Concurrent SN1 and SN2 reactions in the benzylation of pyridines

Article abstract of DOI:10.1002/poc.346

The Menschutkin reactions of 3,4-methylenedioxybenzyl and 3,4-dimethoxybenzyl bromides and also p-methoxybenzyl bromide with Y-substituted pyridines were kinetically studied for a range of amine concentration in acetonitrile. The strongly activated benzyl

Full text of DOI:10.1002/poc.346

JOURNAL OF PHYSICAL ORGANIC CHEMISTRY
J. Phys. Org. Chem. 2001; 14: 123–130
Concurrent SN1 and SN2 reactions in the benzylation of
pyridines
Soo-Dong Yoh,1 Duk-Young Cheong,1 Chung-Heun Lee,1 Sung-Hong Kim,1 Jong-Hwan Park,1
Mizue Fujio2* and Yuho Tsuno2
1Department of Chemistry Education, Kyungpook National University, Taegu 702-701, Korea
2Institute for Fundamental Research of Organic Chemistry, Kyushu University, Hakozaki, Fukuoka 812-8581, Japan
Received 20 June 2000; revised 18 September 2000; accepted 9 November 2000
ABSTRACT: The Menschutkin reactions of 3,4-methylenedioxybenzyl and 3,4-dimethoxybenzyl bromides and also
p-methoxybenzyl bromide with Y-substituted pyridines were kinetically studied for a range of amine concentration in
acetonitrile. The strongly activated benzyl bromides showed a significant positive intercept in the plot of the pseudo-
first-order rate constants against the concentrations of nucleophiles, while less activated benzyl bromides did not give
such significant intercepts. The rate data for respective substrates were fitted to the equation kobs = k1 ‡ k2[Nu]. The
first-order rate constant, k1, is unaffected by the nature of the nucleophile, whereas the second-order rate constant, k2,
increased with increasing nucleophilicity. This was ascribed to the simultaneous occurrence of SN1 and SN2 reactions
without an intermediate mechanism. These results are taken as evidence for the duality of SN1 and SN2 mechanisms in
the Menschutkin reaction in the non-solvolyzing solvent acetonitrile. Copyright 2001 John Wiley & Sons, Ltd.
KEYWORDS: Menschutkin reaction; benzyl bromides; duality of SN1–SN2 mechanisms
INTRODUCTION
analysis in terms of the correlation interaction coeffi-
cients, rij, led to the conclusion that the reaction
proceeded through the SN2 mechanism in which the
transition state coordinate moved to the tight-loose
direction with benzyl Z-substituents and to the early-late
direction with nucleophile Y-substituents.10,11a
During the course of our continuing studies, we in the
IFOC laboratory found the surprising fact in the above
Menschutkin reaction of benzyl tosylates15 that the
strongly activated benzyl tosylates showed a significant
positive intercept in the plot of the pseudo-first-order rate
constants against the concentrations of nucleophiles,
while less activated benzyl tosylates did not give such
significant intercepts. This was ascribed to the simulta-
neous and independent occurrence of SN1 and SN2
reactions without an intermediate mechanism in non-
solvolyzing solvents. These results led to the conclusion
of the duality of displacement mechanism, the SN1 and
SN2 mechanisms, in the borderline region.
The solvolytic and nucleophilic substitution reactions of
benzylic substrates with nucleophiles have long been a
target of world-wide studies.1-6 Various sophisticated
mechanisms other than the classical Ingold SN1 and SN2
mechanisms1 were proposed for displacement reactions
in the so-called borderline case.3,5-7 Especially the
mechanistic transition from SN2 to SN1 in the displace-
ment reaction has still been the subject of considerable
controversy. Sneen proposed a unification of the SN1 and
SN2 mechanisms in which all nucleophilic substitutions
involve the formation of ion pairs.6 Bentley and co-
workers proposed the concept of continuous spectrum of
SN1–SN2 mechanisms, involving a continuity of solvo-
lytic mechanisms from SN1, via SN2 (intermediate), to the
conventional SN2 mechanism.7
We have been also involved in the investigations by
means of the substituent effect analysis on the mechan-
ism of the Menschutkin reactions of benzylic systems
with various nucleophiles.8–19 In previous studies on the
Menschutkin reaction of Z-substituted benzyl X-benze-
nesulfonates with Y-substituted N, N-dimethylanilines in
acetone or acetonitrile,8,10,13,14 the substituent effect
Later, we extended our substituent effect studies on
reaction mechanisms to the Menschutkin reactions of
substituted benzyl bromides with substituted pyridines
and the related nucleophiles in aprotic solvents. Here also
the concurrent SN1 mechanism will be the case.
*Correspondence to: M. Fujio, Institute for Fundamental Research of
Organic Chemistry, Kyushu University, Hakozaki, Fukuoka 812-8581,
Japan.
Contract/grant sponsor: KOSEF; Contract/grant number: BSRI -
1998–1999.
Copyright 2001 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2001; 14: 123–130

124
S.-D. YOH ET AL.
Table 1. Pseudo-®rst-order rate constants (kobs) for the reactions of strongly activated benzyl bromides 1, 2 and 3 with
unsubstituted pyridine in acetonitrile at 50°Ca
p-MeO (1)
3,4-(MeO)2 (2)
4-OCH2O-3 (3)
1
1
1
1
1
1
[Nu] (mol 1
)
105kobs (s 1) 104k2* (lmol 1s
)
105kobs (s
)
104k2* (lmol 1 s
)
105kobs (s
)
104k2* (lmol 1s
)
0.01
0.03
0.05
0.10
0.15
0.20
0.25
0.30
0.35
17.01
48.8
80.2
158.9
235
170.1
162.6
160.4
158.9
156.6
154.6
153.1
151.8
151.0
20.3
53.0
84.7
162
242
318
203
13.18
37.2
61.8
119.7
180
131.8
123.9
123.6
119.7
120.2
119.1
118.5
117.7
176.6
169.4
161.9
161.0
158.8
158.3
157.4
309
238
383
455
528
396
472
296
353
a
k2* values were evaluated using Eqn. (2); k2* = kobs/[Nu].
Katritzky and co-workers5 studied extensively the
substitution reactions of N-alkyl- and -aralkyl-2,4, 6-
triphenylpyridinium salts with neutral amine nucleo-
philes in non-polar solvents. They also found that the
substitution reactions of the N- (m, p-substituted benzyl)
salts with neutral amine nucleophiles in non-polar
solvents occurred by a competition mechanism of
concurrent first- and second-order substitution reactions.
Through detailed discussions with Professor Katritzky,
the authors arrived at the common consensus in their
opinion on the generality of the competitive occurrence
of the concurrent SN1 and SN2 mechanisms. Our special
interest was therefore strongly focused on the duality of
displacement mechanisms, in the borderline region.
In the present study, in order to ascertain the duality of
SN1 and SN2 mechanisms, we undertook precise kinetic
studies on the reactions of strongly activated benzyl
bromides 1–3 with pyridines in acetonitrile, based on a
detailed analysis of the dependence of rate on the
concentration of nucleophiles.
be detectable non-zero intercepts at zero concentration of
the nucleophile.
Apparent second-order rate constants k2* are not a
constant of the substrate bromide for varying pyridine
concentrations but decrease with increasing pyridine
concentration to approach a constant value at higher
concentrations as shown in Tables 1 and 2.
The apparent rate constants kobs for 2 and 3 with a
series of Y-substituted pyridines all exhibit linear
relations against nucleophile concentrations with differ-
ent slopes (k2*) significantly depending on the nucleo-
RESULTS AND DISCUSSION
The apparent rate constants kobs were determined under
the pseudo-first-order conditions at the concentration
(0.0005 M) of substituted benzyl bromides with various
concentrations of Y-substituted pyridines (0.01–0.3 M).
Apparent second-order rate constants (k2*) were derived
in the usual manner by dividing kobs by nucleophile
concentrations:
kobs ˆ kÃ2‰NuŠ
ꢀ2†
In Table 1 are summarized the rate constants for the
reactions in acetonitrile at 50°C of p-methoxybenzyl (1),
3,4-dimethoxybenzyl (2) and piperonyl (3,4-methylene-
dioxybenzyl) (3) bromides with the nucleophile pyridine
(Y = H). The plots of the pseudo-first-order rate con-
stants, kobs, versus nucleophile concentrations for these
substrates are illustrated in Fig. 1, in which there seem to
Figure 1. Plots of pseudo-®rst-order rate constants (kobs) vs
pyridine concentrations for the reactions of strongly acti-
vated benzyl bromides, 1, 2 and 3, with unsubstituted
pyridine in acetonitrile at 50°C
Copyright 2001 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2001; 14: 123–130

CONCURRENT SN1 AND SN2 REACTIONS IN PYRIDINE BENZYLATION
125
Table 2. Pseudo-®rst-order rate constants (kobs) for the reactions of benzyl bromides 2 and 3 with Y-substituted pyridines in
acetonitrile at 50°Ca
4-OCH2O-3 (3)
3,4-(MeO)2 (2)
1
1
1
1
1
Pyridine Y
4-NH2
[Nu] (mol 1
)
105kobs (s
)
104k2* (lmol 1s
)
105kobs (s
)
104k2* (lmol 1s
)
0.01
0.03
0.05
0.08
0.10
0.01
0.03
0.05
0.10
0.15
0.20
0.25
0.30
0.01
0.03
0.05
0.10
0.15
0.20
0.25
0.30
0.01
0.03
0.05
0.10
0.15
0.20
0.25
0.30
164.4
478
791
1280
1590
51.2
149.0
244
483
729
977
1210
1450
22.8
65.6
107.4
212
312
418
528
626
3.76
6.49
9.79
16.82
23.9
30.9
38.5
45.9
1644
1593
1582
1600
1590
512.1
497
487
483
486
489
484
483
228
219
215
212
208
209
211
209
37.6
21.6
19.6
16.8
15.9
15.5
15.4
15.3
197.6
574
948
1520
1900
68.7
197.2
322
1976
1913
1895
1900
1900
687
657
644
631
626
625
628
630
331
295
285
277
275
274
273
274
3-NH2
4-Me
3-Cl
631
940
1250
1570
1890
33.1
88.4
142.5
277
413
548
682
822
7.77
12.94
17.92
29.8
41.6
53.7
65.4
77.0
77.7
43.1
35.8
29.8
27.8
26.9
26.2
25.7
a
k2* values were evaluated using Eqn. (2); k2* = kobs/ [Nu].
philicity of Y-substituted pyridines, i.e. Y: 4-NH2 4
3-NH2 4 4-Me 4 H 4 3-Cl (Table 2).
bromides with pyridines are determined from the slope
and intercept of the linear plot of kobs versus concentra-
tion of pyridines with Eqn. (3), as shown in Table 3. In
the last column in Table 3 are given the compositions (%)
of the unimolecular reaction in the overall reaction at
[Y-pyridine] = 0.1 M derived based on Eqn. (3).
In the reaction of less activated benzyl bromides17 of
which the substituents Z are less electron-donating than
p-Me, the reaction was accurately first-order in pyridine
concentration following the second-order kinetics of the
equation
In Fig. 2, kobs values for 2 are plotted against the
concentrations of a series of substituted pyridines. The
kobs vs [Nu] plots are all linear with different slopes
characteristic of Y-pyridines, and all the linear plots
converge to an identical positive intercept at [Nu] = 0. In
practice, as shown in Fig. 3, the Y = 3-Cl and also Y = H
runs should give a more accurate kobs value of the
intercept, because of distinctly lower slopes of their kobs
vs [Nu] plots.
The slopes of the linear plots should correspond to the
second-order rate constants, k2, for the bimolecular
reactions of the respective bromide with pyridines, and
the intercept is independent of the nucleophiles and their
concentrations, that is, zeroth order in the nucleophile
and first order in the substrate (bromide).
These kinetic results can be fitted into a kinetic
equation as the sum of zero- and first-order terms to the
nucleophile concentration [Nu]:
kobs ˆ k2‰NuŠ
ꢀ4†
Experimentally, the plots of pseudo-first-order rate
constants kobs vs [Nu] were found to be precisely linear
and all to pass through the origin within the experimental
uncertainty, as generally observed for typical SN2
displacement reactions. It is therefore remarkable that
the strongly electron-donating bromides 1–3 appeared to
give significant positive intercepts in the kobs vs [Nu]
plots, suggesting a competition of unimolecular reaction.
Their k2 values exhibit a significant dependence upon the
nucleophilicity of pyridines and the electron-donating
kobs ˆ k1 ‡ k2‰NuŠ
ꢀ3†
The k2 and k1 values for the reactions of benzyl
Copyright 2001 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2001; 14: 123–130

126
S.-D. YOH ET AL.
Figure 3. Dependence of kobs on concentrations of 3-chloro-
and unsubstituted pyridines in the Menschutkin reactions of
benzyl bromides, 2 and 3, in acetonitrile at 50°C
Figure 2. Plots of pseudo-®rst-order rate constants (kobs) vs
nucleophile concentrations for the reactions of 3,4-di-
methoxybenzyl bromide with Y-substituted pyridines in
acetonitrile at 50°C
ecular mechanism is even more significant for secondary
benzylic systems.16 In the case of 1-phenylethyl bro-
mides, the unimolecular k1 term was observed for the
ability of substituents Z. The first-order rate constant, k1,
remains a constant irrespective of nucleophiles and is
zeroth order in the nucleophile, converging to the same
intercept at [Nu] = 0 as shown in Figs 2 and 3.
In the Menschutkin reactions of relevant benzylic
precursors, as summarized in Table 4, the competition of
the unimolecular mechanism (SN1 reaction) appeared to
be more important in the reactions of the benzyl tosylates
than in the corresponding bromides,15 and the unimol-
+
whole range of electron-donating substituents sz ꢁ 0.16
The kinetic Eqn. (3) is compatible with the simulta-
neous and competitive occurrence of independent SN1
and SN2 processes, and the overall reaction can be
depicted by the mechanistic Scheme 1.
Both the unimolecular and bimolecular rate constants
k1 and k2 should show different susceptibilities to the
Table 3. First-order (k1) and second-order (k2) rate constants for the reactions of Z-substituted benzyl bromides with Y-pyridines
in acetonitrile at 50°C
1
1
Z
Y
na
Rb
Slope 104k2 (lmol 1s
)
Intercept, 105k1 (s
)
100k1/(0.1k2 ‡ k1)c
4-OCH2O-3 (3)
4-NH2
3-NH2
4-Me
H
3-Cl
H
4-NH2
3-NH2
4-Me
H
5
8
8
8
8
9
5
8
8
8
8
0.9999
0.9999
0.9999
0.9999
0.9999
0.9999
0.9999
0.9999
0.9999
0.9999
0.9999
1587
484
2.6
2.6
2.6
2.5
2.3
5.6
6.5
6.4
6.4
6.2
5.8
0.2
0.5
208
1.2
117.4
14.46
150.4
1891
625
272
155.7
23.8
2.1
13.8
3.6
0.3
1.0
2.3
3.9
p-MeO (1)
3,4-(MeO)2 (2)
3-Cl
19.5
a
The number of data.
b Correlation coefficient.
c
Percent reaction by SN1 route at [Y-pyridine] = 0.1 M.
Copyright 2001 John Wiley & Sons, Ltd.
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CONCURRENT SN1 AND SN2 REACTIONS IN PYRIDINE BENZYLATION
127
Table 4. First-order (k1) and second-order (k2) rate constants for the Menschutkin reactions of benzylic substrates
Nucleophile
Slope,
Intercept,
1
1
1
Substrate
Z
Nua and solventb 104k2 (lmol
s
)
105k1 (s
)
100k1/(0.1k2 ‡ k1)c
Benzyl bromide
p-MeOd
p-MeOe
p-MeS
p-MeO
p-MeO
H
Py, AN
Py, AN
DMA, AN
DMA, AN
Py, AN
Py, AN
Py, AN
DMA, AN
150.4
68.8
137
5.6
52
3.6
Benzyl tosylatese
203
60
330f
282
1700f
1660
1-Phenylethyl bromidese,g
1-Phenylethyl tosylatee,h
85
5.5
70
58
0.554
4.53
7.98
0.03
10.8
10.7
H
H
a
Nucleophiles, Nu; Py = pyridine; DMA = N, N-dimethylaniline.
b Solvent; AN = acetonitrile.
c
Percent reaction by SN1 route at [Y-pyridine] = 0.1 M.
d At 50°C.
e
At 35°C.
f Estimated by means of the Yukawa-Tsuno correlations for the k1 and k2 processes; Ref. 15.
g Ref. 16.
h Y. Tsuno and M. Fujio, unpublished work data taken from C. Lim, PhD Dissertation, Kyushu University, Fukuoka, 1998.
‡
benzyl Z-substituents reflecting the nature of two com-
peting mechanistic processes. For the benzyl Z-substi-
and 3 gives a r value of ca. 5, for the difference 0.08
‡
in s for 1 and 3. On the other hand, the corresponding
‡
‡
tuent effects, the resonance-enhanced scale s appears
reactivity difference log (k2)1/(k2)3 ꢂ 0.1 for this s
‡
‡
perhaps to be appropriate. The apparent s values for p-
range gives a small r of 1 and also a lower r value of
methoxy and 3,4-methylenedioxy groups were available
from the solvolysis of 1-phenylethyl chlorides, by means
of the Yukawa–Tsuno equation:20
0.5 for electron-withdrawing substituents from pre-
viously reported data.17
‡
The r value of 5 for the unimolecular reaction is
comparable to those for typical SN1 solvolyses of
‡
benzylic substrates. The curved s plot with smaller
‡
logꢀk=k0† ˆ ꢀꢀꢁ0 ‡ rÁꢁR †
ꢀ5†
‡
varying r for the bimolecular reaction is characteristic
of the SN2 mechanism, involving the tight–loose
coordinate shift of the transition state with Z-substituents.
The ionizing power of the solvent will render it
possible to distinguish between the unimolecular SN1 and
the bimolecular SN2 mechanisms. The apparent kobs for
3,4-dimethoxybenzyl bromide (2) with pyridine increases
with increasing content of TFE in the range 0–5% (v/v) in
binary acetonitrile–2,2,2-trifluoroethanol (TFE) mixtures
at 50°C (Table 5). In Fig. 4, the plot of log kobs vs [Nu]
for 2 in neat acetonitrile solution moves upwards in a
In the solvolysis of 1-phenylethyl chlorides, the
apparent s values at r = 1.14 were given as 0.923
‡
for p-MeO and 0.845 for 3,4-methylenedioxy substi-
‡
‡
tuents; the difference (s1 s3 ) should be constant at
0.078 irrespective of minor changes in the r parameter
of the system (Y. Tsuno and M. Fujio, unpublished
‡
work). The s value of 3,4-dimethoxy substituent in the
present system appears to be slightly more negative than
the value for the p-methoxy group; this is reasonable for
‡
the s -type reactions in aprotic acetonitrile solution.
Hence the unimolecular reaction of which the
reactivity difference of log (k1)1/(k1)3 = 0.40 between 1
Table 5. Pseudo-®rst-order rate constants (kobs) for the
reactions of 3,4-dimethoxybenzyl bromide with pyridine in
TFE±acetonitrile mixtures at 50°C
1
105kobs/(s
)
1
[Pyridine] (mol 1
)
2% (v/v) TFE
5% (v/v) TFE
0.01
0.03
0.05
0.10
0.15
0.20
0.25
30.0
63.1
93.8
173.7
253
328
405
485
54.6
89.8
120.6
197.5
279
357
434
511
0.30
105k1 (s
)
16.1
156.2
41.4
157.1
1
104k2 (l mol
s )
1
1
Scheme 1
Copyright 2001 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2001; 14: 123–130

128
S.-D. YOH ET AL.
reaction rate constant kS 1* can be expressed by
N
kS 1* ˆ k1k0 ‰NuŠ=ꢀk ‡ k0 ‰NuŠ†
ꢀ6†
1
N
2
2
Hence, when k2' [Nu] ꢃ k 1, Eqn. (6) should be reduced
to the simple unimolecular rate equation, whereas Eqn.
(6) corresponds to the bimolecular rate equation [Eqn.
(4)] when k 1 ꢃ k2' [Nu]. This constitutes the basis of the
Sneen unified ion-pair merged mechanism6 of nucleo-
philic substitution. Nevertheless, whereas this merged
mechanism may describe either the SN1 or the SN2
mechanism in terms of whether k 1 ꢄ k2' [Nu] or
k
1 ꢃ k2' [Nu], it does not interpret the concurrent SN1
and SN2 mechanisms, i.e. Eqn. (3).
The present results are not compatible with the Sneen
merged mechanism,6 and the simplest scheme of the
whole reaction should be described by Eqn. (3) or Eqn.
(7) with k 1 ꢄ k2' [Nu]:
kobs ˆ k1 ‡ k2‰NuŠ
ˆ k1k0 ‰NuŠ=ꢀk ‡ k0 ‰NuŠ† ‡ k2‰NuŠ
ꢀ7†
1
2
2
Both terms are exactly referred to the classical SN1 and
SN2 mechanisms by the Ingold definition.1 We believe
that the results provide evidence for the duality of
mechanisms at least for highly activated benzyl bromides
even in the presence of a good nucleophile in acetonitrile.
However, if k 1 ꢃ k2' [Nu], the SN1 mechanism does not
compete with the SN2 mechanism from this simplest
Scheme 1.
Figure 4. Plots of pseudo-®rst-order rate constants (kobs) vs
nucleophile concentrations for the reactions of 3,4-di-
methoxybenzyl bromide with pyridine in TFE±acetonitrile
mixtures at 50°C
According to the Winstein ion-pair scheme (Scheme
2),3 when k 1 ꢃ k2' [Nu], the SN1 mechanism should
operate at the second carbocation (or the final ion pair)
intermediate, of which the foregoing transition state is
essentially rate determining. Provided k C ꢄ kn [Nu],
parallel manner with increasing TFE content in solvent;
the increasing TFE content brings about higher inter-
cepts, i.e. enhanced k1 values, without a change in the
slope of the plot, i.e. no change in k2. These results imply
that the unimolecular process should have a highly
carbocationic transition state (most plausibly referred to
as an SN1 mechanism) but the bimolecular process an
essentially neutral or uncharged transition state (SN2
mechanism). Essentially the same solvent effect has been
observed in the reaction of 1-phenylethyl arenesulfona-
tes.21
The SN1 mechanism can be evidenced by the detection
of the return (k 1) process from the intermediate to the
reactant. In the Menschutkin reaction of benzyl tosylate,
the 18O scrambling of the alkoxy oxygen within the
sulfonyl-O labeled tosylates-S(18O)2 was detected with or
without N,N-dimethylanilines in acetonitrile.22 These
findings provide strong support for the concurrent k1
ionization process of an SN1 mechanism.
k
obs can be given by a kinetic equation:
kobs ꢂ ꢀk2 ‡ K1k02†‰NuŠ ‡ K1kc
ꢀ8†
where K1 = k1/k 1. The form of the equation does not
depend on the number of intervening ion-pair inter-
mediates; the term K1k2' [Nu] may be replaced by the sum
of terms [Nu]Æ(K1k2)i. Thus the SN1 and SN2 mechan-
isms remain distinct from their molecularity (or the
kinetic order) in the present reaction.
The Bentley-Schleyer concept of a continuous spec-
trum of SN1–SN2 mechanisms7 involves the SN2 (inter-
We have taken the present results as convincing
evidence for the occurrence of simultaneous SN1 and SN2
mechanisms but against the mechanism with a single
process involving either a common intermediate or a
transition state, in the reaction of activated benzyl
bromides with amines.
Scheme 2
For the so-called SN1 mechanism, the apparent
Copyright 2001 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2001; 14: 123–130

CONCURRENT SN1 AND SN2 REACTIONS IN PYRIDINE BENZYLATION
129
mediate) mechanism, given by the term K1k2' [Nu] in
Eqn. (8), which may correspond to the Sneen SN2
mechanism. Whereas we see a continuous series of SN2
mechanisms of varying tightness for the bimolecular
process on changing the Z substituents, the SN2
(intermediate) should be the loosest (most dissociative)
limit of the SN2 transition state. Nevertheless, this
mechanism is still discernible from the unimolecular
ionization mechanism, even though it closely resembles
in structure the transition state of the SN1 mechanism.15,16
Katritzky and co-workers’ amine exchange of benzyl-
2,4,6-triphenylpyridinium ion is virtually an identity reac-
tion, which is conceivably an ideal system to be described
by a continuous spectrum of SN2 mechanisms of varying
tightness.5 The competition of the unimolecular reaction
must be highly enhanced. The bulky leaving group should
enhance the dissociation but retard the SN2 reaction by
steric hindrance to the approaching nucleophile. In addi-
tion, the aprotic solvent should be favorable for the SN2
mechanism but not unfavorable for the SN1 mechanism of
the positively charged (or almost neutral) leaving groups.
Nevertheless, the duality of SN1–SN2 mechanisms is in fact
independent of the different natures of the leaving groups.
Furthermore, the reactions of p-methoxybenzyl bromide
(1) with pyridines or with thiourea in aqueous acetone
solution were also found to proceed by simultaneous SN1
and SN2 mechanisms.23 The simultaneous occurrence of
independent SN1 and SN2 mechanisms is believed to be
fairly general and not specific to the present Menschutkin
system in aprotic solvents.
0°C for several hours. The product was extracted with
diethyl ether, washed twice, treated with 10% K2CO3
solution and then distilled under reduced pressure. The
crude piperonyl bromide was purified by recrystallization
1
from diethyl ether-hexane; m.p. 48°C (lit.24 49°C); H
NMR (CDCl3), ꢂ 4.71 (s, 2H, CH2), 6.13 (s, 2H,
—OCH2O—), 6.90–7.24 (m, 3H, aromatic). p-MeO
derivative; liquid; 1H NMR (CDCl3), ꢂ 3.79 (s, 3H,
CH3O), 4.61 (s, 2H, CH2), 6.83–7.49 (m, 4H, aromatic).
3,4-(MeO)2 derivative; m.p. 39–41°C; 1H NMR
(CDCl3), ꢂ 4.04 (s, 6H, (CH3O)2), 4.62 (s, 2H, CH2),
7.14–7.48 (m, 3H, aromatic).
Kinetic measurements. The reaction rates of substituted
benzyl bromides with pyridine in acetonitrile at 50°C
were measured using a conductimetric method15 by
following the conductance changes of the quaternary
pyridinium salts formed in the reaction as shown in Eqn.
(1).
All kinetic runs were carried out under the pseudo-
first-order conditions with initial concentrations of 0.01–
0.30 M pyridine, which are 20–600 times larger than the
initial concentration (0.0005 M) of the substrate, benzyl
bromides.
The second- and first-order rate constants k2 and k1 in
Eqn. (3) were determined by the least - squares method as
the slope and intercept of the plot of pseudo-first-order
rate constants kobs vs [Nu]; correlation coefficients R
>0.9999.
Finally, the nature of the Menschutkin reaction as a
typical bimolecular mechanism can also be most clearly
demonstrated by the substituent effects of nucleophiles by
means of the Brønsted-type or the Hammett-type relation-
ships.4a The ry values in the log k2 vs sry relationship19 for
the nucleophile substituent effects of these bromides 2 and
3 (in Tables 1 and 2) are 1.85 and 1.98. These ry
values refer to the Brønsted-type b values, 0.25 and 0.27.
The magnitudes of these ry and b values are very
compatible with the bimolecular process of the dissocia-
tive SN2 mechanism.11 Detailed discussion on this point
will be reported, including full data for electron-with-
drawing Z-benzyl substrates, in separate papers.
Acknowledgements
This work was partially supported by the KOSEF through
the Center for Biofunctional Molecules and the Basic
Research Institute Program, Ministry of Education,
Korea (BSRI - 1998–1999).
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