Effect of substituent in diazotized orthanilic acid on the azo coupling with 7-acetylamino-4-hydroxynaphthalene-2-sulfonic acid in citrate-phosphate buffers

Article abstract of DOI:10.1023/B:RUGC.0000007618.08375.43

Effect of substituent in the para position with respect to the diazo group in diazotized orthanilic acid derivatives on the rate and selectivity of azo coupling with 7-acetylamino-4-hydroxynaphthalene-2-sulfonic acid was studied in citrate-phosphate buffers. The selectivity of azo coupling at the 3-position of the azo component almost does not depend on the nature of electron-donor substituent. Electron-acceptor groups considerably reduce the selectivity of formation of the 3-isomer. Previous conclusions, according to which the rate-determining stages are different depending on the site of azo coupling of diazotized orthanilic acid with 7-acetylamino-4-hydroxynaphthalene-2-sulfonic acid, were found to be also valid for some 5-substituted orthanilic acid derivatives. The rate-determining stage in the azo coupling at the 3-position can change upon introduction of strong electron-acceptor substituents capable of interacting with the diazo group. The contribution of the multicenter mechanism of deprotonation of the σ-complex with participation of water molecules was presumed to increase in going to the diazo components having electron-donor substituents.

Full text of DOI:10.1023/B:RUGC.0000007618.08375.43

Russian Journal of General Chemistry, Vol. 73, No. 7, 2003, pp. 1095 1099. Translated from Zhurnal Obshchei Khimii, Vol. 73, No. 7, 2003,
pp. 1158 1163.
Original Russian Text Copyright
2003 by Kornev, Zheltov.
Effect of Substituent in Diazotized Orthanilic Acid
on the Azo Coupling with 7-Acetylamino-4-hydroxynaphthalene-
2-sulfonic Acid in Citrate Phosphate Buffers
K. A. Kornev and A. Ya. Zheltov
Mendeleev Russian University of Chemical Engineering, Moscow, Russia
Received April 11, 2001
Abstract Effect of substituent in the para position with respect to the diazo group in diazotized orthanilic
acid derivatives on the rate and selectivity of azo coupling with 7-acetylamino-4-hydroxynaphthalene-2-sul-
fonic acid was studied in citrate phosphate buffers. The selectivity of azo coupling at the 3-position of the azo
component almost does not depend on the nature of electron-donor substituent. Electron-acceptor groups
considerably reduce the selectivity of formation of the 3-isomer. Previous conclusions, according to which
the rate-determining stages are different depending on the site of azo coupling of diazotized orthanilic acid
with 7-acetylamino-4-hydroxynaphthalene-2-sulfonic acid, were found to be also valid for some 5-substituted
orthanilic acid derivatives. The rate-determining stage in the azo coupling at the 3-position can change upon
introduction of strong electron-acceptor substituents capable of interacting with the diazo group. The contribu-
tion of the multicenter mechanism of deprotonation of the -complex with participation of water molecules
was presumed to increase in going to the diazo components having electron-donor substituents.
We previously studied the effect of steric and
NH2
NH2
electronic factors on the azo coupling of diazotized
orthanilic and sulfanilic acids, as well as of N,N-di-
alkylamides derived therefrom [1, 2], with 7-acetyl-
amino-4-hydroxynaphthalene-2-sulfonic acid. In con-
tinuation of these studies, we have focused on the
electronic effect of substituent in the diazo component
on the rate and selectivity of azo coupling. According
to published data [3, 4], such an effect may be quite
considerable, especially when the substituent gives
rise to -electron interaction with the reaction center.
Probably, electron density redistribution in the diazo
group and effective positive charge on the terminal
nitrogen atom affect the kinetics of azo coupling to
a greater extent, as compared to steric and electrostatic
obstacles created by the sulfo group in diazotized
orthanilic acid derivatives.
SO3H
Cl
SO3H
O2N
H3C
I
II
NH2
NH2
SO3H
SO3H
H3CO
III
IV
having the opposite signs. The substituents in the
para-position with respect to the amino group in
II and III exert mainly inductive effect on
the aromatic system. Therefore, variation of the selec-
tivity and rate of azo coupling in the series I IV could
provide information on the character and magnitude
of the electronic structure effect on the azo coupling at
positions 1 and 3 of 7-acetylamino-4-hydroxynaph-
thalene-2-sulfonic acid (V).
With the goal of elucidating the role of electronic
properties of substituents, as model compounds we
selected 5-substituted orthanilic acid derivatives, in
which the substituent affects the electronic structure
of the diazo group but exerts no additional steric
hindrance.
OH
3
NHAc
NaO3S
1
Compounds I and IV possess, respectively, elec-
tron-acceptor (NO2) and electron-donor (OCH3)
substituents which are conjugated with the amino group
subjected to diazotization. The influence of the above
groups originates from their strong mesomeric effects
V
Figure 1 show the dependence of the selectivity of
azo coupling on the pH value of buffer solution.
3
1070-3632/03/7307-1095$25.00 2003 MAIK Nauka/Interperiodica

1096
KORNEV, ZHELTOV
1
Table 1. Partial second-order rate constants (l mol 1 s )
for azo coupling of diazotized orthanilic acid derivatives
I IV with 7-acetylamino-4-hydroxynaphthalene-2-sulfonic
acid (V) in citrate phosphate buffer
A different pattern is observed in going to diazo
compounds having electron-acceptor substituents. The
selectivity of azo coupling at the 3-position of acid V
with diazotized 5-chloroorthanilic acid (II) is lower
by 7 17% than the corresponding value for orthanilic
acid. In the reaction with diazotized 5-nitroorthanilic
acid (I), the major product is that formed by azo
coupling at the 1-position of acid V throughout the
Rate
Azo
coupling
at C3
Azo
coupling
at C1
Diazo
component
constant,
l mol 1 s
1
examined range of pH. Here, the selectivity
is
2-Amino-5-nitro-
benzenesulfonic
acid (I)
kROH
kRO
16.3
11.9
lower by a factor of 2.4 6.2, as compared with3 di-
azotized orthanilic acid.
6.04 104 1.35 105
Our results are consistent with the data obtained
while studying azo coupling of substituted benzene-
diazonium salts with 1-naphthol [4, 5]. Assuming that
the conclusions drawn in [4, 5] are also valid for the
series of compounds under study, base catalysis of the
azo coupling at position 3 of acid V is likely to be
much less effective than at position 1. The rate of
deprotonation of the -complex increases relative to
the rate of its formation as the electron-acceptor power
( M effect) of the conjugated substituent rises, for
the latter strongly enhances acidic properties. In the
limiting case, the azo coupling of diazotized 2-amino-
5-nitrobenzenesulfonic acid at both activated positions
of acid V could involve the second stage of the
process as rate-determining.
2-Amino-5-
kROH
kRO
0.465
2780
0.0571
588
chlorobenzenesul-
fonic acid (II)
2-Amino-5-me-
thylbenzenesul-
fonic acid (III)
2-Amino-5-me-
thoxybenzenesul-
fonic acid (IV)
kROH
kRO
8.72 10
39.3
3.13 10
2.99
2
3
kROH
kRO
4.97
0.83
It should be noted that introduction of electron-donor
substituents into position 5 of the diazo component
almost does not affect the selectivity of azo coupling
with acid V. In neutral and alkaline media, the selec-
tivity of the azo coupling of diazotized 5-methyl-
orthanilic acid (III) at the 3-position of V is lower
by 4 5% than the selectivity found for diazotized
unsubstituted orthonilic acid. This value exceeds by
only 1 2% the error in spectrophotometric determina-
tion of the corresponding quantities, so that it can
hardly be taken into account. The selectivities for
orthanilic acid and 5-methoxyorthanilic acid (IV)
are experimentally indistinguishable.
On the basis of the pH dependences of the apparent
rate constants and selectivities of azo coupling with
diazotized compounds I IV, we calculated the partial
rate constants for substitution at positions 1 and 3
of sulfonic acid V (Table 1). The rate of azo coupling
with diazotized compound IV in neutral and acid
media is so small that it becomes comparable with the
rate of side transformations of the diazo compound.
For that reason, we failed to determine the selectivity
at pH <8 and the rate constant kROH. Taking into
ac3count that alkaline medium gives rise to base
catalysis of the deprotonation of -complexes with
hydroxide ions, the kRO values for 2-amino-5-
methoxybenzenesulfonic acid could be somewhat
overestimated.
3
3
0.35
0.30
1.0
0.9
3
0.25
0.20
4
Some general trends in the substituent effect on
the reactivity of diazotized orthanilic acid derivatives
in the azo coupling at positions 1 and 3 of acid V
can be determined by analysis of the obtained data
0.8
0.7
0.15
1
2
0.10
0.05
using the Hammett equation logkR = logkH
+
.
2
4
6
8
10
12
For this purpose, we have plotted the dependences of
pH
log (kR/kH) on the constants
for the following
Fig. 1. Selectivities of the azo coupling at position 3 of
7-acetylamino-4-hydroxynaphthalene-2-sulfonic acid
versus pH of buffer solution: (1) 2-amino-5-nitrobenzene-
sulfonic acid (I), (2) 2-amino-5-chlorobenzenesulfonic
acid (II), (3) 2-amino-5-methylbenzenesulfonic acid (III),
and (4) 2-amino-5-methoxybenzenesulfonic acid (IV).
substituents R: OCH3, CH3, H,p Cl, NO2. Although
the number of points is too small to obtain rigorous
correlations, the observed trends in the variation of
the rates of azo coupling at positions 1 and 3 allowed
us to make some presumptions concerning the reac-
tion mechanism.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 7 2003

EFFECT OF SUBSTITUENT IN DIAZOTIZED ORTHANILIC ACID
1097
3
2
5
4
3
2
1
0
1
2
3
Cl
NO2
NO2
3
1
0
1
5
H
0
H
Cl
Me
OMe
7
Me
2
OMe
0.4 0.2
0.4 0.2
0
0.2 0.4 0.6 0.8 1.0
0.2 0.4 0.6 0.8 1.0
p
p
Fig. 2. Semilog plot of the reduced rate constants for the
azo coupling in position 3 versus substituent constants
Fig. 3. Semilog plot of the reduced rate constants for
the azo coupling in position versus substituent
constants
1
.
.
p
p
The log (kR/kH)
position 3 is a smooth curve having two asymptotic
plot for the azo coupling at
measured the rates of azo coupling and determined
the selectivities of azo coupling at position 3 of
7-acetylamino-4-hydroxynaphthalene-2-sulfonic acid
(V) for diazotized 4-methoxyaniline (VI) and
4-chloroaniline (VII).
p
tangents which cross at a point with
0 (Fig. 2).
The slope of the asymptote relative top the axis is
7, and it approaches a value of 3 in the region corre-
sponding to electron-acceptor substituents. In keeping
with the theoretical data [6], this pattern suggests
either change of the rate-determining stage or different
contributions of the multicenter mechanism of de-
protonation of the -complex with water molecules
in the azo coupling at position 3, depending on the
electronic structure of the diazo component.
NH2
NH2
Cl
H3CO
VI
VII
Only traces of the corresponding 1-isomer were
detected by chromatography among products of azo
coupling of diazotized 4-methoxyaniline, and we
failed to isolate it and determine its yield by spectro-
photometry. The selectivity of azo coupling at
position 3 for diazotized 4-chloroaniline ranges from
0.611 to 0.940, depending on the pH value; the
maximal selectivity is observed in neutral medium.
The second-order rate constants, calculated from the
apparent partial rate constants for azo coupling in the
pH range from 3 to 11, are given in Table 2. It should
be noted that the rate constants for azo coupling at
position 1 almost do not change in going from
4-chloroaniline (VII) to 2-amino-5-chlorobenzene-
sulfonic acid, while the azo coupling at position 3
is characterized by reduction of the partial rate con-
stants: kROH decreases by a factor of 2, and kRO , by
a factor of 3. The rate constant kRO for the azo
coupling at position 3 for 4-methoxyaniline is greater
by a factor of 2.2 than the corresponding rate constant
for 2-amino-5-methoxybenzenesulfonic acid.
The excellent correlation (r = 0.996) between the
rate constants for azo coupling at position 1 and
constants
for all diazo components I IV clearly
p
indicates that the rate-determining stage does not
depend on the substituent (Fig. 3). The above two
relations provide one more support to the assumption
that the rate-determining stages in the azo couplings
at positions 1 and 3 of acid V are different. The sub-
stituent in the diazo component has no appreciable
influence on the previously [1, 2] established relations
holding in the azo coupling at position 3 of azo com-
ponent V.
H
H
<
O
H
O
N=N Ar
SO3
H
Ar
O
N=N
Obviously, the presence of a sulfo group in the
ortho position with respect to the diazo group does
not effect the rate of substitution at position 1; the
strongest inhibitory effect in the azo coupling at
position 3 is observed when the hydroxy group in V
is ionized. These data may be explained only in terms
+ H2O
SO3
In order to estimate the effect of the sulfo group
in ortho position with respect to the diazo group, we
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 7 2003

1098
KORNEV, ZHELTOV
4
Table 2. Partial second-order rate constants for azo
coupling of diazotized orthanilic and sulfanilic acids with
7-acetylamino-4-hydroxynaphthalene-2-sulfonic acid (V)
in cutrate phosphate buffers
(7.3 8.0) 10 M. The initial concentration of the
5
diazo components was (4.3 4.6) 10 M.
Sodium 3-hydroxybenzenesulfonate. 3-Amino-
benzenesulfonic acid, 87 g, was dissolved in 1 l of
water while adding 40% aqueous sodium hydroxide
to pH 7.5 8.5. A 30% solution of sodium nitrite
(35 g) was then added, the mixture was cooled to
5 10 C, and a cold solution of 23 ml of 94% sulfuric
acid in 100 ml of water was added at such a rate that
the temperature did not exceed 15 18 C (the mixture
should be acidic according to Congo Red). The mix-
ture was kept for 30 min at room temperature, and
excess nitrous acid was decomposed by adding solid
sulfamic acid. The mixture was heated to 60 70 C,
kept at that temperature until negative test for diazo
compound with an alkaline solution of H-acid (more
than 15 h), neutralized with barium carbonate, and
filtered to remove barium sulfate. The yellow brown
solution was evaporated to dryness, and the residue
was extracted with 2 l of 96% ethanol. Removal of the
solvent from the extract left 60 g (61%) of sodium
3-hydroxybenzenesulfonate as a light yellow powder.
Rate
Azo
coupling
at C3
Azo
coupling
at C1
Diazo
component
constant,
l mol 1 s
1
4-Chloroaniline
(VI)
4-Methoxy-
aniline (VII)
kROH
kRO
kROH
kRO
0.954
0.0558
574
8530
0.0208
10.9
of our previous conclusions implying different rate-
determining stages in the azo couplings at positions
3 and 1 of acid V, as well as in terms of appreciable
contribution of steric and electronic effects of the
sulfo group in each of the above stages.
EXPERIMENTAL
1
IR spectrum, cm : 1250 (SO2, asym.); 3600, 1200
(OH); 1050 (SO2, sym.).
All kinetic and spectrophotometric measurements
were performed in citrate phosphate buffers [7]. The
pH values were measured with the aid of a pH-121
pH meter equipped with glass and silver chloride
electrodes and calibrated against standard buffer
solutions with pH values of 1.69, 4.01, 6.86, and 9.18.
5-Hydroxy-2-(phenylazo)benzenesulfonic acid.
Sodium 3-hydroxybenzenesulfonate, 38.5 g, was
dissolved in 100 ml of water, the solution was
adjusted to pH 8.9 9.5 by adding 40% aqueous
sodium hydroxide, and the mixture was cooled to
0 5 C. Freshly distilled aniline, 12 ml, was diazotized
according to the procedure described in [8]. Just
before azo coupling, excess nitrous acid was decom-
posed by adding solid sulfamic acid to the solution
of benzenediazonium chloride. The latter was then
added in portions over a period of 3 h with stirring
to the solution of the azo component, maintaining
the pH at 8.9 9.3 by adding 20% aqueous sodium
hydroxide. The misture was left overnight
at 0 5 C, heated to 60 C, stirred for 30 min, and
filtered. The filtrate was adjusted to pH 9.5 by adding
a 10% solution of NaOH, sodium chloride was added
in portions to a concentration of 15 wt %, the mixture
was cooled to room temperature, and colored im-
purities were filtered off. The filtrate was acidified
to pH 2 with 15% hydrochloric acid, and the precip-
itate was filtered off. Yield 11.5 g (64%), violet
powder, Rf 0.35 (Silufol UV-254, pyridine isopentyl
The ratio of isomeric azo compounds was deter-
mined from the electronic absorption spectra which
were recorded on a Specord M-400 spectrophotometer
(Carl Zeiss, Jena) at pH 2.0. The IR spectra were
measured on a Specord M-80 spectrometer (Carl
Zeiss, Jena) from samples dispersed in mineral oil.
1
The H NMR spectra were obtained at 333 K in
DMSO-d6 using a Bruker CXR-200 spectrometer
(200 MHz); tetramethylsilane was used as internal
reference.
Primary kinetic dependences of optical density of
the reaction mixtures were obtained on a Spekol-210
spectrophotometer (Carl Zeiss, Jena) equipped with
a Serial Box Interface external AD converter (Vernier
Software) which was connected to a serial port of
an IBM-compatible PC. The measurements were per-
formed in a 1-cm static cell equipped with a stirrer
and maintained at a constant temperature. The cell
was charged with 0.5 ml of a solution of the azo
component and 1.0 ml of citrate phosphate buffer.
alcohol 25% aqueous ammonia, 7:4:4). IR spectrum,
, cm : 1250 (SO2, asym.); 3600, 1200 (OH), 1050
(SO2, sym.). UV spectrum (water), max, nm (log ):
pH 1.0: 350 (4.13); pH 11.0: 400 (4.18).
1
A
solution of aqppropriate diazo component,
0.485 0.005 ml, was then added through a calibrated
syringe. The optical densities were measured at 20 C,
the initial concentration of azo component V being
Sodium 5-methoxy-2-(phenylazo)benzenesulfo-
nate. Sodium 5-hydroxy-2-(phenylazo)benzenesulfo-
nate, 21.4 g, was dissolved in 50 ml of water, the
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 7 2003

EFFECT OF SUBSTITUENT IN DIAZOTIZED ORTHANILIC ACID
1099
solution was adjusted to pH 9.0 by adding 40%
aqueous NaOH, and the mixture was heated to 60 C.
Freshly distilled dimethyl sulfate, 20 ml, was added
over a period of 5 h under vigorous stirring; during
the addition, the initial pH value was maintained
intermittently by adding 20% aqueous NaOH. The
mixture was kept for 12 h, and the fine crystals were
filtered off, washed with 100 ml of water, and dried.
was combined with the washings and acidified with
hydrochloric acid (Congo Red). The precipitate was
filtered off, washed with water (2 50 ml), recrystal-
lized first from 0.1 N hydrochloric acid and then from
water, and dried at 60 C. Yield 13.1 g (70%), color-
1
less finely crystalline powder. IR spectrum, , cm :
1250 (SO2, asym.), 1060 (SO2, sym). Anilinium salt
C7H9NO3S C6H7N: mp 235 239 C (from 96%
ethanol); published data [9]: mp 237 241 C.
1
Yield 22 g (90%). IR spectrum, , cm : 1250 (SO2,
asym.), 1050 (SO2, sym.). UV spectrum (water),
nm (log ): pH 1.0: 350 (4.16); pH 11.0: 350 (4.17).
,
max
2-Amino-5-chlorobenzenesulfonic acid (II).
A 7.5-ml portion of 92% sulfuric acid was added with
stirring to 16.7 g of 4-chloroaniline (see above). The
salt was sulfonated by sintering at 170 180 C over
a period of 5 h. The end of the reaction was deter-
mined as described above. Removal of unreacted
4-chloroaniline and isolation and purification of
2-amino-5-chlorobenzenesulfonic acid were performed
following the procedures described above for
2-amino-5-methylbenzenesulfonic acid. Yield 25.2 g
2-Amino-5-methoxybenzenesulfonic acid (IV).
Sodium
5-methoxy-2-(phenylazo)benzenesulfonate,
20.0 g, was dissolved in 300 ml of water heated to
80 85 C, 22.0 g of Na2S2O4 was added, and the
mixture was stirred for 30 min (until it became
colorless), heated to 90 95 C, and kept for 10 15 min
at that temperature. The mixture was cooled to 35
40 C and extracted with benzene until the extracts no
longer contained aniline. The aqueous phase was
acidified to pH 5.0 with hydrochloric acid, and the
precipitate was filtered off, washed with 50 ml of
0.1 N hydrochloric acid and 50 ml of water, and
recrystallized from water. Yield 6.3 g (51%) of
chromatographically pure compound IV. Further
acidification of the filtrate obtained after separation
of the first portion gave an additional 2.7 g (22%) of
1
(60%), light grey crystals. IR spectrum, , cm : 1250
(SO2, asym.), 1060 (SO2, sym). Anilinium salt
C6H6NO3S C6H7N, mp 210 212 C (from 96%
ethanol); published data [10]: mp 211 212 C.
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(3H, CH3).
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water was distilled off under reduced pressure (water-
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170 180 C, and the mixture was kept for 3 h at that
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 7 2003