880
S. ALUNNI AND C. ORAZI
anism of a b-elimination reaction activated by other
heteroaromatic substrates, we have studied the N-
[2-(2-quinolyl)ethyl]quinuclidinium bromide system
(1). The elimination reaction was studied in acetohy-
droxamate–acetohydroxamic acid buffers, in order to
compare the results with those from previously studied
systems.5
RESULTS AND DISCUSSION
Kinetic study in OH˱H2O
The b-elimination reaction of 1 in OHÀ–H2O, 50°C,
m = 1 M KCl was followed by monitoring the formation
Figure 1. Dependence of kobs sÀ1) on [acetohydroxamate]
at various pH values for substrate 1. pH = &) 9.15, ~) 8.70,
*) 8.55 and &) 8.30
of
2-vinylquinoline
at
l = 322 nm
(" = 4932
dm3 molÀ1 cmÀ1 in the reaction conditions). The process
is a complete elimination reaction with a second-order
rate constant of kNOH = 12.8 Â 10À3 dm3 molÀ1 sÀ1. The
activation by a quinoline ring (2-isomer) can be
compared with the activation by a pyridine ring (2-
isomer) previously reported5 for N-[2-(2-pyridyl)ethyl]-
formation of 2-vinylquinoline at l = 322 nm. It was noted
that 2-vinylquinoline gives a reversible addition of the
buffer with the formation of N-(2-acetohydroxamate
ethyl)quinoline. However, it was shown that this process
does not alterate the kinetic study of the b-elimination
reaction from 1 by initial rates, since 2-vinylquinoline is
stable enough for the times used to determine the initial
rate measurements under the various reaction conditions
used. In fact, the values of k'obs (sÀ1) calculated up to
20% of the reaction by the ln[(A?ÀA0)/(A?ÀAt)] = k'obst
(with A? = [substrate]/"substrate) were in good agreement
with those calculated by initial rates, following the
reaction up to ꢁ3%. We were not able to isolate the
product of the addition of the buffer to 2-vinylquinoline,
N-(2-acetohydroxamate ethyl)quinoline, probably be-
cause it is very unstable. However, a mixture of 2-
vinylquinoline (10 mg), acetohydroxamic acid (115 mg),
0.77 ml of 1 M KOH and 4 ml of CH3CN, kept at 50°C
for 6 h and extracted with CHCl3, showed, by GC–MS
analysis, the presence of a limited amount of a compound
whose mass spectral data were in agreement with those of
N-(2-acetohydroxamate ethyl)quinoline: m/z 230 (7), 172
(24), 156 (100), 129 (23). Consistently, a reaction
mixture of 1 (8 mg) in 5 ml of acetohydroxamate–
acetohydroxamic acid buffer, pH 9.15, [B] = 0.2 M,
[BH] = 0.2 M kept at 50°C for 5 h and extracted with
CHCl3, showed, by GC–MS analysis, the presence of a
limited amount of the same compound, in addition to the
two products of the elimination reaction, 2-vinylquino-
line and quinuclidine. The kinetic data were treated
following the same procedure as described previously5
for the related systems activated by a pyridine ring. The
contribution of the unprotonated substrate, N, with OHÀ
was subtracted from k'obs to give kobs (sÀ1): kobs = k'obs
ÀkNOH[OHÀ]. The plot of kobs against [acetohydrox-
amate] at various pH values is reported in Fig. 1.
quinuclidinium (kNOH = 0.271 Â 10À3 dm3 molÀ1 sÀ1
,
50°C, m = 1 M KCl). Activation by quinoline is 47 times
higher than that by pyridine; this higher reactivity can be
related to the higher acidity of the protons in the b-
position with respect to the leaving group. Owing to the
high [OHÀ] used (0.1–0.5 mol dmÀ3), in this reaction
medium the reacting species is the unprotonated
substrate, N, as shown by the second-order kinetic law;
the reaction with NH would be on the zero order with
respect to [OHÀ]. In ODÀ–D2O, 50°C, m = 1 M KCl, the
second-order rate constant for 1 is kNOD = 23.2 Â
10À3 dm3 molÀ1 sÀ1. The kNOD/kNOH ratio is 1.8 and this
value is in agreement with a rate-determining proton
transfer.9 An NMR study of H/D exchange in ODÀ–D2O,
50°C, showed the absence of deuterium in the 2-
vinylquinoline formed at the end of the reaction; this
result excludes the E1cb reversible mechanism in this
reaction medium. The two mechanisms in OHÀ–H2O that
are in agreement with the second-order kinetic law and
absence of H/D exchange are the concerted E2 and the
E1cb irreversible process, (E1cb)I. The following dis-
cussion will illustrate how the experimental evidence is
in agreement with a base-induced b-elimination mech-
anism with 1 involving a carbanion intermediate.
Acid±base catalysis
Acid–base catalysis for the b-elimination with 1 was
carried out in acetohydroxamate–acetohydroxamic acid
buffers, at 50°C, m = 1 M KCl. This buffer system and
these reaction conditions were chosen so that the results
could be compared with those of previously studied5
substrates. The pseudo-first-order rate constants, k'obs
(sÀ1), were determined by initial rates by monitoring the
Copyright 2001 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2001; 14: 879–883
Alunni
