Metal Ion Catalysis in the β-Elimination Reactions of N-[2-(4-Pyridyl)ethyl]quinuclidinium and N-[2-(2-Pyridyl)ethyl]quinuclidinium in Aqueous Solution

Article abstract of DOI:10.1021/jo030374l

Catalysis of the β-elimination reaction of N-[2-(4-pyridyl)ethyl]quinuclidinium (1) and N-[2-(2-pyridyl)ethyl]quinuclidinium (2) by Zn²⁺ and Cd²⁺ in OH^-/H₂O (pH = 5.20-6.35, 50 °C, and μ = 1 M KCl) has been studied. In the presence of Zn²⁺, the elimination reactions of both isomers occur from the Zn²⁺-complexed substrates (C). The equilibrium constants for the dissociation of the Zn ²⁺-complexes are as follows: K_d = 0.012 ± 0.003 M (isomer 1) and K_d = 0.065 ± 0.020 M (isomer 2). The value of k_H2O^C for isomer 1 is 4.81 × 10^-6 s ^-1. For isomer 2 both the rate constants for the water and OH^--induced reaction of the Zn²⁺-complexed substrate could be measured, despite the low concentration of OH^- in the investigated reaction mixture [kH₂O^C 0 = 1.97 × 10^-6 s^-1 and k_OH-^C = 21.9 M ^-1 s^-1, respectively]. The measured metal activating factor (MetAF), i.e., the reactivity ratio between the complexed and the uncomplexed substrate, is 8.1 × 104 for the OH^--induced elimination of 2. This high MetAF can be compared with the corresponding proton activating factor (Alunni, S.; Conti, A.; Palmizio Errico, R. J. Chem. Soc., Perkin Trans. 2 2000, 453), PAF = 1.5 × 10⁶ and is in agreement with an E1cb irreversible mechanism (A_xhD _E* + DN) (Guthrie, R. D.; Jencks, W. P. Acc. Chem. Res. 1989, 22, 343). A value of k_H2O^C ≥ 23 × 10 ^-7 s^-1 is estimated for the Cd²⁺-complexed isomer 2, while catalysis by Cd²⁺ has not been observed for isomer 1.

Full text of DOI:10.1021/jo030374l

Meta l Ion Ca ta lysis in th e â-Elim in a tion Rea ction s of
N-[2-(4-P yr id yl)eth yl]qu in u clid in iu m a n d
N-[2-(2-P yr id yl)eth yl]qu in u clid in iu m in Aqu eou s Solu tion
Sergio Alunni,*,† Tiziana Del Giacco,† Paolo De Maria,‡ Giorgia Fifi,† Antonella Fontana,‡
Laura Ottavi,† and Ilaria Tesei†
Dipartimento di Chimica, Universita` degli Studi Perugia, Via Elce di Sotto 8, 06123 Perugia, Italy, and
Dipartimento di Scienze del Farmaco, Universita` “G. D’Annunzio”, Via dei Vestini 31, 66013 Chieti, Italy
alunnis@unipg.it
Received December 8, 2003
Catalysis of the â-elimination reaction of N-[2-(4-pyridyl)ethyl]quinuclidinium (1) and N-[2-(2-
pyridyl)ethyl]quinuclidinium (2) by Zn2+ and Cd2+ in OH-/H2O (pH ) 5.20-6.35, 50 °C, and µ ) 1
M KCl) has been studied. In the presence of Zn2+, the elimination reactions of both isomers occur
from the Zn2+-complexed substrates (C). The equilibrium constants for the dissociation of the Zn2+
-
complexes are as follows: Kd ) 0.012 ( 0.003 M (isomer 1) and Kd ) 0.065 ( 0.020 M (isomer 2).
The value of kCH O for isomer 1 is 4.81 × 10-6 s-1. For isomer 2 both the rate constants for the
2
“water” and OH--induced reaction of the Zn2+-complexed substrate could be measured, despite the
low concentration of OH- in the investigated reaction mixture [kCH O ) 1.97 × 10-6 s-1 and kCOH
)
-
2
21.9 M-1 s-1, respectively]. The measured metal activating factor (MetAF), i.e., the reactivity ratio
between the complexed and the uncomplexed substrate, is 8.1 × 104 for the OH--induced elimination
of 2. This high MetAF can be compared with the corresponding proton activating factor (Alunni,
S.; Conti, A.; Palmizio Errico, R. J . Chem. Soc., Perkin Trans. 2 2000, 453), PAF ) 1.5 × 106 and
is in agreement with an E1cb irreversible mechanism (AxhDE* + DN) (Guthrie, R. D.; J encks, W. P.
Acc. Chem. Res. 1989, 22, 343). A value of kCH O g 23 × 10-7 s-1 is estimated for the Cd2+-complexed
2
isomer 2, while catalysis by Cd2+ has not been observed for isomer 1.
SCHEME 1
In tr od u ction
In previous studies, it was shown that â-elimination
reactions in systems activated by a pyridine ring are
strongly catalyzed by protonation of the pyridine nitrogen
atom.1,3,4,5 The observed proton activating factors (PAF,
i.e., the ratios of second-order rate constants for N-
protonated and unprotonated substrate) are PAF ) 5.3
× 104 with the N-[2-(4-pyridyl)ethyl]quinuclidinium (1)
and PAF ) 1.5 × 106 with N-[2-(2-pyridyl)ethyl]quinu-
clidinium (2) in OH-/H2O at 50 °C and ionic strength µ
) 1 M (KCl). This proton activation can be accounted for
by an E1cb mechanism and by the high stability of the
intermediate formed from the protonated substrate NH+
(Scheme 1).
Reactions that are subjected to electrophilic catalysis
by protons can be catalyzed by metal ions too.6,7 As a
matter of fact, the affinities of a substrate for both proton
and metal ions are related to its (Brønsted and/or Lewis)
basicity. Lewis acid catalysis, for example, provides
alternative pathways for specific acid-catalyzed enoliza-
tion reactions of ketones, and comparison by metal ions
and hydronium ion has recently attracted considerable
interest.8-10 Thus, the Cu2+-catalyzed rate constant of
† Universita` degli Studi Perugia.
‡ Universita` “G. D’Annunzio”.
(1) Alunni, S.; Conti, A.; Palmizio Errico, R. J . Chem. Soc., Perkin
Trans. 2 2000, 453.
(2) Guthrie, R. D.; J encks, W. P. Acc. Chem. Res. 1989, 22, 343.
(3) Alunni, S.; Busti, A. J . Chem. Soc., Perkin Trans. 2 2001, 778.
(4) Alunni, S.; Conti, A.; Palmizio Errico, R. Res. Chem. Intermed.
2001, 27, 653.
(8) Eustace, S. J .; McCann, G. M.; More, O’Ferrall, R. A.; Murphy,
M. G.; Murray, B. A.; Walsh, S. M. J . Phys. Org. Chem. 1998, 11, 519.
(9) De Maria, P.; Fontana, A.; Siani, G.; Spinelli, D. Eur. J . Org.
Chem. 1998, 1867.
(5) Alunni, S.; Laureti, V.; Ottavi, L.; Ruzziconi, R. J . Org. Chem.
2003, 68, 718.
(6) Tee, O. S. Adv. Phys. Org. Chem. 1994, 29, 1.
(7) Suh, J . Acc. Chem. Res. 1992, 25, 273.
(10) Fontana, A.; De Maria, P.; Pierini, M.; Siani, G.; Cerritelli S.;
Macaluso, G. J . Phys. Org. Chem. 2002, 15, 247.
10.1021/jo030374l CCC: $27.50 © 2004 American Chemical Society
Published on Web 04/17/2004
3276
J . Org. Chem. 2004, 69, 3276-3281

â-Elimination Reactions of N-[2-(4-Pyridyl)ethyl]quinuclidinium
enolization of N-methyl-3-acetylpyrrole11 is 800 times
higher than the hydronium-catalyzed rate constant.
Moreover, suitable metal ions can give a “two site
coordination”, and this possibility leads to particularly
effective catalysis. It has been shown12 that complex
formation between 2-acetylimidazole and Zn2+ leads to
rates of enolization which are up to about 8 × 103 times
larger than that of the uncomplexed substrate, while
Cox13 reported that the enolization of 2-acetylpyridine in
the presence of Zn2+ is 2 × 105 faster than in the absence
of the metal ion. More generally, the importance of metal
ion catalysis is highlighted by the role of metal ions in
enzymatic reactions. It has been suggested that metal
ions hold the substrates and the reactive groups on the
active site of the enzyme in the proper steric relation to
each other.14 For example, the Zn2+-catalyzed hydration
of pyridine-2-aldehyde is a valid model for the enzyme
carbonic anhydrase catalyzed hydration of aldehydes and
esters. The second-order rate constant is 6.5 × 106 faster
than that for the “water” reaction, and this rate increase
is only 10-fold less than that brought about by the
enzyme.15
F IGURE 1. Plot of Ptot/M, against time/min, for the elimina-
tion reaction of isomer 1 at different [Zn++]/ M, at pH ) 5.19,
50 °C, and µ ) 1 M (KCl): open square, [Zn++] ) 0.0350 M;
solid up-triangle, [Zn++] ) 0.0220 M; open circle, [Zn++] )
0.0110 M; solid square, [Zn++] ) 0.0061 M.
In the present paper, we report a kinetic study of the
elimination reactions of 1 and 2, in OH-/H2O at 50 °C, µ
) 1 M (KCl), pH range 5.20-6.35 in the presence of Zn2+
and Cd2+, with the aim of comparing the effectiveness of
the proton and of the studied metal ions as reaction
catalysts. Under these conditions, the studied reactions
can be a model for biological and naturally occurring
chemical processes in aqueous environment.
On the other hand,kobs for isomer 2 increases linearly
upon increasing [Zn2+], in the [Zn2+] range 0 < [Zn2+] <
0.04 M. Nevertheless, at pH ) 5.26 it was possible to
increase [Zn2+] up to 0.196 M and a significant curvature
was then observed (Figure 3).
A mechanism consistent with the observed results is
shown in Scheme 2:
Kinetic analysis for the mechanism shown in Scheme
2 by using the steady-state approximation to I and IM
gives eqs 1-3, 6, and 7 (where eq 2 has been previously
derived16).
Resu lts a n d Discu ssion
The pseudo-first-order rate constants (kobs/s-1, initial
rate) of the elimination reaction with substrates 1 and 2
in H2O, at 50 °C and µ ) 1 M (KCl), in the presence of
Zn2+ and Cd2+, were measured by following spectropho-
tometrically the formation of 4-vinylpyridine (P) at
equilibrium with its conjugated acid (PH+) at λ ) 280
nm or 2-vinylpyridine (P and PH+) at λ ) 290 nm. The
concentration of 1 was about 1.2 × 10-3 M and that of 2
was about 1 × 10-3 M. The concentration of Zn2+ was in
the range 0.003-0.04 M for isomer 1 and 0.004-0.04 M
for isomer 2, while the concentration of Cd2+ was in the
range 0.005-0.2 M for isomer 1 and 0.03-0.2 M for
isomer 2. The pH range studied was 5.2-6.35. The plot
of Ptot (i.e. the total concentration [P] + [PH+]) against
time (up to 3% of reaction) is strictly linear (average r )
0.9998) and kobs was calculated as SLOPE/[S0], where [S0]
is the initial concentration of the substrate. A typical plot
of Ptot vs time for isomer 1 at various [Zn2+] and pH )
5.19 is shown in Figure 1.
dPtot
NH+
obs
v )
) k
[NH+] + kCobs[C]
(1)
(2)
dt
NH+
H2O
NH+
k′
+ k -[OH-]
OH
NH+
obs
+
k
) kN2 H
+
+
NH+
H2O
kN2 H + k
+ kNHH [H+]
+
kCH O + kCOH-[OH-]
2
C
kobs ) kI2
(3)
M
kI2 + kH O + kIH+[H ]
IM
+
M
M
2
In all cases, the initial concentration of ZnCl2 or
CdCl2 ) [M0] . [C], then [M0] ) [M], where M is the
metal ion. Under these conditions, from eq 1 and with
the relationships reported in eqs 4 and 5, eq 6 can be
derived.
N
[N][H+]
[NH+]
Under the reaction conditions employed, the pKa of
KNa )
Kd )
(4)
(5)
N
the conjugated acid of 1 is 4.85, whereas the pKa of the
conjugated acid of 2 is 3.81.1
Meta l Ion Ca ta lysis by Zn 2+. The plots of kobs vs
[N][M]
[C]
[Zn2+] for isomer 1 showed a leveling off at high [Zn2+
(one example is shown in Figure 2, at pH ) 6.2).
]
[M0]
NH+
obs
NH+
obs
(11) De Maria, P.; Fontana, A.; Frascari, S.; Ferroni, F.; Spinelli,
D. J . Chem. Soc., Perkin Trans. 2 1992, 825.
(12) De Maria, P.; Fontana, A.; F.; Macaluso, G.; Spinelli, D. Gazz.
Chim. Ital. 1996, 126, 45.
v ) k
R′[S0] + (kCobs - k
R′) ‚
[S0] (6)
[M0] + KdR
(13) Cox, B. G J . Am. Chem. Soc. 1974, 96, 6823.
(14) J encks, W. P. Catalysis in Chemistry and Enzimology; Mcgraw-
Hill: New York, 1969.
where
(15) Pocker, Y.; Meany, J . E. J . Am. Chem. Soc. 1967, 89, 631.
(16) Alunni, S.; Ottavi, L. J . Org. Chem. 2004, 69, 2272.
J . Org. Chem, Vol. 69, No. 10, 2004 3277

Alunni et al.
SCHEME 2
F IGURE 2. Dependence of kobs/s-1, on [Zn2+]/M, for the
elimination reaction in OH-/H2O of isomer 1 at pH ) 6.2, 50
°C, µ ) 1 M (KCl).
Kd and kC can be obtained from eq 7 by two proce-
obs
dures. Equation 7 (kobs vs [M0] plot) is the equation of a
curve, and the curvature, experimentally observable only
for Zn2+, is an indication of a significant complexation of
the metal ion with the substrate. Equation 7 can be
linearized by rearranging it as in eq 8:
KdR
1
1
)
+
NH+
obs
NH+
obs
NH+
obs
kobs - k
R′ (kCobs - k
R′) [M0](kCobs - k
R′)
(8)
F IGURE 3. Dependence of kobs/s-1 on [Zn2+]/M, for the
elimination reaction in OH-/H2O of isomer 2 at pH ) 5.26, 50
°C, µ ) 1 M (KCl).
A first procedure for the evaluation of Kd and kC uses
R′) vs 1/[M0]. A straight line is
expected (average r ) 0.9971) whose intercept, i, and
obs
NH+
obs
a plot of 1/(kobs - k
KNa + [H+]
[H+]
KNa + [H+]
slope are given by eqs 9 and 10:
R )
, R′ )
KaN
1
i )
(9)
NH+
obs
(kCobs - k
R′)
and [S0] is the total concentration of the substrate. It was
NH+
obs
NH+
H2O
previously16 shown that eq 2 reduces to k
) k′
+
KdR
(kCobs - k
NH+
k
-[OH-], owing to the operating (E1cb)I mechanism,
slope )
(10)
NH+
obs
OH
NH+
H2O
R′)
and the values determined are as follows: k′
) 2.54
NH+
× 10-6 s-1 (isomer 1) and k′H O ) 8.75 × 10-7 s-1 (isomer
2
From eqs 9 and 10, eq 11 follows:
NH+
OH
NH+
OH
2), k
) 241 M-1 s-1 (isomer 1), and k
) 290 M-1
-
-
NH+
s-1 (isomer 2). From these values, kobs can be calculated
slope
) KdR
i
(11)
NH+
H2O
at each pH. Even if the k′
term is associated with a
large uncertainty, especially with isomer 2, this term, in
the range of the pH used, does not significantly influence
the calculated parameters of the mechanism. From the
slope of the plot (initial rate) Ptot vs time it is possible to
calculate kobs ) SLOPE/[S0]. The expression for kobs is
given by eq 7:
Kd can be calculated from the known value of R, while
kCobs can be calculated from eq 12 (a rearranged form of
eq 10):
KdR
NH+
obs
kCobs ) k
R′ +
(12)
slope
[M0]
NH+
obs
NH+
obs
A second procedure for the evaluation of Kd and kC
can be a nonlinear fitting of eq 7. According to this
kobs ) k
R′ + (kCobs - k
R′)
(7)
obs
[M0] + KdR
3278 J . Org. Chem., Vol. 69, No. 10, 2004

â-Elimination Reactions of N-[2-(4-Pyridyl)ethyl]quinuclidinium
kCobs ) kCH O + kCOH-[OH-]
(13)
2
On the contrary, if the intermediate IM (Scheme 1) were
formed reversibly (kI2 , kH O + kHI +[H+]) or if the terms
IM
M
M
2
kH O and kIH+[H+] in eq 3 contributed significantly to
IM
M
2
kCobs, the plot of kCobs vs [OH-] would not be expected to be
linear. In our systems, kCH O and kOCH represent the
-
2
pseudo-first-order and second-order rate constants for
carbon deprotonation of the metal ion complexed sub-
strate, C, by the base H2O and OH-, respectively. The
values obtained are reported in Table 1.
The values of Kd and kC for isomer 1, calculated by
obs
the above nonlinear fitting procedure (eq 7), are as
follows: Kd ) 0.012 ( 0.003 M (average value at the
various pHs) and kCobs/s-1 ) 4.55 × 10-6 (pH 5.19), 5.2 ×
10-6 (pH 5.3), 4.72 × 10-6 (pH 5.6), 6.17 × 10-6 (pH 5.9),
6.16 × 10-6 (pH 6.2), and 6.36 × 10-6 (pH 6.35). The
variation of kCobs with [OH-] was very small because of
the small pH range investigated. A plot of kCobs vs [OH-]
gives, by linear regression analyses: kCobs/s-1 ) 4.81 ×
10-6 (sd ) 0.30 × 10-6) + 13.8 (sd ) 4.4) [OH-], r )
0.8425. While the value of kCH O (the intercept) is a
reliable value, that of kCOH- (the s2lope) is associated with
NH+
obs
F IGURE 4. Dependence of 1/[kobs - k
R′]/s on 1/[M0] for
the elimination reaction in OH-/H2O of isomer 2 at pH ) 5.26,
50 °C, µ ) 1 M (KCl).
a large standard deviation. However, given that a kOCH
-
) 18.0 M-1 s-1 is expected from eq 13 to increase the kCobs
of 50% on passing from pH 5.19 to pH 6.35, in the light
of our experimental data we can only estimate a kOCH
<
-
18.0 M-1 s-1 for isomer 1. The values of Kd for the isomers
1 (Kd ) 0.012 ( 0.003 M) and 2 (Kd ) 0.065 ( 0.020 M)
are as expected from the differences in the pKa values of
the two substrates:1 pKa(1) ) 4.85 and pKa(2) ) 3.81. In
fact, the more basic substrate 1 also shows a stronger
complexation with Zn2+. In previously reported studies12
of enolization reactions of some acetylheterocycles evi-
dence of the formation of a complex between the metal
ion (e.g., Zn2+ and Cu2+) and the substrate was obtained
only for the most basic investigated compound (2-acetyl-
imidazole: pKa ) 3.12). Moreover, a value of Kd ) 0.028
M has been reported by Cox13 for the Zn2+-complexed 2-
acetylpyridine (pKa ) 2.64). However, the interaction of
the metal ion with both 2-acetylimidazole and 2-acetylpy-
ridine involves the nitrogen heterocyclic atom and the
carbonyl-oxygen atom.
F IGURE 5. Dependence of kCobs/s-1 on [OH-]/M for the
elimination reaction of isomer 2 catalyzed by Zn2+ in OH-/
H2O at 50 °C, µ ) 1 M (KCl). The point at each pH represents
the average value of two or three sets of experiments.
procedure, a Kd ) 0.065 M has been calculated for isomer
2 at pH ) 5.26; in fact, at this low pH value it was
possible to increase [Zn2+] up to 0.196 M. Under these
conditions, the plot (kobs vs [M0]) shows a significant
curvature (Figure 3). At higher pHs a lower [Zn2+] is
convenient in order to avoid precipitation of Zn(OH)2. The
values of kCobs/s-1 with isomer 2 (calculated with the first
The ratio kCOH-/kN -, i.e. the metal activating factor
OH
(MetAF), is a measure of the activation of the elimination
reaction by the interaction of Zn2+ and Cd2+ with the
pyridine nitrogen atom. The MetAF found for Zn2+ with
3
isomer 2 is 8.1 × 104 while with isomer 1 is <5.2 × 10
procedure), at the four investigated pHs are 2.26 × 10-6
,
2.56 × 10-6, 2.78 × 10-6, and 4.09 × 10-6 at pH ) 5.26,
(See above). The proton activating factors, PAF, for
isomers 1 and 2, previously determined under the same
conditions,1 are a measure of the activation of the
elimination reactions by protonation of the nitrogen atom
of the pyridine ring. It was demonstrated that these base-
induced elimination reactions indeed proceed via NH+,
the nitrogen protonated substrate, and that the mecha-
nism is E1cb (AxhDH + DN). On the other hand the
mechanism of elimination induced by OH- for the un-
protonated substrates, N, can be either E2 or (E1cb)I as
it was not possible to discriminate between the two
pathways.1,5 Consequently, it was not clear whether the
PAFs observed are a measure of the activation by the
proton of the rate determining carbanion intermediate
5.6, 5.9, and 6.2, respectively. The plot of 1/(kobs
-
NH+
k
R′) vs 1/[M0] at pH ) 5.26 for isomer 2 is shown in
obs
Figure 4.
The plot of kCobs vs [OH-] for isomer 2 is shown in
Figure 5.
A good linear correlation has been observed: kCobs/s-1
) 1.97 × 10-6 (sd ) 1.50 × 10-7) + 21.9 (sd ) 2.8) [OH-],
r ) 0.9842. The experimentally observed linear depen-
dence of kCobs on [OH-] is in agreement with an E1cb
irreversible mechanism. In fact, in the condition of
irreversibility kI2 . kH O + kHI +[H+] and eq 3 reduces to
IM
M
M
2
eq 13.
J . Org. Chem, Vol. 69, No. 10, 2004 3279

Alunni et al.
21.6 (( 1.5) × 10-7. To a first approximation this result
implies that the term kCOH-[OH-]/KdR does not contrib-
ute significantly to the Cd2+ catalysis and that catalysis
by Cd2+ is observed for 2 only for the “water”-induced
elimination reaction. The lack of a curvature in the plot
of kobs vs [Cd2+] implies an estimated Kd value > 1 M as
a curvature would be expected for a 20% complexation
TABLE 1. Ra te Con sta n ts for th e Elim in a tion Rea ction
In d u ced by H2O or OH- w ith 1 a n d 2 Com p lexed w ith
Zn 2+ (C) in H2O a t 50 °C, µ ) 1 M (KCl)a
kCH × 106
kCOH
Kd
kNOH × 103 c
b
-
-
2O
(s-1
)
(M-1 s-1
)
(M)
(M-1 s-1
)
1
2
4.81
1.97
<18
21.9
0.012
0.065
3.45
0.27
For comparison, the rate constants, for the same reaction from
at [Cd2+] ) 0.2 M. Considering an average value of the
a
NH+
obs
N
and OH- are reported. N is the unprotonated substrate.
k
R′ (in the pH range 5.29-6.20) of 1.2 × 10-7 s-1 and
Dissociation constants for Zn2+-complexed substrate (C). c Pre-
b
C
H2O
R ) 1, it can be estimated that k
g 23 × 10-7 s-1. On
viously determined (ref 1).
the other hand no catalysis by Cd2+ was observed for
isomer 1, it is not clear if the reason is associated with a
lower energy of stabilization by Cd2+ of the intermediate
with respect to that by Zn2+. It should also be considered
that the water reaction in the absence of metal ion for
isomer 1 is about 10 times larger than with isomer 2,
and that catalysis by Cd2+ could well be covered by the
water reaction.
CHART 1
formation within an (E1cb)I mechanism or if they are
associated with a change in mechanism from E2 (N) to
(E1cb)I (NH+). The value of MetAF by Zn2+ observed for
isomer 2 is only about 10 times lower than that of the
corresponding PAF (1.5 × 106) and accordingly the most
consistent mechanism of elimination of the Zn2+-com-
plexed substrate is probably a (E1cb)I rather than an E2
process. The comparison of the pseudo-first-order rate
Con clu sion s
It has been demonstrated that Zn2+ catalyses the
â-elimination reactions of N-[2-(4-pyridyl)ethyl]quinucli-
dinium and of N-[2-(2-pyridyl)ethyl]quinuclidinium to
4-vinylpyridine and 2-vinylpyridine, respectively. An
increase in reactivity of 8.1 × 104 due to the interaction
of Zn2+ with the nitrogen atom of the pyridine ring was
detected with substrate 2 when the base was OH- (pH
range 5.2-6.3, 50 °C, µ ) 1 M KCl). The strong catalysis
is indicative of an E1cb mechanism for the Zn2+-com-
plexed substrate (C). The values of the pseudo-first-order
rate constants for the “water” elimination reactions of C
are kCH O ) 4.81 × 10-6 s-1 and kHC O ) 1.97 × 10-6 s-1 for
constant, kCH O, for the carbon deprotonation from the
2
two Zn2+-complexed isomers, C, by the base H2O is also
of interest. The measured values [kCH O ) 4.81 (( 0.60) ×
2
10-6 s-1 for isomer 1 and kHC O ) 1.97 (( 0.38) × 10-6 s-1
2
for isomer 2] are similar and this excludes a significant
contribution from the negatively charged carbon atom in
the reaction intermediate. In fact, the formation of a
chelate complex is possible only for isomer 2 (Chart 1)
2
2
isomers 1 and 2, respectively. The similarity of these two
values allows to exclude the formation of a chelate
between the substrate and the metal ion in the transition
state. The calculated values of the equilibrium constant
for the dissociation of the Zn2+-complexes are: Kd ) 0.012
( 0.003 M for isomer 1 and Kd ) 0.065 ( 0.020 M for
C
Finally the ratio kOH-/kC () 1.1 × 10 M for isomer
7
H2O
2) quantifies the higher reactivity of the base OH- than
that of H2O in the elimination reaction of C, as expected
from the high ∆pKa (H2O - H3O+) ) 17.4.
Meta l Ion Ca ta lysis by Cd 2+. The effect of the
addition of Cd2+ to isomer 2 showed a linear dependence
of kobs on [Cd2+] at all the investigated pHs and using
[Cd2+] up to 0.2 M. This has been rationalized in terms
of a limited complexation of 2 with Cd2+. In this situation
the term KdR > [Cd2+] in eq 7 and kobs is given by eq 14.
isomer 2. In the presence of Cd2+ a value of kHC O g 23 ×
2
10-7 s-1 can be estimated for isomer 2. No catalysis by
Cd2+ was observed for isomer 1.
Exp er im en ta l Section
[M0]
NH+
obs
NH+
obs
kobs ) k
R′ + (kCobs - k
R′)
(14)
Ma t er ia ls. Glass distilled and freshly boiled water was
used throughout. Reagent grade potassium chloride and ZnCl2
and CdCl2 were commercial material, N-[2-(4-pyridyl)ethyl]-
quinuclidinium (1) and N-[2-(2-pyridyl)ethyl]quinuclidinium
(2) were prepared according to a previously described proce-
dure.1
KdR
A plot of kobs vs [Cd2+] is expected to be linear with
intercept, i′ (eq 15), and slope, slope′ (eq 16). Equation
16 is derived from eqs 13 and 14 assuming an E1cb
irreversible mechanism in analogy with the process
Kin et ics Mea su r em en t s. Pseudo-first-order rate con-
stants, kobs/s-1, for the elimination reaction of 1 and 2 were
determined by following the formation of the corresponding
4-vinylpyridine at λ ) 280 nm or 2-vinylpyridine at λ ) 290
nm, as previously described.5 The pKa values of 4-vinylpyridine
and of 2-vinylpyridine are 5.06 and 4.77, respectively, under
the adopted experimental conditions. The relatively higher
values determined previously5 were 5.64 and 5.06 respectively
in the presence of acetate/acetic acid buffers. Under the
adopted experimental conditions, the vinylpyridine (P) is in
equilibrium with a significant amount of its conjugated acid,
PH+; the total concentration of the product, Ptot ) P + PH+,
has been calculated by eq 17
catalyzed by Zn2+
.
NH+
obs
i′ ) k
R′
(15)
(16)
NH+
obs
(kCH O - k
R′)
kCOH
2
slope′ )
+
-[OH-]
KdR
KdR
The values of slope′ found at pHs ) 5.29, 5.62, 5.93,
6.1, 6.2, and 6.21 are independent of pH (within the
experimental errors) with an average value of slope′ )
3280 J . Org. Chem., Vol. 69, No. 10, 2004

â-Elimination Reactions of N-[2-(4-Pyridyl)ethyl]quinuclidinium
2-vinylpyridinium and Zn2+ was controlled in several reaction
conditions. The value of pKw at 50 °C and µ ) 1 M (KCl) is
13.23.1
[H+]
(At - A0)
Ptot
)
1 +
(17)
+
P
(
)
[H ]
Ka
ꢀP + ꢀPH
+ Ka
P
P r od u ct An a lysis. In several experiments solutions of 1
or 2 at 50 °C, µ ) 1 M (KCl), at the concentration used for the
kinetic runs and in the presence of Zn2+ or Cd2+ were left to
react for several hours up to ∼5% of the total reaction. The
pH was then increased to 10-11 and the extraction with
n-hexane gave, by GLC analysis, only 4- or 2-vinylpyridine,
respectively, and quinuclidine.
where At is the absorbance at time t, A0 is the absorbance at
P
t ) 0, Ka is the dissociation constant of PH+; ꢀP is the
extinction coefficient of 4-vinylpyridine1 [1634 M-1 cm-1 at 50
°C, µ ) 1 M (KCl) and λ ) 280 nm] or of 2-vinylpyridine1 [3584
M-1 cm-1 at 50 °C, µ ) 1 M (KCl) and λ ) 290 nm] and ꢀPH is
the extinction coefficient of 4-vinylpyridinium5 [8987 M-1 cm-1
at 50 °C, µ ) 1 M (KCl) and λ ) 280 nm] or of 2-vinylpyri-
dinium5 [9773 M-1 cm-1 at 50 °C, µ ) 1 M (KCl) and λ ) 290
nm]. A plot of Ptot against time was linear and the kobs/s-1
values, were calculated from kobs ) SLOPE/[S0], where [S0] is
the initial concentration of the substrate (1 or 2). The pH of
the solution used in the kinetic experiments was adjusted
with small amounts of HCl or KOH in order to have the same
value of pH at the different [Zn2+] values. The pH of the
solution was checked in order to make sure that no variation
of pH would occur during the experiments (the observed
variation of pH was < 0.1 throughout). The UV spectra of the
substrates and of the products were not influenced by the
presence of Zn2+ at the concentration used in the kinetic runs
at the working wavelength. The stability of a solution of 4- or
Ack n ow led gm en t. The authors thank the Minis-
tero dell’Istruzione, dell’Universita` e della Ricerca
(MIUR) and the CNR (Rome) for financial support.
Su p p or tin g In for m a tion Ava ila ble: Observed pseudo-
first-order rate constants, kobs/s-1, for the â-elimination of N-[2-
(4-pyridyl)ethyl]quinuclidinium (1) and N-[2-(2-pyridyl)ethyl]-
quinuclidinium (2) in H2O, 50 °C, and µ ) 1 M (KCl) at
different pH values and in the presence of metal ion Zn2+ or
Cd2+. This material is available free of charge via the Internet
at http://pubs.acs.org.
J O030374L
J . Org. Chem, Vol. 69, No. 10, 2004 3281