Mild, efficient and selective nitration of anilides, non-activated and moderately activated aromatic compounds with ammonium molybdate and nitric acid as a new nitrating agent

Article abstract of DOI:10.1246/cl.2000.48

Ammonium molybdate [Mo(VI)] is operationally simple, environmentally safe and inexpensive reagent. Regioselective nitration of anilides, non-activated and moderately activated aromatic compounds could be afforded by employing ammonium molybdate and nitric acid as mild and effective nitrating agent. This procedure works efficiently under reflux conditions to prepare mononitroderivatives of anilides, non-activated and moderately activated aromatic compounds in good to excellent yield with high regioselectivity.

Full text of DOI:10.1246/cl.2000.48

48
Chemistry Letters 2000
Mild, Efficient and Selective Nitration of Anilides, Non-Activated and Moderately Activated
Aromatic Compounds with Ammonium Molybdate and Nitric Acid as a New Nitrating Agent
Sariah Sana, K. C. Rajanna,* Mir Moazzam Ali, and P. K. Saiprakash†
Post Graduate College, Osmania University, Mirzapur(SGD) 502 249, India.
†Department of Chemistry, Osmania University, Hyderabad 500 007, India.
(Received September 9, 1999; CL-990757)
reaction did not proceed even under reflux conditions for a pro-
longed period. Thus, it is assumed that ammonium molybdate
with nitric acid forms a proper species for nitration. Progress
of the reaction is monitored by a visible change in the colour of
reaction mixture and also from TLC during the course of reac-
tion. After completion of the reaction as indicated by TLC the
reaction mixture is filtered, washed with water and worked up
as usual to give the nitrated products. The results are summa-
rized in Table 1. To check the regioselectivity of the reaction,
the reaction is carried out with different substituted anilides
(entries 2 and 4), which afforded only ortho nitrated products
in excellent ortho selectivity. It shows that nitration is selec-
tive. The reaction first takes place at para position then at
ortho position. The reaction appeared to follow the ortho/para
rules. It is also observed that in any case dinitration did not
take place. To prove the generality of the reaction, the reaction
is carried out with some non-activated and moderately activat-
ed aromatic compounds. Under similar conditions, chloroben-
zene, toluene and ethylbenzene (entries 14, 15 and 16), were
smoothly nitrated selectively giving the respective nitration
products in good yields. However, benzene failed to be nitrat-
ed under the condition employed. The ammonium molybdate
catalyzed nitration of naphthalene, anthracene, α-naphthol, β-
naphthol, 2-aminoanthracene and 1-naphthaldehyde which
proved to be quite satisfactory, giving the nitration products in
nearly quantitative yields (80-95%). The regioselectivity was
higher compared with those observed for classical nitration.
The nitration of activated aromatics such as phenols giving
good nitrating products in less time. The results of the nitration
of phenols and activated aromatic compounds have been com-
municated elsewhere.10
Ammonium molybdate [Mo(VI)] is operationally simple,
environmentally safe and inexpensive reagent. Regioselective
nitration of anilides, non-activated and moderately activated
aromatic compounds could be afforded by employing ammoni-
um molybdate and nitric acid as mild and effective nitrating
agent. This procedure works efficiently under reflux condi-
tions to prepare mononitroderivatives of anilides, non-activated
and moderately activated aromatic compounds in good to
excellent yield with high regioselectivity.
Recent development in the areas such as DOM methodolo-
gy1 has sparked a renaissance in the field of aromatic chem-
istry, due to a high demand for multifunctional aromatic sub-
strates and the inadequacies of existing techniques. In particu-
lar, the nitration of aromatic rings has received considerable
attention due to unsolved problems pertaining to regioselectivi-
ty, over nitration and competitive oxidation of substrates.2,3
Nitro compounds have found their use in many industrial
applications,4 specially, the para isomers are more commercial-
ly desirable products. Therefore, there is an intense need to
develop a novel catalyst to facilitate aromatic nitrations.
Ammonium molybdate [(NH4)6 Mo7O24·4H2O or Mo(VI)]
is operationally simple, environmentally safe and readily avail-
able inexpensive reagent which is found to have many uses as a
mild and selective agent in organic synthesis.5 A perusal of lit-
erature depicts that ammonium molybdate could be conve-
niently used in conjunction with other substances for effective
epoxidations.6 It could be used as a catalyst for the oxidation
of alcohols7 in the presence of H2O2 and also for regioselective
bromination reactions.8
As our efforts were to get nitrated anilides with good
regioselectivity, it was found that ammonium molybdate and
nitric acid can act as a good reagent system. Anilides are com-
pounds used as intermediates in the production of pharmaceuti-
cals and dyes.9 For instance, ParacetamolR is widely used as
antipyritic drug. It is reported that anilides in general and
acetanilides in particular act as cell growth inhibitors in meta-
bolic activities.
Nitration of anilides in presence of ammonium molybdate,
proceeds rapidly affording high yields of the corresponding
mononitro derivatives with high regioselectivity. When the
reaction is conducted in absence of ammonium molybdate, the
Copyright © 2000 The Chemical Society of Japan

Chemistry Letters 2000
49
In order to shed light on the reaction mechanism, the
kinetic work is under investigation to prove the exact path of
the reaction and the formation of intermediate. However, it is
believed that nitration is taking place via the formation of nitro-
nium ion bound molybdenum species. It is also believed that
the mechanism is similar to that of the literature reports.11 The
reaction with 0.25 equivalent or 0.5 equivalent of ammonium
molybdate is very slow. Therefore, reaction is carried out at
1:1:1 molar ratio. The nitrated products were characterized by
5
6
(a) B. M. Trost, and M. Lautens, J. Am. Chem. Soc., 104,
5543 (1982); (b) B. M. Trost, and M. Lautens, J. Am.
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Lautens, Tetrahedron Lett., 24, 4525 (1983); (d) B. M.
Trost, J. I. Yoshida, and M. Lautens, J. Am. Chem. Soc.,
105, 4494 (1983).
(a) H. Mimoun, in "The Chemistry of Functional Group
Peroxides," ed by S. Patai, Wiley, New York, (1982),
p.463; (b) H. Mimoun, Pure Appl. Chem., 53, 2389
(1981); (c) R. A. Sheldon and J. K. Kochi, in "Metal
Catalyzed Oxidations of Organic Compounds," Academic
Press, New York (1981), p.48; (d) K. B. Sharpless, and T.
R. Verhoeven, Aldrichimia Acta, 12, 63074 (1979).
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1
comparison of their spectral (IR, UV, H-NMR, HPLC and
TLC) and physical data with authentic samples.
The results clearly indicate that the direct nitration of
anilides, non-activated and moderately activated aromatic com-
pounds can be achieved successfully by employing ammonium
molybdate and nitric acid as nitrating agent.
In conclusion, the present method of nitration of anilides,
non-activated and moderately activated aromatic compounds
using ammonium molybdate as catalyst with high regioselec-
tivity offers the advantages such as, environmentally safe, read-
ily available inexpensive reagents and mild reaction conditions
with simple work up. Thus, it is believed that the present
method is to be a major step forwarded in the area of clean
technology for aromatic nitration.
7
8
9
(a) B. M. Choudary, Y. Sudha, and P. N. Reddy, Syn. Lett.,
(1994), 450; (b) B. M. Trost, and Y. Mosuyama,
Tetrahedron Lett., 25, 173 (1984).
E. M. Nahmed, and G. Jenner, Tetrahedron Lett., 32, 4917
(1991).
10 S. Sana, M. M. Ali, K. C. Rajanna, and P. K. Saiprakash,
Submitted to Synth. Commun.
References and Notes
11 (a) H. Soto, K. Nagai, H. Yoshioka, and Y. Nagaoka,
Appl. Cat. A, 175, 209 (1998); (b) H. Sato, K. Hirose, K.
Nagai, H. Yoshioka, and Y. Nagaoka, App. Cat. A., 175,
201 (1998).
12 Nitration of Anilides: Dissolve the anilide (1 mmol) in
CHCl3 and add ammonium molybdate (1.235 gms, 1
mmol), 70% HNO3 (0.063 ml, 1 mmol) and reflux for 6 hr.
Check the TLC for completion of the reaction. Filter the
reaction mixture, wash it with water, separate the organic
layer, then dry it over with sodium sulphate (Na2SO4),
evaporate under vacuum, purify with column chromatog-
raphy using chloroform : methanol (9.9 : 0.1) as eluent to
get pure product.
1
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