Guanidinium nitrate: A novel reagent for aryl nitrations

Article abstract of DOI:10.1016/j.tetlet.2004.09.140

Nitration of various aromatic compounds utilising guanidinium nitrate in 85% sulfuric acid as a nitrating agent has been studied.

Full text of DOI:10.1016/j.tetlet.2004.09.140

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 8681–8683
Guanidinium nitrate: a novel reagent for aryl nitrations
M. M. V. Ramana,* S. S. Malik and J. A. Parihar
Department of Chemistry, University of Mumbai, Vidyanagari, Santacruz (E), Mumbai 400098, India
Received 15 August 2004;revised 14 September 2004;accepted 21 September 2004
Available online 8 October 2004
Abstract—Nitration of various aromatic compounds utilising guanidinium nitrate in 85% sulfuric acid as a nitrating agent has been
studied.
ꢀ 2004 Elsevier Ltd. All rights reserved.
Nitration reactions have acquired great importance in
the chemistry of organic compounds as a number of
nitro aromatics find applications as solvents, dyestuffs,
pharmaceuticals, perfumery chemicals, agrochemicals,
reagents and explosives. Nitro compounds also serve
as useful intermediates for the preparation of other
compounds, particularly amines, by reduction. Earlier
work on nitration of organic compounds reports the
use of nitric acid,1 nitrosyl sulfuric acid,2 acetyl nitrate,3
benzoyl nitrate,3 ethyl nitrate,3 acetone cyanohydrin ni-
trate,3 inorganic nitrates,3 nitronium tetrafluoroborate,3
N-nitropyridinium salt,3 nitrosyl chloride,4 nitrogen
oxide,5 urea nitrate,6 trimethylsilyl nitrate7 and nitrat-
ing mixtures3 such as nitric acid–sulfuric acid, nitric
acid–acetic acid, nitric acid–acetic anhydride, nitric
acid–boron trifluoride and metal nitrates–acetic anhy-
dride as the nitrating agents. It is well documented8
that guanidinium nitrate 1 is converted into nitroguan-
idine by the action of sulfuric acid. Further, there is a
report9 wherein nitroguanidine was used to generate
the nitronium ion in sulfuric acid. However surpris-
ingly, 1 has never been utilised for the nitration of aro-
matic compounds. These observations led us to explore
the potential of 1 for nitration of various aromatic
compounds.
NH.HNO3
+
Ar
NO2
Ar
H
H2N
NH2
1
Scheme 1. Nitration of aromatic compound using guanidinium
nitrate 1.
other aromatic compounds having a weakly activating
group (entry 2), activating groups (entries 3–7) and
moderately deactivating groups (entries 8–10) were
investigated. We found that only the mono nitrated
products were obtained in good to excellent yields.
Moreover in all the monosubstituted substrates (entries
3–5, 8–9) except toluene (entry 2), only the p-substituted
nitro compounds were obtained regioselectively. Inter-
estingly the nitration of 2-methoxyacetanilide (entry 6)
and 4-methoxyacetanilide (entry 7) gave only the corre-
sponding 5-nitro and 3-nitro substituted compounds,
respectively, their 4-nitro and 2-nitro isomers were not
formed. In the next series, the reaction of 1 with
aromatic amines (entries 11–20) was investigated. From
Table 1 it can be seen that the nitration of aniline and
m-substituted anilines with 1 is regioselective and
resulted in the formation of the corresponding p-nitro-
anilines (entries 11–13). Whereas the nitration of o-sub-
stituted anilines and p-substituted anilines with 1 gave
the corresponding m-nitroanilines (entries 14–20) in
good yields. No nitration took place at the o-position.
Finally, the nitration of substrates having strongly deac-
tivating group (entries 21–23) and heteroaromatic
compounds such as coumarins (entries 24–26) and
2,2-dimethyl-7-hydroxy-4-chromanone (entry 27) were
explored and the results obtained are shown in Table 1.
Towards this end a series of different aromatic com-
pounds were reacted with 1 in 85% sulfuric acid at 0–
5ꢁC to form the corresponding nitro compounds
(Scheme 1, Table 1). In the first series, the reaction of
1 in 85% sulfuric acid with benzene (entry 1) and the
Keywords: Guanidinium nitrate;Nitration;Regioselectivity.
*
Corresponding author. Tel.: +91 6526091x353;fax: +91 6528547;
e-mail: mmvramana@indiatimes.com
0040-4039/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.09.140

8682
M. M. V. Ramana et al. / Tetrahedron Letters 45 (2004) 8681–8683
Table 1. Nitration of aromatic compounds using guanidinium nitrate 1
Entry
Substrate
Producta
Time (h)
Mpb (ꢁC)
Yieldc (%)
1
Benzene
Toluene
Nitrobenzene
2-Nitrotoluene
4-Nitroacetanilide (3)
3
—
—
89
64
75
68
55
81
82
76
74
91
51
72
75
80
75
70
72
72
76
70
79
76
88
2d
3
3
Acetanilide
Phenol
2.5
2
215
114
143
178
153
83
4
4-Nitrophenol (4)
5e
6
Diphenyl ether
2-Methoxyacetanilide
4-Methoxyacetanilide
Chlorobenzene
Bromobenzene
Methyl cinnamate
Aniline
4,40-Dinitrodiphenyl ether
2-Methoxy-5-nitroacetanilide
4-Methoxy-3-nitroacetanilide
1-Chloro-4-nitrobenzene (3)
1-Bromo-4-nitrobenzene (2)
Methyl 4-nitrocinnamate (4)
4-Nitroaniline
2.5
2
7
2
8
3
9
3
127
161
148
161
136
131
108
142
78
10
11f
12
13
14
15
16
17
18
19
20
21
22
23
3
0.5
1
3-Chloroaniline
3-Methylaniline
4-Bromoaniline
4-Chloroaniline
4-Iodoaniline
4-Methylaniline
4-Methoxyaniline
2-Chloroaniline
2-Methoxyaniline
Acetophenone
Methyl benzoate
Nitrobenzene
3-Chloro-4-nitroaniline
3-Methyl-4-nitroaniline
4-Bromo-3-nitroaniline
4-Chloro-3-nitroaniline
4-Iodo-3-nitroaniline
4-Methyl-3-nitroaniline
4-Methoxy-3-nitroaniline
2-Chloro-5-nitroaniline
2-Methoxy-5-nitroaniline
3-Nitroacetophenone
Methyl 3-nitrobenzoate
1,3-Dinitrobenzene
0.75
1
1
1
0.75
0.5
1
57
121
118
81
0.5
3
3
78
89
3
NO2
O
O
O
O
24
3
3
191
262
84
O
O
O
O
O
HO
HO
25g
41
O2N
CH3
O
CH3
O
COCH3
COCH3
O
HO
HO
HO
26
3
202
85
O2N
CH3
O
CH3
O
CH3
CH3
CH3
HO
CH3
27
3
128
39
O2N
O
O
a Figure in brackets indicates the percentage yield of o-isomer present in the crude product based on GC-analysis.
b Melting points are uncorrected.
c Yield refers to purified products.
d 4-Nitrotoluene (mp 57ꢁC) was also obtained in 18% yield.
e Guanidinium nitrate 1 (2equiv) was used.
f 3-Nitroaniline (mp 114ꢁC) was also obtained in 10% yield.
g 7-Hydroxy-4-methyl-8-nitrocoumarin (mp 256ꢁC) was also obtained in 39% yield.
In conclusion a series of aromatic compounds having
moderately activating, activating, weakly deactivating
and strongly deactivating groups, anilines and heteroaro-
matic compounds have been nitrated successfully in
good yields to give the corresponding nitro compounds.
Experimental simplicity, mild reaction conditions, low
cost of the reagent, easy handling, and absence of di-
nitrated and poly-nitrated products makes 1 a useful
reagent for aryl nitration.
Typical procedure: To a well-stirred mixture of aromatic
compound (0.01mol) and sulfuric acid (85%, 15cm3)
was slowly added guanidinium nitrate
1 (1.22g,
0.01mol) while maintaining the temperature at 0–5ꢁC.

M. M. V. Ramana et al. / Tetrahedron Letters 45 (2004) 8681–8683
8683
After the addition of 1 was complete, the mixture was
Anal. Calcd for C11H11NO5: C, 55.70;H, 4.67;N,
5.90%. Found: C, 55.78;H, 4.52;N, 5.76%.
stirred for an additional 0.5–3h (Table 1) at the same
temperature or at rt (for entries 21–23). The reaction
mixture was poured onto ice water (100cm3) and in
the case of anilines it was poured onto ice cold
NaOH solution (20%, 100cm3). The solid obtained
was filtered, washed thoroughly with water and dried.
Where solid was not obtained the aqueous layer was ex-
tracted with CHCl3 (4 · 50cm3). The combined CHCl3
layer was washed with 10% Na2CO3 (2 · 25cm3), water
(2 · 25cm3) and then dried (anhyd Na2SO4). After
evaporation of the solvent, a brown residue was ob-
tained, which was purified by column chromatography
to afford the corresponding nitro compound. All the
compounds synthesised (entries 1–26) gave satisfactory
physical and spectral data consistent with literature
data.
References and notes
1. Thoma, M. Ger. Offen, 2,745,204 (Cl. C07C129), 1979.
Chem. Abstr. 1979, 90, 38954f.
2. Verma, P. S. J. Am. Chem. Soc. 1925, 47, 143–147.
3. Barton, D.;Ollis, D. Comprehensive Organic Chemistry;
Pergamon: Oxford, 1979, Vol. 6, p 943.
4. Price, C. C. J. Am. Chem. Soc. 1953, 75, 3277–3278.
5. Haines, L. B.;Adkins, H. J. Am. Chem. Soc. 1925, 47,
1419–1426.
6. (a) Mujumdar, M. P.;Kudav, N. A. Indian J. Chem. 1976,
14B, 1012–1013;(b) Sura, T. P.;Ramana, M. M. V.;
Kudav, N. A. Synth. Commun. 1988, 18, 2161–2165.
7. Kimura, M.;Kajita, K.;Naoyuki, O.;Morosawa, S. J. Org.
Chem. 1990, 55, 4887–4892.
7-Hydroxy-2,2-dimethyl-6-nitro-4-chromanone (entry
8. Thoma, M. Belg. 867,685 (Cl. C07C), 1978. Chem. Abstr.
1979, 90, 54504u.
1
27): IR (KBr) t: 1695, 3200cmꢀ1; H NMR (CDCl3,
60MHz): d 1.50 [s, 6H, C(CH3)2], 2.65 (s, 2H, COCH2),
6.66 (s, 1H, Ar-H), 8.70 (s, 1H, Ar-H), 11.25 (s, H, OH).
9. Urbanski, T.;Zylowski, J. B. Acad. Pol. Sci., Ser. Sci.
Chem. 1967, 15, 7–9.