The reaction of 2-phenoxy-3,5-dinitropyridine with substituted anilines in the presence of 1,4-diazabicyclo[2.2.2]octane in dimethyl sulfoxide: Kinetic and equilibrium studies

Article abstract of DOI:10.1002/kin.20389

The reactions of 2-phenoxy-3,5-dinitropyridine (1) with, a series of substituted anilines (4a-d) in dimethyl sulfoxide (DMSO) in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) yield the 2-anilino derivatives without the accumulation of intermediate

Full text of DOI:10.1002/kin.20389

The Reaction of 2-Phenoxy-
3,5-dinitropyridine with
Substituted Anilines
in the Presence of 1,4-
Diazabicyclo[2.2.2]octane
in Dimethyl Sulfoxide:
Kinetic and Equilibrium
Studies
BASIM H. ASGHAR
Department of Chemistry, Faculty of Applied Sciences, Umm Alqura University, P.O. Box: 9569, Makkah, Saudi Arabia
Received 5 June 2008; revised 24 July 2008, 4 September 2008; accepted 5 September 2008
DOI 10.1002/kin.20389
Published online in Wiley InterScience (www.interscience.wiley.com).
ABSTRACT: The reactions of 2-phenoxy-3,5-dinitropyridine (1) with a series of substituted
anilines (4a–d) in dimethyl sulfoxide (DMSO) in the presence of 1,4-diazabicyclo[2.2.2]octane
(DABCO) yield the 2-anilino derivatives without the accumulation of intermediates. The kinetics
is compatible with a two-step reaction involving initial nucleophilic attack followed by either
base-catalyzed or uncatalyzed conversion to the product. The base-catalyzed pathway is likely to
involve rate-limiting proton transfer from the zwitterionic intermediate to base. The results are
compared with those for reactions of 1,3,5-trinitrobenzene (2) and phenyl 2,4,6-trinitrophenyl
ether (3, R = Ph) with anilines. ꢀ 2008 Wiley Periodicals, Inc. Int J Chem Kinet 41: 198–203, 2009
C
withdrawing ring substituents such as the nitro group
strongly accelerates substitution, and ring nitrogen
atoms have also been found to exert a powerful
activating effect [7]. However, ring nitrogen ortho
to the substitution position has generally been found
to be less effective than a corresponding nitro group
[8–12].
INTRODUCTION
Kinetic studies of nucleophilic substitution reactions
of aromatic substrates have been the subject of several
excellent reviews and books [1–4] and are still an area
of active research [5–9]. The presence of electron-
Substitutions involving amine nucleophiles are of
particular interest, since studies have shown that
these may be general base catalyzed, indicating
Correspondence to: Basim H. Asghar; e-mail: Basim15@
yahoo.com.
2008 Wiley Periodicals, Inc.
c
ꢀ

REACTION OF 2-PHENOXY-3,5-DINITROPYRIDINE WITH SUBSTITUTED ANILINES
199
that the rate-limiting step involves proton transfer. In
previous work, the reactions of 1,3,5-trinitrobenzene
(2), which contains no good leaving group,
with anilines in DMSO in the presence of
1,4-diazabicyclo[2.2.2]octane (DABCO), have been
shown to yield anionic σ-adducts. Kinetic and equilib-
rium studies are compatible with a two-step processes
involving initial nucleophilic attack by amine at an un-
substituted ring position followed by proton transfer
from the zwitterionic intermediate to base [13].
In agreement with the classic work of Orvik and
Bunnett [14], the results for ethyl 2,4,6-trinitrophenyl
ether (3) indicated that substitution involves the spe-
cific base-general acid catalysis mechanism, SB-GA,
in which leaving group expulsion is the overall rate-
limiting step. However, the phenoxy group is a con-
siderably better leaving group than the ethoxy group,
and the observation of base catalysis in reactions of
the phenyl aryl ethers was best explained in terms of
rate-limiting proton transfer from a zwitterionic inter-
mediate to base [15,16].
In this paper, kinetic and equilibrium results are
reported for the reactions of 2-phenoxy-3,5-dinitro-
pyridine (1) with a series of substituted anilines (4a–d)
in DMSO in the presence of DABCO (Scheme 1). This
allows the effects of a ring nitrogen in 1 to be compared
with those of a nitro group in 3, R = Ph.
The pKa values for the substituted anilinium ions in
DMSO were available from previous work [13] using
the proton-transfer equilibrium with 2,4-dinitrophenol.
OR
OPh
O2N
NO2
O2N
NO2
O2N
N
NO2
NO2
NO2
1
2
3
R
R
+
PhO
O2N
NH
OPh
N
PhO
O2N
NH2
NH2
O2N
N
N
kB
-
k1
k
-
+
B
B
BH
+
+
+
+
+
k BH
1
-
R
NO2
NO2
Zwitterion,
NO2
Adduct, 6
5
1
4a-d
a, R = 4-OMe
b, R = 4-Me
c, R = H
k2
fast
Hf
R
d, R = 4-Cl
He
OH
NHc
Hd
O2N
N
+
Ha
Hb
NO2
7
Scheme 1 The reactions of 1 with a series of substituted anilines (4a–d) in DMSO in the presence of DABCO.
International Journal of Chemical Kinetics DOI 10.1002/kin

200
ASGHAR
EXPERIMENTAL
H
f
H
He
e
2-Phenoxy-3,5-dinitropyridine (2) was prepared by re-
action of 2-chloro-3,5-dinitropyridine with 1 equiv of
base in the presence of 1.3 equiv of phenol in aque-
ous ethanol, mp 158◦C (lit. [17], 159◦C). Anilines,
DABCO, and DMSO were the purest available com-
mercial samples. Amine salts were prepared in a so-
lution by the accurate neutralization of amines with
concentrated hydrochloric acid.
H
H
d
d
N
-
NHC
N
O2N
O2N
H
N
K
+
BH
B
+
+
H
a
b
NO2
NO2
7
B=DABCO, Piperidine.
1HNMR spectrum was recorded in [2H6]-DMSO
using a Bruker Avance-400 MHz instrument. Mass
spectrum was recorded on a Waters Micromass LCT
spectrometer. UV–visible spectra and kinetic measure-
ments were made with Shimadzu UV-2101 PC or
Perkin Elmer Lambda 2 spectrophotometers. All mea-
surements were made at 25◦C. First-order rate con-
stants, precise to 3%, were evaluated using standard
methods.
Scheme 2
0.548 for reaction with piperidine. The pKa value was
calculated using Eq. (1) to be 11.12 0.05. Data are
shown in Tables I and II.
From previous work, the pKa value for 2,4,6-
trinitrodiphenylamine[13] was 8.20. The lower acidity
of 7 compared with 2,4,6-trinitrodiphenylamine may
be attributed to the less effective mesomeric role that
the ring nitrogen plays in stabilization of the anion
compared with that of the nitro group.
RESULTS AND DISCUSSION
Spectroscopy for
2-Anilino-3,5-dinitropyridine
Kinetic and Equilibrium Studies
The reaction of 1 (0.2 g, 1.3 × 10−3 mol) with aniline
(1 mL, 0.01 mol) in the presence of DABCO (0.1 g,
1 × 10−3 mol) dissolved in ethanol gave 2-anilino-3,5-
dinitropyridine (7). The 1HNMR spectrum recorded in
[2H6]-DMSO showed bands due to Ha and Hb at δ 9.23
and 9.05 ppm, respectively, J = 2.6 Hz. The singlet
at δ 10.56 ppm is attributed to Hc, while bands due
to phenyl protons are observed at δ 7.60, 7.44, and
7.28 ppm with Jde and Jef = 8 Hz.
Kinetic measurements of the reactions with substituted
anilines (4a–d) were generally made in the presence of
DABCO and DABCO hydrochloride (0.01 mol dm−3).
The absorption maxima of the adducts formed is ca.
380 nm. The concentration of 1 was kept at 5 × 10−5
mol dm−3 and was very much lower than that of
the other components, one of the substituted anilines
(4a–d) and DABCO. Under these conditions, accurate
first-order kinetics was observed, and the variation in
value of the rate constant with aniline and DABCO
concentrations was examined. Measurement was also
made in the absence of DABCO, and plots of the
The mass spectrum (ES+) for 7 showed a line at 261
corresponding to C11H9N4O4 (M + H+).
pKa for 2-Anilino-3,5-dinitropyridine
in DMSO
Table I Absorbance Data for 2-Anilino-3,5-
dinitropyridine (5 × 10−5 mol dm−3) in DMSO
Containing Various Concentrations of DABCO at 25◦C
The pKa value for the 2-anilino-3,5-dinitropyridine
in DMSO was measured using the equilibria with
DABCO pKa [18] = 9.06 and piperidine pKa = 10.85.
The reaction involved is shown in Scheme 2.
[DABCO]
(mol dm−3
[DABCO HCl]
Absorbance
(Abs)
10−3
Ka,b
)
(mol dm−3
)
0
0.01
0.01
0.01
0.01
0
0.123
0.212
0.387
0.463
1.06
–
9.5
8.7
8.2
–
pKa = pKa(BH+) − log10 K
(1)
0.1
0.4
0.6
0.4
0.6
Measurements of absorbance were made at 450 nm,
which is the absorption maximum for the anionic form
of 7 in solutions containing excess concentrations of
DABCO or piperidine and the corresponding DABCO
or piperidine hydrochloride ions. The values obtained
for K were 8.8 × 10−3 for reaction with DABCO and
0
1.11
–
a Measurements of absorbance were made at 450 nm.
b Calculated as [Abs − 0.123] [DABCOH+]/[1.15 − Abs]
[DABCO].
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REACTION OF 2-PHENOXY-3,5-DINITROPYRIDINE WITH SUBSTITUTED ANILINES
201
Table II Absorbance Data for 2-Anilino-3,5-dinitro-
pyridine (5 × 10−5 mol dm−3) in DMSO Containing
Various Concentrations of Piperidine at 25◦C
Table IIIa Kinetic Results for the Reaction of 1 with
4-Methoxyaniline (4a) in DMSO at 25◦C
[4a]
[DABCO]a
kobs [4a]
mol−1 dm−3 mol−1 dm−3 mol−1 dm3 s−1 kcalc [4a]
b
[Piperidine]
[Piperidine HCl]
Absorbance
(Abs)
(mol dm−3
)
(mol dm−3
)
Ka,b
0.05
0.075
0.10
0.20
0.30
0.06
0.10
0.15
0.10
0.10
0.10
–
–
–
–
0.0020
0.0034
0.0044
0.0078
0.0110
0.0147
0.017
0.020
0.007
0.013
0.022
0.0023
0.0032
0.0041
0.0076
0.0110
0.0147
0.0160
0.0180
0.0080
0.0110
0.0220
0
0.01
0.01
0.01
0.01
0.01
0.01
0
0.137
0.327
0.402
0.456
0.523
0.614
1.037
–
0.005
0.008
0.010
0.015
0.020
0.100
0.535
0.522
0.549
0.501
0.564
–
–
0.10
0.10
0.10
0.03
0.06
0.15
a Measurements of absorbance were made at 450 nm.
b Calculated as [Abs − 0.137] [PiperideneH+]/[1.037 − Abs]
[Piperidene].
a Solutions containing DABCO also contain DABCO hydrochlo-
ride, 0.01 mol dm−3. Measurements were made at 380 nm.
second-order rate constant, kobs/[aniline], versus ani-
line concentration were linear with positive intercepts.
These results are interpreted in terms of the process
shown in Scheme 1. It is known [15,19] that phenoxide
is a considerably better leaving group than ethoxide, by
a factor of ca. 106. The failure to observe 6, the inter-
mediate on the substitution pathway, may by attributed
to its rapid decomposition by loss of phenoxide. The
assumption that 5 may be treated as a steady-state in-
termediate leads to the rate expression of Eq. (2), where
kAn and kDABCO represent kB for the respective bases.
b Calculated from Eq. (3) with K1kDABCO 0.12 dm6 mol−2 s−1
,
K1kAn 0.035 dm6 mol−2 s−1, and K1k2 6 × 10−4 dm3 mol−1 s−1
.
hydrochloride, which inhibits their formation so that
such adducts were not formed. Previous work [10,20]
at lower base concentrations and in different solvents
did not find evidence for base catalysis. However, the
present work shows that in DMSO such catalysis oc-
curs and values calculated for K1kAn and K1kDABCO
for reactions of 1 are found. Base catalysis indicates
that proton transfer from zwitterion to base is rate
limiting.
The presence of a phenoxy group is not expected
to drastically affect the value of K1 for formation of
zwitterions [21]. The k2 step is likely to involve in-
tramolecular proton transfer from nitrogen to oxygen
coupled with carbon–oxygen cleavage. Leaving group
expulsion is part of the rate-limiting step here.
k1[An](k2 + kAn[An] + kDABCO[DABCO])
Kobs
=
k
−1 + k2 + kAn[An] + kDABCO[DABCO]
(2)
The results, which provide evidence for base catal-
ysis, indicate that the condition k ꢁ k2 + kAn [An]
−1
+ kDABCO[DABCO] applies so that Eq. (2) reduces to
Eq. (3).
kobs = K1[An] (k2 + kAn[An] + kDABCO[DABCO])
(3)
Kinetic measurements at 380 nm showed a single
first-order process. Values of the rate constant, kobs/[4a]
for reaction with 4-methoxyaniline (4a), are given in
Table IIIa.
Table IIIb Kinetic Results for the Reaction of 1 with
Aniline (4c) in DMSO at 25◦C
[4c]
[DABCO]a
kobs [4c]
–1
b
mol−1 dm−3 mol−1 dm−3 mol dm3 s–1 kcalc [4c]
–4
–4
–4
–4
–3
–3
–3
–3
–4
–4
–4
–4
–3
–3
–3
–3
0.10
0.20
0.30
0.40
0.10
0.10
0.10
0.10
–
–
–
1.5 × 10
1.9 × 10
2.2 × 10
2.6 × 10
1.5 × 10
2.8 × 10
4.2 × 10
6.0 × 10
1.5 × 10
1.9 × 10
2.3 × 10
2.7 × 10
1.5 × 10
3.0 × 10
4.3 × 10
5.8 × 10
Data are interpreted in a manner similar to that
given for 3, R = Ph so that Scheme 1 is applica-
ble and Eq. (3) will apply. Values calculated with
K1kDABCO = 0.12 dm6 mol−2 s−1, K1kAn = 0.035 dm6
–
0.05
0.10
0.15
0.20
mol−2
s
−1, and K1k2 = 6 × 10−4 dm3 mol−1 s−1 give
good agreement with values of kobs. Corresponding
data for reaction with aniline (4c) are in Table IIIb.
It is known that reaction at unsubstituted ring po-
sitions to give anionic adducts may precede the at-
tack at the 2-positon [15,19]. In the present work,
measurements were made in the presence of DABCO
a Solutions containing DABCO also contain DABCO hydrochlo-
ride, 0.01 mol dm−3. Measurements were made at 380 nm.
b Calculated from Eq. (3) with K1kDABCO 0.028 dm6 mol−2 s−1
K1kAn 4 × 10−4 dm6 mol−2 s−1, and K1k2 1.1 × 10−4 dm3 mol−1 s−1
,
.
International Journal of Chemical Kinetics DOI 10.1002/kin

202
ASGHAR
Values obtained for K1kDABCO, K1k2, and K1kAn
are summarized in Table IV together with pKa values,
measured in DMSO, for the conjugate acids of the
anilines. The highest value for 4-OMe indicates that the
higher basicity of 4-OMe is reflected in higher values
+
NH2
6
R
NH3
5
R
+
+
Scheme 3
of K1k2, K1kAn, and K1kDABCO. Values of K1kDABCO
,
K1k2, andK1kAn decrease strongly as the substituent R
is made more electron withdrawing.
It should be noted that since proton transfer is rate
determining in all these reactions, it is not possible to
The proton-transfer process, kDABCO, will be a
strongly favored process thermodynamically. This is
because proton transfer is to a strong base (DABCO).
Values would, in absence of steric effects, be close to
the diffusion limit. The reaction center in 5 is quite
hindered, hence values will be lower than the diffu-
sion limit. However, since the steric effects will be the
same for 4a–4d, values of kDABCO will be the same for
each aniline. Hence, changes in K1kDABCO in 4a–4d
reflect changes in values of K1, the equilibrium con-
stant for formation of zwitterions, rather than changes
in kDABCO.
A linear plot, not shown, of values of log K1kDABCO
versus Hammett σ values gives a slope, ρ, of −2.0.
Since values of kDABCO are expected to be indepen-
dent of the nature of the remote substituent, this
ρ value reflects the substituent effect on values of K1.
The negative value obtained is consistent with the in-
crease in positive charge on nitrogen associated with
the formation of 5.
Values of K1k2 show similar changes with the nature
of the substituent to values of K1kDabco. Both fall by a
factor of 10 going from 4a to 4d. The implication is
that values of k2 vary very little with the nature of the
substituent R.
Values of K1kAn decrease much more dramati-
cally going from 4a to 4d (factor of 350). This in-
dicates that the kAn process is far more favorable with
4-methoxyaniline than with 4-chloroaniline. A possi-
ble explanation is that the proton-transfer equilibrium
is not strongly thermodynamically favored (Scheme 3).
Hence as the basicity of the aniline decreases, the rate
constant for the process is reduced.
obtain values for the rate constants k1−1
.
The results for reaction of 1 are compared in
Table IV with results for the comparable reactions of 3,
R = Ph with aniline (4c). They show that both values
of K1kDABCO and K1kAn are considerably higher for 3
than for 1. Both electronic and steric factors will be
important in determining the relative reactivities. Pro-
ton transfer from the zwitterions to DABCO will be
strongly favored thermodynamically so that steric ef-
fects will be dominant in determining values of kDABCO
.
Replacing the ortho-nitro group in 3 with ring nitrogen
in 1 will make the reaction center more accessible to
the approaching base so that kDABCO should be higher
for reaction with 1 than with 3. The fact that the product
K1kDABCO has a higher value for the reaction of 3 (ratio
3: 1 is 57) indicates that the value of K1 must be consid-
erably higher for 3 than for 1. Two factors responsible
for this will be the greater electron-withdrawing influ-
ence of the ortho-NO2 group in 3 than the ring nitrogen
in 1, and also the greater relief of steric strain present
in the parent molecule 3 as the 1-substituent is rotated
from the ring plane on formation of the zwitterion [3,4].
The ratio of the values of K1kAn for 3:1 is 680
and is higher than the corresponding ratio of values
of K1kDABCO. This is likely to result from a reduc-
tion in the value of kAn in the reaction of 1, since the
proton-transfer process involved (see Scheme 3) is less
thermodynamically favorable than in the correspond-
ing reaction involving 3.
The results in Table IV show that the value of
K1kDABCO for reaction of 2 is higher than for the reac-
tion of 3 or 1. The predominant factor here, as discussed
previously [16], will be the higher value of kDABCO
Table IV Summary of Results for the Reactions of Anilines (4a–d) with 2-Phenoxy-3,5-dinitropyridine (1) and Related
Compounds in DMSO at 25◦C
Parent
Aniline
K1kDABCO (dm6 mol−2 s−1
)
K1kAn (dm6 mol−2 s−1
)
K1k2 (dm3 mol−1 s−1
)
pK
a
1
1
1
1
4a 4-OMe
4b 4-Me
4c H
4d 4-Cl
4c H
0.12
0.052
0.028
0.012
1.6
0.035
7.1 × 10−3
4 × 10−4
1 × 10−4
0.27
6 × 10−4
2.5 × 10−4
1.1 × 10−4
6 × 10−5
0.050
5.08
4.48
3.82
2.86
3.82
3.82
3, R = Pha
2b
4c H
28
0.14
–
a Results from [16].
b Results from [13].
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REACTION OF 2-PHENOXY-3,5-DINITROPYRIDINE WITH SUBSTITUTED ANILINES
203
associated with the lower steric hindrance to proton
transfer when reaction occurs at an unsubstituted ring
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12. Emokpae, T. A.; Hirst, J.; Uwakwe, P. U. J Chem Soc,
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I would like to thank Dr. M. R. Crampton, Durham
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International Journal of Chemical Kinetics DOI 10.1002/kin