Steric hindrance as a key factor on proton transfer in the σ-adduct forming reactions of o-substituted anilines with 1,3,5-trinitrobenzene in dimethylsulfoxide

Article abstract of DOI:10.1007/s00706-008-0913-5

Kinetic and equilibrium studies are reported of the reactions of 1,3,5-trinitrobenzene (TNB) with a series of o-substituted anilines in dimethyl sulfoxide (DMSO) in the presence of 1,4-diazabicyclo[2.2.2.]octane (DABCO). The pK_a values in DMSO for the aniline derivatives were measured using the proton-transfer equilibrium with 2,4-dinitrophenol. Kinetic studies are compatible with a two-step process involving initial nucleophilic attack on TNB by amine to give a zwitterionic intermediate which may transfer an acidic proton to DABCO to yield the anionic product. The results indicate steric hindrance to proton transfer in reactions involving 2,6-disubstituted anilines.

Full text of DOI:10.1007/s00706-008-0913-5

Monatsh Chem 139, 1191–1195 (2008)
DOI 10.1007/s00706-008-0913-5
Printed in The Netherlands
Steric hindrance as a key factor on proton transfer in the r-adduct
forming reactions of o-substituted anilines with 1,3,5-trinitrobenzene
in dimethylsulfoxide
Basim H. Asghar
Department of Chemistry, Faculty of Applied Sciences, Umm Al-Qura University, Makkah, Saudi Arabia
Received 8 February 2008; Accepted 20 February 2008; Published online 11 April 2008
#
Springer-Verlag 2008
Abstract Kinetic and equilibrium studies are reported
of the reactions of 1,3,5-trinitrobenzene (TNB) with
a series of o-substituted anilines in dimethyl sulf-
oxide (DMSO) in the presence of 1,4-diazabicy-
action with aniline does not occur since the initial
formation of the zwitterion is thermodynamically
unfavorable; the pK value for protonated aniline is
a
3.82 in DMSO [6]. However, Buncel et al. important-
ly showed that the presence of a strong base, such as
the methoxide ion or DABCO, made the second step
(proton transfer) sufficiently thermodynamically fa-
vorable as to allow observation of the anilide adduct
[7–10]. Kinetic studies in the presence of DABCO
showed that proton transfer was rate limiting [11–
16]. Buncel and Eggimann [11] have previously ex-
amined the kinetics of the reaction of 1 with unsub-
stituted aniline in the presence of DABCO, but in
clo[2.2.2.]octane (DABCO). The pK values in DMSO
a
for the aniline derivatives were measured using the
proton-transfer equilibrium with 2,4-dinitrophenol.
Kinetic studies are compatible with a two-step pro-
cess involving initial nucleophilic attack on TNB by
amine to give a zwitterionic intermediate which may
transfer an acidic proton to DABCO to yield the an-
ionic product. The results indicate steric hindrance to
proton transfer in reactions involving 2,6-disubstitut-
ed anilines.
þ
the absence of added DABCOH . Under these con-
ditions the reaction in Scheme 1 gives first order
kinetics in the forward direction and second order
kinetics in the reverse direction, making the evalua-
tion of rate constants more difficult. More recently
kinetic and equilibrium results have been reported
for the reactions of 1,3,5-trinitrobenzene (TNB) with
some substituted anilines in the presence of DABCO
in DMSO [16].
In this paper kinetic and equilibrium results are
reported for the reactions of 1 with a series of aniline
derivatives (2a–2f) carrying substituents close to the
reaction centre in the presence of DABCO in DMSO.
Measurements were made in the presence of
DABCO and its hydrochloride salt allowing a more
complete evaluation of the competing processes
compared with that achieved in earlier studies. The
Keywords Kinetic; o-Substituted anilines; ꢀ-Adducts; 1,3,5-
Trinitrobenzene; Steric hindrance.
Introduction
The reaction of 1,3,5-trinitrobenzene (1) with ali-
phatic amines in dimethyl sulfoxide (DMSO) results
in the spontaneous formation of anionic ꢀ-adducts
[1, 2]. Kinetic studies are consistent with the two
step process and show that the proton-transfer step
may be rate-limiting [3–5]. The corresponding re-
Correspondence: Basim H. Asghar, Department of Chemistry,
Faculty of Applied Sciences, Umm Al-Qura University,
P.O. Box 9569, Makkah, Saudi Arabia. E-mail: Basim15@
yahoo.com

1
192
B. H. Asghar
Scheme 1
pK values for the substituted anilinium ions in
a
the aniline hydrochloride. For less basic amines
where concentrations of hydrochloride lower than
DMSO were measured according to reported meth-
ods [16]. The results provide evidence that although
there is little steric hindrance to nucleophilic attack
to give the zwitterionic intermediates 3, there is a
pronounced reduction in rate constants for the pro-
ton-transfer step in 2,6-disubstituted anilines.
0.01 mol dm 3 were required, the ionic strength
ꢁ
was maintained at 0.01 mol dm 3 with tetraethylam-
ꢁ
monium chloride. Representative data are shown in
Table 1, and pK values are listed in Table 2.
a
Table 1 Absorbance data for 2,4-dinitrophenol, 1ꢂ
ꢁ
4
ꢁ3
Results and discussion
10 mol dm , in DMSO containing 2b and its hydrochlo-
ride at 25 C
ꢃ
The pK values for substituted anilinium ions
a
ꢄa b
[2b]=
mol dm
[2b HCl]=
ꢁ3
Abs
(430 nm)
Abs
K
in DMSO
ꢁ3
mol dm
The pK values for a number of amines in DMSO
a
0.00
0.05
0.20
0.01
0.01
0.01
0.01
0.01
0.00
0.00
0.006
0.082
0.263
0.354
0.452
1.41
0.006
0.081
0.259
0.347
0.441
1.40
–
have been reported previously [6]. The value for an-
iline is 3.82, and for DABCO 9.06. However, the pKa
values for substituted anilines used in the present
work in DMSO have not been reported previously.
In the present work a spectrophotometric method
using 2,4-dinitrophenol (DNP) as an indicator was
applied, as previously [6] reported, to measure
values of the equilibrium constant, K, for the process
0.0114
0.0111
0.0109
0.0113
–
0
0
0
0
.30
.40
.30
.60
1.43
1.40
–
a
ꢄ
Abs values have been corrected for absorption by 2b
Calculated as K ¼
ꢄ
b
ðAbs ꢁ0:006Þ½2bꢅHClꢆ
ꢄ
½1:40ꢁAbs ꢆ½2bꢆ
shown in Eq. (1). The pK value of DNP is known
a
Table 2 pK Values for substituted anilinium ions in DMSO
a
[
17] to be 5.12 ꢀ 0.04 in DMSO, so values of
þ
a
K
pK (AnH ) for the substituted anilines were calcu-
a
Anilines
pKa
(DMSO)
pKa
(water)
b
lated using Eq. (2). Measurements of absorbance
were made at 430 nm, which is the absorption maxi-
mum of the 2,4-dinitrophenolate anion in solutions
containing excess concentrations of the aniline 2
and corresponding anilinium ions. In some cases it
was necessary to make small corrections for the ab-
sorbance due to the substituted aniline. Wherever
possible measurements were made with solutions
2
2
2c
a
b
0.010 ꢀ 0.002
3.12 ꢀ 0.07
–
0.0113 ꢀ 0.0002
0.172 ꢀ 0.006
3.17 ꢀ 0.01 3.90
4.36 ꢀ 0.01 4.90
2.05 ꢀ 0.05 3.20
1.40 ꢀ 0.05 2.60
0.41 ꢀ 0.11 0.95
ꢁ
ꢁ
3
4
2d
(0.855 ꢀ 0.105)ꢂ10
4
2
2
e
f
(1.93 ꢀ 0.02)ꢂ10
(0.194 ꢀ 0.057)ꢂ10ꢁ
a
Defined in Eq. (1)
Ref. [18]
containing a concentration of 0.01 mol dm 3 of
ꢁ
b

Steric hindrance as a key factor on proton transfer
1193
ð1Þ
þ
PK ðAnH Þ ¼ log K þ pK ðDNPÞ
ð2Þ
The treatment of the zwitterions 3 in Scheme 1 as
steady state intermediates leads to Eq. (3), where
a
a
The high acidity of the 2-cyanoanilinium ion in
DMSO can be attributed to the electron-withdrawing
effect of the CN group. It is interesting that the pres-
ence of two o-substituents in the anilinium ions
formed from 2a and 2b greatly increases their acid-
ity compared to 2c. It is known [6] that DMSO is a
good hydrogen-bond acceptor, particularly from
charged species, so that these increases are likely to
result from steric inhibition of solvation by DMSO
of the anilinium ions.
[
An] represents the concentration of the subsitituted
aniline and [B] represents the concentration of the
base.
k ½Anꢆk ½Bꢆ þ k k
þ
½BHþꢆ
1
B
ꢁ1 BH
kobs
¼
ð3Þ
k
þ k ½Bꢆ
ꢁ1
B
Results are compatible only with the condition
k
transfer. Eq. (3) then simplifies to Eq. (4), where
K ¼ k =k .
ꢇ k ½Bꢆ, corresponding to rate limiting proton
ꢁ1
B
1
1
ꢁ1
þ
þ
Kinetic and equilibrium studies
Kobs ¼ K1kB½Anꢆ½Bꢆ þ kBH ½BH ꢆ
ð4Þ
Spectrophotometric measurements were made at
the absorption maximum of the adducts formed,
Buncel and Eggimann [11] have previously exam-
ined the kinetics of the reaction of 1 with unsubsti-
tuted aniline in the presence of DABCO, but in the
4
40 nm, using the stopped-flow technique. The con-
ꢁ
5
ꢁ3
þ
centration of 1 was kept at 4ꢂ10 mol dm and
was very much lower than that of the other compo-
nents, one of the substituted anilines 2a–2f and
DABCO. All measurements were made in the pres-
absence of added DABCOH . Under these condi-
tions the reaction in Scheme 1 gives first order ki-
netics in the forward direction and second order
kinetics in the reverse direction, making the evalua-
tion of rate constants more difficult. They showed,
importantly, that the proton-transfer step was rate
limiting. It was also shown [13] that stabilisation
þ
ꢁ3
ence of DABCOH , 0.01 mol dm . This kept the
ionic strength of the solutions constant and inhibited
any possible reaction between 1 and DABCO. Under
these conditions, accurate first-order kinetics were
observed and the variation in value of the rate con-
stant with aniline and DABCO concentrations was
examined. Specimen data are shown in Table 3.
þ
of DABCOH by association with chloride ions
may result in increases in the overall equilibrium
constant for adduct formation. Hence in the present
work all rate measurements were made with a low
and constant concentration of chloride ions.
Table 3 Kinetic results for the reaction of 1 with 2b in
Buncel and Eggimann [11] assumed that only
DABCO would be effective as a base in the pro-
ton-transfer stage of the reaction. However, it has
been shown [15] in a related system that even though
aniline is a much weaker base it might also con-
tribute to the proton transfer equilibrium. Thus, it
is known that the trinitrocyclohexadienate group
in 3, even though negatively charged, is electron-
withdrawing [3, 4, 9, 19]. Hence 3 will be more
acidic than the corresponding anilinium ion, so the
proton-transfer step 3 Ð 4 will be thermodynamical-
ly favored even when the reaction involves aniline as
a
DMSO at 25 C
ꢃ
ꢁ
3
ꢁ3
ꢁ1
b
calc
ꢁ1
=s
[
2b]=mol dm
[DABCO]=mol dm
kobs=s
k
0
0
0
0
0
0
.10
.10
.10
.05
.15
.20
0.10
0.20
0.30
0.10
0.10
0.10
0.034
0.044
0.052
0.037
0.046
0.048
0.038
0.046
0.054
0.034
0.042
0.046
a
þ
ꢁ3
All solutions contain DABCOH , 0.01 mol dm . Measure-
ments were made at 440 nm using the stopped-flow method
b
6
ꢁ2 ꢁ1
Calculated from Eq. (4) with K k
1
¼ 0.8 dm mol
s
DABCO
þ
3
ꢁ1 ꢁ1
þ
and kDABCOH ¼ 3.0 dm mol
s
B and the corresponding anilinium ion as BH .

1
194
B. H. Asghar
Table 4 Summary of results for the reactions of 1 with 2a–2f
ꢃ
effect is to the proton transfer step from the zwitter-
ionic intermediate 3 to DABCO.
and DABCO in DMSO at 25 C
þ
a
Aniline
K kDABCO=
1
kDABCOH =
K K
1
=
DABCO
ꢁ1
6
dm mol
ꢁ2 ꢁ1
3
dm mol
ꢁ1 ꢁ1
3
dm mol
s
s
Rate constants for proton transfer
2
2
2
2
2
2
a 2,6-Et
b 2,6-Me
c 2,4-Me 35
d 2-F
e 2-Cl
f 2-CN
0.3
0.8
2.20
3.00
258
8.00
2.61
2.70
0.14
0.26
0.14
0.22
0.23
0.15
In previous work Buncel and Eggimann [11] pro-
9
3
ꢁ1 ꢁ1
posed a value for kDABCO of 1ꢂ10 dm mol s ,
which is close to the diffusion limit. However, it is
now known [4, 20] that in DMSO values for such
proton transfers may be slowed down by hydrogen-
bonding to the solvent as shown for 5.
1.8
0.6
0.4
a
þ
Calculated as K1kDABCO=kDABCOH
It is necessary to break the hydrogen bond before
the proton transfer. Steric congestion at the reaction
centre may also reduce proton transfer rates [3, 4,
2
1, 22]. Thus, previous studies have indicated steric
þ
Fig. 1 Plots of log kDABCOH and log K1kDABCO for the re-
action of 1 with anilines versus the pK values of the corre-
sponding anilinium ions. The slopes are 0.54 and 0.51
hindrance to proton transfer when reaction involves
a bulky secondary amine, such as piperidine, acting
as both nucleophile and proton-acceptor base [3, 4,
a
23]. Proton transfer rates may also be reduced by the
Variations in the values of kobs with the concen-
trations of both of aniline and DABCO were used
pressure of a ring-substituent bulkier than hydrogen
at the reaction center [21, 22].
to calculate the values of the parameters K1kDABCO
þ
,
kDABCOH . The data are summarized in Table 4.
Here, for 2c–2f where steric effects to proton
transfer seem to be small it is reasonable, as previ-
þ
K K
(¼ K k
=kDABCOH ) which show lit-
tle variation with the nature of the substituent since
ously, [16] to assume a value for k
DABCO
of 1ꢂ
1
DABCO
1 DABCO
8
3
ꢁ1
10 dm mol , which is reduced below the diffu-
sion limit only by hydrogen-bonding to the solvent.
However, for 2a and 2b where steric effects are in
evidence the value of kDABCO will be further reduced.
A reduction of ca. twenty five was estimated from
the vertical difference between the points for 2a
and 2b and the straight lines in Fig 1. This would
changes in K1kDABCO are compensated by similar
þ
changes in kDABCOH
.
The present work is concerned with anilines 2a–
f carrying substituents close to the reaction centre.
Figure 1 shows logarithmic plots of the values of log
2
þ
kDABCOH and log K k
versus the pKa values of
1 DABCO
the corresponding anilinium ions. This shows that
for anilines 2a and 2b which have two groups at
o-positions values are considerably below the lines
defined by the other substituents. These deviations
are likely to result from steric effects. These might
involve either steric hindrance to nucleophilic at-
lead to a value of k
for 2a and 2b of 4ꢂ
DABCO
6
10 dm mol . On this basis it is possible to calcu-
3
ꢁ1
late values for KDABCO using Eq. (5).
kDABCO
KDABCO ¼ k
ð5Þ
þ
DABCOH
tack, which would affect values of K , or steric hin-
1
The results in Table 5 show that values of KDABCO
increase in value as the ring-substituents R are made
more electron-withdrawing. These increases reflect
increasing acidity of the zwitterionic intermediates
3. Interestingly, values of KDABCO for 2a and 2b are
drance to proton transfer, which would affect values
þ
of kDABCOH and also kDABCO. The observation that
þ
both values of K1kDABCO and values of kDABCOH are
lowered in 2a and 2b indicates that the major steric

Steric hindrance as a key factor on proton transfer
1195
ꢃ
Table 5 Derived values for the reaction of 1 in DMSO
made at 25 C. First-order rate constants, precise to ꢀ3%,
were evaluated using standard methods.
a
þ
Aniline
K (AnH )=
ꢁ
KDABCO
K1=
dm mol
a
mol dm
3
3
ꢁ1
Acknowledgements
ꢁ
ꢁ
ꢁ
ꢁ
4
4
5
3
6
6
ꢁ8
ꢁ7
ꢁ7
ꢁ8
ꢁ9
ꢁ9
2
2
2
2
2
2
a 2,6-Et
b 2,6-Me
c 2,4-Me
d 2-F
e 2-Cl
f 2-CN
7.58ꢂ10
6.76ꢂ10
4.36ꢂ10
8.91ꢂ10
0.04
1.8ꢂ10
1.3ꢂ10
8.0ꢂ10
2.0ꢂ10
3.5ꢂ10
1.8ꢂ10
6.0ꢂ10
4.0ꢂ10
I would like to thank Dr. M.R. Crampton, Durham University,
UK for his voluble advice.
5
7
7
7
3.87ꢂ10
1.25ꢂ10
3.83ꢂ10
3.70ꢂ10
0.39
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and DMSO were the purest available commercial samples
from Aldrich. Amine salts were prepared in solution by the
accurate neutralisation of amines with concentrated hydro-
chloric acid. UV-Vis spectra and kinetic measurements were
made with an Applied Photophysics SX-17MV stopped-flow
instrument, or with Shimadzu UV-2101 PC or Sp6-550 UV=
vis Pye unicam spectrophotometers. All measurements were