Intramolecular nucleophilic assistance in the solvolyses of benzyl derivatives: Solvolyses of o-nitrobenzyl bromide and tosylate

Article abstract of DOI:10.3184/030823407X207059

The specific rates of solvolysis of onitrobenzyl p-toluenesulfonate (1) have been measured in a wide range of solvents. Comparison with the previously studied para-isomer (2) indicates very similar behaviour (dominant S _N2 pathway) in solvents without fluoroalcohol content. With an appreciable fluoroalcohol component, the specific rates are considerably higher than those predicted based on the comparison with the solvolysis of 2 and intramolecular participation by the ortho-nitro group is implicated. Consistent with this postulate, in 97% 2,2,2-trifluoroethanol, the entropy of activation for the solvolysis is considerably less negative for 1 than for 2. Measurements in four representative solvents of the specific rates of solvolysis of the bromides led to k_OTs/k_Br ratios of 10 to 30, consistent with appreciable nucleophilic assistance (by either solvent or nitro group) in the rate-determining step. For the solvents with an appreciable fluoroalcohol content, an analysis using the extended Grunwald-Winstein equation shows a negligible sensitivity towards changes in solvent nucleophilicity and a low (m = 0.27 ± 0.02) sensitivity towards changes in solvent ionising power. The low m value may result from a favourable solvation of the leaving group being partially counterbalanced by an unfavourable solvation of the nucleophilic nitro group.

Full text of DOI:10.3184/030823407X207059

210 RESEARCH PAPER
APRIL, 210–215
JOURNAL OF CHEMICAL RESEARCH 2007
Intramolecular nucleophilic assistance in the solvolyses of benzyl
derivatives: solvolyses of o-nitrobenzyl bromide and tosylate
Dennis N. Kevill*a and Jin Burm Kyongb
aDepartment of Chemistry and Biochemistry, Northern Illinois University, DeKalb, Illinois, 60115-2862, USA
bDepartment of Chemistry and Applied Chemistry, Hanyang University, Ansan-si, Gyeonggi-do 426-791, Korea
The specific rates of solvolysis of o-nitrobenzyl p-toluenesulfonate (1) have been measured in a wide range of
solvents. Comparison with the previously studied para-isomer (2) indicates very similar behaviour (dominant SN2
pathway) in solvents without fluoroalcohol content. With an appreciable fluoroalcohol component, the specific rates
are considerably higher than those predicted based on the comparison with the solvolysis of 2 and intramolecular
participation by the ortho-nitro group is implicated. Consistent with this postulate, in 97% 2,2,2-trifluoroethanol,
the entropy of activation for the solvolysis is considerably less negative for 1 than for 2. Measurements in four
representative solvents of the specific rates of solvolysis of the bromides led to kOTs/kBr ratios of 10 to 30, consistent
with appreciable nucleophilic assistance (by either solvent or nitro group) in the rate-determining step. For the
solvents with an appreciable fluoroalcohol content, an analysis using the extended Grunwald–Winstein equation
shows a negligible sensitivity towards changes in solvent nucleophilicity and a low (m = 0.27 ± 0.02) sensitivity
towards changes in solvent ionising power. The low m value may result from a favourable solvation of the leaving
group being partially counterbalanced by an unfavourable solvation of the nucleophilic nitro group.
Keywords: solvolysis, o-nitrobenzyl derivatives, intramolecular nucleophilic assistance
About 40 years ago, Andrews, Keefer and coworkers studied
the effects of ortho-substitution on nucleophilic displacement
reactions of benzylic and benzhydrylic derivatives.1-3
They proposed that ortho-substituents which possess a
nucleophilic centre are capable of giving intramolecular
assistance to reaction, and they showed that, in favourable
situations, products consistent with such an interaction are
formed. For a benzylic attack, the process can be formulated
as in eqn (1). In many instances, the initial product undergoes
further reactions with or without opening of the initially-
formed ring.
Despite a third of the product apparently being formed as
in eqn (2), the overall rate of reaction was only 62% of that
for the parallel solvolysis of p-nitrobenzyl p-toluenesulfonate
(2), where solvent assistance in an SN2 process is well
established.6,7 This value is similar to values of 88% reported2
both for hydrolysis of 1 in 90% aqueous acetone at 32.5°C
and for solvolyses of the corresponding chlorides in 50%
aqueous acetone at 60°C.1,8 The values of just a little less than
unity for the ratio of the specific rates of hydrolysis suggests
the operation of an SN2 pathway for both 1 and 2, with a steric
retardation of solvent attack upon the ortho-isomer 1 being
partially counterbalanced by the accompanying operation of
an intramolecular attack pathway [eqn (2)], available only for
the reactions of 1.
An alternative pathway for the hydrolyses of 1 would
involve an initial direct substitution reaction to give the
corresponding alcohol, followed by a slow conversion into
o-nitrosobenzaldehyde. Such a conversion has been observed
in the presence of strong acids,4,9 but not under the much milder
conditions of a low concentration of acid in 50% acetonitrile.
Unfortunately, neither the concentration of reactant (which
determines the amount of acid produced) nor values for the
product ratio as a function of time were reported.
X
Z+
Y
CH2
:Z
Y
CH2
(1)
X-
The organic product from the hydrolysis of o-nitrobenzhydryl
bromide in 90% aqueous acetone was found to be o-nitro-
sobenzophenone,2 presumably formed by ring closure as
in eqn (1) followed by proton removal with ring opening.3,4
It was further proposed2 that the o-nitro group was much less
efficient in competing with alternative pathways in reactions
of benzylic systems. A more recent study,5 at 47.5°C in
50% aqueous acetonitrile, found that, after solvolysis of
o-nitrobenzyl p-toluenesulfonate (tosylate) 1 for 6 h, 35%
of o-nitrosobenzaldehyde and 65% o-nitrobenzyl alcohol
were the only observed organic products. The formation of
the o-nitrosobenzaldehyde was proposed to follow a parallel
pathway [eqn (2)] to that previously put forward2 for the
formation of the o-nitrosobenzophenone in the solvolysis of
the o-nitrobenzhydryl bromide.
In an attempt to define better the reaction pathways for
reactions of o-nitrobenzyl derivatives under solvolytic
conditions, we have applied the extended Grunwald–Winstein
equation10 [eqn (3)] to the solvolyses of 1.
log(k/ko) = l NT + mYx + c
(3)
In eqn (3), k and ko are the specific rates of solvolysis of a
substrate RX in a given solvent and in 80% ethanol, respectively;
l is the sensitivity to changes in solvent nucleophilicity (NT);11
m is the sensitivity to changes in solvent ionising power (YX,
for leaving group X);12 c is a constant (residual) term. This
analysis has been coupled with a consideration of activation
parameters and with a comparison with corresponding reactions
of the p-isomer (2), thoroughly studied previously in terms
of specific rates7,13 and followed by the application of eqn (3)14
or related equations.7,13 Parallel studies of the solvolyses of
o- and p- nitrobenzyl bromides allow the determination of
the tosylate/bromide leaving group effect ratios. This ratio
is a useful tool in mechanistic investigations of nucleophilic
substitution reactions.15
H
O
TsO
CH2
O
O-
O
C
CH2
N+
N+
N=O
O
(2)
-OTs-
:B
+BH+
1
* Correspondent. E-mail:dkevill@niu.edu
PAPER: 07/4504

JOURNAL OF CHEMICAL RESEARCH 2007 211
the solvolyses of two ortho-substituted benzyl bromides,
which were known to have the possibility of intramolecular
nucleophilic attack at the α–carbon. The substrates used in
these investigations were o-carboxybenzyl bromide (3),16
p-carboxybenzyl bromide (4),16 o-carbomethoxybenzyl
bromide (5),17 and p-carbomethoxybenzyl bromide (6).17
Results
The specific rates of acid production from o-nitrobenzyl
tosylate (1) were obtained in 27 solvents at 45.0°C (Table 1).
The solvents consisted of ethanol, methanol, 2,2,2-
trifluoroethanol (TFE) and of mixtures of water with these
three solvents and with 1,1,1,3,3,3-hexafluoro-2-propanol
(HFIP), acetone and acetonitrile. Also used in the study was
the full range of TFE–ethanol mixtures. The measurements
in 80% ethanol (v/v) and 97% TFE (w/w) were also made at
three additional temperatures and all four temperatures were
used to calculate enthalpies (ΔH‡) and entropies (ΔS‡) of
activation (footnotes to Table 1).
The specific rates of solvolyses of o-nitrobenzyl bromide
were measured at 45.0 or 62.5°C in 80% ethanol, 50% ethanol,
97% TFE, and 70% TFE. Identical determinations with the
para-isomer were made in 80% ethanol, 50% ethanol, and 70%
TFE. These values are given in Table 2. In 97% TFE, the rates
for the para-isomer were too low for accurate measurement.
CH2Br
CH2Br
CH2Br
CH2Br
COOH
COOCH3
COOCH3
COOH
3
5
4
6
For the para-isomer 4, an acceptable correlation, using eqn
(3) correlation coefficient (R) of 0.973, was obtained16 over
the full range of solvents, with an l value of 1.24 ± 0.09
and an m value of 0.59 ± 0.05. These values are consistent
with a bimolecular process with appreciable nucleophilic
participation by the solvent. The products were those of direct
displacement of bromide by the hydroxylic components of the
Discussion
We have recently reported our studies concerning the utility
of eqn (3) in investigations of the reaction mechanisms for
Table 1 Specific rates of solvolysis of o-nitrobenzyl p-toluenesulfonate (k0) at 45.0°C and a comparison with the corresponding
values for the p-isomer (kp), plus NT and YOTs values for the solvents, and estimated percentages of overall reaction proceeding by
the intramolecular pathway
c
d
Solventa
105ko/s-1
ko/kp b
NT
YOTs
%Intrae
100% EtOH
90% EtOH
80% EtOH
70% EtOH
50% EtOH
100% MeOH
90% MeOH
80% MeOH
60% MeOH
50% MeOH
80% Acetone
60% Acetone
50% Acetone
50% CH3CN
100% TFE
97% TFE
0.980 0.008
2.40 0.03
3.74 0.10f
5.04 0.02
10.0 0.1
0.54
0.50
0.51
0.50
0.55
0.66
0.37
0.16
–1.95
–0.77
0.00
0.47
1.29
–0.92
–0.05
0.47
1.52
2.00
–0.94
0.66
1.26
1.20
1.77
1.83
1.90
2.00
2.14
3.61
2.90
2.40
2.26
0.98
0.21
–0.44
–1.18
26
22
0.00
23
–0.20
–0.58
0.17
23
19
2.78 0.05
4.96 0.03
7.99 0.08
16.4 0.1
17
–0.01
–0.06
–0.54
–0.75
–0.37
–0.52
–0.70
(–1.06)h
–3.93
–3.30
–2.55
–1.98
–1.73
–5.26
–3.84
–2.94
–2.49
–1.76
–0.94
–0.34
0.08
17
0.63
0.61
0.60
0.51
0.52
0.53
0.65
14
14
23.6 0.2
13
0.398 0.003
1.66 0.03
3.35 0.08
3.00 0.18g
3.29 0.06
2.87 0.08i
2.63 0.04
3.76 0.06
5.07 0.07
8.32 0.07
4.51 0.07
3.82 0.05
4.08 0.08
1.93 0.06
1.42 0.09
1.22 0.05
1.14 0.02
(119)
78
56
61
79
33.0k
10.5k
2.8k
95
90% TFE
108
80
70% TFE
50% TFE
1.2k
65
97% HFIP
90% HFIP
70% HFIP
50% HFIP
80T–20El
100
(118)
102
87
3.74
1.36
0.81
0.57
82
60T–40El
69
40T–60El
53
20T–80El
36
aMixed at 25.0°C on a volume–volume basis, except for TFE–H2O and HFIP–H2O mixtures, which are on a weight-weight basis.
c
e
bThe kP values are from ref 7. Values from ref 11. dValues from ref 12. Based on estimated logkintra values, calculated as 0.274
f
NT-5.068 (see discussion section). Also values of 1.15 0.01 at 35.1°C, 11.6 0.2 at 58.1°C, and 17.3 0.2 at 62.5°C; activation
parameters (based on the four temperatures) of 19.4 0.8 kcal mol-1 for DH‡
and -17.9 2.6 cal mol-1K-1 for DS‡
.
gAlso a
value of 3.87 0.06 at 47.5°C (ref. 5 gives this 105k0 value as 3.63 s-1). hNTD value, based on solvolyses of the S-methylt3h1i8o.2phenium
ion (ref 11b). iAlso values of 0.921 0.031 at 35.1°C, 10.3 0.1 at 58.1°C, and 15.4 0.2 at 62.5°C; activation parameters (based on
four temperatures) of 20.4 0.3 kcal mol-1 for DH‡318.2 and -15.3 1.1 cal mol-1K-1 for DS‡318.2. j Using a value of for 105kP of 0.0869,
obtained (ref. 7) from values at other temperatures. k Using interpolated 105kP values of 0.251 in 90% TFE, 1.33 in 70% TFE, and 4.17
in 50% TFE (estimated from the values at the volume–volume compositions reported in ref. 7). lT–E are TFE–ethanol mixtures.
318.2
Table 2 Specific rates of solvolysis of o- and p-nitrobenzyl bromides (ko and kp) and ko/kp and kOTs/kBr ratios
a
a
Solvent
Temp/°C
105ko/s-1
kOTs/kBr
105kP/s-1
kOTs/kBr
ko/kP
80% EtOH
80% EtOH
50% EtOH
97% TFE
70% TFE
45.0
62.5
45.0
62.5
45.0
0.304 0.004
1.74 0.02
0.813 0.018
0.508 0.005
0.154 0.003
12.3
9.9
12.3
30.3
24.4
0.323 0.009
1.83 0.02
22.7
0.94
0.95
0.91
0.891 0.009
20.5
b
0.057 0.002
15.9
2.68
aRatio of the specific rates of solvolyses with tosylate or bromide as the leaving group (tosylate values from Table 1). b Very slow reaction.
PAPER: 07/4504

212 JOURNAL OF CHEMICAL RESEARCH 2007
solvent. For the corresponding ortho-isomer 3, the products
in ethanol and aqueous ethanol were primarily (>90%) the
phthalide,16 presumably formed by intramolecular nucleophilic
attack by the carboxyl group. Despite the formation of
the ring-closed product, application of eqn (3) showed an
appreciable dependence on the solvent nucleophilicity value
but with a rather inferior correlation (R = 0.933). The l value
was 0.90 ± 0.14 and the m value was 0.49 ± 0.10. This
combination of observations is best rationalised by invoking
general-base catalysis by the solvent to the intramolecular
substitution process, with the basicity of the solvent being
only approximately related to its nucleophilicity [eqn (4)].
Accordingly, the kinetic behaviour of 1 should be closer
to that observed for solvolyses of 5 than that observed for
solvolyses of 3.
While an ortho-nitro group was found to function efficiently
in the solvolyses of o-nitrobenzhydryl bromide, with ortho/
para ratios in the 100–25,000 range, it was found2 to be much
less effective in the solvolyses of 1, with the ortho-isomer
reacting in 90% acetone slightly slower than the para-isomer,
the ratio of 0.88 being identical to that previously observed17
in 50% acetone for the bromides. It was concluded2 that
the study was “not definitive” as regards nucleophilic
participation by the ortho-nitro group in the solvolyses of 1
in aqueous acetone. In a subsequent study,3 it was suggested
that participation by an ortho-subsituent will be promoted by
use of a solvent “less favourably constituted to provide for
nucleophilic solvation of carbon at the reaction centre.” This
statement also provides an early formulation of the concept
of stabilisation of developing charge on the α–carbon by
nucleophilic solvation. The use of solvents with an appreciable
fluoroalcohol content will satisfy the proposed3 requirement,
since the NT values will be appreciably negative. Indeed the
use of these solvents as low nucleophilicity and high ionising
power solvents is well established.11,19,20 The present kinetic
studies are carried out with a wide range of solvent type,
including solvents rich in TFE and HFIP.
S
Br
O
CH2
O
H
CH2
O
H
C
C=O
(4)
O
SOH2+Br +
The ortho-isomer 3 reacted considerably faster than the para-
isomer 4: by a factor of 59 in 80% ethanol and 157 in 70%
TFE (both values at 45°).
If the pathway of eqn (4) is correct, then markedly
different behaviour is to be expected for 5, which has the
acidic hydrogen of the carboxylic acid replaced by a methyl
group. In contrast, the corresponding para-isomer 6 should
show solvolytic behaviour not appreciably altered from that
observed for 4. These predictions are borne out in practice.17
All of the solvolyses of 6 proceed with very similar rates to the
corresponding solvolyses of 4. For the 16 solvents for which
values are available under identical conditions, the ratio for
the specific rates of solvolyses of 6 relative to 4 varies from
0.8 to 1.7. As one would expect from this observation, the
l value of 1.17 and the m value of 0.57 are also very similar to
those for 4.
For solvolyses in solvents without any fluoroalcohol
content, a good linear free energy relationship (LFER) was
given between the specific rates of solvolyses of 5 and 6 with
a slope of 1.00, intercept of 0.05 and correlation coefficient (r)
of 0.994. Of especial interest was the observation that placing
the specific rates in TFE-containing solvents on the LFER
plot, showed appreciable positive deviations for the added data
points, consistent with a superimposed intramolecular reaction
pathway. In a separate consideration of the solvolyses of 5 in
TFE-containing solvents, a good correlation was obtained,
after deduction of the predicted intermolecular component,
for six solvents using the simple (original18) Grunwald–
Winstein equation [eqn (3) without the lNT term]. The slope
of a plot of log k against YBr was 0.24 ± 0.02 (correlation
coefficient of 0.999). For reaction of 5 in 100% ethanol
about 11% of the ring-closed phthalide was observed, and
this percentage rose to 43% in 50% ethanol. The ortho/para
rate ratio was remarkably constant at 1.8 to 2.5 in mixtures
of water with ethanol, methanol, and acetone. It rose with
increasing TFE content, reaching a value of 69 in 90% TFE.17
The intramolecular participation by an ortho-nitro group
[eqn (2)] will have characteristics similar to those for a
carboalkoxy (or carboaroxy3) group, where an intermediate as
in eqn (5) (formulated for the methyl ester) will be expected.1
In the recently reported17 study this then transfers the methyl
group so as to give the observed1,17 phthalide.
A previous correlation,14 using eqn (3) of the specific rates
of solvolysis of 2 at 45.0°C in 34 solvents, led to a good
correlation (R = 0.987) over the full range of solvents with an
l value of 1.04 and an m value of 0.65, typical values for an SN2
process. The present study of the specific rates of solvolysis of
1 shows, as predicted above, behaviour similar to that of 5.
An LFER plot of log(k/k0) values for 1 (using k values from
Table 1) against log(k/k0) values for 2 (k values from the
literature13) shows an excellent linear correlation (r = 0.995)
in ethanol, methanol, and mixtures of water with ethanol,
methanol, acetonitrile, and acetone (Fig. 1); the slope of the
plot (m value) is 1.03 ± 0.03 and the intercept is 0.05 ± 0.02
[eqn (6)]. Consistent with this behaviour, for these solvents,
the ratio of the specific rates of solvolyses (ko/kp) varies only
slightly, with a range of 0.50 to 0.66. An earlier value of 0.88
in 90% acetone at 32.5°C has been reported,2 in the present
log(k/ko)ortho = 1.03 log(k/ko)para + 0.05
(6)
CH2
CH2
O
C
O
Fig. 1 Plot of log(k/ko) for solvolyses of o-nitrobenzyl tosylate
against log(k/ko) for solvolyses of p-nitrobenzyl tosylate at
45.0°C for solvolyses in solvents not containing a fluoroalcohol
component.
C=O-CH3
O
CH3
(5)
PAPER: 07/4504

JOURNAL OF CHEMICAL RESEARCH 2007 213
Fig3 Plotof(5+logk)againstYOTs valuesfortheintramolecular
component to the reaction of o-nitrobenzyl tosylate.
Fig 2 Plot of log(k/ko) for solvolyses of o-nitrobenzyl tosylate
against log(k/ko) for solvolyses of p-nitrobenzyl tosylate at
45.0°C for all the studied solvents.
component (kintra), after subtraction of the SN2 component, are
used in the correlation. With the one-term equation, values are
obtained of 0.27 ± 0.02 for m, –5.07 ± 0.04 for c, 0.980 for r,
and 213 for the F-test value (Figure 3). There is essentially
no improvement to the correlation on application of the two-
term equation, with values of –0.02 ± 0.02 for l, 0.25 ± 0.03
for m, –5.08 ± 0.04 for c, 0.981 for R, and 104 for the F-test
value. The data are best described using the one-term equation
with kintra values [eqn (7)]. The low m value may result from a
study only acetone contents of 80% or less were studied.
The ko/kP ratio is higher for TFE–H2O solvents, reaching
a value of 33 for 97% TFE. Accordingly, the fluoroalcohol-
containing solvents lie above the plot shown in Fig. 1,
as is demonstrated in Fig. 2. In Fig. 2 the specific rates for
p-nitrobenzyl tosylate solvolysis in HFIP–H2O mixtures are
estimated values, obtained using values14 for l of 1.04, for m
of 0.65 and for c of 0.00 together with a value for ko of 7.32 ×
10-5 s-1 within eqn (3).
logkintra = 0.27YOTs–5.07
(7)
The deviations from the plot can be taken as a measure
of the extent of an additional mechanism, presumably
the intramolecular participation mechanism of eqn (2).
With 90% or more fluoroalcohol content, over 95% of the
reaction follows the intramolecular pathway. Those solvents
with in excess of 60% of the overall reaction proceeding
by the intramolecular pathway are listed in Table 3. The
listed specific rates are treated by the simple and extended
Grunwald–Winstein equations [eqn (3) without or with the
lNT term]. Using uncorrected values, designated as ko (from
Table 1), a plot of the logarithm of the specific rate value
against YOTs leads to a slope (m value) of 0.22 ± 0.02, c value
of –4.90 ± 0.05, r value of 0.954, and F-test value of 92 with
the one-term equation and 0.03 ± 0.03 for l, 0.25 ± 0.04 for
m, –4.88 ± 0.05 for c, 0.960 for R, and 47 for the F-test value
with the two-term equation.
combination of internal assistance from the nitro group,
which would be expected to lower the value to about 0.5
(the value for methyl p-toluenesulfonate solvolyses when
eqn (3) is employed11), and the influence of the solvent on
the nucleophilicity of the nitro group, with increased solvent
electrophilicity favouring the expulsion of the leaving group
but, also, favouring increased solvation of the nitro group
with a reduction in its nucleophilicity. The c values can be
considered as a measure of the logko value (in 80% ethanol)
for the intramolecular pathway. It corresponds to a ko value of
0.85 × 10-5 s-1, 23% of the overall specific rate in this solvent.
The kintra values can be calculated for any other compositions of
known YOTs and, for aqueous methanol and ethanol, the
percentages of overall reaction proceeding by the intramolec-
ular pathway vary from 13 to 26% (last column of Table 1).
The values calculated for aqueous acetone appear to be
unreasonably high. This is especially obvious for the solvolysis
As one would anticipate, the correlations are considerably
improved when the estimated values for the intramolecular
Table 3 Estimated specific rate values, at 45.0°C for the SN2 component in the solvolyses of o-nitrobenzyl tosylate in fluoroalcohol-
containing solvents and the accompanying contributions from the intramolecular pathway
d
Solventa
105ko b/s-1
%SN2c
105ko
intra
SN2
100% TFE
97% TFE
90% TFE
70% TFE
50% TFE
97% HFIP
90% HFIP
70% HFIP
50% HFIP
80T–20E
60T–40E
0.00414
0.0221
0.131
0.13
0.84
4.9
18.3
31.0
0.03
0.64
3.2
3.29
2.84
2.51
3.07
3.50
8.32
4.48
3.70
3.79
1.66
0.85
0.689
1.57
0.00250
0.0289
0.122
0.294
7.2
14.1
40.0
0.270
0.568
aOn weight-weight basis, except the TFE–ethanol (T–E) mixtures are on a volume–volume basis. bEstimated from the SN2 values
for p-nitrobenzyl tosylate using eqn (6). Some of the required p-nitrobenzyl tosylate values were by interpolation (TFE–H2O) or
estimated using log(k/ko) = 1.04NT + 0.65YOTs (ref. 14) cUsing overall specific rates from Table 1. d For each solvent, the koSN2 values
are subtracted from the ko values of Table 1.
PAPER: 07/4504

214 JOURNAL OF CHEMICAL RESEARCH 2007
in 80% acetone, where the calculated intramolecular specific
rate is 20% higher than the overall experimental value. Also,
in Fig. 2, the 80% acetone data point lies considerably below
the plot, suggesting that some additional factor may be
operating in the aqueous-acetone mixtures. The percentages
are also much higher than the aqueous ethanol and aqueous
methanol values for 60% and 50% acetone and for 50%
CH3CN. The value of 61% intramolecular rection estimated
for 50% CH3CN is of especial interest because product
studies are available5 at a temperature (47.5°C) which is only
slightly higher. The product studies showed a 35% yield of
the ring closure/ring opening product, o-nitrosobenzaldehyde,
and 65% of the direct replacement substitution product,
o-nitrobenzyl alcohol.
The indicated pathway to the aldehyde is as in eqn (2).
However, the ring-closed intermediate could in addition to
undergoing proton abstraction from the α–carbon, leading to
elimination reaction, also undergo nucleophilic attack at the
carbon atom to give a second route to the substitution product.
Accordingly, the 35% yield of nitrosoaldehyde must be
considered as a minimum value for the extent of intramolecular
participation, and there is not necessarily any conflict with our
estimated value of 61%. The calculations indicate (Table 1)
that the intramolecular pathway dominates for solvolyses of 1
in solvents rich in fluoroalcohol and its participation does not
fall to below 10% in any of the studied solvents.
participation, not appreciably different to the values in
aqueous ethanol or to corresponding values for the solvolyses
of 2, instances where solvent attack either dominates or is
the exclusive pathway. This is not surprising because kOTs
/
kBr ratios (in the absence of steric crowding26) are usually
taken to reflect the charge development on the leaving group,
which in turn is closely related to the extent of bond breaking.
The attack by solvent or by internal nucleophile will involve
similar extents of bond fission to the nucleofuge at the
transition state.
The activation parameters have been determined for both 1
and 2 in 80% ethanol and 97% TFE (Table 1). In 80% ethanol,
consistent with a bimolecular solvolysis dominating for both
substrates, the values are similar. For 1, the values are 19.4 kcal
mol-1 for ∆H‡ and –17.9 cal mol-1K-1 for ∆S‡ and, for 2, the
respective values are 18.2 kcal mol-1 and –20.4 cal mol-1K-1.
In 97% TFE, the values for 1 are 20.4 kcal mol-1 and –15.3
cal mol-1K-1, and these values are quite different, especially
as regards the ∆S‡ value, to those for 2 of 18.0 kcal mol-1 and
–29.8 cal mol-1K-1. The much higher (less negative) entropy of
activation for 1 in 97% TFE is consistent27 with the proposed
change from a bimolecular pathway for 2 to a unimolecular
pathway for 1.
Conclusions
The variation of the specific rates of solvolysis of o-nitrobenzyl
tosylate (1) with solvent composition in mixtures of water
with ethanol, methanol, acetonitrile, and acetone closely
parallels that for solvolyses of p-nitrobenzyl tosylate (2).
In extending to fluoroalcohol-containing solvents, it has
previously been shown14 that the behaviour of 2 can
be correlated over a wide range of solvents using the
Grunwald–Winstein equation [eqn (3)], with l and m values
consistent with an SN2 pathway. However, the specific rates
of solvolyses of 1 turn upward, consistent with the incursion
of an intramolecular pathway [eqn (2)]. In solvents rich in
fluoroalcohol, essentially all of the reaction of 1 follows the
intramolecular pathway.
Analysis of the specific rates for intramolecular reaction of
1 in fluoroalcohol-containing solvents by use of the extended
Grunwald–Winstein equation shows a negligible dependence
on solvent nucleophilicity and the data are best analysed
using the simple (original) equation [eqn (3) without the l NT
term]. The dependence on solvent ionising power is also low
(m = 0.27). Extrapolation to other solvents, using eqn (7),
indicates an appreciable contribution (>13%) by the
intramolecular pathway across the full range of solvents.
The observation5 of 35% o-nitrosobenzaldehyde [eqn
(2)] from solvolysis in 50% acetonitrile at 47.5°C is at
a value lower that that estimated in this study (61%) for
intramolecular reaction at 45.0°C. This could be due to the
approximate nature of the extrapolation or it could be, at
least in part, a consequence of substitution (to give the
alcohol) accompanying elimination (to give the aldehyde) in
the ring-opening reaction of the intermediate formed by the
intramolecular attack..
The low
m value observed is reminiscent of the
results21 from correlation analyses of the specific rates of
solvolyses of mustard chlorohydrin22,23 [eqn (8)] and related
compounds.23,24
CH2
+
R'OH
Cl-
RSCH2CH2Cl
R S
RSCH2CH2OR'+
R'OH2 + Cl-
+
(8)
CH2
These reactions also involve intramolecular nucleophilic
participation and the analyses [eqn (3)] of seven substrates of
the general type indicated showed low to negligible l values
accompanied by m values in the range of 0.33 to 0.47.21
The observation of a low m value associated with a low
or negligible l value is often rationalised in terms of an
early transition state. Since the reaction pathway involves
intramolecular nucleophilic attack, it should lead to the
rather low m values that would be predicted, based on SN2
solvolyses, for a rate-determining nucleophilic attack. These
analyses could also be influenced by increased solvent
electrophilicity leading to a reduction in the nucleophilicity of
the internal nucleophile.
Another measure of the extent of bond-breaking to the
leaving group is the kOTs/kBr ratio.15,25 This is the ratio of
the relevant rate coefficients when the only variant is either
tosylate or bromide as the leaving group. In Table 2, specific
rates are reported for the solvolyses of o- and p-nitrobenzyl
bromides in aqueous ethanol and aqueous-TFE solvents.
For two aqueous-ethanol compositions the ko/kP specific rate
ratio of 0.93 ± 0.02 was almost identical to a value for 0.88
in 50% acetone at 60°C1,8 and somewhat higher than the
corresponding value (Table 1), of 0.53 ± 0.02 for solvolyses
of 1. In 70% TFE, the value rose to 2.7, essentially identical to
the value of 2.8 obtained for the solvolyses of 1.
The m value of 0.27 is unusually low, especially for a
reaction without any appreciable dependence on solvent
nucleophilicity. The low value probably results from an
inverse relationship between the nucleophilicity of the nitro
group in a given solvent and the hydrogen-bonding ability of
the solvent, with the latter property also being an important
component of the scale of solvent ionising power. The net
result of an increase in solvent ionising power would be
a balance between improved leaving–group ability and
decreased nucleophilicity of the internal nucleophile. Low
m values were also observed21 in the correlations of the
For solvolyses of o-nitrobenzyl derivatives, the kOTs/kBr
ratios (Table 2) were in the range of 10 to 12 in aqueous
ethanol and somewhat higher, at 24–30, in aqueous TFE.
For solvolyses of the corresponding para-derivatives, the
ratios in aqueous ethanol were larger (20-30) and the ratio in
70% TFE was somewhat lower, at 16. The values in aqueous
TFE for solvolyses of the ortho-derivatives are, despite the
suggestion that they react primarily with intramolecular
PAPER: 07/4504

JOURNAL OF CHEMICAL RESEARCH 2007 215
1970, 92, 5452.
specific rates of ring-closure reactions of mustard compounds
(RSCH2CH2Cl) and related substrates.
4
5
6
7
R.P. Austin and J.H. Ridd, J. Chem. Soc., Perkin Trans. 2, 1994, 1411.
L.-J. Chen and L.T. Burka, Tetrahedron Lett., 1998, 39, 5351.
D.N. Kevill and H. Ren, J.Org. Chem., 1989, 54, 5654.
M. Fujio, T. Susuki, M. Groto, Y. Tsuji, K. Yatsugi, S.H. Kim, G.A.-W.
Ahmed and Y. Tsuno, Bull. Chem. Soc. Jpn., 1995, 68, 673.
S.C.J. Oliver, Rec.Trav. Chim., 1930, 49, 697.
Studies of the corresponding bromides of 1 and 2 led to kOTs
/
kBr ratios of 10–30. These are within the range of values for a
substitution with rate-determining nucleophilic participation.
The values are not informative as to whether this participation
is intermolecular or intramolecular. Activation parameters
were determined for 1 and 2 in 80% ethanol and 97% TFE.
The entropies of activation were similar in 80% ethanol
(reactions of both 1 and 2 predominantly bimolecular) but,
in 97% TFE, the value for 1 is considerably less negative
than for 2, consistent with the proposed unimolecular and
bimolecular pathways.
8
9
J. Bakke, Acta Chem. Scand. B, 1974, 28, 645.
10 (a) S. Winstein, E. Grunwald and H.W. Jones, J Am. Chem. Soc., 1951,
73, 2700; (b) F.L. Schadt, T.W. Bentley and P.v.R. Schleyer, J. Am. Chem.
Soc., 1976, 98, 7667; (c) M. Fujio, M. Groto, T. Yoshino, K. Funatsu,
Y. Tsuji, S. Ouchi and Y. Tsuno, Mem. Fac. Sci., Kyushu Univ., Ser. C.,
1987, 16, 85.
11 (a) D.N. Kevill and S.W. Anderson, J. Org. Chem., 1991, 56, 1845;
(b) D.N. Kevill, in Advances in Quantitative Structure-Property
Relationships, M. Charton (ed.), JAI Press: Greenwich, CN, 1996, vol.
1, pp. 81-115.
12 T.W. Bentley and G. Llewellyn, Prog. Phys. Org. Chem., 1990, 17, 121.
13 D.N. Kevill and M.J. D’Souza, J. Chem. Soc., Perkin Trans., 2, 1997,
257.
14 D.N. Kevill, M.J. D’Souza and H. Ren, Can. J. Chem., 1998, 76, 751.
15 H.M.R. Hoffmann, J. Chem. Soc., 1965, 6733; (b) T.H. Lowry and
K.S. Richardson, Mechanism and Theory in Organic Chemistry, 3rd edn.
Harper and Row, New York, NY, 1987, pp. 373-375.
16 J.W. Ra, J.B. Kyong, and D.N. Kevill, Bull. Korean Chem. Soc., 2002, 23,
1680.
17 J.B. Kyong, H. Won, Y.H. Lee and D.N. Kevill, Bull. Korean Chem. Soc.,
2005, 26, 661.
18 E. Grunwald, and S. Winstein, J. Am. Chem. Soc., 1948, 70, 846.
19 M.J. D’Souza, M.E. Boggs and D.N. Kevill, J. Phys. Org. Chem., 2006,
19, 173.
20 D.N. Kevill, S.W. Anderson and E.K. Fujimoto, in Nucleophilicity, eds.
J.M. Harris and S.P. McManus (eds), Advances in Chemistry Series,
No. 215, American Chemical Society, Washington, DC, 1987; pp. 269-
283.
21 D.N. Kevill and M.J. D’Souza, J. Chem. Res, (S), 1994, 190.
22 S.P. McManus, K. Yorks, N. Neamati-Mazraeh, and J.M. Harris, Polym.
Preprints (ACS Polym. Div.), 1985, 26(2), 265.
Experimental
Commercially available o-nitrobenzyl bromide (purity 98%)
and p-nitrobenzyl bromide (purity 99%) were used as received.
The o-nitrobenzyl p-toluenesulfonate (1) was prepared as previously
described,2,28 except that, after neutralisation of the reaction mixture
with sulfuric acid, the aqueous solution was extracted twice with
50 ml portions of diethyl ether. The combined ether layers were
washed with water and dried over MgSO4. The solvent was
removed under reduced pressure and the product was recrystallised
from diethyl ether: m.p. 90–94° (lit.2 80–90 dec). Anal. Cald. for
C14H13NO5S: C,54∙71; H,4∙21; N,4∙56. Found: C,54∙9; H,4∙05; N,4∙4.
Elemental analyses were carried out using a PerkinElmer 2400,
Series 2 CHNS/O Analyzer.
The determinations of the specific rates of solvolysis and the
purifications of the solvents were as previously described.11a,29 The
regression analyses were carried out using commercially available
statistical packages.
This research was supported, in part, by the donors of the
American Chemical Society Petroleum Research Fund.
J.B.K. thanks Hanyang University for a sabbatical leave,
which allowed the major part of this research to be carried out
at Northern Illinois University.
23 (a) S.P. McManus, N. Neamati-Mazraeh, B.A. Hovanes, M.S. Paley and
J.M. Harris, J. Am. Chem. Soc., 1985, 107, 3393; (b) S.P. McManus,
M.R. Sedaghat-Herati, R.M. Karaman, N. Neamati-Mazraeh, S.M. Cowell
and J.M. Harris, J. Org. Chem., 1989, 54, 1911.
24 (a) S.P. McManus, M.R. Sedaghat-Herati, and J.M. Harris, Tetrahedron
Lett., 1987, 28, 5299; (b) N. Neamati-Mazraeh and S.P. McManus,
Tetrahedron Lett., 1987, 28, 837; (c) S.P. McManus, N. Neamati-
Mazraeh, R.M. Karaman and J.M. Harris, J. Org. Chem., 1986, 51, 4876;
(d) S.P. McManus, and D.H. Lam, J. Org. Chem., 1978, 43, 650.
25 C.K. Ingold, Structure and Mechanism in Organic Chemistry, 2nd edn.
Cornell University Press, Ithaca, NY, 1969, pp. 453-457.
26 R.C. Bingham and P.v.R. Schleyer, J. Am. Chem. Soc., 1971, 93, 3189.
27 C.A. Bunton, Nucleophilic Substitution at a Saturated Carbon Atom,
Elsevier, New York, NY, 1963, pp. 70-72.
Received 1 March 2007; accepted 1 April 2007
Paper 07/4504 doi: 10.3184/030823407X207059
References
1
2
3
A. Singh., L.J. Andrews and R.M. Keefer, J. Am. Chem. Soc., 1962, 84,
1179.
A.D. Mease, M.J. Strauss, I. Horman, L.J. Andrews and R.M. Keefer,
J. Am Chem. Soc., 1968, 90, 1797.
S. Kim, S.S. Friedrich, L.J. Andrews and R.M. Keefer, J. Am. Chem. Soc.,
28 J.K. Kochi and G.S. Hammond, J. Am. Chem. Soc., 1953, 75, 3445.
29 J.B. Kyong, B.C. Park, C.–B. Kim and D.N. Kevill, J. Org. Chem., 2000,
65, 8051.
PAPER: 07/4504