NT Ai t Br aL t Ee S1 a. lt Ns aitration of Phenol with an Equivalent of
Highly Efficient Nitration of Phenolic
Compounds in Solid Phase or Solution
Using Bi(NO
3
)
3
‚5H O as Nitrating Reagent
2
Hong-Bin Sun,†,‡ Ruimao Hua,*,† and Yingwu Yin*,‡
Department of Chemistry, Tsinghua University, Key
Laboratory of Organic Optoelectronics & Molecular
Engineering of Ministry of Education, Beijing 100084,
China, and Department of Chemistry, Tsinghua University,
Key Laboratory of Bioorganic Phosphorus Chemistry of
Ministry of Education, Beijing 100084, China
b
b
entry
M(NO3)2-3
reaction conditions 2a (%) 2a′ (%)
1
2
3
4
5
6
7
8
9
Bi(NO3)3‚5H2O grinding, <5 min
Bi(NO3)3‚5H2O in acetone, <5 min
Fe(NO3)3‚9H2O grinding, <5 min
Ni(NO3)3‚9H2O grinding, >10 min
34
46
29
37
47
31
Received July 15, 2005
Ba(NO3)2
grinding, >10 min
Ca(NO3)2‚4H2O grinding, >10 min
Cu(NO3)2‚3H2O grinding, >10 min
no reaction
KNO3
AgNO3
grinding, >10 min
grinding, >10 min
}
a
The reactions were carried out using 1.0 mmol of phenol and
.0 mmol of nitrate salts. Isolated yield based on the amount of
b
1
phenol used.
nitrate salts as nitrating reagents required either special
solvents or co-reagents.
3 3
Bi(NO ) had been employed as a co-catalyst in the
8
nitration of phenolic compounds with 65% nitric acid and
as a nitrating reagent of aromatic compounds catalyzed
by montmorillonite KSF. In this paper, we report the
Bi(NO3)3‚5H2O was used as an efficient nitrating reagent
in the nitration of phenolic compounds to give nitrated
phenols in good to high yields. The nitration reaction
proceeded smoothly by grinding 1 equiv of phenol, 2-meth-
ylphenol, 4-methylphenol, or 4-chlorophenol and Bi(NO3)3‚
9
results of our investigation on the nitration of phenolic
compounds using Bi(NO
3
)
3 2
‚5H O as a nitrating reagent
in the solid phase or in solution at ambient temperature
(22-30 °C), and this nitrating reaction could proceed
without catalyst and co-reagent.
5
H2O, and the nitration of other phenolic compounds could
be performed in acetone at ambient temperature (22-30 °C).
Table 1 summarized the results of nitration of phenol
a with a number of nitrate salts. When 1 equiv of 1a
1
Nitroaromatic compounds are one of the most impor-
tant classes of organic compounds, and they can be
prepared from the nitration of relative aromatic com-
pounds. A mixture of concentrated nitric acid and sulfuric
acid has been used as the most common nitrating reagent
for the nitration of benzene, alkylbenzene, and less
(
2) (a) Gigante, B.; Prazeres, A. O.; Marcelo-Curto, M. J.; Cornelis,
A.; Laszlo, P. J. Org. Chem. 1995, 60, 3445-3447. (b) Rodrignes, J. A.
R.; Filho, A. P. de Oliveira; Moran, P. J. S.; Custodio, R. Tetrahedron
1
999, 55, 6733-6738. (c) Iranpoor, N.; Firouzabadi, H.; Heydari, R.
Synth. Commun. 1999, 29, 3295-3302. (d) Tasneem; Ali, M. M.;
Rajanna, K. C.; Saiparakash, P. K. Synth. Commun. 2001, 31, 1123-
1128. (e) Bahulayan, D.; Narayan, G.; Sreekumar, V.; Lalithambika,
M. Synth. Commun. 2002, 32, 3565-3574. (f) Tanemura, K.; Suzuki,
T.; Nishida, Y.; Satsumabayashi, K.; Horaguchi, T. J. Chem. Res.
Synop. 2003, 497-499. (g) Joshi, A. V.; Baidoosi, M.; Mukhopadhyay,
S.; Sasson, Y. Org. Process Res. Dev. 2003, 7, 95-97. (h) Muathen, H.
A. Molecules 2003, 8, 593-598. (i) Iranpoor, N.; Firouzabadi, H.;
Heydari, R. Synth. Commun. 2003, 33, 703-710. (j) Lancaster, N. L.;
Liopis-Mestre, V. Chem. Commun. 2003, 2812-2813. (k) Prakash, G.
K. S.; Panja, C.; Mathew, T.; Surampudi, V.; Petasis, N. A.; Olah, G.
A. Org. Lett. 2004, 6, 2205-2207.
1
reactive aromatic compounds, but highly reactive aro-
matic compounds, particularly easily oxidized substrates
such as aniline, phenols, pyrroles, etc., require mild
nitration conditions; thus, a wide variety of nitrating
2
reactions have been developed. Because nitrophenols are
very important organic synthetic intermediates, it is still
an interesting subject of organic synthesis to develop the
nitrating procedures of phenolic compounds under mild
(
3) Dove, M. F. A.; Manz, B. Montgomery, J.; Pattenden, G.; Wood,
conditions. The recent development of nitration of phe-
S. A. J. Chem. Soc., Perkin Trans. 1 1998, 1589-1590.
3
(4) Rajagopal, R.; Srinivasan, K. V. Synth. Commun. 2003, 33, 961-
3 3
nolic compounds using nitrate salts such as VO(NO ) ,
9
66.
4
5
6
Fe(NO
3
)
3
‚9H
2
O, (Me
, as the nitrating reagents has been reported.
However, the reported nitration procedure by using
4
N)NO
3
,
Mg(NO
3
)
2
‚6H
2
O, and
(
5) Shackelford, S. A.; Anderson, M. B.; Christie, L. C.; Goetzen, T.;
7
NaNO
3
Guzman, M. C.; Hananel, M. A.; Kornreich, W. D.; Li, H.; Pathak, V.
P.; Rabinovich, A. K.; Rajapakse, R. J.; Truesdale, L. K.; Tsank, S. M.;
Vazir, H. N. J. Org. Chem. 2003, 68, 267-275.
(
6) Zolfigol, M. A.; Ghaemi, E.; Madrakian, E. Synth. Commun. 2000,
*
To whom correspondence should be addressed. (R.H.) Fax: 86-
30, 1689-1694.
1
0-62792596.
(7) (a) Zolfigol, M. A.; Ghaemi, E.; Madrakian, E. Molecules 2001,
6, 614-620. (b) Zolfigol, M. A.; Ghaemi, E.; Madrakian, E. Synlett 2003,
191-194. (c) Zolfigol, M. A.; Madrakian, E.; Ghaemi, E. Molecules 2002,
7, 734-741.
†
Key Laboratory of Organic Optoelectronics & Molecular Engineer-
ing of Ministry of Education.
‡
Key Laboratory of Bioorganic Phosphorus Chemistry of Ministry
of Education.
3 3
(8) Bi(NO ) used as co-catalyst in the nitration of phenolic com-
(
1) (a) Schofield, K. Aromatic Nitration; Cambridge University
pounds by 65% nitric acid has been reported; see: Shi, M.; Cui, S.-C.
Adv. Synth. Catal. 2003, 345, 1197-1202.
Press: Cambridge, 1980. (b) Olah, G. S.; Malhotra, R.; Narang, S. C.
Nitration: Methods and Mechanism; VCH Publishers: New York,
989. (c) Ridd, J. H. Chem. Soc. Rev. 1991, 20, 149-165.
(9) Samajdar, S.; Becker, F. F.; Banik, B. K. Tetrahedron Lett. 2000,
41, 8017-8020.
1
1
0.1021/jo0514669 CCC: $30.25 © 2005 American Chemical Society
Published on Web 09/29/2005
J. Org. Chem. 2005, 70, 9071-9073
9071