Surface-mediated highly efficient regioselective nitration of aromatic compounds by bismuth nitrate

Article abstract of DOI:10.1016/S0040-4039(00)01397-6

Montmorillonite impregnated with bismuth nitrate was found to be an excellent reagent for aromatic nitration in high yield. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01397-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 8017–8020
Surface-mediated highly efficient regioselective nitration of
aromatic compounds by bismuth nitrate
Susanta Samajdar, Frederick F. Becker and Bimal K. Banik*
Department of Molecular Pathology, The University of Texas, M. D. Anderson Cancer Center, Box 89,
1515 Holcombe Boulevard, Houston, TX 77030, USA
Received 7 August 2000; accepted 14 August 2000
Abstract
Montmorillonite impregnated with bismuth nitrate was found to be an excellent reagent for aromatic
nitration in high yield. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: bismuth nitrate; clay; nitration; aromatic compounds.
We have been engaged in the development of aromatic compounds as anti-tumor agents and
have shown structure–activity relationships with several diamides and diamines to which a
polycyclic aromatic ring was bound.1 The nitro compounds required for the synthesis of these
derivatives were prepared by the conventional nitric acid–sulfuric acid or nitroniun tetra-
fluoborate methods.2 We became concerned about the disposal of the large amount of
acid-waste that resulted. To avoid this complication and the associated hazards, we set out to
test the nitrating abilities of nitrate-salts under solid phase conditions in a projected route to
develop a simple synthesis of the nitro compound in a relatively short period of time.
Surface-mediated organic reactions are undergoing extensive investigation because they are
more ecologically friendly.3 For example, montmorillonite which is commercially available has
shown considerable promise as a solid support in carrying out different chemical reactions.
Montmorillonite clay impregnated with anhydrous cupric nitrate termed as ‘claycop’ was used
for aromatic nitration reaction.4 A large excess of acetic anhydride was required when claycop
was used as the nitrating agent. The actual nitrating species was believed to be acetyl nitrate.4
Similarly, a clay with ferric nitrate termed as ‘clayfen’ was used as the reagent for the nitration
of estrone, though yields were poor.5 In addition, extreme precautions were necessary for the
preparation of this reagent.6 Sulfuric acid supported on silica gel catalyzed nonselective nitration
of simple aromatic compounds has also been reported.7
* Corresponding author.
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01397-6

8018
Based on our own work on bismuth8 salts, we became interested in exploring trivalent
bismuth nitrate as the nitrating agent under solid support. These experiments have culminated
in a facile synthetic method of convenient aromatic nitration by bismuth nitrate supported on
montmorillonite, taking only a few minutes. We also demonstrated that bismuth nitrate-medi-
ated nitration is effective for the nitration of polycyclic aromatic hydrocarbons.9
Mixing the starting materials with bismuth nitrate and montmorillonite with tetrahydrofuran
and evaporation of the solvent under rotavapor comprise the reaction conditions for successful,
regiospecific nitration with several aromatic compounds including multicyclic ring systems. The
nitration of aromatic compounds by our method is shown in Table 1. A comparison with other
solid supports, such as silica gel, acidic alumina, and ground molecular sieves was also carried
out. Anisole (entry 7), naphthalene (entry 1), fluorene (entry 4), chrysene (entry 2), and
dibenzofluorene (entry 3) were regiospecifically converted into the corresponding nitro com-
pounds by bismuth nitrate–montmorillonite in excellent yield. Interestingly, the site of the
electrophilic attack by this reagent was found to be identical to the conventional nitric acid or
acetyl nitrate-mediated nitration reaction (Scheme 1). The reaction of naphthalene using silica
gel as support under identical conditions as described with montmorillonite failed to produce the
nitro derivative, although the same mixture upon microwave irradiation afforded the nitronaph-
thalene in 70% yield. Acidic alumina and molecular sieves alone failed to give any product with
or without acid. The results indicated that montmorillonite is the solid support of choice for
aromatic nitration.
Scheme 1.
2-Naphthol (entry 7) produced only the dinitro derivative and phenol (entry 5) produced a
mixture of 2- and 4-nitrophenol in a ratio of 1:3. The formation of the dinitro derivatives and
mixtures of nitro derivatives with phenolic substrates indicated lesser selectivity under this
condition.
In order to confirm the reactivity of phenolic substrates, we carried out nitration of estrone
with bismuth nitrate–montmorillonite with the aim of synthesizing the biologically active 2 or
4-nitro estrones. In conformity with our results with phenolic substrates, the reaction produced
a mixture of 2-nitro and 4-nitro estrones in a ratio of 1:1 in 94% yield (entry 8). The nitration
of estrone by freshly prepared clayfen using bentonite K-10 demonstrated the production of
2-nitroestrone in 55% yield by stirring the reaction mixture in toluene overnight.5 However,
when we followed this procedure, we isolated a mixture of 2-nitro and 2,4-dinitro estrones in
90% yield (12 h).
Our results indicate that the nitration reaction depends strongly on the nature of the solid
support. Further, two solid adsorbents of identical structure with different surface area (particle
size) can give different product distribution. Based on a recent publication,10 we believe that the
binding of bismuth nitrate to the free hydroxyl group of the multi-metallic montmorillonite is
important and that this complex produces the nitronium ion. Clearly, the failure of bismuth
nitrate to produce any product with alumina and only 70% with silica gel (under microwave
irradiation), despite the presence of surface hydroxyl groups, strengthens the importance of the
composition of the solid support.

8019
Table 1
Montmorillonite/Bi(NO3)3-mediated nitration of aromatic compounds
In summary, we have shown a simple, rapid and convenient method for the aromatic nitration
with bismuth nitrate in the presence of montmorillonite at room temperature. The superiority of
this method over others includes a very rapid reaction (approximate 30 minutes instead of 24
hour) with readily available reagents. Further, our method requires no strong acid for the
preparation of the surface,7 no acetic anhydride for the reaction5 and it can be applied to a wide
range of substrates including complex polyaromatic hydrocarbons9 and results in high overall
yield.11

8020
Acknowledgements
We gratefully acknowledge the funding support received for this research project from the
Golden Family Fund for cancer research and NIH Cancer Center Support Grant, 5-P30-
CA16672-25, in particular the shared resources of the Pharmacology and Analytic Center
Facility.
References
1. Becker, F. F.; Banik, B. K. Bioorg. Med. Chem. 1998, 50, 2877.
2. For some examples of aromatic nitration with mixed acids see: (a) Olah, G. A.; Malhotra, R.; Narang, S. C. In
Nitration Methods and Mechanisms; VCH: New York, 1989. (b) Schofield, K. In Aromatic Nitration; Cambridge
University Press: Cambridge, 1980.
3. Laszlo et al. extensively studied aromatic nitration under solid phase conditions. For example, see: (a) Cornelis,
A.; Delaude, L.; Gertmans, A.; Laszlo, P. Tetrahedron Lett. 1988, 29, 5657. (b) Laszlo, P.; Cornelis, A. Aldrichim.
Acta 1988, 21, 97. (c) Laszlo, P.; Vandormael, J. Chem. Lett. 1988, 1843. (d) Laszlo, P.; Cornelis, A.; Gerstmans,
A.; Laszlo, P. Chem. Lett. 1988, 1839.
4. For nitration with claycop, see: Gigantee, B.; Prazeres, A. O.; Marcelo-Curto, M. J.; Cornelis, A.; Laszlo, P. J.
Org. Chem. 1995, 60, 3445 and references cited therein.
5. Cornelis, A.; Laszlo, P.; Pennetreau, P. J. Org. Chem. 1983, 48, 4771.
6. Cornelis, A.; Laszlo, P. Synthesis 1985, 909.
7. Riego, J. M.; Sedin, Z.; Zaldivar, J. M.; Marziano, N. C.; Tortato, C. Tetrahedron Lett. 1996, 37, 513.
8. (a) Banik, B. K.; Venkatraman, M. S.; Mukhopadhyay, C.; Becker, F. F. Tetrahedron Lett. 1998, 39, 7243. (b)
Banik, B. K.; Ghatak, A.; Venkatraman, M. S.; Becker, F. F. Synth. Commun. 2000, 2701. (c) Banik, B. K.
Ghatak, A.; Mukhopadhyay, C.; Becker, F. F. J. Chem. Res. (S) 2000, 108.
9. For the use of polyaromatic nitro compounds, see: (a) Becker, F. F. B.; Mukhopadhyay, C.; Hackfeld, L.; Banik,
I.; Banik, B. K. Bioorg. Med. Chem. 2000, submitted for publication. (b) Banik, B. K.; Becker, F. F. Curr. Med.
Chem. 2000, submitted for publication.
10. Kropp, J. P.; Breton, G. W.; Fields, J. D.; Tung, J. C.; Loomis, B. R. J. Am. Chem. Soc. 2000, 122, 4280.
11. A representative procedure is as follows: the compound to be nitrated (1 mmol) and montmorillonite KSF (500
mg, Aldrich) were added to a suspension of bismuth nitrate (1 mmol) in THF (10 mL). The solvent was then
evaporated under reduced pressure and dried in a vacuum pump for 5 min. The mixture was then repeatedly
washed with dichloromethane (ca. 25 mL) and it was concentrated to afford the crude product. The pure product
was isolated after column chromatography by crystallization.
.