Faujasite catalyzed nitrodeiodination of iodopyrazoles

Article abstract of DOI:10.1016/j.catcom.2013.07.032

Nitrodeiodination of iodopyrazoles using nitric acid/Faujasite has been investigated. The present procedure is simple, rapid and convenient and requires no sulfuric acid or oleum and may be applied for the synthesis of several nitropyrazoles in good yield

Full text of DOI:10.1016/j.catcom.2013.07.032

Catalysis Communications 42 (2013) 35–39
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Catalysis Communications
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Short Communication
Faujasite catalyzed nitrodeiodination of iodopyrazoles
⁎
P. Ravi , Surya P. Tewari
Advanced Centre of Research in High Energy Materials, University of Hyderabad, Hyderabad 500 046, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 21 May 2013
Received in revised form 11 July 2013
Accepted 17 July 2013
Available online 26 July 2013
Nitrodeiodination of iodopyrazoles using nitric acid/Faujasite has been investigated. The present procedure is
simple, rapid and convenient and requires no sulfuric acid or oleum and may be applied for the synthesis of
several nitropyrazoles in good yields in drug and pharmaceutical industries.
© 2013 Elsevier B.V. All rights reserved.
Keywords:
Faujasite
Iodopyrazoles
Heterogeneous catalysis
Nitropyrazoles
1. Introduction
desirable route to prepare C-polynitropyrazoles in higher yields. We
have synthesized 3(5),4-dinitropyrazole and 3,4,5-trinitropyrazole in
Nitropyrazoles have been used as biologically active compounds
including antibiotics or their analogues, agrochemicals, dyestuffs, phos-
phores, non-linear optical materials and recently as energetic materials
[1]. The presence of nitro group in the pyrazole ring considerably en-
larges the possibility of functionalization of various types of pyrazole de-
rivatives [2]. The methods to synthesize nitropyrazoles are diverse and
depend upon the nature of substituent groups in the pyrazole ring, the
electron density distribution in it, nitration mixtures, nitration condi-
tions, and so on. Pyrazoles are nitrated with fuming nitric acid, nitric-
sulfuric acid, nitric acid-acetic anhydride, nitric acid-trifluoro acetic an-
hydride or nitromethane-nitronium tetrafluoroborate. In many cases, it
is impossible to introduce NO2 group into the desired position of the
pyrazole ring and therefore indirect methods are used. Hüttel and
Büchele [3] described the rearrangement of N-nitropyrazoles into 4-
nitropyrazoles in cold sulfuric acid solution. Janssen et al. synthe-
sized 3(5),4-dinitropyrazole from 3(5)-nitropyrazole under Morgan–
Ackerman nitration conditions [4,5]. 1-Methyl-3(5)-nitropyrazole,
1-methyl-4-nitropyrazole and 1-methyl-3(5),4-dinitropyrazole were
synthesized from 1-methylpyrazole refluxing in nitric–sulfuric acid
mixture [6–8]. N-Nitropyrazoles in anisole, xylene, benzonitrile, chloro-
benzene, nitrobenzene, n-decane, mesitylene, N-methylformamide, or
propylene glycol at 120–190 °C for 3–7 h were rearranged into 3-
nitropyrazole, 3(5),4-dinitropyrazole and 3,5-dinitropyrazole [6–8]. C-
Nitropyrazoles were formed quantitatively and in some instances
denitration of N-nitropyrazoles during thermal isomerization was
observed. The oxidative iodination of pyrazoles prior to nitration is a
good yields from 3(5),4-diiodopyrazole and 3,4,5-triiodopyrazole re-
spectively using fuming nitric acid and nitric–sulfuric acid mixture
[9,10].
The traditional nitration methodologies usually suffer from low
yields, starting material availability, harsh conditions, and/or difficulty
to separate isomer formation prompted researchers to search for the
alternative methodologies. The limitations and drawbacks of usual
methods such as tedious work-up, strongly acidic media, oxidation
ability of reagents (e.g., nitric acid), thermal isomerizations and safety
problems can be avoided using metal nitrates impregnated on solid sup-
ports. The supported metal nitrates such as Bi(NO3)3.5H2O/SiO2 [11,12],
AgNO3/BF3 [13], Cu(NO3)2/clay [14], Ce(NH4)2(NO3)6/H2SO4/SiO2 [15],
Fe(NO3)3/clay [16] and metal nitrates/clay activated by acetic anhydride
[17] have been used for the nitration of aromatic compounds. We have
used HNO3/silica and HNO3/silica-sulfuric acid for the nitrolysis of
iodopyrazoles [10]. It was demonstrated that nitrogen (IV) oxide in
the presence of Faujasite nitrates both pyrazole and N-nitropyrazole
[18]. Faujasite is easier to handle because it holds the acidity internally,
readily separable from the products by simple filtration, recyclable and
requires milder reaction conditions. Unlike the more hazardous acid
catalysts (e.g., sulfuric acid, hydrofluoric acid, solid phosphoric acid,
etc.,) Faujasite is recyclable with greater ease and lower expense, lead-
ing to less waste and fewer byproducts. Furthermore more hazardous
strong acids, many steps, low yields and much waste can be avoided
and greater returns shall be achieved. To the best our knowledge syn-
thesis of nitropyrazoles from iodopyrazoles using nitric acid over
Faujasite catalyst (H-form) has not been reported elsewhere. We report
herein the synthesis of nitropyrazoles in good to higher yields from
iodopyrazoles using nitric acid/Faujasite at room temperature for the
first time.
⁎
Corresponding author. Tel.: +91 40 23134303; fax: +91 40 23012800.
E-mail address: rpiitb@hotmail.com (P. Ravi).
1566-7367/$ – see front matter © 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.catcom.2013.07.032

36
P. Ravi, S.P. Tewari / Catalysis Communications 42 (2013) 35–39
2. Experimental section
3. Results and discussion
2.1. General
Faujasites due to their high degree of hydration, high selectivity, ex-
ceptional stability and low density are extremely useful as catalysts in
many organic reactions. The framework of Faujasite structure is open
with complete sodalite-type cages and with very large cavities having
12-membered ring openings [19,20]. The reactions are known to take
place within the pores of catalyst, which allows a greater degree of
product control. The solid catalyst accommodates up to 260 molecules
of H2O per unit cell. We have chosen Faujasite (H-form) as catalyst for
the nitrolysis (i.e., nitrodeiodination) of iodopyrazoles. Fuajasite was ac-
tivated at 120 °C for 6 h before used in the nitrolysis. The iodopyrazole
together with nitric acid/Fuajasite in THF have been stirred and the
evaporation of solvent under vacuum comprises the reaction conditions
for successful and regiospecific nitration. To establish the optimum
conditions several reactions were performed on 4-iodopyrazole (1a)
and 4-iodo-1-methypyrazole (1b) as the model substrates varying the
amounts of Fuajasite at room temperature (Scheme 1). We found that
there was no remarkable change in the yields of 2a and 2b when the re-
actions prolonged or increased the amount of catalyst. The replacement
of iodine proceeded easily in nitric acid over Fuajasite. Table 1 summa-
rizes the nitrodeiodination of series of iodopyrazoles and their corre-
sponding nitropyrazoles.
Generally, pyrazoles are nitrated in the 4-position facilitated by
electron-donating and retarded by electron-withdrawing groups. The
substrates with electron-donating groups readily underwent nitration
in excellent yields (72%) and the deactivated substrates underwent
nitration in good yields (N60%). The free 3- and 5-positions of pyrazoles
are strongly deactivated by the nitro group in the 4-position thus the
yields are lower despite of harsh conditions and the nature of nitration
mixture. On the other hand 1-phenylpyrazole and its analogues under-
went substitution in the 4-position of the pyrazole ring [18]. 1-Phenyl-
4-iodopyrazole (7a), 1-(p-nitrophenyl)-4-iodopyrazole (8a) and 1-
benzyl-4-iodopyrazole (9a) nitrolysed into 1-phenyl-4-nitropyrazole
(7b), 1-(p-nitrophenyl)-4-nitropyrazole (8b) and 1-benzyl-4-nitro-
pyrazole (9b) respectively.
All the reagents and solvents were obtained from Merck, Alfa-Aesar
or Aldrich and used without further purification. Thin layer chromatog-
raphy (silica gel GF-254 type) was routinely used to monitor the prog-
ress of reactions. Melting points were recorded by a capillary melting
point apparatus and were uncorrected. IR spectra were recorded on
Perkin Elmer FT-IR-1600 spectrophotometer in KBr matrix. The signals
are reported in wave numbers (cm−1). 1H NMR and 13C NMR spectra
were recorded on 300 MHz Varian instrument with DMSO-d6 and
CDCl3 solvents. The chemical shift values are reported in δ units (ppm)
relative to TMS as an internal standard. GC-MS was carried out with
glass columns packed with 3% OV-17 on Chromosorb W (100–120
mesh) treated with DMCS in a Varian 1400 instrument fitted with
flame ionization detector, nitrogen being used as carrier gas. Faujasite
(H-form, SiO2/Al2O3 mole ratio of 80, surface area of 780 m2/g) and
nitric acid (d 1.52 g/cm3) were used for the nitrolysis of iodopyrazoles.
2.1.1. General procedure for the synthesis of mononitropyrazoles
To iodopyrazole (1 mmol) dissolved in THF (10 mL), Fuajasite
(250 mg) was added. Nitric acid (d 1.52 g/cm3, 10 mL) was added
slowly and the mixture was stirred at room temperature for required
time. The catalyst was recovered by filtration and the filtrate was
extracted repeatedly with dichloromethane. The solvent was removed
under vacuum to obtain nitropyrazole.
2.1.2. General procedure for the synthesis of dinitropyrazoles
To iodopyrazole (1 mmol) dissolved in THF (10 mL), Fuajasite
(500 mg) was added. Nitric acid (d 1.52 g/cm3, 20 mL) was added slow-
ly and the mixture was stirred at room temperature for required time.
The catalyst was recovered by filtration and the filtrate was extracted
with dichloromethane. The solvent was removed under reduced pres-
sure to get dinitropyrazole.
Diiodopyrazoles (3c and 5c) and triiodopyrazoles (10a and 11a)
were also nitrolysed into dinitro pyrazoles (4 and 6) and trinitro-
pyrazoles (10b and 11b) respectively in good yields. Dinitropyrazoles
are utterly deactivated by vicinal nitro groups thus hindering the substi-
tution in the 5-position of pyrazole ring. The presence of vicinal nitro
groups in 4 and 6 deactivated the 5-position and consequently the
nitrolysis has not been observed rather quantitative iodopyrazoles
were recovered. 3,4,5-Trinitropyrazole (10b) is neither hygroscopic
nor highly acidic in nature [19]. It displays low sensitivity to external
stimuli and outstanding thermal and chemical stability of nitrated aro-
matic compounds. The exceptional stability/or low sensitivity of 10b is
because of its low acidity (pKa 2.35). 1-Methyl-3,4,5-trinitropyrazole
(11b) has been considered as the next generation melt-cast explosive
[9]. The product obtained after the nitrolysis of 3,4,5-triiodo-1-
2.1.2.1. 1-Methyl-3(5),4-dinitropyrazole (6). IR, υ (KBr) cm−1: 1551,
1533, 1522, 1371 and 1342 (C–NO2); 2994(C–H). 1H NMR (300 MHz,
CDCl3, 300 K) δ (ppm) = 4.04(s, 3-H); 8.33 (s, 5-H). 13C NMR
(300 MHz, CDCl3, 300 K) δ (ppm) = 38.3 (t, CH3); 147 (C-3); 127
(C-4); 133 (C-5). EI-MS: m/z 172 (M+•). Anal. calcd for C4H4N4O4
27.91; H 2.30; N 32.52; found C 27.88; H 2.34; N 32.54.
C
2.1.3. General procedure for the synthesis of trinitropyrazoles
To iodopyrazole (1 mmol) dissolved in THF (10 mL), Fuajasite
(500 mg) was added. Nitric acid (d 1.52 g/cm3, 30 mL) was added slow-
ly and the mixture was stirred at room temperature for required time.
The catalyst was recovered by filtration and the filtrate was extracted
with dichloromethane. The solvent was removed under vacuum to ob-
tain trinitropyrazole.
2.1.3.1. 3,4,5-trinitropyrazole (10b). IR, υ (KBr) cm−1: 1554, 1521, 1445,
1413, 1371, 1346 and 1284 (C–NO2); 3145 (N–H). 1H NMR (300 MHz,
CDCl3, 300 K) δ (ppm) = 12.1(s, 1H, NH). 13C NMR (300 MHz, CDCl3,
300 K) δ (ppm) = 123 (C-4); 144 (C-3); 347 (C-5). EI-MS: m/z 203
(M+•). Anal. calcd for C3HN5O6 C 17.71; H 0.54; N 34.54; found C
17.72; H 0.46; N 34.44.
2.1.3.2. 1-Methyl-3,4,5-trinitropyrazole (11b). IR, υ (KBr) cm−1: 1552,
1532, 1454, 1384, 1323(C–NO2); 2994 (CH3). 1H NMR (300 MHz,
CDCl3, 300 K) δ (ppm) = 4.3 (s, 3H). 13C NMR (300 MHz, CDCl3,
300 K) δ (ppm) = 43.5 (t, CH3); 124 (t, C4); 136 (t, C3); 148 (t, C5).
EI-MS: m/z 217 (M+). Anal. calcd for C4H3N5O6 C 22.15; H 1.35; N
32.22; found C 22.5; H 1.3.
Scheme 1. Faujasite catalyzed nitrodeiodination of iodopyrazoles.

P. Ravi, S.P. Tewari / Catalysis Communications 42 (2013) 35–39
37
Table 1
Faujasite (H-form) catalyzed nitrodeiodination of iodopyrazoles.
Entry
Substrate
Product
Time (h)
3.5
Yield (%)
72
m.p (°C)
Found
Literature
1
164–165
162–164[3]
2
3
3.5
64
73
92–93
91–92[8]
3
135–136
134–136[4]
4
5
3.5
65
73
187–188
126–127
186–187[4]
124–127[5]
3
6
7
8
3
68
57
65
16–162
96–97
87–88
160–162[3]
97–98[5,6]
87–89[4]
3
3.5
9
3.5
62
57
86–87
20–21
87–89[4]
21–22[8]
10
4
11
4
64
20–21
21–22[8]
(continued on next page)

38
P. Ravi, S.P. Tewari / Catalysis Communications 42 (2013) 35–39
Table 1 (continued)
Entry
Substrate
Product
Time (h)
3.5
Yield (%)
62
m.p (°C)
Found
Literature
12
13
126–127
125–126[7]
3.5
61
161–162
162–163[7]
14
3.5
63
92–93
91–92[21]
15
16
3.5
3.5
72
63
88–89
20–21
87–89[4]
21–22[8]
17
18
5
5
68
63
190–191
91–92
188–190[22]
91–93[22]
methylpyrazole (11a) has been found to contain b8% yields of 3,5-
diiodo-4-nitropyrazole and 5-iodo-3,4-nitropyrazole. The nitrolysis of
11a with nitric acid for 3.5 h gave higher yield (63%) of trinitropyrazole
(11b).
for 12 h Faujasite was reused and showed good activity for the synthesis
of nitropyrazoles.
In order to ascertain the generality of nitrodeiodination and its appli-
cability to the synthesis of nitropyrazoles we have nitrolysed 3a–c, 10a
and 11a and found that the vicinal electron-withdrawing groups had
not prevented nitrolysis in the 4-, or 3(5)-position in the pyrazole
ring. The nitrolysis of iodopyrazoles for 3 to 5 h showed the absence
of starting compounds. It has been found that nitrolysis of iodonitro-
pyrazoles (5a and 5b) required more time and only yielded 6 at
57% and 64% respectively. The determination of position of the nitro
group was based on the variation in the reactivity towards electron-
withdrawing groups in the 3(5)- or 4-position of the ring and the com-
parison of IR, 1H NMR, 13C NMR and mass spectra of nitropyrazoles. Last-
ly we also have tested the catalyst recycling on the nitrodeiodiantion of
1a and 1b. After filtration, washing with methanol, and heating at 120 °C
4. Conclusions
We have used nitric acid/Faujasite (H-form) for the nitrolysis of
iodopyrazoles and obtained nitropyrazoles in good to higher yields at
room temperature. The present procedure appears to be attractive for
the synthesis of nitropyrazoles and their derivatives in drug and phar-
maceutical industries. Exceptionally higher yield of nitropyrazoles has
been obtained however, compounds 2a, 2b, 4, and 6 found to be ex-
tremely resistant to nitrolysis. The nitrolysis of iodopyrazoles takes
place only when Faujasite is added or the polyiodopyrazoles are heated
with nitric acid. The failure to synthesize nitropyrazoles or partially
nitrodeiodinated compounds is presumably due to the use of relatively
less concentrated nitric acid.

P. Ravi, S.P. Tewari / Catalysis Communications 42 (2013) 35–39
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