Selective nitration of aromatic compounds with bismuth subnitrate and thionyl chloride

Article abstract of DOI:10.3390/80700593

Bismuth subnitrate/thionyl chloride have been found to be an efficient combination of reagents for nitration of a wide range of aromatic compounds in dichloromethane. Phenols, in particular, were easily mononitrated and dinitrated with the reagents by controlling the stoichiometry.

Full text of DOI:10.3390/80700593

Molecules 2003, 8, 593-598
molecules
ISSN 1420-3049
http://www.mdpi.org/
Selective Nitration of Aromatic Compounds with Bismuth
Subnitrate and Thionyl Chloride
Hussni A. Muathen *
Department of Chemistry, Umm Alqura University, P.O.Box 7283, Makkah, Saudi Arabia
* Author to whom correspondence should be addressed; e-mail: hussnimuathen@yahoo.com
Received: 1 June 2003; in revised form: 26 June 2003 / Accepted: 27 June 2003 / Published: 15 July
2003
Abstract: Bismuth subnitrate/thionyl chloride have been found to be an efficient
combination of reagents for nitration of a wide range of aromatic compounds in
dichloromethane. Phenols, in particular, were easily mononitrated and dinitrated with
the reagents by controlling the stoichiometry,
Keywords: Bismuth subnitrate; thionyl chloride; nitration; aromatic compounds; phenols.
Introduction
Aromatic nitro compounds represent versatile intermediates for a wide range of industrial products,
like pharmaceuticals, dyestuffs and explosives [1-4]. The introduction of a nitro group into an aromatic
ring is commonly performed in strongly acidic polar media [5]. The problems associated with mixed
nitric and sulfuric acids have prompted the search for alternative methods [6,7].
The use of metal nitrates in aromatic nitration has received particular attention, e.g.: AgNO3 / BF3
[8], Cu(NO3)2 / clay [9], ceric ammonium nitrate (CAN) / H2SO4 / SiO2 [10], Fe(NO3)3 / clay [11],
VO(NO3)3 [12] and some other metal nitrates / clay activated by acetic anhydride [13]. However, most
of these nitrates require certain manipulations before use, in addition to their limited applications to
reactive aromatics like phenols [14,15].

Molecules 2003, 8
594
Bismuth (III) compounds have received particular attention as low toxicity reagents and catalysts
for various organic transformations [16,17]. We hereby introduce a mild and selective method for
aromatic nitration using bismuth subnitrate and thionyl chloride in dichloromethane.
Results and Discussion
Bismuth nitrate exists in three forms: bismuth (III) nitrate pentahydrate [Bi(NO3)3·5H2O)][18];
bismuth oxynitrate [BiONO3], and bismuth subnitrate basic [Bi5O(OH)9(NO3)4] [19]. Bismuth (III)
nitrate pentahydrate supported on montmorillonite was used as a nitrating agent for active aromatics,
such as phenol, anisole and polycyclic compounds [20]. The reagent requires special preparation and
has limited use with reactive aromatic compounds.
The commercially available bismuth subnitrate, which is prepared by hydrolysis of trinitrate, is not
toxic [21]. It is used to treat gastric disorders [22]. To the best of our knowledge, it has not been used
as a nitrating agent.
Bismuth subnitrate is inactive, on its own, towards aromatic nuclei in organic solvents. Thus,
several catalysts to activate the subnitrate were considered. Thionyl chloride was reported to produce
thionyl chloride nitrate [ClSO(ONO2)] and thionyl nitrate [OS(ONO2)2] when treated with silver
nitrate. Both nitrate species have failed in nuclear nitration of aromatic compounds. Only phenols
reacted with both species to give o-nitrated products (Scheme 1) [23].
Scheme 1
THF
PhOH
SOCl2
AgNO3
PhONO2
ClSO(ONO2)
+
When bismuth subnitrate (0.25 equiv.) was added to a solution of the aromatic substrate and
thionyl chloride in dichloromethane at room temperature, a pale yellow color began to develop and the
nitration process started to take place (Scheme 2). The results are summarized in Tables 1-3.
Scheme 2
NO2
R
2SOCl2
R
+ 1/4 Bi5O(OH)9(NO3)4
r. t.

Molecules 2003, 8
595
Table 1. Nitration of Some Aromatic Compounds with Bismuth Subnitrate
Sub:NO3 Time
Entry
Substrate
benzene
Product
nitrobenzene
Yield%
ratio
1 : 1
1 : 1
h
6
3
1.
2.
87
62
27
74
84
16
52
12
76
75
74
18
60
27
49
toluene
2-nitrotoluene
4- nitrotoluene
4- nitro-m-xylene
2-nitromesitylene
2-nitroacetanilide
4-nitroacetanilide
2-nitroanisole
3.
4.
5.
m-xylene
mesitylene
acetanilide
1 : 1
1 : 1
1 : 1
3
2
3
6.
anisole
1 : 1
2
4-nitroanisole
7.
8.
9.
4-bromoanisole 4-bromo-2-nitroanisole
2-chloroanisole 2-chloro-4-nitroanisole
bromobenzene 2-bromonitrobenzene
4- bromonitrobenzene
1 : 1
1 : 1
1 : 1
6
5
9
10.
chlorobenzene 2-chloronitrobenzene
4- chloronitrobenzene
1 : 1
9
Table 2. Nitration of Polycyclic Aromatics with Bismuth Subnitrate
Sub:NO3 Time Yield
Entry
Substrate
naphthalene
Product
ratio
1 : 1
1 : 1
h
2
2
%
68
76
1.
2.
1-nitronaphthalene
1-nitro-2-methyl
naphthalene
2-methylnaphthalene
3.
4.
5.
6.
7.
8.
acenaphthene
biphenylene
fluorene
5-nitroacenaphthene
2-nitrobiphenylene
2-nitrofluorene
1 : 1
1 : 1
1 : 1
1 : 1
1 : 1
1 : 1
2
1
2
2
1
1
72
81
74
64
75
73
phenanthrene
pyrene
9-nitrophenanthrene
1-nitropyrene
biphenyl
4-nitrobiphenyl

Molecules 2003, 8
596
Table 3. Nitration of Phenols with Bismuth Subnitrate
Sub:NO3 Time Yield
Entry Substrate
Product
ratio
1 : 1
h
%
1.
2.
3.
phenol
phenol
o-cresol
2-nitrophenol
0.5
42
4- nitrophenol
46
72
14
56
28
83
86
82
52
22
70
78
72
63
78
2,4-dinitrophenol
1 : 2
1 : 1
2
2,6- dinitrophenol
2-methyl-4-nitrophenol
2-methyl-6-nitrophenol
4,6-dinitro-2-methylphenol
4-methyl-2-nitrophenol
2,6-dinitro-4-methylphenol
2-bromo-4-nitrophenol
2-bromo-6-nitrophenol
2-bromo-4,6-dinitrophenol
4-chloro-2-nitrophenol
4-chloro-2,6-dinitrophenol
4-nitrosalicyldehyde
2,4-dinitrophenol
0.5
4.
5.
6.
7.
o-cresol
1 : 2
1 : 1
1 : 2
1 : 1
2
0.5
1
p- cresol
p- cresol
2-bromophenol
1
8.
2- bromophenol
4-chlorophenol
4- chlorophenol
salicyldehyde
4-nitrophenol
1 : 2
1 : 1
1 : 2
1 : 1
1 : 1
3
1
3
3
3
9.
10.
11.
12.
Benzene and methylbenzenes were nitrated in excellent yield with bismuth subnitrate. The reaction
was selective, and no dinitro or side-chain substitution products were detected. The reaction rate of
methylbenzenes increased with the increasing number of methyl groups. Polycyclic aromatic
hydrocarbons can be efficiently mononitrated in good yields. Biphenylene, in particular, afforded 2-
nitrobiphenylene as the only product in high yield (Scheme 3). The tricyclic hydrocarbon has been
reported to undergo an addition reaction in acidic media because of the strained four-membered ring
[24], although isolation of 2-nitro and 2,6-dinitrobiphenylene in low yield was also reported [25].
Scheme 3
NO2
SOCl2
-
+
NO3
81%
With regards to phenols, the present procedure has several advantages over some other reported
methods, which suffer usually from drawbacks like overreactivity, oxidation ability of the reagents,
strongly acidic media, toxicity of the metal cations and tedious work up [26]. The reagents can

Molecules 2003, 8
597
selectively mononitrate phenols with different functional groups, regardless of their activity, to give
ortho and para derivatives. Dinitration is also possible with phenol, cresols and halophenols using the
appropriate proportions of the reagents. On the other hand, when the same procedure was applied to
phenol using Bi(NO3)3, Cu(NO3)2, or AgNO3, and thionyl chloride a mixture of mono and dinitro-
phenols was isolated. Moderately reactive aromatic compounds, i.e. anisole and acetanilide react with
the reagents to give mainly para- derivatives in high yields. Haloanisoles can be also nitrated in good
yields. Despite their reduced activity, halobenzenes also react with the reagents. The reaction is slower
but gives the corresponding ortho- and para-nitro derivatives in good yields.
No mechanistic work has been carried out. However, it is established that thionyl chloride reacts
with metal nitrate in THF to give thionyl chloride nitrate [23]. We believe that the nitrate may
disproportionate in the more polar dichloromethane to give sulfur dioxide and nitryl chloride (NO2Cl),
which might be the nitrating species. Our speculation is based on observed slow evolution of SO2 at
room temperature (Scheme 4).
Scheme 4
CH2Cl2
NO2Cl
+
SO2
ClSO(ONO2)
r. t.
Experimental
General
Substrates used were of laboratory reagent grade. Bismuth subnitrate was obtained from Alfa
Aesar. Thionyl chloride was purified by fractional distillation from quinoline. Product mixtures were
analyzed by TLC and GLC. The products were identified by comparison of their NMR, IR spectra,
TLC and physical data with those of authentic samples.
Typical procedure
A round-bottomed flask (100mL) fitted with a condenser was charged with the aromatic substrate
(5mmol), dry dichloromethane (50mL) and thionyl chloride (1.20g, 10mmol). The mixture was stirred
and bismuth subnitrate 80% (2.20g, 1.25mmol) was added. After vigorous stirring at room temperature
for the specified reaction time, the mixture was filtered to remove the inorganic materials. The filtrate
was washed with dilute HCl and water to remove any traces of bismuth(iii) salts and dried (Na2SO4). It
was evaporated in vacuo to give the crude products, which were separated by column chromatography
on silica gel eluting with chloroform-petroleum ether. In the case of nitrophenols, the filtrate was
washed only with cold saturated sodium chloride solution, dried and evaporated in vacuo at room
temperature.

Molecules 2003, 8
598
References
1. Olah, G.A.; Malhorta,R.; Narang, S.C. Nitration Methods and Mechanisms; VCH: New York,
1989.
2. Becker, F. F. Banik, B.K. Bioorg. Med. Chem. 1998, 50, 2877.
3. Zollinger, H. Color Chemistry: Properties and Applications of Organic Dyes, 2nd Edition; John
Wiley: New York, 1991.
4. Meyer, R.; Kholar, J.; Homburg, A. Explosives, 5th Edition; John Wiley: New York, 2002.
5. Ward, E.R. Chem. Ber. 1979, 15, 297.
6. Smith, M.B; March, J. March’s Advanced Organic Chemistry, 5th Edition; John Wiley: New
York, 2001; p. 696.
7. Ridd, J.H. Acta Chem. Scand. 1998, 52, 11.
8. Olah, G.A.; Fung, A.P.; Narang, S.C.; Olah, J.A. J.Org. Chem. 1981, 46, 3533.
9. Gigantee, B.; Prazeres, A.O.; Marcelo-Curto, M.J.; Cornelis, A.; Laszlo, P. J. Org. Chem. 1995,
60, 3445.
10. Mellor, J.M.; Mittoo, S.; Parkes, R; Millar, R.W. Tetrahedron 2000, 56, 8019.
11. Cornelis, A.; Laszlo, P. J. Org. Chem. 1983, 48, 4771.
12. Dove, M.F.A.; Manz, B.; Montgomery, G.; Pattenden, G.; Wood, S.A. J. Chem. Soc., Perkin
Trans. 1 1998, 1589.
13. Cornelis, A.; Delaude, L.; Gerstmans, A.; Laszlo, P. Tetrahedron Lett. 1988, 29, 5909.
14. Bisarya, S.C.; Joshi, S.K.; Holkar,A.G. Synth. Commun. 1993, 23, 1125.
15. Zolfigol, M.A.; Ghaemi, E.; Madrakian, E. Molecules 2001, 6, 614.
16. Leonard, N.M.; Wieland, L.C.; Mohan, R.S. Tetrahedron 2002, 58, 8373.
17. Suzuki, H.; Ikegami, T.; Matano, Y. Synthesis 1997, 3, 249.
18. Mellor, J.W. Compr. Treat. Inorg. Theor. Chem. 1929, 9, 705.
19. Rajah, C.A. Dtsch. Apoth. Ztg. 1935, 1714.
20. Samajdar, S.; Becker, F.F.; Banic, B. K. Tetrahedron Lett. 2000, 41, 8017.
21. Sundvall, B., Acta Chem. Scand (A), 1979, 33, 219.
22. Hejazi, R., Amiji, M. Int. J. Pharm., 2002, 235, 87.
23. Hakimelahi, G.H., Sharghi, H., Zarrinmayeh, H, Khalafi-Nezhad , A. Helv. Chim. Acta, 1984, 67,
906.
24. Barton, J.W.; Whitaker, K.E. J. Chem. Soc. (C) 1968, 1663.
25. Baker, W.; Barton, J.W.; McOmie, J.F. J. Chem.Soc. 1958, 2666.
26. Zolfigol, M.A.; Madrakian, E.;Ghaemi, E. Molecules, 2002, 7, 734.
Sample availability: Not available
© 2003 by MDPI (http://www.mdpi.org). Reproduction is permitted for noncommercial purposes.