
d[NpOH or NpO-]/dt ) -d[substrate]/dt )
k
obsd[substrate]
where kobsd ) k0 + k′2[amine]. The second-order rate
constants for the reactions, k′2, were obtained from plots
of kobsd vs [amine]. The k0 terms for uncatalyzed reactions
are negligible in most cases compared to those for the
aminolysis, and they are not shown in Scheme 1.
Three sets of bases were used in this study. A set of
six or nine pyridines with a pKa range in ACN of >6
units, a set of six or seven alicyclic amines for which the
pKa range spanned ∼2 or ∼3 units, respectively, and a
set of four quinuclidines spanning over 4 pKa units were
used. The kinetic data for the pyridinolysis of NPMS and
of NPBS are given in Tables S1 and S2 of the Supporting
Information, respectively. Kinetic data for aminolysis
with the set of alicyclic amines are in Tables S3 and S4
of the Supporting Information, respectively, and data for
the aminolysis of NPBS with quinuclidines are in Table
S5 of the Supporting Information.
Brønsted-type plots of log k′2 against amine pKa have
been made for the pyridinolysis of NPMS and NPBS in
Figure 1 and for the aminolysis with alicyclic amines and
quinuclidines in Figure 2. The most notable feature is
the leveling off of the Brønsted plots seen in both figures
for four of the five plots. This type of effect has been
(13) Spillane, W. J .; McGrath, P.; Brack, C.; Barry, K. J . Chem. Soc.,
Chem. Commun. 1998, 1017.

Rate-Determining Step during Aminolysis
J . Org. Chem., Vol. 66, No. 19, 2001 6315
Ta ble 1. Activa tion P a r a m eter s for th e Am in olysis of 4-Nitr op h en yl N-Ben zylsu lfa m a te (NP BS) in ACN
pyridinea
2-NH2
2-NH2-4-CH3
4-(CH3)2N
∆Hq, kJ mol-1
∆Sq, J mol-1 K-1
alicyclic amine
morpholine
N-formylpiperazine
N-(2-aminoethyl)piperazine
piperazine
∆Hq, kJ mol-1
∆Sq, J mol-1 K-1
58.9 ( 6
63 ( 5
66 ( 7
66 ( 6
-112 ( 10
-90 ( 8
-55 ( 6
-55 ( 6
46 ( 5
43 ( 4
77 ( 8
75 ( 7
-140 ( 15
-143 ( 15
-10 ( 1
4-pyrrolidino
-15 ( 1
a
Arrhenius plots were made using the four or five temperatures and corresponding k′2 values in Table S2 (pyridines) and in Table S4
(alicyclic amines) of the Supporting Information. The errors shown are standard deviations.
Ta ble 2. Exp er im en ta l p Ka Va lu es in ACN for
observed by a number of groups14-17 using carbon sub-
Su lfa m a tes NP BS, NP MS, NP MMS, a n d NP P S
strates and has been interpreted in terms of a mecha-
nistic change within the E1cB mechanism. At the lower
ester
expa
NPBSb
NPMSc
NPMMSd
NPPSe
17.68 ( 0.5
17.94 ( 0.5
18.56 ( 0.3
19.1 ( 0.1
amine pKa values, an (E1cB)irrev reaction takes place with
k2 . k-1[R2R3NH2+], and at higher pKa values, a change
to an (E1cB)rev mechanism occurs when k-1[R2R3NH2
]
+
. k2 (Scheme 1). Thus at lower pKa values, bimolecular
formation of the conjugate base 2 of substrate 1 followed
by rapid leaving group departure occurs. At higher amine
pKa values, departure of ONp from 2 is rate-determining
and â2 ≈ 0. In both cases, the products are nitrophenol 4
and the sulfamide 5 (Scheme 1). A sulfonylamine 37 may
be involved.
The â value for the straight line obtained for NPMS
with a set of six pyridines (Figure 1) is 0.45 (r ) 0.966).
The â1 value for the lower part of the NPBS plot with
pyridines is 0.6 (r ) 0.983, five points), and â2 is
approximately 0 (Figure 1). Two of the pyridines in Table
S2 (Supporting Information), 2,4,6-trimethyl- and 2-amino-
4,6-dimethylpyridine, are not plotted because they both
deviate well below the line in the figure. Because both
are quite hindered at either side of the pyridine ring
nitrogen, i.e., the 2- and 6-positions, their deviation is
understandable.
a
b
The method of ref 12 was modified. 4-Nitrophenyl N-benz-
ylsulfamate. c 4-Nitrophenyl N-methylsulfamate. 4-Nitrophenyl
N-2-methoxy-5-methylphenylsulfamate. e 4-Nitrophenyl N-phenyl-
sulfamate.
d
plateau region of Figure 2). Examination of the literature
supports this use of entropy changes. Thus, typical E2,
(E1cB)irrev, BAC2, and SN2 processes have entropies in the
range of about -55 to about -170 J mol-1 K-1, while less
negative values in the range of -40 to +150 J mol-1 K-1
have been associated with the (E1cB)rev mechanism.19
Some of the entropies calculated previously in this
laboratory were in error, though the conclusions regard-
ing the role of entropy in the mechanism were correct.20
The correct values are presented in Table 1.
In Figure 1, the reaction of NPMS with a set of
pyridines does not show biphasic Brønsted behavior.
However, in Figure 2 with a set of (stronger) alicyclic
amines, NPMS produces a biphasic Brønsted plot. In
earlier work20 using NPPS with alicyclic amines and
NPMMS with a set of pyridine bases, straight line
Brønsted plots were obtained in each case.
The reason for this contrasting behavior became ap-
parent when the pKa’s in ACN were measured for NPMS,
NPBS, NPMMS, and NPPS (Table 2). For NPBS, the
series of bases used are in all cases sufficient to achieve
substantial proton removal from the substrate, and thus,
the change in rate-determining step within the E1cB
mechanism is observed. With NPMS, this is not realized
with pyridines, but when a stronger set of bases is
employed, biphasic Brønsted behavior again occurs. With
NPPS and NPMMS, the sets of bases used were not
sufficient to achieve substantial removal of the substrate
proton, and thus, the more usual straight line Brønsted
plots were observed.20,22
In Figure 2, the lower part of the NPMS plot with
alicyclic amines gives a â1 value of 0.64 (r ) 0.990, six
points), the lower part of the NPBS plot with quinucli-
dines gives a â1 value of 0.7 (r ) 0.992, three points),
and for NPBS with alicyclic amines, the â1 value is 0.7
(r ) 0.999, four points).
The change from a general to a specific base catalysis
situation expected for such a mechanistic change within
the E1cB mechanism18 is clear from Figures 1 and 2. This
changeover can also be supported by examining the
entropy changes taking place. The expectation would be
that there should be a shift from a dependence on base
(bimolecular) to no dependence on base (unimolecular)
and that there should be an increase (less negative
values) in entropy. This is borne out by activation
parameters (Table 1) that were calculated from rate data
at various temperatures for NPBS (Tables S2 and S4,
Supporting Information). For the pyridines, the entropy
is seen to change from approximately -100 J mol-1 K-1
(lower pKa values) to approximately -55 J mol-1 K-1
(higher pKa values in the plateau region of Figure 1), and
for the alicyclic amines, the variation is even greater
ranging from about -140 J mol-1 K-1 (lower pKa values)
to about -12 J mol-1 K-1 (higher pKa values in the
The change in the rate-determining step seen in four
of the Brønsted plots in Figures 1 and 2 occurs at
approximately the point where the substrate pKa is equal
to the pKa of the catalytic amine, i.e.,
∆pKa ) pKR2R3NH + - pKa(sulfamate) ≈ 0
2
(14) Heo, C. K. M.; Bunting, J . W. J . Org. Chem. 1992, 57, 3570.
(15) Fishbein, J . C.; J encks, W. P. J . Am. Chem. Soc. 1988, 110,
5075.
(16) Thea, S.; Kashefi-Naini, N.; Williams, A. J . Chem. Soc., Perkin
Trans. 2 1981, 65 and earlier papers.
(17) King, J . F.; Beatson, R. P. Tetrahedron Lett. 1975, 973.
(18) Cockerill, A. F.; Harrison, R. G. Mechanisms of elimination and
addition reactions involving the X)Y groups. In Chemistry of double
bonded functional groups; Patai, S., Ed.; Wiley: London. 1977; Part
1, Suppl. A.
(19) Vigroux, A.; Bergin, M.; Bergonzi, C.; Tisnes, P. J . Am. Chem.
Soc. 1994, 116, 11787 and earlier papers. Mowafak Al Sabbagh, M.;
Calman, M.; Calman, J . P. J . Chem. Soc., Perkin Trans. 2 1984, 1233
and earlier papers. Cervasco, G.; Thea, S. J . Org. Chem. 1995, 60, 70
and earlier papers. Nome, F.; Erls, W.; Correia, V. R. J . Org. Chem.
1981, 46, 3802. Broxton, T. Aust. J . Chem. 1985, 38, 77. Leffek, K. T.;
Schroeder, G. Can. J . Chem. 1982, 60, 3077. J arczewski, A.; Schroeder,
G. Pol. J . Chem. 1978, 52, 1985.
(20) Spillane, W. J .; McGrath, P.; Brack, C.; Barry, K. J . Chem. Soc.,
Chem. Commun. 1998, 1017.

6316 J . Org. Chem., Vol. 66, No. 19, 2001
Spillane et al.
Sch em e 2a
a
Key: AH ) substrate; B ) catalytic base.
One cannot pinpoint this exactly, and in the case of the
quinuclidines, this is particularly so because there is a
substantial difference between the pKa of each quinucli-
dine.
Finally, in connection with this work, a few other
points need to be addressed. A referee has pointed out
that a more adequate picture of the proton-transfer
process, which is central to the reaction mechanism, can
be represented by Scheme 2. In an aprotic solvent such
as ACN (dielectric constant of 36.6), the diffusion apart
of the ions (d f f) is a slow process and this may well be
the actual crucial rate-determining step with amines of
lower pKa (â1 part) in the curved Brønsted plots in
Figures 1 and 2. These curved plots should be classical
Eigen diagrams because the leveling off of the line arises
at approximately ∆pKa ) 0.
On the plateau (â2 area), the proton transfer process
should be very rapid (diffusion-controlled) and the kinet-
ics are now determined by the unimolecular breakup of
the sulfamate anion. From Figures 1 and 2, it is clear
that the sulfamate esters react more rapidly with the
alicyclic amines and the quinuclidines than with the
pyridines. This arises because the former bases are
stronger than the pyridines.
The sulfamide product 5 from the alicyclic base will
be of the type R2R3NSO2-, and the products from the
quinuclidines and pyridines will be of the type mN+SO2-.
The latter have been discussed by us previously.8 When
the pyridine contains a second basic group such as
4-amino, the situation is the same because the ring
nitrogen in 4-aminopyridine has a pKa in water of 9.12,
while the pKa for the dissociation of the protonated amino
group is -6.1 and thus the more basic site is at the ring
nitrogen.21
F igu r e 3. More O’Ferrall-J encks-type plot for the situation
when the first step (TS1) is kinetically unimportant and the
second step (expulsion of -ONp, TS2) dominates.
4-nitrophenyl N,N-dimethylsulfamate, Me2NSO2ONp,
which cannot undergo an elimination reaction, reacts far
more slowly than other esters having the same leaving
group and containing an -NH entity.
Sulfamate esters of type 1 bearing a hydrogen on the
nitrogen have pKa values of ∼8 in aqueous organic
media,7,9 and this coupled with a good leaving group
appears to predispose them toward elimination.
When a More O’Ferrall-J encks-type plot is used, the
situations arising during the E1cB changeover in mech-
anism can be represented in Figure 3. In the bottom left-
hand corner (R), the substrate and base are located, and
the upper right-hand corner (P) represents the final
products. Path a represents a concerted E2-type mech-
anism, and the paths for E1 and E1cB mechanisms are
marked. The figure (shaded area) shows the (E1cB)rev
pathway when â2 ) 0 and removal of the substrate proton
is unimportant kinetically but expulsion of the leaving
group is rate-determining. This is represented by a much
smaller TS1 (step 1) area compared to the TS2 (step 2)
area. The situation would be reversed, area TS1 greater
than area TS2, for weaker bases for which â1 ≈ 0.7, and
the (E1cB)irrev mechanism would operate.
The possibility that the biphasic behavior observed in
this work might be due to a change in mechanism from
E2 to (E1cB)rev seems unlikely because in much of our
other work22 we have found straight-line Brønsted plots
with â values of 0.2-0.4 and these have been interpreted
in terms of E2 mechanisms with some degree of
“carbanionic” E1cB-like character. In eliminations, â
values of 0.2-0.4 are associated with transition states
with carbocation-type character (E2-type), while larger
â values (0.6-0.9) are considered to be indicators of more
carbanion-like transition states.23
This current work appears to be the first example of
an E1cB mechanistic change involving a nitrogen sub-
strate. Though a similar type of plot to those in Figures
1 and 2 has been observed for the decomposition of
carbamates some years ago, this was interpreted in
another way.24
Ackn owledgm en t. Andrew B. O’Byrne, Chris Brack,
and Paul McGrath thank Enterprise Ireland for re-
search grants received. Dr. A. Bruzzi of the Public
Analysts Laboratory, Galway, is thanked for carrying
out the Karl Fischer analysis.
The possibility of an SN2-type mechanism arising has
been dismissed before,7 principally upon the basis that
(21) Perrin, D. D. Dissociation Constants of Organic Bases in
Aqueous Solution: supplement 1972; IUPAC, Commission on Elec-
troanalytical Chemistry; Butterworths: London, 1972.
(22) Spillane, W. J .; Brack, C. J . Chem. Soc., Perkin Trans. 2 1998,
2381.
(23) England, B. D.; McLennan, D. J . J . Chem. Soc. B 1966, 696
and accompanying papers. Hudson, R. F.; Klopman, G. J . Chem. Soc.
1964, 5. Gandler, J . R.; Yokoyama, T. J . Am. Chem. Soc. 1984, 106,
130.
Su p p or tin g In for m a tion Ava ila ble: Tables S1-S5 con-
taining k′2 and kobsd data. This material is available free of
charge via the Internet at http://pubs.acs.org.
J O015691B
(24) Caplow, M. J . Am. Chem. Soc. 1968, 90, 6795.