Anilinolysis of nitro-substituted diphenyl ethers in acetonitrile: the effect of some ortho-substituents on the mechanism of SNAr reactions

Article abstract of DOI:10.1002/kin.20457

Rate data are reported for the reactions of a series of X-phenyl 2,4,6-trinitrophenyl ethers 1a-e [X = H, 4-NO₂,2-NO₂, 2,4-(NO₂)₂, or 2,6-(NO₂)₂] with substituted anilines 2a-e [Y = H, 2-CH

Full text of DOI:10.1002/kin.20457

Anilinolysis of Nitro-
Substituted Diphenyl Ethers
in Acetonitrile: The Effect of
Some Ortho-Substituents
on the Mechanism of SNAr
Reactions
CHUKWUEMEKA ISANBOR, THOMAS A. EMOKPAE
Chemistry Department, University of Lagos, Akoka Lagos, Nigeria
Received 18 April 2009; revised 6 August 2009; accepted 10 August 2009
DOI 10.1002/kin.20457
Published online in Wiley InterScience (www.interscience.wiley.com).
ABSTRACT: Rate data are reported for the reactions of a series of X-phenyl 2,4,6-trinitrophenyl
ethers 1a–e [X = H, 4-NO2, 2-NO2, 2,4-(NO2)2, or 2,6-(NO2)2] with substituted anilines 2a–e
[Y = H, 2-CH3, 2,4-(CH3)2, 2,6-(CH3)2, or N-CH3] in acetonitrile as solvent. For individual
amine, kinetic data show that there is little steric hindrance to attack at the 1-position of the
parent molecules, even in the presence of di-ortho substitution. With each substrate, however,
there is evidence for significant steric interactions; such effects leading to rate retardation were
very severe for 2,6-dimethylaniline 2d (2,6-(CH3)2) and N-methylaniline 2e (Y = N-CH3), the
deactivating effect of N-CH3 in most cases is slightly higher than that of 2,6-(CH3)2. However,
the reactions with 2e are base catalyzed whereas those of 2d are not. The corresponding
reactions with aniline 2a (Y = H) and mono-ortho methyl-substituted aniline 2b (Y = CH3) are
wholly base catalyzed. Only with the dinitro substrates, an uncatalyzed reaction is observed
and when X = 2,6-(NO2)2 this pathway takes all the reaction flꢀux. A rationale is provided for
C
the dichotomy of amine effects observed in this investigation. 2009 Wiley Periodicals, Inc.
Int J Chem Kinet 42: 37–49, 2010
INTRODUCTION
In activated aromatic nucleophilic substitution reac-
Correspondence to: Thomas A. Emokpae; e-mail: temokpae@
tions (SNAr), considerable attention has been attached
to the observation of base catalysis by primary and
secondary amines and its signiÞcance [1–4]. The pres-
ence or absence of base catalysis, exerted by the
nucleophile itself or by an externally added base,
yahoo.com.
Supporting Information related to values of kobs for the reactions
of 2d with the diphenyl ethers 1e and for the reactions of 2c with
1f (Tables S1 and S2, respectively) is available in the online issue at
www.interscience.wiley.com.
c
ꢀ
2009 Wiley Periodicals, Inc.

38
ISANBOR AND EMOKPAE
has played an important role in deciding whether
formation or decomposition of the intermediate com-
plex is rate limiting [5]. While the factors affecting the
incidence of base catalysis have been extensively dis-
cussed and in most cases substantiated experimentally,
only meagre attention has been given to the effects
of ortho-substitution in the nucleophile. This may be
due to complications arising from the ortho-effect of
most substituents. Apart from the simple steric effect
owing to a bulky substituent [6], other factors have
been considered, such as the steric inhibition of reso-
nance [7], the Þeld effect [8], and the intramolecular
hydrogen bonds [9,10]. It has been shown generally
that steric effects are not linearly dependent in various
reactions [11] but rather vary nonlinearly with the sub-
stituent, becoming suddenly appreciable at its certain
size. The universal scales of steric effect, therefore,
have no physical applicability and little practicability
only in combination with other parameters. In this re-
spect, the steric effect differs from inductive and also
from resonance effects [12].
We found recently that in the reactions of ring-
substituted anilines with 2,4-dinitrophenyl phenyl
ether 1d in acetonitrile, conversion of the zwitteri-
onic intermediate to the products was rate limiting and
involved both uncatalyzed k2 and base-catalyzed kAn
pathways. Alkyl substituents at the 2-position resulted
in considerable reduction in reactivity. These effects
were more pronounced for the base-catalyzed path-
way, and in 2,6-dimethylaniline the uncatalyzed path-
way took all the reaction ßux [13]. Similarly, in the
reactions with aniline in acetonitrile of a series of sub-
stituted phenyl 2,4,6-trinitrophenyl ethers, there was
evidence of base catalysis, interpreted as rate-limiting
deprotonation of the zwitterionic intermediate. Only
with the dinitro-derivatives was an uncatalyzed reac-
tion involving intramolecular proton transfer observed,
and when the substituent was the 2,6-dinitro group
(1e), the reaction was not amine catalyzed [14]. These
studies were independently limited to investigation of
the effect of substituent on the phenolic-leaving group
or in attacking nucleophile. In the present study, we
have employed not only the substituents X in the leav-
ing group in 1 but also substituents Y in the attack-
ing aniline nucleophile 2. To deal with an effect that
can be classiÞed as purely steric, we restricted the in-
vestigation to methyl-substituent in the nucleophile.
The ortho-methyl group has been shown to have weak
polar effect and appreciable steric effect in SNAr re-
actions [15]. Herein we report the results of detailed
kinetic studies in acetonitrile of the reactions of a se-
ries of nitro-activated aryl phenyl ethers 1a–e and with
anilines carrying methyl substituent at the ortho posi-
tion(s) 2a–d and with N-methylamine 2e.
X
CH3
O
NH2
HN
O2N
NO2
Y
NO2
2a–d (Y=CH3)
2e
1a–e
1a X=H
2a Y=H
2b Y=2-CH3
2c Y=2,4-(CH3)2
2d Y=2,6-(CH3)2
1b X=4-NO2,
1c X=2-NO2
1d X=2,4-(NO2)2
1e X=2,6-(NO2)2
1f X=Cl.
Our goal was to (i) determine the effect of steric
crowding at the reaction center on the individual step
depicted in Scheme 1 and (ii) compare the kinetic pa-
rameters for the reactions of 2e, N-methylaniline with
those for other sterically hindered anilines carrying
methyl group(s) close to the reaction center 2a–d. Ki-
netic data for the reactions of 2a, 2e, with 1b together
with those of 2a–d with 1d have been reported else-
where [13,14,16].
EXPERIMENTAL
The diphenyl ethers 1a–e and 1-chloro-2,4,6-
trinitrobenzene 1f were available from the previous
work [13,14,16]. Anilines and acetonitrile were the
1
purest available commercial samples. H NMR spec-
tra in CD3CN were recorded with Varian Mercury
400 MHz or a Bruker Avance-400 MHz instruments.
UV–vis spectra and kinetic measurements were made
at 25◦C using a Perkin–Elmer Lambda 2, Varian Cary
100, or a Shimadzu UV PC spectrophotometer. First-
order rate constants were measured with the aniline
concentration in large excess of substrate concentra-
tion, 5 × 10−5 mol dm−3, and were evaluated using
standard methods. Values are precise to 3%. Kinetic
measurements with N-methylaniline were made using
1H NMR spectroscopy in deuterated solvents and are
precise to 5%.
RESULTS AND DISCUSSION
The reactions of individual diphenyl ether 1a–e with
the anilines 2a–d in acetonitrile gave the expected
products of substitution of the phenoxide in quantita-
tive yield. Spectroscopic data are collected in Table I.
Visible spectra at the completion of the measured pro-
cess were in all identical to those of the independently
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ANILINOLYSIS OF NITRO-SUBSTITUTED DIPHENYL ETHERS IN ACETONITRILE
39
X
X
X
Y
Y
O
O
HN
NH2
NH2
O
O2N
NO2
O2N
NO2
+ Y-PhNH2
NO2
O2N
k1
k
kAn
+ Y- PhNH3
+
Y
kAnH
NO2
NO2
NO2
1 a–e
3
2 a–d
4
Fast
k2
1a X=H
2a Y=H
1b X=4-NO2,
1c X=2-NO2
1d X= 2,4-(NO2)2
1e X=2,6-(NO2)2
1f X=Cl.
2b Y=2-CH3
2c Y=2,4-(CH3)2
2d Y=2,6-(CH3)2
Y
NH
OH
O2N
NO2
+
+ Y-PhNH2
X
NO2
5
6
Scheme 1
prepared products 5 in the solution of the same amine
concentration. There was no evidence either from the
spectra or the kinetics for the accumulation of interme-
diate such as 3 or 4 on the reaction pathway. Kinetic
measurements were made spectrophotometrically by
monitoring the increase of the absorption maximum
due to product as a function of time. With concentra-
tions of anilines 0.01–0.8 mol dm−3 in large excess of
the concentration of diphenyl ethers 5.0 × 10−5 mol
dm−3, Þrst-order kinetics were observed and rate con-
stants, kobs, were evaluated by standard methods. Val-
ues are precise to 3%. Division by the concentration
of anilines of values of kobs gave second-rate constants,
kA, collected in Tables II and III.
Previous studies of the reactions of aliphatic amines
with strongly activated compounds such as 1a in ace-
tonitrile and in DMSO have shown that substitutions
may be preceded by formation under kinetic control
Table I 1H NMR Shifts in CD3CN for Reactants and Products
1H NMR Shiftsa
Compound
H3,5
H2ꢁ
H3ꢁ
H4ꢁ
Other
1a, X = H
9.03
9.11
9.01
9.18
8.92
8.99
8.78
9.04
8.92
8.85
7.00
7.15
–
–
–
7.18
–
–
–
6.86
7.40
8.26
8.16
8.43
8.34
7.39
6.82
6.72
7.12
7.26
7.25
–
–
–
1b, X = 4-NO2
1c, X = 2-NO2
1d, X = 2,4-(NO2)2
1e, X = 2,6-(NO2)2
5a, Y = H
7.68
7.36
7.66
7.29
7.04
–
7.41(H5ꢁ), 7.24 (H6ꢁ)
–
8.34 (H5ꢁ)
10.02 (NH)
5b, Y = 2-CH3
5c, Y = 2,4-(CH3)2
5d, Y = 2,6-(CH3)2
10, Y = N-CH3
2.20 (2ꢁ Me), 6.95 (H5ꢁ), 7.17 (H6ꢁ), 9.70 (NH)
2.16 (2ꢁMe), 2.38 (4ꢁMe), 7.17 (H5ꢁ), 7.26 (H6ꢁ), 9.72 (NH)
2.16 (Me), 10.10 (Me)
7.20
7.00
3.27 (Me)
aCompounds 1 are X-substituted phenyl 2,4,6-trinitrophenyl ethers. 5 and 10 are 2,4,6-trinitrodiphenylamine, and its N-methyl derivative,
respectively. Ortho coupling, J = 7–8 Hz, is observed.
International Journal of Chemical Kinetics DOI 10.1002/kin

40
ISANBOR AND EMOKPAE
Table II Kinetic Resultsa for the Reactions of X-Phenyl-2,4,6-trinitrophenyl Ether 1a–e with 2-Methylaniline 2b
in Acetonitrile at 25◦C
kA(10−4 dm3 mol−1 s−1
1b,
)
1a,
X = H
1c,
X = 2-NO2
1d,
1e,
X = 2,6-(NO2)2
[2-Methylaniline] (mol dm−3
)
X = 4-NO2
X = 2,4-(NO2)b2
0.005
0.01
0.015
0.02
0.025
0.03
0.04
0.05
0.06
0.08
0.1
566
550
0.7
2.07
3.78
48
50
53
55
56
1.55
4.33
550
2.35
2.88
3.60
5.67
7.0
8.67
544
542
533
6.42
8.03
70
79
83
5.58
7.07
13.0
1.63
12.30
14.93
520
483
aSecond-order rate constant (values are precise to 3%).
bValues are from [13].
Table III Kinetic Resultsa for the Reactions of X-Phenyl-2,4,6-trinitrophenyl Ether 1a–e with 2,4-Dimethylaniline
(DMA) 2c in Acetonitrile at 25◦C
kA(10−3 dm3 mol−1 s−1
)
1a,
X = H
1c,
X = 2-NO2
1b,
X = 4-NO2
1d,
X = 2,4-(NO2)b2
1e,
X = 2,6-(NO2)2
[2,4-DMA] (mol dm−3
)
0.002
0.005
0.01
0.015
0.02
0.025
0.03
0.04
0.05
0.06
258
256
237
25
26
27
28
0.81
2.17
1.83
243
243
234
229
1.17
1.55
2.83
3.67
4.33
5.17
2.68
3.25
29
2.28
5.03
aSecond-order rate constant (values are precise to 3%).
bValues are from [13].
of adducts 7 or 8 resulting from the unsubstituted C-3
position followed by isomerization to give the thermo-
dynamically most stable substitution product at C-1
(Scheme 2). The values of the equilibrium constant
for such process depend on the degree of ring activa-
tion, the strength of the amine, and also on the solvent.
In acetonitrile, values are ca. 104 less than in DMSO
and this was attributed to the greater ability of DMSO
than of acetonitrile to solvate the ionic species [17].
However, with weaker aromatic amines used in this
investigation, such adducts were not observed.
The results are best analyzed in terms of the process
in Scheme 1. Base catalysis is attributed to rate-limiting
proton transfer from 3 to base followed by rapid
OPh
OPh
OPh
O2N
NO2
NR1R2
O2N
NO2
NHR1R2
k3
O2N
NO2
+ 2R1R2NH
kAm
+ NH2R1R2
+ R1R2NH
+
kAmH
k−3
H
H
NO2
NO2
NO2
8
1a
7
Scheme 2
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ANILINOLYSIS OF NITRO-SUBSTITUTED DIPHENYL ETHERS IN ACETONITRILE
41
0.0016
0.0014
0.0012
0.001
0.0008
0.0006
0.0004
0.0002
0
0
0.02
0.04
0.06
0.08
0.1
0.12
(a)
6000
5000
4000
3000
2000
1000
0
0
20
40
60
80
100
120
(b)
Figure 1 (a) Plot of kA versus the amine concentration and (b) plot of 1/kA versus 1/[An] for the reaction of 4-nitrophenyl-
2,4-6-trinitrophenyl ether 1b with 2-methylaniline 2b in acetonitrile at 25◦C.
expulsion of the phenoxide. The treatment of the zwit-
terion 3 as steady-state intermediates leads to Eq. (1),
where [An] represents the concentration of substituted
anilines.
Reaction with Aniline and Ortho-
Substituted Anilines
For the reactions of the individual diphenyl ethers 1a–c
with 2a–c, plots of kA versus the amine concentration
pass through the origin, indicating that the uncatalyzed
kobs
k1(k2 + kAn[An])
−1 + k2 + kAn[An]
kA =
=
(1)
pathway (k2 in Scheme 1) is unimportant and curves
with decreasing slope as the aniline concentration is
increased (a representative plot for the reaction of 1a
with 2b is shown in Fig. 1a). Hence, Eq. (1) reduces to
Eq. (3). This in turn may be written as Eq. (4).
[An]
k
An alternative form of this equation is Eq. (2), where
K1 = k1/k is the equilibrium constant for the for-
−1
mation of the zwitterionic intermediate.
K1k2 + K1kAn[An]
kA =
(2)
k2
kAn[An]
kobs
k1kAn[Aniline]
1 +
+
kA =
=
(3)
k
k
[Aniline]
k
−1 + kAn[Aniline]
−1
−1
International Journal of Chemical Kinetics DOI 10.1002/kin

42
ISANBOR AND EMOKPAE
1a
10
2e
2e
Time (h)
264
10
10
1a
8a
168
144
120
96
48
16
9.5
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
ppm
1
Figure 2 H NMR spectrum of the reaction of phenyl-2,4,6-trinitrophenyl ether 1a, 0.04 mol dm−3, with N-methylaniline
2e, 0.8 mol dm−3, in CD3CN taken over 11 days at 25◦C. [Color Þgure can be viewed in the online issue, which is available at
www.interscience.wiley.com.]
K1kAn
the reactions of 2d with the diphenyl ethers 1e and for
the reactions of 2c with 1f are available as Supporting
Information in Tables S1 and S2, respectively.
kA =
(4)
kAn[Aniline]
1 +
k
−1
Reactions with N-Methylaniline
Values of k1, K1kAn, and kAn/k obtained by stan-
−1
dard methods from the reciprocal plots of kA versus
[An] (a typical plot for the reactions of 1a with 2b is
shown in Fig. 1b) are assembled later in Table VI. How-
ever, the plots (not shown) of kA versus the amine con-
centration for 1d, the 2,4-dinitro derivative, are linear
with distinct intercepts (R2 = 0.998–0.999), indicat-
ing the contribution of the uncatalyzed pathway. Hence
Eq. (5) applies; values of K1kAn and K1k2 in Table VI
later in the paper are extracted from the intercepts and
slopes of the plots.
As observed in the previous investigation, reactions
with excess 2e were inconveniently slow that studies by
conventional UV–visible spectroscopy were not suc-
1
cessful. However, H NMR measurements with high
concentration of reagents in CD3CN show the devel-
opment of bands over several days attributable to the
expected products. A representative 1H NMR spectrum
of the reaction of phenyl-2,4,6-trinitrophenyl ether 1a,
0.04 mol dm−3, with N-methylaniline, 0.8 mol dm−3
,
in CD3CN taken over 11 days at 25◦C is shown in
Fig. 2.
kA = K1k2 + K1kAn[An]
(5)
The increase in the intensity of the band at δ 8.85
due to the product 10 was used for kinetic measure-
ments; with N-methylaniline 2e in large excess of
the concentration of the substrates 1a–e, a Þrst-order
Kinetic measurements for the reactions of 1a–e with
2d (2,6-(CH3)2) show precise Þrst-order dependence
on the amine concentration. This indicates in terms
of Scheme 1 that nucleophilic attack is rate limiting.
The results yielded values of k1 collected along with
those previously obtained for the 1-chloro-derivative 1f
[18–22] in Table VII later in the paper. Values of kobs for
ꢁ
process was observed whose rate constant, kobs , was
evaluated by standard methods. Typical data for the re-
action of 2,4-dinitrophenyl-2,4,6-trinitrophenyl ether
1d, 0.04 mol dm−3, with N-methylaniline 2e, 0.4 mol
dm−3, are presented in Table IV. Division of kobs by
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ANILINOLYSIS OF NITRO-SUBSTITUTED DIPHENYL ETHERS IN ACETONITRILE
43
Table IV Kinetics of Reaction of
preted in a manner similar to that given for aniline
so that Scheme 3 is applicable. Hence, the condition
2,4-Dinitrophenyl-2,4,6-trinitrophenyl Ether 1d, 0.04
mol dm−3, with N-Methylaniline 2e, 0.4 mol dm−3, in
CD3CN at 25◦C
k
ꢂ kAn [An] holds and Eq. (1) reduces to Eq. (6),
−1
where kAn represents the pathway catalyzed by aniline.
This is the same kinetic pattern observed in the previ-
ous work for the reaction of 2e with 1b [16]. The only
parameter which can be determined is K1kAn. Values
for this parameter are summarized in Table VI.
Relative Concentrationsa
Time (104 s)
A
C
kobs(×10−5 s−1 b
)
0.07
0.66
1.38
1.98
5.50
7.98
8.92
9.94
16.70
98.9
91.5
83.4
77.0
46.0
31.8
27.8
24.0
8.7
1.1
8.5
1.4
1.4
1.3
1.3
1.4
1.4
1.4
1.4
1.5
16.6
23.0
54.0
68.2
72.2
76.0
91.3
kA = K1kAn[An]
(6)
However, the plots of kA versus the N-methylaniline
concentration for 1c and 1d, the 2-nitro- and 2,4-
dinitro derivatives, had deÞnite intercepts represent-
ing the contribution of the uncatalyzed pathway.
Equation (2) applies, and the values of K1kAn, and
aDetermined by 1H NMR integration of bands at δ 9.18 due to
A, 2,4-dinitrophenyl 2,4,6-trinitrophenyl ether, and at δ 8.85 due to
C, N-methyl 2,4,6-trinitrodiphenylamine.
K1k2, and kAn/k are collected in Table VI. For 1e,
−1
the 2,6-dinitro derivative, the values of kA are indepen-
dent of the aniline concentration, indicating that either
the condition k2 + kAn ꢂ k holds so that kA = k1
and/or the condition k2 ꢂ −kA1 n [An] applies so that
kA = k1k2/(k−1 + k2). Values of the Þrst-order rate
constants (kobs) increase linearly with the amine con-
centration (0.001–0.04) and allow the determination of
values of k1 assembled in Table VI.
bCalculated as kobs = (1/t) ln(100/A).
the N-methylaniline concentration leads to values of
kA assembled in Table V. As in the case with aniline,
the plot of the second-order rate constants kA for the
reaction of 1a with 2e varies linearly with the amine
concentration exhibiting null intercept. Data are inter-
Table V Kinetic Resultsa for the Reactions of X-Phenyl-2,4,6-trinitrophenyl Ether 1a–e with N-Methylaniline 2e in
CD3CN at 25◦C
kA(10−5 dm3 mol−1 s−1
)
1a,
X = H
1c,
X = 2-NO2
0.3
1b,
X = 4-NOb2
1d,
X = 2,4-(NO2)2
1e,
X = 2,6-(NO2)2
[N-Methylaniline](mol dm−3
)
0.2
0.25
0.4
0.6
0.8
0.46
0.49
0.63
0.79
3.5
5.2
6.9
0.1
0.09
0.11
0.15
0.85
1.0
1.18
0.1
aMeasured by integration of 1H NMR bands, with substrate 0.04 mol dm−3. Values are precise to 10%.
bData are from [16].
X
X
CH3
O
OH
NH
HN
CH3
NO2
N
CH3
NO2
O
O2N
NO2
+
k2
kAn
O2N
O2N
+ PhNHCH3
k1
k
+
2
+ PhNHCH3
X
NO2
NO2
NO2
1 a-e
2e
9
8
10
Scheme 3
International Journal of Chemical Kinetics DOI 10.1002/kin

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ISANBOR AND EMOKPAE
Table VI Summary of Rate Data for Reaction of X-Phenyl-2,4,6-trinitrophenyl Ethers 1a–e, with Aniline 2a–e in
Acetonitrile at 25◦C
k1 (dm3
mol−1 s−1
K1k2 (×10−2
K1kAn
(dm6 mol−2 s−1
kAn/k
(dm3 mol−1
)
−1
Nucleophile
Substrate, X
)
dm3 mol−1 s−1
)
)
2a, Y = Ha
1a, H
1b, 4-NO2
1c, 2-NO2
1d, 2,4-(NO2)2
1e, 2,6-(NO2)2
1a, H
1.96 0.5
1b, 4-NO2
1c, 2-NO2
1d, 2,4-(NO2)b2
1e, 2,6-(NO2)2
1a, H
0.24 0.10c
0.26 0.08
0.32 0.10
0.8 0.3
1.5 0.2
4.11 0.4 × 10−3
0.48 0.02
1.03 0.03
0.95 0.03
2.2 0.20
2
4
3
1
1
1
0.08 0.01
Large
2.8 0.5
2b, Y = 2-CH3
8.07 0.2 × 10−3
3.32 0.3 × 10−3
2.2 0.1 × 10−2
1.5 0.1×10−2
4.0 0.2 × 10−2
6.61
6.4
1
1
3.67 0.3 × 10−3
4.5 × 10−3
<1
4.9 0.5 × 10−2
2.3 0.2 × 10−2
2.7 0.5 × 10−2
1.4 0.3 × 10−2
2c, Y = 2,4-(CH3)2
2d, Y = 2,6-(CH3)2
2e, N-CH3
4.0 0.2 × 10−2
9.8 0.6 × 10−2
0.13 0.003
1.81 0.5
1b, 4-NO2
1c, 2-NO2
1d, 2,4-(NO2)b2
1e, 2,6-(NO2)2 0.23 0.1
1a, H
3.69
8.8
1
1
2.0 0.3×10−2
0.2 0.01
<1
1b, 4-NO2
1c, 2-NO2
1d, 2,4-(NO2)b2
1e, 2,6-(NO2)2
1a, H
2.0 0.1 × 10−5
2.0 0.1 × 10−5
6.0 0.5 × 10−5
1.6 0.1 × 10−4
–
1.85 0.1 × 10−6
1.60 0.1 × 10−5
8.0 0.4 × 10−6
9.0 0.5 × 10−5
1b, 4-NO2
1c, 2-NO2
2.0 0.1 × 10−6
1.0 0.05 × 10−6
1d, 2,4-(NO2)2
1e, 2,6-(NO2)2
1.0 0.05 × 10−6
aData are from [14, 16].
bData are from [13].
cError limits are standard deviations.
sharply with that of ρx determined for the aminolyses
of X-substituted phenyl benzoates. The Hammett
correlation with σ-constants exhibits good linearity
with large slope (ρx = 3.54) for the reaction with
piperidine, implying that the leaving group departure
occurs at the rate-determining step [23].
For the reactions of individual substrate with ani-
line and ortho-substituted anilines (2a–c), there was
evidence of signiÞcant steric interactions. Values of k1
listed in Table VII show a strong dependence on the
nature of the substituent Y in the nucleophile. This in-
dicates a product-like transition state for nucleophilic
attack where bonding between the nucleophile and the
ring is well developed. SpeciÞcally, the substitution of
a 2-methyl group into aniline reduces the values of rate
constants k1 by factors of between 30 and 80. Inter-
estingly, the factor of 30 obtained in the reaction with
1e, the 2,6-dinitro derivative, is the same as that ob-
served with 1f, the 1-chloro derivative [18]. The corre-
sponding factors for the reactions with 2d are between
COMPARISON
Rate Constants for Nucleophilic Attack
It is evident from the data in Table VI that values of k1,
the rate constant for nucleophilic attack by individual
aniline, increase slightly with increasing electron
withdrawal by the X-substituent in the leaving group.
Previous results [16] for the reaction with aniline and
derivatives of 1 gave a linear Hammett plot, with a
small ρ value of 0.5, which indicates that the bulk of
the negative charge is delocalized conjugatively into
the trinitrophenyl ring. Substituents in the incipient
leaving group will, therefore, have only a small
increase on charge delocalization. This is compatible
with an “early” transition state for nucleophilic
attack with relatively little bond formation. For such
reactions, steric hindrance will be insigniÞcant in
determining the value of k1. The magnitude of ρx
for the reaction in this and previous studies contrasts
International Journal of Chemical Kinetics DOI 10.1002/kin

ANILINOLYSIS OF NITRO-SUBSTITUTED DIPHENYL ETHERS IN ACETONITRILE
45
Table VII Summary of Values of k1/dm3 mol−1 s−1 for the Reactions of Diphenyl ether 1a–d and
1-chloro-2,4,6-trinitrobenzene 1f with Substituted Anilines 2a–e in Acetonitrile at 25◦C
Substrate 1a–f, k1 (dm3 mol−1 s−1
)
Nucleophile
1a, H
1b, 4-NO2
1c, 2-NO2
1d, 2,4-(NO2)a2
1e, 2,6-(NO2)2
1fb
2a, Hc
2b, 2-CH3
0.24
4.11 × 10−3
0.023
0.26
3.32 × 10−3
0.32
3.67 × 10−3
0.8
1.5
0.049
0.23
0.2
6.9 × 10−3
2c, 2,4-(CH3)2
2d, 2,6-(CH3)2
2e, N-CH3
0.027
2.0 × 10−5
0.014
2.0 × 10−5
1.5 × 10−5
3.5 0.1 × 10−2
4.66 × 10−5
6.0 × 10−5
1.6 × 10−4
1.0 × 10−6
5.32 × 10−6
aData from [13].
bData for reaction of 2a,b and 2d are obtained from [18]. Data for reaction with 2c are from the present work. Data for reaction with 2e are
calculated using values of k1 = 2.91 dm3 mol−1
s
−1, Ea = 54 kJ mol−1, and ꢀH‡ = 51.0 kJ mol−1 obtained at 50◦C from [50].
cData from [14].
1.3 × 104 and 1.6 × 104. The relative reactivity ratio
drops to 4.3 × 103 for the reaction of 2d with 1f, the
1-chloro analogue [19]. The huge deactivating effect
exhibited by 2d was previously analyzed in terms of
primary steric effect, steric occlusion of solvation of
the transition state, and secondary steric effect. Two
methyl groups, located at the 2- and 6-positions of ani-
line, may prevent coplanarity and hence conjugation
between the amino group and the aromatic ring. The
secondary steric effect of a 2-methyl group was found
to be insigniÞcant, but that of the 2,6-dimethyl group
was enormous [20–22].
As can be seen in Tables VI and VII, 2e exerts a
dramatic decrease in reactivity with respect to 2a with
a 2a/2e reactivity ratio of ca. 1 × 105. The superior
reactivity of 2a when compared with 2e can be reason-
ably attributed to the greater steric requirement of the
secondary amine. Furthermore, steric hindrance to nu-
cleophilic attack in most cases is slightly more severe
with 2e than with 2d. On the whole, for reactions with
individual substrate, the values of k1 decrease in the
order 2a > 2c> 2b > 2d > 2e reßecting the order of
steric hindrance exerted by the methyl group(s).
ter, greater with secondary than with primary amines
[27,28] and the presence of a group that is bulkier than
hydrogen at the site of nucleophilic attack [29]. The de-
crease in the value of kAn is thought to reßect increas-
ing steric hindrance to the approach of the reagents.
Hence, steric rather than electronic factors determine
the rate constant for such proton transfer. The reac-
tions between 2a–e and 1e and those of 2d with 1a–e
show Þrst-order dependence on the concentration of the
amine. This corresponds to the condition kAn ꢂ k−1 so
that kA = k1. The reactions of 2a–c and of 2e with 1a–d
were, however, base catalyzed. In general, the data dis-
played in Table VI show that, for the reactions of indi-
vidual aniline, the values of K1kAn increase regularly as
X substituent becomes more electron withdrawing; the
increases are relatively small and reasonably attributed
to increases in K1 as the electron withdrawal at the 1-
position increases. Similarly, increases in kAn/k−1 will
reßect decreases in k−1. As argued previously [13,16],
the results are consistent with a reactant-like transi-
tion state in which the bond formation between the
nucleophile and the substrate is not greatly advanced
in the transition state. Steric hindrance would, there-
fore, be insigniÞcant in determining reactivity. It may,
as observed in the 2,6-disubstituted compounds, de-
crease the rate of intermolecular proton transfer (kAn
)
Base Catalysis
to a catalyzing base but may not be severe enough to
cause a change in the reaction order in PhNH2 with-
out the assistance of electronic effects. This is borne
out by the similarity in the kinetic behavior observed
previously for compounds in the methyl series [X =
H, 2-CH3, 3-CH3, 4-CH3 2,4-(CH3)2, or 2,6-(CH3)2].
Substitutions in this series are wholly amine catalyzed
even in the presence of di-ortho methyl groups [14].
On the other hand, the appearance of the k2 step in the
reaction of 1c, 1d, and 1e depends on the electronic
nature of the substituent X in the leaving group, which
increases with decreasing pKa of the conjugate acid.
With 1e, the 2,6-dinitro derivative, the steric hindrance
Base catalysis in the reactions of nitro aryl phenyl
ethers 1a–e depends on the values of kAn/k−1; a lower
value of this ratio, leading to the condition k1 ꢂ kAn
,
results in the reactions showing susceptibility to base
catalysis. It has been argued previously [24–26] that,
with strongly activated substrates such as 1a–d, the
zwitterions are considerably stronger acids than the
corresponding ammonium ions so that the proton trans-
fer process, kAn, is thermodynamically favored in the
direction 3 → 4. However, the values of kAn may ap-
proach the diffusion limit but are known to be reduced
by increasing steric congestion at the reaction cen-
International Journal of Chemical Kinetics DOI 10.1002/kin

46
ISANBOR AND EMOKPAE
to intermolecular transfer to base is sufÞcient to make
the base-catalyzed pathway insigniÞcant relative to the
k2 pathway [14].
This reßects the condition k ꢂ k2 ꢂ kAn [An] so
−1
that kA = k1k2/k
It is worth noting that values of
−1.
K1kAn decrease in the order 2a > 2c > 2b > 2e, the
same trend as was observed for the rate constant for nu-
cleophilic attack. This could be taken as an indication
that steric effects are related to the values of the rate
constant for proton transfer, which diminish with the
bulk of the amine. On the contrary, since k2 involves an
intramolecular proton transfer, the steric effect should
be small. Hence, the major steric effect on K1k2 values
is likely to be on the equilibrium formation of the zwit-
terionic intermediate, yielding reduced values of K1.
The slight increase in the values of K1k2 for 2c as com-
pared to 2b is reasonably attributed to electronic effect.
The change in the mechanistic pathway was more
magniÞed when the reactions were conducted in ben-
zene. For X = H, 2-CH3, 3-CH3, and 4-CH3, 2,4-
(CH3)2 and 2,6-(CH3)2, the plots of the second-order
rate constant versus [An] had upward curvatures, which
corresponds to a parabolic dependence of kA versus
[An] and a fourth-order kinetic law. For the nitro series,
the change in the kinetic form for the reactions of ani-
line with ethers containing unsubstituted or mononitro-
substituted leaving groups is from a third-order depen-
dence on the aniline concentration to a second-order
dependence for the leaving group containing 2, 4-,
3,4-, and 2,5-dinitro groups, to kA = k1 for the 2,6-
dinitrophenoxy group. The trend was rationalized by
the cyclic transition state mechanism and ascribed to
changes in the transition state for the decomposition
of the intermediate from eight- to six- to four-member
rings (containing two, one, and no moles in aniline, re-
spectively), brought about by increases in the leaving
group ability of the nucleofuge [30,31].
The reactions of 2-substituted anilines with sub-
strates 1a–c are wholly base catalyzed, but the reac-
tions with 1d involved both the catalyzed and the un-
catalyzed pathways. For these reactions, there is, as
in the case of k1, evidence for unfavorable steric in-
teraction, which is known to be of greater magnitude
the later the transition state. Thus, the 2-methyl group
introduced into aniline reduces the values of K1kAn by
factors of between 30 and 80. These results accord bet-
ter with a “late” transition state for nucleophilic attack
with considerable charge development. Sterically hin-
dered anilines for such reactions can decrease not only
the reaction rate but also the reaction orders in PhNH2.
This reduction is slightly lower for the K1k2 value, indi-
cating that steric effects in anilines retard the catalyzed
step a little more than the spontaneous decomposition
of the zwitterionic intermediate [32–34]. Substituents
THE DICHOTOMY OF AMINE EFFECTS
The absence of intercepts in the linear plots of kA versus
[An] in the reactions of 2a–c and 2e with nitro phenyl
aryl ether 1a,1c shows that the reactions are catalyzed
wholly by the nucleophiles in a linear fashion indicat-
ing that the value of kAn/k−1 is relatively low (<5 dm3
mol−1); deprotonation of the zwitterionic intermediate
3 formed along reaction coordinate is therefore rate
limiting.
The values of the parameter K1kAn are lowered by
a factor of ca. 105 for 2e relative to 2a. The dramatic
reduction, as discussed previously, is attributed to in-
creased steric hindrance both in the formation of the
zwitterionic intermediate and in the proton transfer
process [16]. An alternative but quite unlikely explana-
tion to be considered is the role of hydrogen bonding
known to occur [7,16] between ammonio hydrogen
atoms of 3 and the oxygen atoms of the ortho-nitro
group. Such intramolecular hydrogen bonding that af-
fects the hydrogen to be transferred has been invoked
to explain the dichotomy of the amine effect usually
observed in the reactions of aliphatic primary and sec-
ondary amines of similar basicity. The inßuence on
in the ortho-position(s) of aniline decrease k2/k val-
k
will be approximately the same for both primary
−1
−1
ues probably by increasing k due to relief of strain,
and secondary amines, but the effect on the expul-
sion of the leaving group will, however, be different
as the hydrogen bond must be broken when the nu-
cleophile is a secondary amine but not when it is a
primary amine. In the case of primary amines, there
will always be a free transferable proton, thus reduc-
ing the susceptibility to base catalysis. While this may
be a plausible explanation for the dichotomy of the
amine effect between 2d and 2e, the fact that the corre-
sponding reactions with 2a, a primary aromatic amine,
are base catalyzed vitiates the hydrogen bond theory.
Furthermore, our recent observation of base catalysis
in the reactions of piperidine with 2-trißuoromethyl
−1
and reactivity is decreased despite favorable electronic
effect of the methyl group. On the other hand, ortho-
substitution in aniline reduces kAn/k−1 by reducing the
rate of proton transfer, kAn; although it may be argued
that there is also an increase in the rate of decompo-
sition of the intermediate to reactants, k−1, because of
the steric congestion, the inßuence of steric effect is
more pronounced for K1kAn than for K1k2 [35]. Thus,
for all reactions of 2d, hindrance of approach to the
reaction center is so severe as to make the kAn coef-
Þcient vanishingly small compared to k2 and so the
catalytic pathway cannot be detected experimentally.
International Journal of Chemical Kinetics DOI 10.1002/kin

ANILINOLYSIS OF NITRO-SUBSTITUTED DIPHENYL ETHERS IN ACETONITRILE
47
4-nitro- (involving a bulky trißuoromethyl group with
negligible hydrogen-bonding acceptor properties) but
not with 2-nitro-4-trißuoromethyl phenyl ethers adds
to the growing body of evidence that in acetonitrile
such hydrogen bonding at least in strongly activated
substrates is not a major factor [36,37].
The overall equilibrium constant for this process
(1.7 × 10−5) is, however, very small due the loss in
resonance of 2a in formation of the conjugate acid
TBN.NH2Ph+ + PhNH2 → TNB.NH Ph− + PhNH+3
Hence a much stronger base such as Dabco is needed
to displace the equilibrium in the direction of the prod-
ucts. The equilibrium transformation of the zwitteri-
onic complex to the anionic σ-complex, being directly
related to the basicity of the abstracting base, is favored
in the Dabco system by ca. 104 [48]. It is, therefore,
likely that, due to severe steric requirement, the depro-
tonation process involving 2,6-dimethylaniline acting
both as a nucleophile and a proton-accepting base will
be more kinetically disfavored. If this is the explanation
in the TNB/PhNH2/Dabco system, then the change in
the kinetic form observed in our system can be recon-
ciled on the basis that 2d may not be particularly ef-
fective in abstracting the proton from the zwitterionic
intermediate 3 because of greater loss of resonance due
to severe steric requirement relative to aniline. There is,
therefore, a pronounced reduction in the rate constant
for the proton transfer step involving 2d; under such
circumstances, decomposition of the adduct 3 would
occur largely by the uncatalyzed pathway.
It is curious that in the present system, while the re-
actions of 1a–d with 2a and 2e are base catalyzed, no
base catalysis was observed with 2,6-dimethylaniline
2d. In terms of the mechanism depicted in Scheme 1,
these changes are equivalent to a shift from the kinetic
condition k ꢂ kAn to k ꢃ kAn as the nucleophile
−1
−1
is changed from 2a or 2e to 2d (a relatively weaker
nucleophile [38]). This does not appear to be reason-
able. Usually when amines of the same type and under
the same conditions react by different mechanisms,
there is a considerable difference in their basicities;
the change is ascribed to a decrease in the strength of
C–N bond with a decrease in amine basicity leading to
an increase in k [39]. This implies that reactions of
−1
2d should be more prone to base catalysis than those of
2a or 2e. Experimental results obtained in this inves-
tigation, however, indicate the reverse. It is interesting
to note that similar effects have been observed recently
by Crampton and co-workers [40,41] in σ-complex
formation reactions involving 1,3,5-trinitrobenzene
(TNB), Dabco, and the same set of substituted anilines
in DMSO. For this system, Buncel and Eggimann [42]
reported that the proton transfer stage was solely cat-
alyzed by Dabco, i.e., catalysis by 2a or 2e and the
solvent dimethyl sulfoxide was not signiÞcant. How-
ever, it has been shown in a related system that even
though aniline is a much weaker base, it might also con-
tribute to the proton transfer equilibrium [43]. Thus, it
is known that the trinitrocyclohexadienate group in 3,
even though negatively charged, is electron withdraw-
ing relative to hydrogen [44–47]. Hence, 3 will be more
acidic than the corresponding anilinium ion so that the
proton transfer step 3 → 4 will be thermodynamically
favored even when the reaction involves aniline as the
base and the corresponding anilinium ion as BH+.
Another factor that may contribute to the change
of mechanism is the relative magnitude of k−1, the
rate constant for the reversion of 3 to reactants for the
three anilines 2a, 2d, and 2e. With 2e as nucleophile
in the TBN/PhNH2/Dabco system, k is an order of
−1
magnitude higher than in the case of 2a, reßecting the
release of strain in the zwitterionic intermediate as it
reverts to the reactants. The k is likely to be larger
−1
for 2a than 2d probably due to stabilization of the
transition state for the decomposition of zwitterionic
adduct to reactants for aniline by interaction of the
partially liberated lone pair of electrons on the nitrogen
atom with the aromatic ring of the amine as shown in
11. Such stabilization may be reduced in the case of 12
for the reaction with 2d because of the presence of two
methyl groups in the 2- and 6-positions of the aniline.
X
H3C
NO2
H3C
NO2
H
+
H
+
H
+
O
N
N
O
N
O
H
NO2
O2N
NO2
O2N
H
NO2
H3C
H
H3C
NO2
O2N
NO2
N+
NO2
11
NO2
–O
O–
12
13
International Journal of Chemical Kinetics DOI 10.1002/kin

48
ISANBOR AND EMOKPAE
The uncatalyzed step (k2) is likely to proceed by a
ßux. With N-methyl aniline, the uncatalyzed pathway
becomes signiÞcant when the nucleofuge contains an
ortho nitro group. Our Þndings, therefore, provide an
interesting example of how gradual increase of crowd-
ing in the transition state may give rise to a change in
the nature of the rate-determining step in the substitu-
tion pathway. The difference in the kinetic behavior of
2a and 2d may be a strong evidence for some unusual
steric interactions in zwitterion 3.
unimolecular mechanism involving the intramolecular
catalysis of the nucleofuge expulsion (depicted in 13),
mentioned as a possibility by Kirby and Jencks [2]. In a
reasonable good donor solvent like acetonitrile (DN =
14.1 kcal/mol) [49], the presence of the methyl group
in the 2- and 6-positions of aniline prevents amine as-
sociation or effective solvation. It also reduces the nu-
cleophilicity of the amine with a concomitant increase
in acidity of the ammonio proton in the intermedi-
ate 3d as compared to that of 3a. Bernasconi and de
Rossi [6] have stated that the increase in the acidity
of the ammonio proton in the intermediate 3 increases
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International Journal of Chemical Kinetics DOI 10.1002/kin