Salicylic acid nitration by means of nitric acid/acetic acid system: Chemical and kinetic characterization

Article abstract of DOI:10.1021/op060148o

The nitration of salicylic acid by means of HNO₃/AcOH is investigated, and the results are compared with those obtained using different nitrating systems: HNO₃/H₂SO₄/H₂O (mixed acid), HNO₃/Ac₂O/AcOH, aqueous HNO₃ (70% by weight) at 343 K. Little differences are found in terms of yield of the desired product (5-nitrosalicylic acid) among HNO₃/AcOH mixture, mixed acid, and HNO₃/Ac₂O/AcOH systems, aqueous HNO ₃ giving the poorest results. However according to the data collected during the present investigation the use of the system HNO₃/AcOH presents some advantages with respect to the others for the separation and purity of desired product, waste minimization, and safety improvements. The reaction kinetics for the nitration of salicylic acid with this system is also investigated. A global second-order kinetic law (one for the substrate, one for nitric acid) is used in the analysis of the data collected for the formation of the two mononitroderivatives (3-nitro- and 5-nitrosalicylic acids) and of the side product 2-nitrophenol.

Full text of DOI:10.1021/op060148o

Organic Process Research & Development 2006, 10, 1199−1204
Salicylic Acid Nitration by Means of Nitric Acid/Acetic Acid System: Chemical
and Kinetic Characterization
Roberto Andreozzi,† Marisa Canterino,† Vincenzo Caprio,† Ilaria Di Somma,*,† and Roberto Sanchirico‡
UniVersita` di Napoli “Federico II”, p.le V. Tecchio, 80-80125 Naples, Italy, and Istituto di Ricerche sulla Combustione
(CNR), p.le V. Tecchio, 80-80125 Naples, Italy
Abstract:
implementation, this factor should be considered extensively
from the early stages of the process development.
The nitration of salicylic acid by means of HNO3/AcOH is
investigated, and the results are compared with those obtained
using different nitrating systems: HNO3/H2SO4/H2O (mixed
acid), HNO3/Ac2O/AcOH, aqueous HNO3 (70% by weight) at
343 K. Little differences are found in terms of yield of the
desired product (5-nitrosalicylic acid) among HNO3/AcOH
mixture, mixed acid, and HNO3/Ac2O/AcOH systems, aqueous
HNO3 giving the poorest results. However according to the data
collected during the present investigation the use of the system
HNO3/AcOH presents some advantages with respect to the
others for the separation and purity of desired product, waste
minimization, and safety improvements. The reaction kinetics
for the nitration of salicylic acid with this system is also
investigated. A global second-order kinetic law (one for the
substrate, one for nitric acid) is used in the analysis of the data
collected for the formation of the two mononitroderivatives (3-
nitro- and 5-nitrosalicylic acids) and of the side product
2-nitrophenol.
The present work aims at studying the nitration of salicylic
acid (AS) for the production of 5-nitrosalicyclic acid by
comparing the effectiveness of different nitrating systems.
This compound is an important intermediate for chemical
and pharmaceutical industries. The derivative amine (me-
salazine) is currently used as active species for the treatment
of various pathologies such as ulcerative colitis and Crohn’s
disease.5,6 From a literature survey it is highlighted that there
are two nitrating systems that have been normally adopted
for the production of the target compound: HNO3/H2SO4/
H2O (mixed acid)7,8 and HNO3 (70% by weight) at 343 K.8-10
A further system that, from literature indications, could be
used in this process is the mixture HNO3/Ac2O/AcOH. In
fact this system has been found to give good results in the
nitration of deactivated substrate.11 Unfortunately the HNO3/
Ac2O/AcOH system evolves through the formation of
acetylnitrate, an unstable intermediate, thus resulting in a
less safe process.12-14 On the basis of these considerations a
further system that could be proposed for the production of
5-nitrosalicylic acid is the mixture HNO3/AcOH. The
elimination of acetic anhydride could result into a reduction
in the formation of the acetylnitrate. This last system shows
some additional useful advantages in a possible industrial
application with respect to the use of HNO3 at 70% by
weight. In fact the reactivity of the system HNO3/AcOH
allows working at a temperature lower than that used with
the sole HNO3 thus resulting in a more inherently safe
process. Moreover, it is possible to separate the desired
product at high purity by filtration. Simple considerations
may not allow us to establish what is the safest nitrating
system between mixed acid and HNO3/AcOH mixture. From
a general point of view it can be put forward that both of
them may originate runaway phenomena as a result of a loss
1. Introduction
Nitrations are among the most common reactions carried
out at industrial scale. Nitrated products are used directly or
as intermediates in dyes, explosives, pesticides, and the
pharmaceutical industry.1,2 Although these reactions have
been widely studied in the past,3,4 the interest is still alive
from theoretical and practical points of view. The most
common nitrating system currently adopted at the industrial
scale is represented by the classic mixed acid (HNO3/H2-
SO4/H2O). Among the drawbacks associated to its use, poor
selectivity, waste disposal, and process safety are often
reported. With respect to the last aspect, it is useful to
remember that, due to its exothermic behaviour and to the
inherent thermal instability of the products, nitrations are
along with polymerizations among the most dangerous
reactions due to the thermal runaway phenomena at industrial
levels. It is evident that, in view of an industrial process
(5) Forbes, A.; Cartwright, A.; Marchant, S.; McIntyre, P. Aliment. Pharmacol.
Ther. 2003, 17 (10), 1207.
(6) Podolsky, D. K. J. Gastroenterol. 2003, 38 (Suppl. 15), 63.
(7) Zaiyou, T.; Tiansui, L.; Gengxin, Z.; Zhufen, L.; Xiaobin, X.; Lianfang,
X.; Bin, L. Guangzhou Huagong 2003, 31 (1), 37.
(8) Mayo, D. W.; Pike, R. M.; Trumper, P. K.; Microscale Organic Laboratory,
3rd ed.; John Wiley and Sons, Inc.: New York, 1994.
(9) Hong, L. Huagong Shikan 2000, 14 (9), 39.
* Corresponding author. Telephone: +39 081 7682225. Fax: +39 081
5936936. E-mail: idisomma@unina.it.
† Universita` di Napoli “Federico II”.
‡ Istituto di Ricerche sulla Combustione (CNR).
(1) Olah, G. A.; Malhotra, R.; Narang, S. C. Organic Nitro Chemistry Series-
Nitration Methods and Mechanisms; VCH: New York, 1989.
(2) Hoggett, J. G.; Monodie, R. B.; Penton, J. R.; Schofield, K. Nitration and
aromatic reactiVity; Cambridge at the University press: London, 1971.
(3) Robinson, R. Two Lectures on An Outline of An Electrochemical (Electronic)
Theory of the Course of Organic Reactions; Institute of Chemistry: London,
1932.
(10) Jinjiang, Z.; Cuilin, H.; Guangjian, F. Zhongguo Yiyao Gongye Zazhi 1991,
22 (7), 295.
(11) Smith, K.; Gibbins, T.; Millar, R. W.; Claridge, R. P. J. Chem. Soc., Perkin
Trans. 1 2000, 2753.
(12) Andreozzi, R.; Marotta, R.; Sanchirico, R. J. Hazard. Mater. 2002, 90 (2),
111.
(13) Mantsch, O.; Bodor, N.; Hodosan, F. ReV. Roum. Chim. 1968, 13 (11), 1435.
(14) Mantsch, O.; Bodor, N. ReV. Roum. Chim. 1969, 14 (10), 1295.
(4) Ingold, C. K. Chem. ReV. 1934, 15, 225.
10.1021/op060148o CCC: $33.50 © 2006 American Chemical Society
Published on Web 10/26/2006
Vol. 10, No. 6, 2006 / Organic Process Research & Development
•
1199

Table 1. Experimental conditions adopted in preliminary runs
T
nAS
nHNO
nAcOH
nH SO4
nAc O
2
2
no.
system
mixed acid
HNO3/Ac2O/AcOH
HNO3/AcOH
[K]
[mol × 10-2]
[mol × 130-2]
[mol × 10-2]
[mol × 10-2]
[mol × 10-2]
nAS/nHNO
3
1
1
2
3
4
288
288
288
343
0.60
0.60
0.60
0.43
3.0
3.0
3.0
1.3
6.1
/
5
1
1.46
1.46
0.60
/
5
1
/
5
1
HNO3 (w/w 70%)
/
3
of the thermal control with a possible accidental triggering
of the decomposition of the intermediate and product
nitroderivatives. Safety investigations on these aspects for
the system HNO3/AcOH are reported by the authors else-
where.12 Moreover, at least in principle, the possibility cannot
be ruled out of detonation of the mixture HNO3/AcOH if
properly initiated and confined. However no data are
available in the literature for a HNO3/AcOH mixture as
diluted as those used in the present investigations.15
In the present work the nitration by HNO3/AcOH is
studied from chemical and kinetic points of view. A
comparison of the yields of 5-nitrosalicylic acid obtained
with this system with those found in the nitration of salicylic
acid by means of the other three systems is also performed.
and weighed. In the second case, the whole reactor content
has been quenched with urea, and the resulting samples
dissolved in methanol. The collected solutions have been then
submitted to HPLC analysis.
3. Results and Discussions
3.1. Preliminary Experiments. Aiming both to verify
the data reported in the literature7-11 and to highlight the
differences among the systems investigated in the present
work, a series of preliminary nitrations of the substrate has
been performed. The nitration of salicylic acid has been thus
studied by using HNO3/H2SO4/H2O (the mixed acid), aque-
ous HNO3 (70% by weight), HNO3/Ac2O/AcOH, and HNO3/
AcOH systems. Their main characteristics and the adopted
operating conditions are reported in Table 1.
For system no. 1 of Table 1 (mixed acid) the ratio nHNO
/
3
2. Experimental Section
1
nH SO ) /2 has been used in all the runs which have been
2
4
2.1. Materials and Methods. For all isothermal experi-
ments a jacketed glass magnetically stirred (volume: 2.0 ×
10-2 L) reactor has been used. The temperature has been
kept at a desired value by using (cooling fluid: water) a
Julabo F32 refrigerated/heating circulator. With the main
system (HNO3/AcOH) all runs have been carried out by
charging the solution of acetic acid and substrate in the
reactor and then adding nitric acid in batch mode.
The concentration of the involved species as a function
of reaction time has been recorded by submitting chemically
quenched samples (with the addition of a solution of urea
and methanol) collected during the experiments to HPLC
analysis using a Hewlett-Packard model 1100 II, equipped
with a UV-vis detector and a Phenomenex Synergi 4 µ polar
RP/80A column. The following operating conditions have
been adopted: the mobile phase has been formed by 80%
of a buffer solution (vol %: CH3OH 5%, H3PO4 0.4%, H2O
94.6%) and 20% of acetonitrile; the signals have been
acquired at 240, 280, 350 nm; the column temperature has
been kept at 298 K; and the flow rate was set at 1 × 10-3
L‚min-1.
For all the experiments analytical grade reagents have
been used (H2SO4 98% by Fluka and the others by Sigma
Aldrich).
Due to the lower solubility of mononitroderivative acids
with respect to salicylic acid, in some runs a heterogeneous
final mixture has been obtained. In this case both to confirm
the information concerning the global yields and to charac-
terize the solid, the runs have been performed twice, once
separating the solid from the liquid phase and once recover-
ing the whole reactor content.
carried out. The nitrating system has been prepared directly
in the reactor, and salicylic acid added after the reaction
temperature has been stabilized. The gathered data indicate
a total yield of 50.4% mol/mol and a purity of the separated
5-nitrosalicylic acid of 68% w/w, with 32% of 3-nitrosalicylic
acid, after a reaction time of 135 min.
For system no. 2 of Table 1, the runs have been carried
out charging the reactor with the solution of acetic acid/
acetic anhydride/substrate; once the reaction temperature has
been stabilized 1.89 g of concentrated nitric acid have been
added in batch mode to the mixture. The chemical analysis
allowed deriving a total yield in 5NS of 50.3% and a purity
of the solid of 75%.
For system no. 4 salicylic acid has been added to 1.176
g of the aqueous solution of nitric acid previously charged
in the reactor. During this phase the evolution of red fumes
has been observed. The system has been kept under
isothermal conditions for 60 min and then cooled at 298 K.
A homogeneous system has been collected at the end of the
run, directly diluted in methanol, and submitted to HLPC
analysis. A total yield in the desired product of 40.9% has
been recorded.
Also in the case of the alternative system of nitration here
proposed, HNO3/AcOH mixtures (no. 3), in all the adopted
experimental conditions the formation of a solid has been
verified.
To assess the influence of the feed ratio, salicylic acid/
nitric acid, on yields and purity of the precipitated solid, a
series of runs (nAS/nAcOH ) 0.4 in all cases) has been carried
out with an nAS/nHNO ratio equal to 1/5, 1/7, and 1/10. The mean
3
values obtained for the total yields, the purity of the
recovered solid, defined as the weight percentage of 5-nit-
rosalicylic acid, and the molar percentage of formed 5-nit-
rosalicylic acid which precipitates are shown in Figure 1.
In the first case, the final mixture has been filtered, and
the solid recovered has been washed with cold water, dried,
(15) Vidal, P.; Presles, H. C. R. Acad. Sci. Paris 1991, t. 313, serie II, 1383.
1200
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Vol. 10, No. 6, 2006 / Organic Process Research & Development

Figure 3. Concentration profiles in the nitration of salicylic
acid with the system HNO3/AcOH (T ) 298 K): AS, salicylic
acid; 5NS, 5-nitrosalicylic acid; 3NS, 3-nitrosalicylic acid; 2NP,
2-nitrophenol.
Figure 1. Total yields, purity, and precipitated amount of
5-nitrosalicylic acid against the molar ratio nAS/nHNO obtained
3
at 288 K for the system AS/HNO3/AcOH.
Scheme 1. AS, salicylic acid; 5-NS, 5-nitrosalicylic acid;
2-NP, 2-nitrophenol; 3-NS, 3-nitrosalicylic acid
Figure 2. Best results for the total yield and purity obtained
using the various nitrating systems.
The results in this figure point out that, as the molar ratio
nAS/nHNO decreases, the percentage of formed 5-nitrosalicylic
3
acid present as precipitated solid with respect to the total
amount formed slightly decreases, whereas the solid purity
increases, the yield for this product remaining practically
constant. It is noteworthy to observe that for a ratio nAs/
CSA(0) ) 0.053 mol L-1, CHNO (0) ) 0.265 mol L-1, and
3
C
AcOH(0) ) 17.5 mol L-1 (nAS/nHNO 1/5) has been
)
3
performed.
1
nHNO ) /10 more than 92% of 5-nitrosalicylic acid which
The reaction development has been monitored submitting
to HPLC analysis the samples withdrawn from the reactor
at fixed intervals of time and quenched with urea.
3
formed during the reaction separates from the solution and
that 96% by weight of the recovered solid is represented by
this isomer.
In Figure 3 the data collected during a run performed at
298 K are shown. The profiles in Figure 3 indicate that the
main products of reaction are 5-nitrosalicylic (5-NS) and
3-nitrosalicylic acid (3-NS) with a minor occurrence of
2-nitrophenol (2-NP), whose presence could be ascribed to
an ipsonitration process involving the substrate.1 Trace
concentrations of 3,5-dinitrosalicylic acid (3,5-DNS), 2,4-
dinitrophenol (2,4-DNP), and 2,6-dinitrophenol (2,6-DNP)
have been also recorded in all the runs. All the results
gathered during this set of experiments are summarized in
the reactions in Schemes 1 and 2.
In Figure 2 the results obtained in the nitration of salicylic
acid with all the systems adopted in the present study are
compared. For the system HNO3/AcOH the data collected
1
in the runs with a nAS/nHNO ratio equal to /5 have been
3
inserted in this figure to make the comparison easier.
The data shown in the figure indicate that the system
HNO3/AcOH is the most interesting among those tested in
the present work. In fact, although for three of them (nos. 1,
2, and 3, Table 1), both comparable yield and selectivity
are obtained, the adoption of the HNO3/AcOH system makes
it possible to eliminate the use of sulfuric acid (with respect
to mixed acid) with reduced problems of waste disposal and
that of acetic anhydride (with respect to the system 2),
leading to a more inherently safe nitrating system. The
proposed system presents some advantages also with respect
to the use of aqueous HNO3 solutions being capable of the
latter, ensuring only a lower yield for 5-nitrosalicyclic acid
(Figure 2) at a significantly higher working temperature.
3.2. Kinetic Assessment. On the basis of the above-
reported considerations it is evident the importance of
achieving a kinetic characterization of the nitration process
of salicylic acid by means of the mixture HNO3/AcOH. To
this aim a series of isothermal experiments (T ) 285, 288,
293, and 298 K) with the following initial concentrations,
Only scant indications2 have been found in the literature
on the reaction kinetics for the adopted nitrating system. In
particular, it has been reported that, depending on the nature
of the substrate, its initial concentration and that of nitric
acid and water, its reaction order may be zero or 1,2 although
no clear indications on how to determine the correct value
have been given. After a preliminary analysis of the results
collected during the present investigation, which easily
allowed ruling out zero-order kinetics with respect to the
substrate, a possible scheme for the nitration of salicylic acid
has been proposed (Scheme 3).
It has been reported2 that nitric acid exists almost
completely not dissociated in a solvent like acetic acid, and
therefore, if it is assumed that the rate of the step (c) is fast
Vol. 10, No. 6, 2006 / Organic Process Research & Development
•
1201

Scheme 2. 5NS, 5-nitrosalicylic acid; 2NP, 2-nitrophenol;
3NS, 3-nitrosalicylic acid; 3,5DNS, 3,5-dinitrosalicylic acid;
2,4DNP, 2,4-dinitrophenol; 2,6DNP, 2,6-dinitrophenol
Figure 4. 1/k2S against the multiplier g for the runs performed
at different initial water content.
been recorded, and an experimental kinetic constant (kS) for
the nitration has been derived modeling collected data by
means of a simple second-order rate law.
On the basis of relationship (d) in which
KA
1
k′ ) k
) k′′
) kS
(e)
Scheme 3. ArH: aromatic compound
CH O
f
x
CH O
2
x
2
squaring and taking the reciprocal of (e) it is possible to
obtain the following relationship:
C
H2O
1
kS2
)
(f)
k′′2
+
with respect to that of (b), the following condition CNO
=
2
-
CNO holds. In light of this assumption the equilibrium
3
A linear relationship could be thus expected by plotting 1/
k2 against CH O
constant KA [step (a)] can be written as
.
S
2
In Figure 4 the plot obtained by using the data collected
2
NO2
C
+C
KA )
H O f
2
during the experiments at varying initial water contents is
shown. The diagram of the figure confirms the rate depen-
dence upon water concentration found in relationship (f).
The overall second-order kinetic equation (d) has been
considered also for the ipsonitration process (reaction 3 of
Scheme 1)16 leading to the following mass-balance equations
according to Schemes 1 and 2 (for each reaction the kinetic
constant is given by ki ) kio exp(-Ei/RT)):
2
C
HNO3
in which f takes into account the activity coefficients of the
species in the equilibrium (a).
The nitronium ion concentration can be thus calculated
as
KA
1
C
)
C
HNO3
+
dC
NO2
5NS ) k1CASCHNO - k4C5NSCHNO - k5C5NSCHNO (1)
C
H2O
x
x
f
3
3
3
dt
dC
and the following relationship is derived for the reaction rate
3NS ) k2CASCHNO - k8C3NSCHNO - k9C3NSCHNO (2)
dt
3
3
3
dC
-
ArH ) kCNO +C
)
ArH
dC
2NP ) k3CASCHNO - k6C2NPCHNO - k7C2NPCHNO (3)
dt
2
dt
3
3
3
KA
k
CHNO CArH = k′CHNO CArH (d)
3 3
dC
AS ) -k1CASCHNO - k2CASCHNO - k3CASCHNO (4)
dt
CH O
f
x
2
3
3
3
Equation (d) indicates that according to the proposed
dC
dCAS dC5NS dC3NS dC2NP
HNO3
reaction scheme (Scheme 3) the nitration of an aromatic
species with theHNO3/AcOH mixture proceeds in agreement
with a second-order kinetic law, the kinetic constant being
dependent upon the reciprocal of the root square of the water
concentration.
) 2
+
+
+
(5)
dt
dt
dt
dt
dt
The values for the kinetic parameters of the reaction 4-9
have been taken from the results of a recent investigation of
the authors17 (see Table 2).
If it is possible to neglect in eq (d) the contribution of
the water formed during the nitration process and the changes
of f, the ratio under the square root keeps constant. A set of
runs at different initial water concentrations has been
performed to confirm the dependence found in relationship
(d). In each run the concentration decay of salicylic acid has
The system of eqs 1-5 has been solved in an optimization
procedure in which the concentration profiles, calculated at
(16) Chockalingam, S.; Subbu, P.; Natesan, A. J. Chem. Soc., Perkin Trans. 2
1985, (12), 1855.
(17) Andreozzi, R.; Caprio, V.; Di Somma, I.; Sanchirico, R. J. Hazard. Mater.
2006, 134, 1-7.
1202
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Vol. 10, No. 6, 2006 / Organic Process Research & Development

Table 2. Kinetic constants of reactions 4-9 (L mol-1 s-1
285 K 288 K 293 K 298 K
)
k4 5.16 × 10-9 9.76 × 10-9 2.75 × 10-8 7.47 × 10-8
k5 1.86 × 10-9 3.39 × 10-9 8.93 × 10-9 2.78 × 10-8
k6 9.38 × 10-6 1.64 × 10-5 4.06 × 10-5 9.74 × 10-5
k7 6.20 × 10-6 1.11 × 10-5 2.83 × 10-5 7.03 × 10-5
k8 6.01 × 10-8 1.15 × 10-7 3.29 × 10-7 9.07 × 10-7
k9 1.10 × 10-7 2.17 × 10-7 6.56 × 10-7 1.91 × 10-6
Figure 8. Calculated (continuous line) and experimental data
(symbols) for the run performed at 293 K: AS, salicylic acid;
5NS, 5-nitrosalicylic acid; 3NS, 3-nitrosalicylic acid; 2NP,
2-nitrophenol.
Figure 5. Calculated (continuous line) and experimental data
(symbols) for the run performed at 298 K: AS, salicylic acid;
5NS, 5-nitrosalicylic acid; 3NS, 3-nitrosalicylic acid; 2NP,
2-nitrophenol.
Figure 9. Predicted (continuous line) and experimental data
(symbols) for the run performed at 293 K with a starting
substrate concentration equal to 0.084 mol/L: AS, salicylic acid;
5NS, 5-nitrosalicylic acid; 3NS, 3-nitrosalicylic acid; 2NP,
2-nitrophenol.
different temperatures, have been compared with the experi-
mental data. Some examples of comparison between calcu-
lated (continuous line) and experimental data (symbols) are
shown in Figure 5-8.
Figure 6. Calculated (continuous line) and experimental data
(symbols) for the run performed at 285 K: AS, salicylic acid;
5NS, 5-nitrosalicylic acid; 3NS, 3-nitrosalicylic acid; 2NP,
2-nitrophenol.
As a result of this optimization procedure, the kinetic
parameters for reactions 1, 2, and 3 (Scheme 1) have been
evaluated (Table 3).
The model so obtained has been validated by means
of data recorded during a set of runs performed at start-
ing conditions different from those adopted during the
parameter estimation. In Figure 9 an example is shown of a
comparison among the concentrations predicted by the
model, using the kinetic values reported in Tables 2 and 3
and those experimentally recorded in a run with an initial
substrate concentration two times higher than those previ-
ously used.
These results indicate that the proposed model well
predicts the behaviour of the studied system at varying
experimental conditions.
Figure 7. Calculated (continuous line) and experimental data
(symbols) for the run performed at 288 K: AS, salicylic acid;
5NS, 5-nitrosalicylic acid; 3NS, 3-nitrosalicylic acid; 2NP,
2-nitrophenol.
Table 3. Kinetic parameters assessed for the reaction reported in Scheme 1
10 [L mol-1 s-1 E1 [kJ mol-1 k20 [L mol-1 s-1 E2 [kJ mol-1
k
]
]
]
]
k30 [L mol-1 s-1
]
E3 [kJ mol-1
]
(2.53 ( 0.15) × 10+19
124.37 ( 0.17
(1.38 ( 0.11) × 10+19
123.90 ( 0.17
(5.37 ( 1.2) × 10+18
124.66 ( 0.42
Vol. 10, No. 6, 2006 / Organic Process Research & Development
•
1203

4. Conclusion
kinetic law for the analysis of the data collected during the
nitration experiments made it possible to identify kinetic
parameters for the formation of the two mononitroderivatives
and 2-nitrophenol.
The nitration of salicylic acid has been studied using
different systems: mixed acid, mixture HNO3/Ac2O/AcOH,
mixture HNO3/AcOH, and aqueous HNO3 (70% by weight)
at 343 K. The results collected during the present investiga-
tion indicate that with all the adopted systems the main
reaction products are 3-nitro- and 5-nitrosalicylic acid with
a minor occurrence of 2-nitrophenol which forms through
an ipsonitration mechanism. Small differences have been
observed among the first three systems in terms of the overall
yield for 5-nitrosalicylic acid, aqueous nitric acid solutions
giving the poorest results. However the system HNO3/AcOH
demonstrated some advantages with respect to the others for
the separation and purity of desired product, waste minimiza-
tion, and safety improvements. Kinetic investigations per-
formed on salicylic acid nitration with this system allowed
assessing that the nitration and ipsonitration are both
regulated by a second-order kinetic law. The use of this
SYMBOL LIST
ki0
Ei
ki
Pre-exponential factor of ith reaction (rate law depending)
Activation energy of ith reaction (kJ mol-1
Kinetic constant of ith reaction (rate law depending)
)
R
Universal constant of gas (J mol-1 K-1
Time (s)
)
t
Cj
KA
Concentration of jth species (mol L-1
Equilibrium constant (mol L-1
)
)
Received for review July 24, 2006.
OP060148O
1204
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Vol. 10, No. 6, 2006 / Organic Process Research & Development